Common Regulators

---

Complex: Phosphatidylinositol 3-kinase

URN: urn:agi-complex:3000112
Total Controls: 0
Total Nodes: 18
Total Members: 18
Connectivity: 2117
Name: Phosphatidylinositol 3-kinase

Cell Localization: Cell Localization

LocusLink ID: 472, 5286, 5287, 5288, 5289, 5290, 5291, 5293, 5294, 5295, 5296, 8503, 10870, 23049, 23533, 30849, 116986, 118788

---

Protein: TIAM1

Connectivity: 134
Hugo ID: 11805
Name: TIAM1
Description: T-cell lymphoma invasion and metastasis 1
URN: urn:agi-llid:7074

GO Cellular Component: plasma membrane

Cell Localization:
Cytoplasm
Plasma membrane

GO Biological Process:
ephrin receptor signaling pathway
intracellular signaling cascade
positive regulation of axonogenesis
signal transduction
small GTPase mediated signal transduction

MGI ID: 103306

Swiss-Prot Accession: Q13009

OMIM ID: OMIM:600687

Alias:
Tiam1
T-cell lymphoma invasion and metastasis 1
human T-lymphoma invasion and metastasis inducing TIAM1 protein
LOC304109
T-cell lymphoma invasion and metastasis I
TIAM I
T-lymphoma invasion and metastasis inducing protein 1
T-lymphoma invasion and metastasis inducing protein I

Organism:
Rattus norvegicus
Mus musculus
Human

LocusLink ID: 304109, 21844, 106270, 7074

Pathway: New Pathway(3)

Unigene ID:
Rn.38763
Mm.124100
Hs.115176

Group: protein binding

---

Protein: RAC1

Connectivity: 759
Notes: The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.
Hugo ID: 9801
Name: RAC1
Description: RAS-related C3 botulinum substrate 1
URN: urn:agi-llid:5879

GO Cellular Component:
cytoplasm
cytoplasmic vesicle
extrinsic to plasma membrane
lamellipodium

Cell Localization: Cytoplasm

GO Biological Process:
cell adhesion
cell motility
dendrite morphogenesis
endocytosis
hyperosmotic response
inflammatory response
intracellular signaling cascade
lamellipodium biogenesis
positive regulation of actin filament polymerization
response to wounding
small GTPase mediated signal transduction
morphogenesis
protein transport

State:
ras-related C3 botulinum toxin substrate 1 isoform Rac1
ras-related C3 botulinum toxin substrate 1 isoform Rac1b
ras-related C3 botulinum toxin substrate 1 isoform Rac1c

State Description:
Transcript Variant: This variant (Rac1) has a 57 bp in-frame deletion of exon 3b in the coding region, as compared to the variant Rac1b.
Transcript Variant: This variant (Rac1b) includes the alternatively spliced 57 bp region (exon 3b) that is missing in transcript variant Rac1.
Transcript Variant: This variant (Rac1c) differs in the 5′ UTR and lacks an in-frame portion of the 5′ coding region, compared to variant Rac1. These differences cause translation initiation at a downstream ATG resulting in isoform Rac1c which is short…

MGI ID: 97845

Swiss-Prot Accession: P15154

OMIM ID: OMIM:602048

Alias:
Rac1
ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)
D5Ertd559e
HAP-2
RAS-related C3 botulinum substrate 1
TC-25
RAC1_HUMAN
GTP-binding protein rac1
p21-Rac1
GTP-binding protein rac I
p21-Rac I
Rac(V12)
Ras-like protein TC25
RAS-related C3 botulinum substrate I
ras-related C3 botulinum toxin substrate 1
ras-related C3 botulinum toxin substrate 1 isoform Rac I
ras-related C3 botulinum toxin substrate 1 isoform Rac1
ras-related C3 botulinum toxin substrate 1 isoform Rac1b
ras-related C3 botulinum toxin substrate I
rho family, small GTP binding protein Rac I
rho family, small GTP binding protein Rac1
DNA segment, Chr 5, ERATO Doi 559, expressed
rho family, small GTP binding Rac

Organism:
Rattus norvegicus
Mus musculus
Human

LocusLink ID: 171377, 19353, 52352, 5879

RGD ID: 619755

Pathway:
CREB signaling
p38 Signaling
New Pathway(3)

Unigene ID:
Rn.29157
Mm.292510
Hs.413812

Group: nucleotide binding

---

Functional Class: integrin

Name: integrin
URN: urn:agi-go:0008305
Total Controls: 0
Total Nodes: 0
Total Members: 0
Connectivity: 650

---

Functional Class: RAS small monomeric GTPase

Name: RAS small monomeric GTPase
URN: urn:agi-go:0003930
Total Controls: 0
Total Nodes: 0
Total Members: 0
Connectivity: 1833

---

Complex: integrin

Name: integrin
URN: urn:agi-complex:3108305
Total Controls: 0
Total Nodes: 0
Total Members: 0
Connectivity: 945

---

Protein: TNFRSF6

Connectivity: 1140
Notes: The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. At least eight alternatively spliced transcript variants encoding seven distinct isoforms have been described. The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform.
Hugo ID: 11920
Name: TNFRSF6
Description: tumor necrosis factor receptor superfamily, member 6
URN: urn:agi-llid:355

GO Cellular Component:
integral to membrane
membrane
external side of plasma membrane
cytosol
soluble fraction

Cell Localization: Plasma membrane

GO Biological Process:
apoptosis
immune response
signal transduction
induction of apoptosis via death domain receptors
programmed cell death, activated T-cells
programmed cell death, inflammatory cells
programmed cell death, transformed cells
anti-apoptosis
induction of apoptosis
protein complex assembly
regulation of apoptosis

State:
isoform 1 precursor
isoform 2 precursor
isoform 3 precursor
isoform 4 precursor
isoform 5 precursor
isoform 6 precursor
isoform 7 precursor

State Description:
Transcript Variant: This variant (1) encodes the longest isoform (1).
Transcript Variant: This variant (2) lacks an in-frame coding segment compared to variant 1, resulting an isoform (2) that lacks an internal region, as compared to isoform 1.
Transcript Variant: This variant (3) lacks a coding segment, which leads to a translation frameshift, compared to variant 1. The resulting isoform (3) contains a distinct and shorter C-terminus, as compared to isoform 1.
Transcript Variant: This variant (4) lacks a coding segment, which leads to a translation frameshift, compared to variant 1. The resulting isoform (4) contains a distinct and shorter C-terminus, as compared to isoform 1.
Transcript Variant: This variant (8) lacks two coding segments, which leads to a translation frameshift, compared to variant 1. The resulting isoform (4) contains a distinct and shorter C-terminus, as compared to isoform 1.
Transcript Variant: This variant (5) lacks two coding segments, which leads to a translation frameshift, compared to variant 1. The resulting isoform (5) contains a distinct and shorter C-terminus, as compared to isoform 1.
Transcript Variant: This variant (6) lacks two coding segments, which leads to a translation frameshift, compared to variant 1. The resulting isoform (6) contains a distinct and shorter C-terminus, as compared to isoform 1.
Transcript Variant: This variant (7) lacks a coding segment, which leads to a translation frameshift, compared to variant 1. The resulting isoform (7) contains a distinct and shorter C-terminus, as compared to isoform 1.

MGI ID: 95484

Swiss-Prot Accession: P25445

OMIM ID: OMIM:134637, OMIM:601859

Alias:
Tnfrsf6
Tumor necrosis factor receptor superfamily, member 6
Fas antigen (ATP1)
Fas
lpr
APT1
CD95
APO-1
TNFR6
Fas antigen
lymphoproliferation
FAS1
FASTM
TNR6
apoptosis antigen 1
APO-1 cell surface antigen
TNR6_HUMAN
apoptosis-mediating surface antigen Fas precursor
APO I
Apo-1 antigen
apoptosis (APO-1) antigen 1
apoptosis (APO-1) antigen I
apoptosis antigen I
Apoptosis-mediating surface antigen FAS
APT I
FAS I
FASL receptor
FasR
Tumor necrosis factor receptor superfamily member 6 precursor
lymphoproliferation protein
(FAS)

Organism:
Rattus norvegicus
Mus musculus
Human

LocusLink ID: 246097, 14102, 107133, 355

RGD ID: 619831

Pathway:
Death receptor signaling
FAS signaling
Mitochondrial control of Apoptosis
p38 Signaling
Apoptosis
New Pathway(3)

Unigene ID:
Mm.1626
Hs.82359

Group:
Receptors
protein binding

---

Protein: MMP14

Connectivity: 205
Notes: Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP’s are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion.
Hugo ID: 7160
Name: MMP14
Description: matrix metalloproteinase 14 (membrane-inserted)
URN: urn:agi-llid:4323

GO Cellular Component:
extracellular matrix
integral to membrane
extracellular space
integral to plasma membrane

Cell Localization: Extracellular

GO Biological Process:
proteolysis and peptidolysis
collagen catabolism

EC Number: 3.4.24.-

MGI ID: 101900

Swiss-Prot Accession: P50281

OMIM ID: OMIM:600754

Alias:
Mmp14
Mt1-mmp
matrix metalloproteinase 14, membrane-inserted
membrane type 1-matrix metalloproteinase
matrix metalloproteinase 14 (membrane-inserted)
Membrane type 1-MMP
MMP-X1
MTMMP1
membrane-type matrix metalloproteinase 1
membrane-type-1 matrix metalloproteinase
matrix metalloproteinase 14 preproprotein
Membrane- type matrix metalloproteinase 1
Membrane- type matrix metalloproteinase I
Membrane-type- 1 matrix metalloproteinase
MMP-X I
MT-MMP 1
MTMMP I
MT-MMP I

Organism:
Rattus norvegicus
Mus musculus
Human

LocusLink ID: 81707, 17387, 105482, 4323

RGD ID: 620198

Pathway: New Pathway(3)

Unigene ID:
Rn.10371
Mm.280175
Hs.2399

Group:
Extracellular proteins
metal ion binding

---

Protein: EGR1

Connectivity: 809
Notes: The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentiation and mitogenesis. Studies suggest this is a cancer suppressor gene.
Hugo ID: 3238
Name: EGR1
Description: early growth response 1
URN: urn:agi-llid:1958

GO Cellular Component: nucleus

Cell Localization: Nucleus

GO Biological Process:
learning and/or memory
positive regulation of transcription from Pol II promoter
regulation of transcription, DNA-dependent
thymocyte differentiation

MGI ID: 95295

Swiss-Prot Accession: P18146

OMIM ID: OMIM:128990

Alias:
Egr1
Ngf1
Ngfi
NGFI-A
Krox-24
zif-268
early growth response 1
nerve growth factor-induced gene
egr
TIS8
Zenk
Egr-1
NGFIA
Zfp-6
ETR103
Krox-1
Krox24
NGF1-A
Zif268
A530045N19Rik
AT225
G0S30
zinc finger protein 225
transcription factor ETR103
nerve growth factor-induced protein A
early growth response I
EGR I
Krox I
Krox-24 protein
Ngf I
Transcription factor ETR103
Zfp VI
AT-225
AT(225)

Organism:
Rattus norvegicus
Mus musculus
Human

LocusLink ID: 24330, 24595, 13653, 1958

RGD ID: 2544

Pathway: New Pathway(3)

Unigene ID:
Rn.9096
Mm.181959
Hs.326035

Group:
Transcription factors
metal ion binding

---

Complex: platelet-derived growth factor

URN: urn:agi-complex:3000217
Total Controls: 0
Total Nodes: 9
Total Members: 9
Connectivity: 1406
Name: platelet-derived growth factor

Cell Localization: Cytoplasm

LocusLink ID: 1890, 5154, 5155, 5156, 5157, 5159, 6942, 56034, 80310

---

Protein: MT1A

Connectivity: 26
Hugo ID: 7393
Name: MT1A
Description: metallothionein 1A
URN: urn:agi-llid:4489

GO Cellular Component:
cytosol
lysosome
nucleus
cytoplasm

Cell Localization:
Cytoplasm
Nucleus

GO Biological Process:
nitric oxide mediated signal transduction
zinc ion homeostasis
transcription

EC Number: 2.7.7.6
MGI ID: 102725
Swiss-Prot Accession: P04731
OMIM ID: OMIM:156350

Alias:
Mt1a
Mt
Metallothionein 1 A
Polr2k
MafY
RPB12
RPABC4
RPB7.0
polymerase (RNA) II (DNA directed) polypeptide K
ABC10-alpha
metallothionein-I activator
RPB10alpha
metallothionein 1A
MGC32848
metallothionein 1A (functional)
Metallothionein-IA
MT1

Organism:
Rattus norvegicus
Mus musculus
Human

LocusLink ID: 24567, 17749, 4489
RGD ID: 3117

Pathway:
New Pathway
New Pathway(2)
New Pathway(3)

Unigene ID:
Rn.54397
Mm.305482
Hs.440939

Group: metal ion binding

---

Protein: COL18A1

Connectivity: 134
Notes: This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. The proteolytically produced C-terminal fragment of type XVIII collagen is endostatin, a potent antiangiogenic protein. Mutations in this gene are associated with Knobloch syndrome. The main features of this syndrome involve retinal abnormalities so type XVIII collagen may play an important role in retinal structure and in neural tube closure. Three transcripts have been identified for this gene.
Hugo ID: 2195
Name: COL18A1
Description: collagen, type XVIII, alpha 1
URN: urn:agi-llid:80781

GO Cellular Component:
collagen type XVIII
basement membrane
collagen
cytoplasm
extracellular matrix
extracellular space
membrane

Cell Localization: Extracellular

GO Biological Process:
angiogenesis
cell adhesion
development
phosphate transport
positive regulation of apoptosis
positive regulation of cell migration
positive regulation of cell proliferation
negative regulation of cell proliferation
organogenesis
visual perception

State:
alpha 1 type XVIII collagen isoform 1 precursor
alpha 1 type XVIII collagen isoform 3 precursor
alpha 1 type XVIII collagen isoform 2 precursor

State Description:
Transcript Variant: This variant (1) does not contain exons 1 and 2 but does contain exon 3 as compared to variant 2. Isoform 1, known as the long form, is the longest protein.
Transcript Variant: This variant (3) shares the same exon organization as variant 1 but it differs from variant 1 in using an alternative splice site in exon 9. The use of this splice site results in the loss of 129 nt at the beginning of exon 9 but do…
Transcript Variant: This variant (2) contains exons 1 and 2 but does not contain exon 3 as compared to variant 1. Isoform 2, known as the short form, has a unique N-terminus and is the shortest isoform.

MGI ID: 88451
Swiss-Prot Accession: P39060

OMIM ID:
OMIM:120328, OMIM:267750

Alias:
Col18a1
collagen, type XVIII, alpha 1
collagen type XVIII alpha 1
collagen type XVIII, alpha 1
endostatin
procollagen, type XVIII, alpha 1
alpha 1 type XVIII collagen isoform 1 precursor
alpha 1 type XVIII collagen isoform 2 precursor
alpha 1 type XVIII collagen isoform 3 precursor
Col18a I
Collagen alpha 1(XVIII) chain precursor
collagen, type XVIII, alpha I
procollagen, type XVIII, alpha I
alpha 1 type XVIII collagen
collagen, type XVIII, alpha
procollagen, type XVIII, alpha

Organism:
Rattus norvegicus
Mus musculus
Human

LocusLink ID: 85251, 12822, 1309, 51695, 80781

RGD ID: 70936

Pathway:
New Pathway
New Pathway(2)
New Pathway(3)

Unigene ID:
Rn.12030
Mm.4352
Hs.413175

Group:
Extracellular proteins
protein binding
extracellular matrix structural constituent

---

Protein: NRCAM

Connectivity: 27
Notes: The cell adhesion molecules (CAMs) are a subset of the immunoglobin (Ig) superfamily found in the nervous systems of both vertebrates and invertebrates. They are usually surface membrane proteins with multiple Ig domains at their N termini followed by several fibronectin type III repeats and either a transmembrane intracellular domain or a glycophosphatidylinositol-linked membrane anchor at the C terminus (Lane et al., 1996 [PubMed 8812479]).[supplied by OMIM]
Hugo ID: 7994
Name: NRCAM
Description: neuronal cell adhesion molecule
URN: urn:agi-llid:4897

GO Cellular Component:
plasma membrane
extracellular space
integral to membrane
external side of plasma membrane
integral to plasma membrane
neuronal cell projection

Cell Localization: Plasma membrane

GO Biological Process:
cell adhesion
axonogenesis
cell-cell adhesion
central nervous system development
clustering of voltage gated sodium channels
fasciculation of neuron
neuronal migration
positive regulation of neuron differentiation
regulation of axon extension
synaptogenesis

MGI ID:
104750
2442157

Swiss-Prot Accession: Q92823
OMIM ID: OMIM:601581

Alias:
Nrcam
neuron-glia-CAM-related cell adhesion molecule
Bravo
C130076O07Rik
RIKEN cDNA C130076O07 gene
neuronal cell adhesion molecule
mKIAA0343
C030017F07Rik
KIAA0343
NRCAM protein
RIKEN cDNA C030017F07 gene

Organism:
Rattus norvegicus
Mus musculus
Human

LocusLink ID: 25691, 18179, 77467, 110778, 319504, 4897

RGD ID: 3209

Pathway:
New Pathway
New Pathway(2)
New Pathway(3)

Unigene ID:
Rn.10691
Mm.208439
Hs.7912

Group:
Receptors
protein binding

---

Protein: COL7A1

Connectivity: 9
Notes: This gene encodes the alpha chain of type VII collagen. The type VII collagen fibril, composed of three identical alpha collagen chains, is restricted to the basement zone beneath stratified squamous epithelia. It functions as an anchoring fibril between the external epithelia and the underlying stroma. Mutations in this gene are associated with all forms of dystrophic epidermolysis bullosa. In the absence of mutations, however, an acquired form of this disease can result from an autoimmune response made to type VII collagen.
Hugo ID: 2214
Name: COL7A1
Description: collagen, type VII, alpha 1 (epidermolysis bullosa, dystrophic, dominant and recessive)
URN: urn:agi-llid:1294

GO Cellular Component:
collagen
extracellular space
basement membrane
collagen type VII
cytoplasm

Cell Localization: Extracellular

GO Biological Process:
cell adhesion
epidermis development
phosphate transport

MGI ID: 88462
Swiss-Prot Accession: Q02388
OMIM ID: OMIM:120120, OMIM:132000, OMIM:131750, OMIM:226600, OMIM:604129, OMIM:131850, OMIM:607523, OMIM:131705

Alias:
Col7a1
procollagen, type VII, alpha 1
EBD1
EBR1
EBDCT
collagen, type VII, alpha 1 (epidermolysis bullosa, dystrophic, dominant and recessive)
LC collagen
long chain collagen
collagen VII, alpha-1 polypeptide
alpha 1 type VII collagen precursor
Col7a I
Collagen alpha 1(VII) chain precursor
collagen, type VII, alpha 1 (epidermolysis bullosa, dystrophic, dominant an
EBD I
EBR I
Long-chain collagen
procollagen, type VII, alpha I
collagen, type VII, alpha 1 (epidermolysis bullosa, dystrophic, and)
procollagen, type VII, alpha

Organism:
Mus musculus
Human

LocusLink ID: 12836, 102759, 1294

Pathway:
New Pathway
New Pathway(2)
New Pathway(3)

Unigene ID:
Mm.6200
Hs.1640

Group:
Extracellular proteins
protein binding
extracellular matrix structural constituent

---

Protein: SP1

Connectivity: 1073
Hugo ID: 11205
Name: SP1
Description: Sp1 transcription factor
URN: urn:agi-llid:6667

GO Cellular Component:
nucleus
transcription factor complex

Cell Localization: Nucleus

GO Biological Process:
regulation of transcription from Pol II promoter
regulation of transcription, DNA-dependent
positive regulation of transcription, DNA-dependent

MGI ID: 98372

Swiss-Prot Accession: P08047
OMIM ID: OMIM:189906

Alias:
Sp1
Sp1 transcription factor
Sp1-1
trans-acting transcription factor 1
SP1_HUMAN
transcription factor Sp1
LOC144467
hypothetical protein BC012008
Sp1 I
specificity protein 1
specificity protein I
trans-acting transcription factor I
Transcription factor Sp I
TSFP I
TSFP1
SP I

Organism:
Rattus norvegicus
Mus musculus
Human

LocusLink ID: 24790, 20683, 6667, 144467
RGD ID: 3738
Pathway: New Pathway(3)

Unigene ID:
Rn.44609
Mm.4618
Hs.9460

Group:
Transcription factors
nucleic acid binding
metal ion binding

---

Complex: catenin

URN: urn:agi-complex:3116342
Total Controls: 0
Total Nodes: 12
Total Members: 12
Connectivity: 599
Name: catenin
Cell Localization: Nucleus
LocusLink ID: 1495, 1496, 1499, 1500, 1501, 3728, 8727, 9743, 51339, 56259, 56998, 57680

---

Functional Class: thrombin

Name: thrombin
URN: urn:agi-enz:3.4.21.5
Total Controls: 0
Total Nodes: 3
Total Members: 3
Connectivity: 1540
Cell Localization: Extracellular

Alias:
thrombin
fibrinogenase
thrombase
thrombofort
topical
thrombin-C
tropostasin
activated blood-coagulation factor II
blood-coagulation factor IIa
factor IIa
E thrombin
beta-thrombin
gamma-thrombin

LocusLink ID: 29251, 14061, 2147
EC Number: 3.4.21.5

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:1958:out-urn:agi-llid:4489::unknown
Nodes: EGR1 —> MT1A
References: 1
Connectivity: 2
Effect: unknown
MedLine Reference: 12598657:1092
Sentence: The inhibition of Pitx-1-induced MT1 expression by Egr-1 was dose-dependent (Fig. 3 C ), and was in sharp contrast to the synergistic Pitx-1:Egr-1 interaction observed in LHeta-luciferase promoter-reporter experiments (Fig. 3 D ) and reported previously ( 20 ).

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-complex:3116342:out-urn:agi-llid:960::positive
Nodes: catenin –+> CD44
References: 1
Connectivity: 2
Journal: PNAS
Journal Reference: v98 i18 p10356 (2001)
Journal Link: http://www.pnas.org/cgi/content/full/98/18/10356
MedLine Reference: 11526241:1024
Sentence: Not only target genes like c-myc ( 9 ) and cyclin D1 ( 10 ) but also genes necessary for invasive growth, like matrilysin ( 11 , 12 ), fibronectin ( 13 ), CD44 ( 14 ), and uPAR ( 15 ), are activated by nuclear beta-catenin.

---

Regulation

Effect: unknown
URN: urn:agi-Regulation:inout-urn:agi-llid:7074:out-urn:agi-llid:960::unknown
Nodes: TIAM1 —> CD44
References: 1
Connectivity: 2
Journal: Mol. Cell. Biol
Journal Reference: v22 i12 p4073 (2002)
Journal Link: http://mcb.asm.org/cgi/content/full/22/12/4073
MedLine Reference: 12024020:1030
Sentence: Tiam1 has been reported to interact with the hyaluronic acid receptor CD44 through this region, stimulating Tiam1-mediated Rac signaling and tumor cell migration ( 4 ).

---

Regulation

Effect: negative
URN: urn:agi-Regulation:inout-urn:agi-go:0008305:out-urn:agi-llid:5880::negative
Nodes: integrin —| RAC2
References: 1
Connectivity: 2
MedLine Reference: 14660749:6
Sentence: We provide evidence that integrins inhibit Rac2 activation via a membrane-associated guanine nucleotide exchange factor, likely to be Vav1.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:7040:out-urn:agi-llid:6446::positive
Nodes: TGFB1 –+> SGK
References: 1
Connectivity: 2
Effect: positive
MedLine Reference: 10220500:7
Sentence: In addition to spatial correlation of transforming growth factor (TGF)-beta1 protein and h-sgk mRNA expression, h-sgk transcription in human Intestine 407 and HepG2 cells as well as in U937 monocytes/macrophages was strongly induced by TGF-beta1 in vitro.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-complex:3000217:out-urn:agi-llid:960::positive
Nodes: platelet-derived growth factor –+> CD44
References: 1
Connectivity: 2
MedLine Reference: 9190898:5
Sentence: Wortmannin, a specific inhibitor of phosphoinositide 3-kinase (PI 3-kinase) partly reduced IGF-1 and PDGF induced CD44v6 expression.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:7040:out-urn:agi-llid:1294::positive
Nodes: TGFB1 –+> COL7A1
References: 3
Connectivity: 2
Effect: positive
MedLine Reference: 9582342:0
Sentence: We have previously shown that transforming growth factor-beta (TGF-beta) increases type VII collagen gene (COL7A1) expression in human dermal fibroblasts in culture (Mauviel, A., Lapi??re, J.-C., Halcin, C., Evans, C. H., and Uitto, J. (1994) J. Biol. Chem. 269, 25-28).
MedLine Reference: 10086338:0
Sentence: We have previously demonstrated that transforming growth factor-beta (TGF-beta) and pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta, synergistically enhance the expression of type VII collagen gene (COL7A1) in human dermal fibroblasts in culture (Mauviel et al., 1994).
MedLine Reference: 15047696:3

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:3553:out-urn:agi-llid:3176::positive
Nodes: IL1B –+> HNMT
References: 2
Connectivity: 2
MedLine Reference: 8653552:3
Sentence: Simultaneously IL-1 beta increased activity of HDC and histamine-N-methyltransferase (HMT), a neuronal histamine catabolizing enzyme.
MedLine Reference: 9933502:2
Sentence: IL-1beta increased the activities of both histidine decarboxylase (HDC), an HA synthesizing enzyme, and HA-N-methyltransferase (HMT), an HA catabolizing enzyme.

---

MolTransport

Transport Type: unknown
URN: urn:agi-MolTransport:inout-urn:agi-go:0004697:out-urn:agi-llid:1832::negative
Nodes: PKC —| DSP
References: 1
Connectivity: 2
Effect: negative
MedLine Reference: 7698224:7
Sentence: TPA also induced translocation of both the desmoyokin/AHNAK protein and desmoplakin, which was completely inhibited by PKC inhibitors.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:355:out-urn:agi-llid:960::unknown
Nodes: TNFRSF6 —> CD44
References: 1
Connectivity: 2
Effect: unknown
MedLine Reference: 12202399:7
Sentence: Injection of SEA into mice deficient in CD44 and Fas (CD44 KO/lpr) led to an increased primary response when compared to mice that expressed CD44 but not Fas (CD44 WT/lpr), suggesting that the enhanced response to SEA was dependent on CD44 but not Fas expression.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:7040:out-urn:agi-llid:1604::negative
Nodes: TGFB1 —| DAF
References: 1
Connectivity: 2
Effect: negative
MedLine Reference: 12791098:4
Sentence: Interleukin-1beta (IL-1beta) consistently downregulated the expression of CD46 and CD59; IL-4 consistently downregulated the expression of CD46 and transforming growth factor-beta1, consistently downregulated the expression of both CD46 and CD55.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:4018:out-urn:agi-llid:9590::unknown
Nodes: LPA —> AKAP12
References: 1
Connectivity: 2
Effect: unknown
MedLine Reference: 12372401:2
Sentence: We report that platelet-derived growth factor-BB (PDGF-BB), lysophosphatidic acid (LPA), and eicosapentaenoic acid (EPA) potently modulate SSeCKS gene expression in cultured smooth muscle (RASM) cells relative to other bioactive ligands tested.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-complex:3000217:out-urn:agi-llid:9590::positive:phosphorylation
Mechanism: phosphorylation
Nodes: platelet-derived growth factor –+> AKAP12
References: 1
Connectivity: 2
MedLine Reference: 12083796:8
Sentence: Moreover, PDGF could induce SSeCKS tyrosine phosphorylation in the absence of FAK activation, suggesting a role for FAK SH2-based docking rather than kinase activity.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:3630:out-urn:agi-llid:5209::unknown
Nodes: INS —> PFKFB3
References: 1
Connectivity: 2
Effect: unknown
MedLine Reference: 12007784:3
Sentence: We report here the PFKFB-3 gene expression control by insulin in the human colon adenocarcinoma HT29 cell line.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:5594:out-urn:agi-llid:3183::positive
Nodes: MAPK1 –+> HNRPC
References: 1
Connectivity: 2
MedLine Reference: 11406297:7
Sentence: We propose a model for the biphasic decay of APP mRNA in which ERK activation by PMA causes sequential upregulation of two APP mRNA binding proteins, nucleolin and hnRNP C.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:3553:out-urn:agi-llid:1604::unknown
Nodes: IL1B —> DAF
References: 1
Connectivity: 2
Effect: unknown
MedLine Reference: 10931136:5
Sentence: The combination of tumour necrosis factor-alpha, IL-1beta, and IL-6 caused increased expression of CD55 (three-fold) and CD59 (two-fold) and decreased expression of CD46 at day 3 post-exposure.

---

Regulation

Effect: unknown
URN: urn:agi-Regulation:inout-urn:agi-go:0008305:out-urn:agi-llid:960::unknown
Nodes: integrin —> CD44
References: 2
Connectivity: 2
MedLine Reference: 11139477:10
Sentence: Blocking ss(1)-integrins completely inhibited contraction of collagen, but gels containing HA required CD44 and ss(1)-integrin blockade for complete inhibition.
MedLine Reference: 9052764:12
Sentence: Increased expression of CD44H and of the amount of ligands for CD44H and integrins induced by TGF-beta1 promotes early development of peritoneal dissemination.

---

Regulation

Effect: negative
URN: urn:agi-Regulation:inout-urn:agi-llid:6714:out-urn:agi-llid:9590::negative
Nodes: SRC —| AKAP12
References: 2
Connectivity: 2
MedLine Reference: 11112996:0
Sentence: Rat aortic smooth muscle cells (RASM) express the src suppressed C-kinase substrate (SSeCKS), which is thought to be an integral regulatory component of cytoskeletal dynamics and G-protein coupled-receptor signaling modules.
MedLine Reference: 12808449:3
Sentence: Here we report that src-suppressed C-kinase substrate (SSeCKS) decreases the expression of vascular endothelial growth factor (VEGF) through AP-1 reduction and stimulates expression of angiopoietin-1 (Ang-1), an antipermeability factor in astrocytes.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:7040:out-urn:agi-llid:1311::positive
Nodes: TGFB1 –+> COMP
References: 1
Connectivity: 2
MedLine Reference: 11145932:4
Sentence: Serum, as well as transforming growth factor (TGF)beta1 and TGF-beta3, stimulated COMP/TSP-5 mRNA expression.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-enz:3.4.21.5:out-urn:agi-llid:6446::positive
Nodes: thrombin –+> SGK
References: 1
Connectivity: 2
MedLine Reference: 10589686:5
Sentence: In addition, thrombin, which may play a role in the progression of renal disease, increased Sgk message in cell culture.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:7040:out-urn:agi-llid:960::unknown
Nodes: TGFB1 —> CD44
References: 2
Connectivity: 2
Effect: unknown
MedLine Reference: 8335902:8
Sentence: TGF-beta 1 also down-regulated CD45RB and increased CD44 expression on responsive CD8+ and CD45RBhi T cells, thereby leading to a population of T cells enriched in mature phenotype.
MedLine Reference: 7576948:8
Sentence: In contrast, cytokines such as IFN gamma, TNF alpha, or growth factors such as bFGF, SCF and TGF beta were ineffective in modulating CD44 expression.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:4018:out-urn:agi-llid:2995::positive
Nodes: LPA –+> GYPC
References: 1
Connectivity: 2
Journal: JPET
Journal Reference: v294 i3 p1076 (2000)
Journal Link: http://jpet.aspetjournals.org/cgi/content/full/294/3/1076
MedLine Reference: 10945862:1015
Sentence: LPA mediates its effects by activating G protein- coupled (GPC ) receptors; at least three GPC receptors mediating effects of LPA have recently been cloned (Goetzl and An, 1998 ; Bandoh et al., 1999 ; Im et al., 2000 ).

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:5879:out-urn:agi-llid:960::positive
Nodes: RAC1 –+> CD44
References: 1
Connectivity: 2
Journal: J. Immunol
Journal Reference: v167 i1 p123 (2001)
Journal Link: http://www.jimmunol.org/cgi/content/full/167/1/123
MedLine Reference: 11418640:1247
Sentence: We find that selective pharmacological agonists of Rho family proteins RhoA, Rac1, and Cdc42 are able to accelerate CD44 cleavage.

---

Promoter Binding

Nodes: SP1 —> CD44
References: 1
Connectivity: 2
URN: urn:agi-PromoterBinding:inout-urn:agi-llid:6667:out-urn:agi-llid:960:
Journal: J. Biol. Chem
Journal Reference: v272 i22 p14139 (1997)
Journal Link: http://www.jbc.org/cgi/content/full/272/22/14139
MedLine Reference: 9162042:1030
Sentence: Despite the existence of three consensus hexanucleotide GGGCGG sequences, Sp1 binding to the CD44 gene upstream region has not been demonstrated.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:355:out-urn:agi-llid:5880::positive
Nodes: TNFRSF6 –+> RAC2
References: 2
Connectivity: 2
MedLine Reference: 8824295:1070
Sentence: Inhibition of endogenous Ras using transdominant inhibitory N17Ras prevents Fas-induced Rac 1 and Rac 2 stimulation, whereas the control vector pEF does not affect Fas-induced cell activation.
MedLine Reference: 9268362:1156
Sentence: Transfection of N17 Rac1 also prevents the activation of Rac2 by Fas as demonstrated previously ( 9 ).

---

ProtModification

URN: urn:agi-ProtModification:in-urn:agi-go:0004697:out-urn:agi-llid:9590:
Nodes: PKC —> AKAP12
Modification Type: phosphorylation
References: 1
Connectivity: 2
MedLine Reference: 8910468:1270
Sentence: Although SSeCKS and MARCKS share little sequence similarity past their PKC phosphorylation sites, they share several biochemical and structural characteristics common to other PKC substrates implicated in the regulation of cytoskeletal architecture such as igloo , GAP-43, and neurogranin.
Journal: J. Biol. Chem
Journal Reference: v271 i45 p28430 (1996)
Journal Link: http://www.jbc.org/cgi/content/full/271/45/28430

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-go:0003930:out-urn:agi-llid:5880::positive
Nodes: RAS small monomeric GTPase –+> RAC2
References: 1
Connectivity: 2
Journal: J. Biol. Chem
Journal Reference: v271 i42 p26389 (1996)
Journal Link: http://www.jbc.org/cgi/content/full/271/42/26389
MedLine Reference: 8824295:1070
Sentence: Inhibition of endogenous Ras using transdominant inhibitory N17Ras prevents Fas-induced Rac 1 and Rac 2 stimulation, whereas the control vector pEF does not affect Fas-induced cell activation.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:6667:out-urn:agi-llid:128::unknown
Nodes: SP1 —> ADH5
References: 1
Connectivity: 2
Effect: unknown
MedLine Reference: 9867805:1015
Sentence: The content of Sp1, Sp3, and Sp4 in different cells may be critical factors regulating transcription of the ADH5/ FDH gene.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-complex:3108305:out-urn:agi-llid:5880::positive
Nodes: integrin –+> RAC2
References: 1
Connectivity: 2
MedLine Reference: 12676940:1226
Sentence: Furthermore, we found that the eta2 integrin-induced accumulations of Rac1, Rac2, p47 phox , and p67 phox in the membrane fraction were significantly impaired in PMNs that had been pretreated with PP1.

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:4323:out-urn:agi-llid:4489::unknown
Nodes: MMP14 —> MT1A
References: 1
Connectivity: 2
Effect: unknown
Journal: J. Biol. Chem
Journal Reference: v278 i40 p38765 (2003)
Journal Link: http://www.jbc.org/cgi/content/full/278/40/38765
MedLine Reference: 12878590:1156
Sentence: Surprisingly, the cytoplasmic domain of MT1- MMP appeared to reduce the invasiveness of cells expressing the exchange construct MT1/MT3-C1 ( Fig. 4 , group 9 versus group 10 ), suggesting that it encodes a negative signal for MT-MMP function as suggested previously ( 26 ).

---

Regulation

Effect: unknown
URN: urn:agi-Regulation:inout-urn:agi-llid:6714:out-urn:agi-llid:80781::unknown:phosphorylation
Mechanism: phosphorylation
Nodes: SRC —> COL18A1
References: 1
Connectivity: 2
Journal: J. Biol. Chem
Journal Reference: v278 i39 p37895 (2003)
Journal Link: http://www.jbc.org/cgi/content/full/278/39/37895
MedLine Reference: 12851410:1216
Sentence: In addition, we observed that endostatin induced Src-dependent phosphorylation of p190RhoGAP with concomitant down-regulation of RhoA activity.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:5594:out-urn:agi-llid:6446::positive
Nodes: MAPK1 –+> SGK
References: 1
Connectivity: 2
Journal: J. Biol. Chem
Journal Reference: v278 i8 p5871 (2003)
Journal Link: http://www.jbc.org/cgi/content/full/278/8/5871
MedLine Reference: 12488318:1037
Sentence: Sgk is also transcriptionally induced by growth pathway signaling by serum ( 16 ), insulin and insulin-like growth factor-1 ( 17 , 40 ), follicle-stimulating hormone ( 41 ), cAMP ( 42 ), and activators of extracellular signal-regulated kinase (Erk) signaling pathways, fibroblast growth factor, platelet-derived growth factor, and TPA (12- O – tetradecanoylphorbol-13-acetate) ( 43 ).

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:207:out-urn:agi-llid:9891::positive
Nodes: AKT1 –+> ARK5
References: 3
Connectivity: 2
MedLine Reference: 12409306:1028
Sentence: Furthermore, Akt-activated ARK5 phosphorylated ATM both in vivo and in vitro and led to the phosphorylation of p53.
MedLine Reference: 13679856:1
Sentence: The activation of ARK5 is triggered by Akt, and ARK5 induces tumor cell survival during nutrient starvation.
MedLine Reference: 15060171:2

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:5594:out-urn:agi-llid:4734::positive
Nodes: MAPK1 –+> NEDD4
References: 1
Connectivity: 2
Journal: J. Biol. Chem
Journal Reference: v277 i16 p13539 (2002)
Journal Link: http://www.jbc.org/cgi/content/full/277/16/13539
MedLine Reference: 11805112:1300
Sentence: In conclusion, the current study identifies a mechanism by which ERK down-regulates ENaC by enhancing channel association with Nedd4.

---

ProtModification

Effect: unknown
URN: urn:agi-ProtModification:in-urn:agi-llid:207:out-urn:agi-llid:6446::unknown
Nodes: AKT1 —> SGK
Modification Type: phosphorylation
References: 2
Connectivity: 2
MedLine Reference: 11410590:1200
Sentence: Wild- type SGK displayed little activity toward the amino-terminal fragment of FKHR (Fig. 3 B , lanes 5 and 6 ), which contains one Akt phosphorylation site, Thr 24 .
MedLine Reference: 11154281:1155
Sentence: These experiments show that SGK, like Akt, phosphorylates FKHRL1 in vitro but that SGK and Akt display a difference in the efficacy with which they phosphorylate the three FKHRL1 phosphorylation sites.

---

Regulation

Effect: negative
URN: urn:agi-Regulation:inout-urn:agi-llid:5879:out-urn:agi-llid:5880::negative
Nodes: RAC1 —| RAC2
References: 2
Connectivity: 2
MedLine Reference: 11278678:1216
Sentence: Transgenic expression of WT Rac2 increases the amount of active Rac2 in transduced cells ( lanes 2 and 6 , upper panel ), and this enhanced Rac2 activity results in a decrease in active Rac1 ( lanes 2 and 6 , lower panel ).
MedLine Reference: 9268362:1144
Sentence: N17 Rac1 inhibits the activation of both Rac1 and Rac2 after Fas receptor stimulation as demonstrated previously ( 49 ).

---

Expression

URN: urn:agi-Expression:inout-urn:agi-llid:6714:out-urn:agi-llid:960::positive
Nodes: SRC –+> CD44
References: 1
Connectivity: 2
Effect: positive
Journal: J. Biol. Chem
Journal Reference: v276 i12 p9273 (2001)
Journal Link: http://www.jbc.org/cgi/content/full/276/12/9273
MedLine Reference: 11108719:1028
Sentence: The expression of activated oncogenes like v-Ras, v-Src, and v-Fos, which promote transformation and invasion, have been reported to induce CD44 expression ( 8-10 ).

---

Regulation

Effect: unknown
URN: urn:agi-Regulation:inout-urn:agi-complex:3000112:out-urn:agi-llid:960::unknown
Nodes: Phosphatidylinositol 3-kinase —> CD44
References: 1
Connectivity: 2
MedLine Reference: 10896935:1011
Sentence: The active mutant p110 subunit of PI3K has also been shown to enhance the CD44 cleavage, suggesting that PI3K mediates the Ras-induced CD44 cleavage.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:7074:out-urn:agi-llid:5880::positive
Nodes: TIAM1 –+> RAC2
References: 2
Connectivity: 2
MedLine Reference: 10559246:1133
Sentence: In BW 5147 T-lymphocyte cells, Madin Darby canine kidney cells and NIH3T3, cells Tiam1 specifically activates Rac, 2 suggesting that some cell-type variations may exist in the specificity of GEF proteins.
MedLine Reference: 14675773:3
Sentence: In contrast, Rac2 displays a slower nucleotide association and is more efficiently activated by the Rac-GEF Tiam1.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-go:0003930:out-urn:agi-llid:960::positive
Nodes: RAS small monomeric GTPase –+> CD44
References: 2
Connectivity: 2
MedLine Reference: 10896935:1011
Sentence: The active mutant p110 subunit of PI3K has also been shown to enhance the CD44 cleavage, suggesting that PI3K mediates the Ras-induced CD44 cleavage.
MedLine Reference: 8521619:6
Sentence: These results taken together demonstrate that ras-dependent regulation of CD44 may correlate with tumor progression and metastasis in vivo, possibly (although not exclusively) supporting CD44’s importance in metastatic progression.

---

Regulation

Effect: unknown
URN: urn:agi-Regulation:inout-urn:agi-complex:3000112:out-urn:agi-llid:5880::unknown
Nodes: Phosphatidylinositol 3-kinase —> RAC2
References: 1
Connectivity: 2
MedLine Reference: 10364257:1140
Sentence: The mechanism by which PI3K activates Rac2 in neutrophils is presently unknown.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-complex:3116342:out-urn:agi-llid:4897::positive
Nodes: catenin –+> NRCAM
References: 1
Connectivity: 2
Journal: Genes & Dev
Journal Reference: v16 i16 p2058 (2002)
Journal Link: http://www.genesdev.org/cgi/content/full/16/16/2058
MedLine Reference: 12183361:1025
Sentence: We identified Nr-CAM, a neuronal cell adhesion molecule (Grumet et al. 1991 ), as a major target whose expression was dramatically induced by both beta-catenin and plakoglobin.

---

ProtModification

URN: urn:agi-ProtModification:in-urn:agi-llid:6446:out-urn:agi-llid:4734:
Nodes: SGK —> NEDD4
Modification Type: phosphorylation
References: 1
Connectivity: 2
MedLine Reference: 11742982:1043
Sentence: As shown in Figure 2 B, Sgk1 did not efficiently phosphorylate the paralog Nedd4-1, which contains no consensus sequences for Sgk1-dependent phosphorylation and does not seem to be primarily involved in ENaC regulation ( Kamynina et al ., 2001a ).
Journal: EMBO
Journal Reference: v20 i24 p7052 (2001)
Journal Link: http://embojournal.npgjournals.com/cgi/content/full/20/24/7052

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:3630:out-urn:agi-llid:6446::positive
Nodes: INS –+> SGK
References: 10
Connectivity: 2
MedLine Reference: 10357815:1101
Sentence: This activation of HA-SGK and concomitant gel shift promoted by insulin or IGF-1 was inhibited by pretreatment of cells with LY294002.
MedLine Reference: 11096081:1027
Sentence: Furthermore, insulin as well as insulin-like growth factors stimulate Sgk activity by a mechanism requiring the participation of phosphatidylinositol 3-kinase.
MedLine Reference: 11278835:1147
MedLine Reference: 11751930:1041
MedLine Reference: 12590200:1
MedLine Reference: 12628440:0
MedLine Reference: 12912918:0
MedLine Reference: 12923071:2
MedLine Reference: 11154281:1135
MedLine Reference: 11756538:1043

---

Regulation

Effect: negative
URN: urn:agi-Regulation:inout-urn:agi-go:0004697:out-urn:agi-llid:960::negative
Nodes: PKC —| CD44
References: 1
Connectivity: 2
Journal: Endocrinology
Journal Reference: v141 i1 p247 (2000)
Journal Link: http://endo.endojournals.org/cgi/content/full/141/1/247
MedLine Reference: 10614645:1210
Sentence: In accordance, the induction of PKC is known to down-regulate LHR expression and function in Leydig tumor cells ( 39 ).

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-llid:4323:out-urn:agi-llid:960::positive
Nodes: MMP14 –+> CD44
References: 1
Connectivity: 2
MedLine Reference: 12145196:1011
Sentence: The PEX domain of MT1-MMP was indispensable in promoting cell migration and CD44H shedding.

---

Promoter Binding

Nodes: EGR1 —> CD44
References: 1
Connectivity: 2
Effect: unknown
URN: urn:agi-PromoterBinding:inout-urn:agi-llid:1958:out-urn:agi-llid:960::unknown
MedLine Reference: 12670907:1011
Sentence: We also identified an Egr-1-binding site in the mouse CD44 gene promoter that accounts for its responsiveness to HGF/SF in melanoma cells.

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-complex:3108305:out-urn:agi-llid:960::positive
Nodes: integrin –+> CD44
References: 1
Connectivity: 2
MedLine Reference: 11959814:1106
Sentence: Correlating with integrin-mediated up-regulation of cell motility, CD44 cleavage was detectable when v-Crk-induced 3Y1 cells were treated with fibronectin (Fig. 5 D ) .

---

Regulation

Effect: positive
URN: urn:agi-Regulation:inout-urn:agi-enz:3.4.21.5:out-urn:agi-llid:5880::positive
Nodes: thrombin –+> RAC2
References: 2
Connectivity: 2
MedLine Reference: 12171785:1055
Sentence: Thrombin and Ang II induce consumption of NAD(P)H and translocation of p47phox and Rac2 to the cell membrane, indicating an activation mechanism similar to that used by the neutrophil oxidase.
MedLine Reference: 10391925:1015
Sentence: Furthermore, thrombin increased expression of p47 phox and Rac2 and stimulated their translocation to the cell membrane.

---

Functional Class: PKC

Name: PKC
URN: urn:agi-go:0004697
Total Controls: 0
Total Nodes: 0
Total Members: 0
Connectivity: 3317

---

Protein: LPA

Connectivity: 682
Hugo ID: 6667
Name: LPA
Description: lipoprotein, Lp(a)
URN: urn:agi-llid:4018
GO Cellular Component: extracellular
Cell Localization: Extracellular
GO Biological Process:
circulation
lipid metabolism
lipid transport
proteolysis and peptidolysis
EC Number: 3.4.21.-
Swiss-Prot Accession: P08519
OMIM ID: OMIM:152200
Alias:
LP
AK38
lipoprotein, Lp(a)
Apolipoprotein Lp(a)
antiangiogenic AK38 protein
Apo(A)
Apolipoprotein(A) precursor
LP(A)
LPA
Organism: Human
LocusLink ID: 4018
Pathway: New Pathway(3)
Unigene ID: Hs.512581

---

Protein: ARK5

Connectivity: 12
Name: ARK5
Description: AMP-activated protein kinase family member 5
URN: urn:agi-llid:9891
GO Biological Process: protein amino acid phosphorylation
EC Number: 2.7.1.37
MGI ID: 1925226
OMIM ID: OMIM:608130
Alias:
B230104P22Rik
RIKEN cDNA B230104P22 gene
AW494241
expressed sequence AW494241
AMP-activated protein kinase family member 5
AMP-activated protein kinase family member V
ARK5
KIAA0537 gene product
similar to Probable serine/threonine-protein kinase KIAA0537
Organism:
Mus musculus
Human
LocusLink ID: 77976, 103332, 103457, 9891
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Mm.25874
Hs.200598
Group: nucleotide binding

---

Protein: RAC2

Connectivity: 97
Notes: The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.
Hugo ID: 9802
Name: RAC2
Description: ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)
URN: urn:agi-llid:5880
Cell Localization: Plasma membrane
GO Biological Process:
small GTPase mediated signal transduction
signal transduction
MGI ID:  97846
Swiss-Prot Accession: P15153
OMIM ID: OMIM:602049, OMIM:608203
Alias:
Rac2
RAS-related C3 botulinum substrate 2
AI452260
expressed sequence AI452260
Gx
EN-7
HSPC022
ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)
small G protein
Ras-related C3 botulinum toxin substrate 3 (rho family, small GTP-binding protein Rac2)
EN VII
p21-Rac2
RAS-related C3 botulinum substrate II
Ras-related C3 botulinum toxin substrate 2
Ras-related C3 botulinum toxin substrate II
rho family, small GTP binding protein Rac2
Organism:
Mus musculus
Human
LocusLink ID: 19354, 105812, 105850, 5880, 28963
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Mm.1972
Hs.301175
Group: nucleotide binding

---

Protein: HNRPC

Connectivity: 31
Notes: This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has one RRM domain that binds to RNAs. Two alternatively spliced transcript variants have been described for this gene.
Hugo ID: 5035
Name: HNRPC
Description: heterogeneous nuclear ribonucleoprotein C (C1/C2)
URN: urn:agi-llid:3183
GO Cellular Component:
nucleus
pronucleus
ribonucleoprotein complex
viral nucleocapsid
heterogeneous nuclear ribonucleoprotein complex
Cell Localization: Nucleus
GO Biological Process: RNA splicing
State:
heterogeneous nuclear ribonucleoprotein C isoform b
heterogeneous nuclear ribonucleoprotein C isoform a
State Description:
Transcript Variant: This variant (2) lacks 39 bases in the coding region compared to variant 1. Thus, this isoform b is 13 amino acids shorter than isoform a but it maintains the same reading frame.
Transcript Variant: This variant (1) encodes the full length isoform.
MGI ID: 107795
Swiss-Prot Accession: P07910
OMIM ID: OMIM:164020
Alias:
Hnrpc
Hnrnpc
Hnrpc1
Hnrpc2
hnRNPC1
hnRNPC2
hnrnp-C
hnRNP C1
hnRNP C2
heterogeneous nuclear ribonucleoprotein C1
heterogeneous nuclear ribonucleoprotein C2
D14Wsu171e
HNRNP
heterogeneous nuclear ribonucleoprotein C (C1/C2)
nuclear ribonucleoprotein particle C1 protein
nuclear ribonucleoprotein particle C2 protein
heterogeneous nuclear ribonuclear protein C (C1/C2)
heterogeneous nuclear ribonuclear protein C isoform a
heterogeneous nuclear ribonuclear protein C isoform b
heterogeneous nuclear ribonuclear protein C1
heterogeneous nuclear ribonuclear protein C2
Heterogeneous nuclear ribonuclear proteins C1 and C2
Heterogeneous nuclear ribonuclear proteins C1/C2
heterogeneous nuclear ribonucleoprotein C isoform a
heterogeneous nuclear ribonucleoprotein C isoform b
Heterogeneous nuclear ribonucleoproteins C1 and C2
Heterogeneous nuclear ribonucleoproteins C1/C2
hnRNP C1 / hnRNP C2
hnRNP C1/C2
hnRNPC I
Hnrpc I
nuclear ribonuclear protein particle C1 protein
nuclear ribonuclear protein particle C2 protein
Organism:
Mus musculus
Human
LocusLink ID: 15381, 15385, 15386, 28125, 105946, 3183
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Mm.274690
Hs.476302
Group: nucleic acid binding

---

Protein: GYPC

Connectivity: 70
Notes: Glycophorin C (GYPC) is an integral membrane glycoprotein. It is a minor species carried by human erythrocytes, but plays an important role in regulating the mechanical stability of red cells. A number of glycophorin C mutations have been described. The Gerbich and Yus phenotypes are due to deletion of exon 3 and 2, respectively. The Webb and Duch antigens, also known as glycophorin D, result from single point mutations of the glycophorin C gene. The glycophorin C protein has very little homology with glycophorins A and B.
Hugo ID: 4704
Name: GYPC
Description: glycophorin C (Gerbich blood group)
URN: urn:agi-llid:2995
GO Cellular Component: integral to plasma membrane
Cell Localization: Plasma membrane
GO Biological Process:
N-linked glycosylation
O-linked glycosylation
organogenesis
State:
glycophorin C isoform 1
glycophorin C isoform 2
State Description:
Transcript Variant: This variant (1) includes all 4 exons and encodes the full length protein.
Transcript Variant: This variant (2) is missing exon 2 and specifies the Yus phenotype.
MGI ID: 1098566
Swiss-Prot Accession: P04921
OMIM ID: OMIM:110750, OMIM:248310
Alias:
Gypc
Cd236r
glycophorin C
Gerbich antigen
0610037F22Rik
GE
GPC
glycophorin C (Gerbich blood group)
GLPC
Glycoconnectin
glycophorin C isoform 1
glycophorin C isoform 2
glycophorin C isoform I
glycophorin C isoform II
Glycophorin D
Glycoprotein beta
RIKEN cDNA 0610037F22 gene
Sialoglycoprotein D
similar to glycophorin C isoform 2
similar to glycophorin C isoform II
Organism:
Mus musculus
Human
LocusLink ID: 14935, 71683, 109659, 2995
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Mm.292145
Hs.81994

---

Protein: DSP

Connectivity: 35
Notes: Desmosomes are the most common type of intercellular junction in vertebrate epithelial cells. They are characterized by 2 forms of interaction with other cellular structures. First, they form membrane anchorage sites for intermediate-size filaments, which are seen as electron-dense plaques evident beneath the plasma membrane. Second, a specific membrane core domain interacts with a corresponding domain of the plasma membrane of an adjacent cell, apparently mediating intercellular adhesion in a stable way. The desmosome intermediate filament complex is thought to impart tensile strength and resilience to the epithelium. Desmosomal proteins can be divided into 2 groups based on whether they fractionate with the urea-insoluble ‘core’ or the urea-soluble ‘plaque’ components. Desmoglein (MIM 125670) is, for example, a protein of the core. The main proteins of the plaque comprise the desmoplakins and plakoglobin (MIM 173325).[supplied by OMIM]
Hugo ID: 3052
Name: DSP
Description: desmoplakin
URN: urn:agi-llid:1832
GO Cellular Component:
desmosome
mitochondrion
cell-cell adherens junction
cytoskeleton
intermediate filament
Cell Localization: Plasma membrane
GO Biological Process: epidermis development
MGI ID: 109611
Swiss-Prot Accession: P15924
OMIM ID: OMIM:125647, OMIM:607450, OMIM:605676, OMIM:607655
Alias:
Dsp
DP
desmoplakin I/II
2300002E22Rik
DPI
DPII
KPPS2
PPKS2
desmoplakin (DPI, DPII)
250/210 kDa paraneoplastic pemphigus antigen
desmoplakin
similar to dJ512B11.1 (Desmoplakin I (DPI))
Organism:
Mus musculus
Human
LocusLink ID: 13515, 76767, 109620, 1832
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Mm.314703
Hs.519873
Group: structural constituent of cytoskeleton

---

Protein: ADH5

Connectivity: 41
Notes: This gene encodes glutathione-dependent formaldehyde dehydrogenase or class III alcohol dehydrogenase chi subunit, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class III alcohol dehydrogenase is a homodimer composed of 2 chi subunits. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrimation, rhinitis, pharyngitis, and contact dermatitis.
Hugo ID: 253
Name: ADH5
Description: alcohol dehydrogenase 5 (class III), chi polypeptide
URN: urn:agi-llid:128
Cell Localization: Cytoplasm
GO Biological Process:
retinoid metabolism
alcohol metabolism
ethanol oxidation
EC Number:
1.1.1.1
1.2.1.1
MGI ID: 87929
Swiss-Prot Accession: P11766
OMIM ID: OMIM:103710
Alias:
Adh5
Adh3
Adh-5
GSNOR
alcohol dehydrogenase 5 (class III), chi polypeptide
S-nitrosoglutathione reductase
FDH
ADHX
ADH-3
formaldehyde dehydrogenase
glutathione-dependent formaldehyde dehydrogenase
Alcohol dehydrogenase (class III), chi polypeptide
class III alcohol dehydrogenase 5 chi subunit
alcohol dehydrogenase (NAD)
aldehyde reductase
aliphatic alcohol dehydrogenase
chi chain of alcohol dehydrogenase III
chi subunit alcohol dehydrogenase 5
chi subunit alcohol dehydrogenase V
clutathione-dependent formaldehyde dehydrogenase
ethanol dehydrogenase
Glutathione- dependent formaldehyde dehydrogenase
NAD-dependent alcohol dehydrogenase
NADH-alcohol dehydrogenase
NADH-aldehyde dehydrogenase
NAD-specific aromatic alcohol dehydrogenase
primary alcohol dehydrogenase
Organism:
Mus musculus
Human
LocusLink ID: 11532, 128, 2223
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Mm.3874
Hs.78989
Group:
oxidoreductase activity
metal ion binding
lipid binding

---

Protein: PFKFB3

Connectivity: 8
Hugo ID: 8874
Name: PFKFB3
Description: 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3
URN: urn:agi-llid:5209
Cell Localization: Cytoplasm
GO Biological Process:
fructose 2,6-bisphosphate metabolism
metabolism
regulation of glycolysis
EC Number: 2.7.1.105
MGI ID: 2181202
Swiss-Prot Accession: Q16875
OMIM ID: OMIM:605319
Alias:
Pfkfb3
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3
iPFK-2
inducible 6-phosphofructo-2-kinase
E330010H22Rik
E330010H22
IPFK2
6PF-2-K/Fru-2,6- P2ASE brain/placenta-type isozyme
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase III
RIKEN cDNA E330010H22 gene
RIKEN cDNA
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 117276, 170768, 269236, 5209
RGD ID: 619776
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Rn.10791
Mm.19669
Hs.195471
Group: nucleotide binding

---

Protein: MAPK1

Connectivity: 2588
Notes: The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.
Hugo ID: 6871
Name: MAPK1
Description: mitogen activated protein kinase 1
URN: urn:agi-llid:5594
GO Cellular Component:
cytosol
insoluble fraction
cytoplasm
nucleus
Cell Localization:
Cytoplasm
Nucleus
GO Biological Process:
cell cycle
intracellular signaling cascade
nuclear translocation of MAPK
positive regulation of transcription
protein amino acid phosphorylation
protein kinase cascade
signal transduction
organogenesis
phosphorylation
chemotaxis
induction of apoptosis
response to stress
synaptic transmission
EC Number:
2.7.1.-
2.7.1.37
State Description:
Transcript Variant: This variant (1) contains a different 3′ UTR region, however, encodes the same protein as compared to variant 2.
Transcript Variant: This variant (2) contains a different 3′ UTR region, however, encodes the same protein as compared to variant 1.
MGI ID: 1346858
Swiss-Prot Accession: P28482
OMIM ID: OMIM:176948
Alias:
Mapk1
Erk2
Rsk-1
mitogen activated protein kinase 1
extracellular-signal-regulated kinase 1
ERK
MAPK2
PRKM2
Prkm1
p41mapk
p42mapk
9030612K14Rik
p40
p41
ERT1
MK01
p40-ARC
p41-ARC
mitogen-activated protein kinase 1
protein tyrosine kinase ERK2
mitogen-activated protein kinase 2
extracellular signal-regulated kinase 2
MK01_HUMAN
MAP kinase 1
C78273
ERT I
Extracellular regulated kinase 2
Extracellular regulated kinase II
Extracellular signal- regulated kinase 2
Extracellular signal- regulated kinase II
MAP kinase 1
MAP kinase I
MAP kinase 2
MAP kinase II
MAPK I
mitogen activated protein kinase I
Mitogen-activated protein kinase II
p42 mitogen activated protein kinase 1
PRKM I
protein kinase, mitogen-activated 1
protein kinase, mitogen-activated I
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 116590, 19093, 26413, 74546, 98012, 106103, 106324, 5594
RGD ID: 70500
Pathway:
IL-2 signaling
IL-3 signaling
IL-6 signaling
Inhibition of Apoptosis
Insulin pathway
Insulin Receptor Signaling
Integrin Signaling
Jak-Stat Pathway from IL6 Receptor
MAPK signaling
Toll-Like Receptor pathway
CREB signaling
EGF signaling
Erk-PI3K in Collagen Binding
G-protein Coupled Receptor signaling
Antiapoptotic Pathways From IGF-1R
MAPK-ERK in Growth and Differentiation
Mitochondrial control of Apoptosis
NGF signaling
PDGF signaling
Apoptosis
New Pathway(3)
Unigene ID:
Rn.34914
Mm.196581
Hs.324473
Group:
Kinases
nucleotide binding

---

Protein: SRC

Connectivity: 1629
Notes: This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene.
Hugo ID: 11283
Name: SRC
Description: Rous sarcoma oncogene
URN: urn:agi-llid:6714
GO Cellular Component: intracellular
Cell Localization:
Cytoplasm
Plasma membrane
GO Biological Process:
cell growth and/or maintenance
intracellular signaling cascade
protein amino acid phosphorylation
regulation of cell cycle
protein kinase cascade
signal complex formation
EC Number: 2.7.1.112
State: proto-oncogene tyrosine-protein kinase SRC
State Description:
Transcript Variant: This variant (1) represents the longer transcript. Both isoforms 1 and 2 encode the same protein.
Transcript Variant: This variant (2) differs in the 5′ UTR compared to variant 1. Both isoforms 1 and 2 encode the same protein.
MGI ID: 98397
Swiss-Prot Accession: P12931
OMIM ID: OMIM:190090
Alias:
Src
c-Src
tyrosine protein kinase pp60-c-src
v-Src
Rous sarcoma oncogene
ASV
p60-Src
v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)
tyrosine kinase pp60c-src
tyrosine-protein kinase SRC-1
protooncogene SRC, Rous sarcoma
v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog
AW259666
expressed sequence AW259666
Proto-oncogene tyrosine-protein kinase SRC
SRC I
SRC protein kinase
SRC protein tyrosine kinase
SRC-1 kinase
tyrosine protein kinase SRC-1
v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog
SRC1
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 83805, 20779, 99351, 6714
RGD ID: 620795
Pathway:
ACH-R in apoptosis
Integrin Signaling
Erk-PI3K in Collagen Binding
G-protein Coupled Receptor signaling
MAPK-ERK in Growth and Differentiation
New Pathway(3)
Unigene ID:
Rn.112600
Mm.22845
Hs.436015
Group:
nucleotide binding
protein binding

---

Protein: AKAP12

Connectivity: 54
Notes: The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinases A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms.
Hugo ID: 370
Name: AKAP12
Description: A kinase (PRKA) anchor protein (gravin) 12
URN: urn:agi-llid:9590
GO Cellular Component: cytoplasm
Cell Localization: Plasma membrane
GO Biological Process:
signal transduction
protein targeting
G-protein coupled receptor protein signaling pathway
State:
A-kinase anchor protein 12 isoform 1
A-kinase anchor protein 12 isoform 2
State Description:
Transcript Variant: This variant (1) encodes the longer isoform (1), compared to variant 2.
Transcript Variant: This variant (2) has an alternate 5′ segment, compared to variant 1, that results in a distinct 5’UTR and 5′ coding region. Isoform 2 has a distinct and shorter N-terminus compared to isoform 1.
MGI ID: 1932576
Swiss-Prot Accession: Q02952
OMIM ID: OMIM:604698
Alias:
Akap12
A kinase (PRKA) anchor protein (gravin) 12
Srcs5
SSeCKS
Tsga12
gercelin
testis specific gene A12
v-src suppressed transcript 5
AKAP250
kinase scaffold protein gravin
A-kinase anchor protein, 250kDa
myasthenia gravis autoantigen gravin
A kinase (PRKA) anchor protein 12
A-kinase anchor protein 12
A-kinase anchor protein 250 kDa
Gravin
PRKA anchor protein 12
v-src suppressed transcript V
A kinase (PRKA) anchor protein 12 isoform 1
A kinase (PRKA) anchor protein 12 isoform 2
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 83425, 20785, 22091, 83397, 103188, 9590, 9590
RGD ID: 70988
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Rn.122094
Mm.27481
Hs.197081
Group: protein binding

---

Protein: HNMT

Connectivity: 24
Hugo ID: 5028
Name: HNMT
Description: histamine N-methyltransferase
URN: urn:agi-llid:3176
Cell Localization: Cytoplasm
GO Biological Process:
regulation of neurotransmitter levels
respiratory gaseous exchange
EC Number: 2.1.1.8
MGI ID: 2153181
Swiss-Prot Accession: P50135
OMIM ID: OMIM:605238
Alias:
Hnmt
histamine N-methyltransferase
1500031F01Rik
histamine 1-methyltransferase
histamine 1-methyltransferases
histamine methyltransferase
histamine methyltransferases
histamine-methylating enzyme
imidazolemethyltransferase
imidazolemethyltransferases
S-adenosylmethionine-histamine N-methyltransferase
S-adenosylmethionine-histamine N-methyltransferases
HMT
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 81676, 76347, 99068, 109094, 140483, 3176
RGD ID: 71049
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Rn.13145
Mm.33120
Hs.42151

---

Protein: DAF

Connectivity: 113
Hugo ID: 2665
Name: DAF
Description: decay accelerating factor for complement (CD55, Cromer blood group system)
URN: urn:agi-llid:1604
GO Cellular Component:
integral to plasma membrane
membrane
soluble fraction
Cell Localization:
Cytoplasm
Plasma membrane
GO Biological Process:
complement activation, classical pathway
Swiss-Prot Accession: P08174
OMIM ID: OMIM:125240
Alias:
Daf
decay-accelerating factor
TC
CD55
decay accelerating factor for complement (CD55, Cromer blood group system)
Decay-accelerating factor of complement
CD55 antigen
Complement decay-accelerating factor precursor
complement-glycosylphosphatidylinositol
complement-transmembrane
Daf I
Daf1
Daf2
Daf-GPI
Daf-TM
GPI-DAF
TM-DAF
Organism:
Rattus norvegicus
Human
LocusLink ID: 64036, 1604
RGD ID: 620651
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Rn.18841
Hs.408864

---

Protein: TGFB1

Connectivity: 2195
Notes: TGFB is a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types. TGFB acts synergistically with TGFA (MIM 190170) in inducing transformation. It also acts as a negative autocrine growth factor. Dysregulation of TGFB activation and signaling may result in apoptosis. Many cells synthesize TGFB and almost all of them have specific receptors for this peptide. TGFB1, TGFB2 (MIM 190220), and TGFB3 (MIM 190230) all function through the same receptor signaling systems.[supplied by OMIM]
Hugo ID: 11766
Name: TGFB1
Description: transforming growth factor, beta 1 (Camurati-Engelmann disease)
URN: urn:agi-llid:7040
GO Cellular Component:
extracellular matrix
extracellular space
Cell Localization: Extracellular
GO Biological Process:
cell growth
cell proliferation
defense response
inflammatory response
lung development
lymph gland development
myogenesis
necrosis
negative regulation of cell proliferation
organogenesis
protein amino acid phosphorylation
regulation of cell cycle
regulation of cell growth
regulation of cell proliferation
regulation of myogenesis
regulation of protein-nucleus import
skeletal development
transforming growth factor beta receptor signaling pathway
growth
anti-apoptosis
cell-cell signaling
MGI ID: 98725
Swiss-Prot Accession: P01137
OMIM ID: OMIM:190180, OMIM:131300
Alias:
Tgfb1
transforming growth factor, beta 1
transforming growth factor beta-1
transforming growth factor, beta-1
TGF1_RAT
transforming growth factor beta-1 precursor
Tgfb
Tgfb-1
TGF-beta 1
CED
DPD1
TGF1
transforming growth factor, beta 1 (Camurati-Engelmann disease)
diaphyseal dysplasia 1, progressive
TGF1_HUMAN
transforming growth factor beta 1 precursor
beta 1 transforming growth factor
Camurati-Engelmann disease
diaphyseal dysplasia 1, progressive (Camurati-Engelmann disease)
DPD I
HGNC:2997
TGF beta
Tgfb I
TGF-beta I
transforming growth factor, beta
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 59086, 21803, 7040, 43846
RGD ID: 69051
Pathway: New Pathway(3)
Unigene ID:
Rn.40136
Mm.248380
Hs.1103
Group:
Ligands
receptor binding

---

Protein: SGK

Connectivity: 170
Notes: This gene encodes a serine/threonine protein kinase that is highly similar to the rat serum-and glucocorticoid-induced protein kinase (SGK). This gene was identified in a screen of hepatocellular genes regulated in response to cellular hydration or swelling. Cellular hydration is a catabolic signal, stimulating glycogenolysis and proteolysis, and inhibiting protein and glycogen synthesis. This kinase has been shown to be important in activating certain potassium, sodium, and chloride channels. Expression of this gene in hepatocytes is stimulated by transforming growth factor-beta (TGF-beta) which participates in the pathophysiology of diabetic complications. Since both TGF-beta expression and SGK expression are elevated in diabetic nephropathy, this suggests an involvement of SGK in the development of this condition.
Hugo ID: 10810
Name: SGK
Description: serum/glucocorticoid regulated kinase
URN: urn:agi-llid:6446
GO Cellular Component: nucleus
Cell Localization:
Cytoplasm
Nucleus
GO Biological Process:
apoptosis
protein amino acid phosphorylation
sodium ion homeostasis
response to stress
sodium ion transport
EC Number: 2.7.1.37
MGI ID: 1340062
Swiss-Prot Accession: O00141
OMIM ID: OMIM:602958
Alias:
Sgk
serum/glucocorticoid regulated kinase
Sgk1
serine/threonine protein kinase SGK
Sgk I
similar to serum and glucocorticoid-regulated kinase
similar to serum and glucocorticoid-regulated kinase – rat
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 29517, 20393, 6446
RGD ID: 3668
Pathway:
Insulin Receptor Signaling
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Rn.4636
Mm.28405
Hs.296323
Group:
Kinases
nucleotide binding

---

Protein: NEDD4

Connectivity: 51
Hugo ID: 7727
Name: NEDD4
Description: neural precursor cell expressed, developmentally down-regulated 4
URN: urn:agi-llid:4734
GO Cellular Component:
cytosol
intracellular
ubiquitin ligase complex
Cell Localization: Cytoplasm
GO Biological Process:
protein modification
ubiquitin cycle
MGI ID: 97297
Swiss-Prot Accession: P46934
OMIM ID: OMIM:602278
Alias:
Nedd4a
Nedd4
neural precursor cell expressed, developmentally down-regulated gene 4A
Neural precursor cell expressed developmentally down-regulated gene 4
Nedd4-1
neural precursor cell expressed, developmentally down-regulated gene 4
neural precursor cell expressed, developmentally down-regulated gene 4
mKIAA0093
E430025J12Rik
KIAA0093
neural precursor cell expressed, developmentally down-regulated 4
AA959633
AL023035
Nedd4 I
neural precursor cell expressed, developmentally down-regulated IV
neural precursor cell expressed, developmentally down-regulated gene IV
neural cell expressed, developmentally down-regulated gene
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 25489, 17999, 102429, 102641, 102670, 4734
RGD ID: 3157
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Rn.99540
Mm.279923
Hs.1565

---

Protein: CD44

Connectivity: 472
Notes: The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis.
Hugo ID: 1681
Name: CD44
Description: CD44 antigen (homing function and Indian blood group system)
URN: urn:agi-llid:960
GO Cellular Component:
integral to membrane
membrane
plasma membrane
external side of plasma membrane
integral to plasma membrane
Cell Localization:
Plasma membrane
Cytoplasm
GO Biological Process:
cell adhesion
defense response
ureteric bud branching
cell-cell adhesion
cell-matrix adhesion
State:
CD44 antigen isoform 1 precursor
CD44 antigen isoform 2 precursor
CD44 antigen isoform 3 precursor
CD44 antigen isoform 4 precursor
CD44 antigen isoform 5 precursor
State Description:
Transcript Variant: This variant (1) represents the longest transcript. It encodes the longest isoform (1).
Transcript Variant: This variant (2) lacks an in-frame coding exon compared to variant 1. The resulting isoform (2) lacks an internal region, as compared to isoform 1.
Transcript Variant: This variant (3), also known as CD44R, lacks multiple coding-exons compared to variant 1. The translation remains in-frame. The resulting isoform (3) lacks an internal segment, as compared to isoform 1.
Transcript Variant: This variant (4) lacks multiple coding-exons compared to variant 1. The translation remains in-frame. The resulting isoform (4) lacks an internal segment, as compared to isoform 1.
Transcript Variant: This variant (5) lacks multiple coding-exons compared to variant 1. The translation frame is changed. The resulting isoform (5), also known as CD44 isoform RC, has a distinct and shorter C-terminus, as compared to isoform 1.
MGI ID: 88338
Swiss-Prot Accession: P16070
OMIM ID: OMIM:107269
Alias:
Cd44
CD44A
METAA
RHAMM
CD44 antigen
Cell surface glycoprotein CD44 (hyaluronate binding protein)
Ly-24
Pgp-1
HERMES
AW121933
IN
INLU
MC56
MDU2
MDU3
MIC4
Pgp1
CDW44
MUTCH-I
CD44R
CD44 antigen (homing function and Indian blood group system)
CDW44 antigen
Hermes antigen
hyaluronate receptor
monoclonal antibody A3D8
phagocytic glycoprotein I
Lutheran inhibitor, dominant
antigen gp90 homing receptor
heparan sulfate proteoglycan
cell adhesion molecule (CD44)
cell surface glycoprotein CD44
extracellular matrix receptor-III
GP90 lymphocyte homing/adhesion receptor
ECMR-III
MGC10468
AW146109
CD44 antigen (homing function)
CD44 antigen isoform 1 precursor
Epican
GP90 lymphocyte homing/adhesion receptor
Heparan sulfate proteoglycan MC56
homing function and Indian blood group system
HUTCH-I
similar to transmembrane glycoprotein
HYALURONATE BINDING PROTEIN
LHR
Lutheran inhibitor, dominant (monoclonal antibody A3D8)
Lutheran inhibitor, (monoclonal antibody A3D8)
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 25406, 12505, 99328, 99339, 960, 8055
RGD ID: 2307
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Rn.1120
Mm.330428
Hs.306278
Group:
protein binding
glycosaminoglycan binding

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Protein: COMP

Connectivity: 19
Notes: The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfides. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Mutations can cause the osteochondrodysplasias pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED).
Hugo ID: 2227
Name: COMP
Description: cartilage oligomeric matrix protein
URN:
urn:agi-llid:1311
GO Cellular Component:
extracellular space
extracellular
extracellular matrix
Cell Localization:
Extracellular
Cytoplasm
GO Biological Process:
cell adhesion
skeletal development
MGI ID: 88469
Swiss-Prot Accession: P49747
OMIM ID: OMIM:600310,OMIM:132400, OMIM:177170
Alias:
Comp
cartilage oligomeric matrix protein
EDM1
EPD1
PSACH
epiphyseal dysplasia, multiple 1
pseudoachondroplasia (epiphyseal dysplasia 1, multiple)
cartilage oligomeric matrix protein(pseudoachondroplasia, epiphyseal dysplasia 1, multiple)
cartilage oligomeric matrix protein (pseudoachondroplasia, epiphyseal dysplasia 1, multiple)
cartilage oligomeric matrix protein precursor
cartilage oligomeric matrix protein precursor
EDM I
EPD I
epiphyseal dysplasia, multiple I
cartilage oligomeric matrix protein(pseudoachondroplasia, epiphyseal dyspla
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 25304, 12845, 1311, 1904, 5659
RGD ID: 2378
Pathway:
New Pathway
New Pathway(2)
New Pathway(3)
Unigene ID:
Rn.10343
Mm.45071
Hs.1584
Group:
protein binding
metal ion binding
extracellular matrix structural constituent

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Protein: INS

Connectivity: 3659
Notes: After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into two chains (peptide A and peptide B) that are covalently linked via two disulfide bonds. Binding of this mature form of insulin to the insulin receptor (INSR) stimulates glucose uptake. A variety of mutant alleles with changes in the coding region have been identified.
Hugo ID: 6081
Name: INS
Description: insulin II
URN: urn:agi-llid:3630
GO Cellular Component:
extracellular
extracellular space
nucleus
small nucleolar ribonucleoprotein complex
Cell Localization: Extracellular
GO Biological Process:
activation of MAPK
glucose metabolism
glucose transport
physiological process
regulation of phosphorylation
ER-overload response
NOT activation of JUNK
insulin receptor signaling pathway
lipid catabolism
regulation of apoptosis
cell surface receptor linked signal transduction
cell-cell signaling
energy pathways
lipid metabolism
MGI ID: 96573
Swiss-Prot Accession: P01308
OMIM ID: OMIM:176730, OMIM:125850
Alias:
Ins2
insulin 2
Mody
Ins-2
Mody4
insulin II
AA986540
expressed sequence AA986540
proinsulin precursor
Ins2-rs I
Ins2-rs1
insulin
insulin 1
insulin I
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 24506, 16334, 101480, 3630
RGD ID: 2916
Pathway:
Insulin pathway
Insulin Receptor Signaling
New Pathway(3)
Unigene ID:
Rn.989
Mm.4946
Hs.89832
Group:
Ligands
receptor binding

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Protein: IL1B

Connectivity: 1870
Notes: The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2.
Hugo ID: 5992
Name: IL1B
Description: interleukin 1, beta
URN: urn:agi-llid:3553
GO Cellular Component:
extracellular
extracellular space
Cell Localization: Extracellular
GO Biological Process:
cell proliferation
immune response
inflammatory response
regulation of cell cycle
cytokine and chemokine mediated signaling pathway
neutrophil chemotaxis
positive regulation of chemokine biosynthesis
positive regulation of interleukin-6 biosynthesis
antimicrobial humoral response (sensu Vertebrata)
apoptosis
cell-cell signaling
negative regulation of cell proliferation
signal transduction
MGI ID: 96543
Swiss-Prot Accession: P01584
OMIM ID: OMIM:147720
Alias:
Il1b
interleukin 1 beta
interleukin 1, beta
Il-1b
IL-1beta
IL-1
IL1F2
catabolin
preinterleukin 1 beta
interleukin 1, beta proprotein
IL1B_HUMAN
interleukin-1 beta precursor
IL1-BETA
IL-1 beta
Interleukin IL1 beta
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 24494, 16176, 3553
RGD ID: 2891
Pathway:
New Pathway(3)
Unigene ID Rn.9869
Mm.222830
Hs.126256
Group:
Ligands
receptor binding

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Protein: AKT1

Connectivity: 2075
Notes: The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery.
Hugo ID: 391
Name: AKT1
Description: thymoma viral proto-oncogene 1
URN: urn:agi-llid:207
GO Cellular Component:
cytoplasm
lamellipodium
nucleus
Cell Localization:
Cytoplasm
Nucleus
GO Biological Process:
anti-apoptosis
positive regulation of cell growth
protein amino acid phosphorylation
signal transduction
apoptosis
apoptotic mitochondrial changes
cell growth and/or maintenance
germ cell development
protein catabolism
protein ubiquitination
regulation of cell cycle
G-protein coupled receptor protein signaling pathway
nitric oxide biosynthesis
response to heat
EC Number: 2.7.1.-
MGI ID: 87986
Swiss-Prot Accession: P31749
OMIM ID: OMIM:164730, OMIM:181500
Alias:
Akt1
Akt
v-akt murine thymoma viral oncogene homolog 1
thymoma viral proto-oncogene
RAC protein kinase alpha RAC-PK alpha
murine thymoma viral (v-akt) oncogene homolog 1
PKB
PKB/Akt
PKBalpha
thymoma viral proto-oncogene 1
RAC
PRKBA
KRAC
Murine thymoma viral (v-akt) oncogene homolog-1
serine/threonine protein kinase
KRAC_HUMAN
Akt1/PKB protein kinase
RAC-ALPHA
Akt I
Akt/PKB
AKTI
C-AKT
Murine thymoma viral (v-akt) oncogene homolog I
PKB alpha
Protein kinase B
RAC-alpha serine/threonine kinase
RAC-PK-alpha
serine/threonine protein kinase B
thymoma viral proto-oncogene I
v-akt murine thymoma viral oncogene homolog I
Organism:
Rattus norvegicus
Mus musculus
Human
LocusLink ID: 24185, 50586, 11651, 207
RGD ID: 2081
Pathway:
ACH-R in apoptosis
AKT signaling
Inhibition of Apoptosis
Insulin Receptor Signaling
Jak-Stat Pathway from IL6 Receptor
PTEN signaling
CREB signaling
Antiapoptotic Pathways From IGF-1R
Mitochondrial control of Apoptosis
Apoptosis
New Pathway(3)
Unigene ID:
Rn.11422
Mm.6645
Hs.368861
Group:
Kinases
nucleotide binding