STRINGSTRING
SLIT2 SLIT2 PIK3CG PIK3CG ROBO2 ROBO2 FREM1 FREM1 GDNF GDNF TNXB TNXB ILK ILK BMP7 BMP7 CTNS CTNS INSL3 INSL3 ASPH ASPH GATA3 GATA3 WT1 WT1 ITGA8 ITGA8 PIK3CD PIK3CD PAX7 PAX7 ATRX ATRX BMP8B BMP8B CDC5L CDC5L PKHD1 PKHD1 HPSE2 HPSE2 SOX3 SOX3 PAX2 PAX2 TBX18 TBX18 CHD1L CHD1L DSTYK DSTYK RET RET GFRA1 GFRA1 SRGAP1 SRGAP1 SMAD4 SMAD4 DACT1 DACT1 EYA2 EYA2 SMAD3 SMAD3 SLIT3 SLIT3 SIX5 SIX5 SIX2 SIX2 AGXT AGXT WNT4 WNT4 FREM2 FREM2 LIN7C LIN7C PIK3CA PIK3CA TBC1D1 TBC1D1 SALL1 SALL1 TGFB1 TGFB1 WFS1 WFS1 ZBTB24 ZBTB24 AQP2 AQP2 TGFBR3 TGFBR3 BMP4 BMP4 SALL4 SALL4 PIK3CB PIK3CB GREM1 GREM1 FRAS1 FRAS1
Nodes:
Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
Node Color
colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
Edges:
Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding to each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
Your Input:
SLIT2Slit homolog 2 protein C-product; Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. In spinal chord development may play a role in guiding commissural axons [...] (1529 aa)
PIK3CGPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates [...] (1102 aa)
ROBO2Roundabout homolog 2; Receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development; Belongs to the immunoglobulin superfamily. ROBO family. (1394 aa)
FREM1FRAS1-related extracellular matrix protein 1; Extracellular matrix protein that plays a role in epidermal differentiation and is required for epidermal adhesion during embryonic development; Belongs to the FRAS1 family. (2179 aa)
GDNFGlial cell line-derived neurotrophic factor; Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high- affinity dopamine uptake; Belongs to the TGF-beta family. GDNF subfamily. (228 aa)
TNXBTenascin-X; Appears to mediate interactions between cells and the extracellular matrix. Substrate-adhesion molecule that appears to inhibit cell migration. Accelerates collagen fibril formation. May play a role in supporting the growth of epithelial tumors. (673 aa)
ILKIntegrin-linked protein kinase; Receptor-proximal protein kinase regulating integrin-mediated signal transduction. May act as a mediator of inside-out integrin signaling. Focal adhesion protein part of the complex ILK-PINCH. This complex is considered to be one of the convergence points of integrin- and growth factor-signaling pathway. Could be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells. Phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B. (452 aa)
BMP7Bone morphogenetic protein 7; Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis. (431 aa)
CTNSCystinosin; Cystine/H(+) symporter thought to transport cystine out of lysosomes. Plays an important role in melanin synthesis, possibly by preventing melanosome acidification and subsequent degradation of tyrosinase TYR; Belongs to the cystinosin family. (400 aa)
INSL3Insulin-like 3 A chain; Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor; Belongs to the insulin family. (157 aa)
ASPHAspartyl/asparaginyl beta-hydroxylase; [Isoform 1]: specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins; Belongs to the aspartyl/asparaginyl beta-hydroxylase family. (758 aa)
GATA3Trans-acting T-cell-specific transcription factor GATA-3; Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes. Binds to the consensus sequence 5'-AGATAG-3'. Required for the T-helper 2 (Th2) differentiation process following immune and inflammatory responses. (444 aa)
WT1Wilms tumor protein; Transcription factor that plays an important role in cellular development and cell survival. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'. Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may act as transcription factors. Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing. Isoform 1 has [...] (302 aa)
ITGA8Integrin alpha-8 heavy chain; Integrin alpha-8/beta-1 functions in the genesis of kidney and probably of other organs by regulating the recruitment of mesenchymal cells into epithelial structures. It recognizes the sequence R-G-D in a wide array of ligands including TNC, FN1, SPP1 TGFB1, TGFB3 and VTN. NPNT is probably its functional ligand in kidney genesis. Neuronal receptor for TNC it mediates cell-cell interactions and regulates neurite outgrowth of sensory and motor neurons. (1063 aa)
PIK3CDPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell recepto [...] (1044 aa)
PAX7Paired box protein Pax-7; Transcription factor playing a role in myogenesis through regulation of muscle precursor cells proliferation. (520 aa)
ATRXTranscriptional regulator ATRX; Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase a [...] (2492 aa)
BMP8BBone morphogenetic protein 8B; Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis (By similarity); Belongs to the TGF-beta family. (402 aa)
CDC5LCell division cycle 5-like protein; DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR). (802 aa)
PKHD1Fibrocystin; May be required for correct bipolar cell division through the regulation of centrosome duplication and mitotic spindle assembly. May be a receptor protein that acts in collecting-duct and biliary differentiation. (4074 aa)
HPSE2Inactive heparanase-2; Binds heparin and heparan sulfate with high affinity, but lacks heparanase activity. Inhibits HPSE, possibly by competing for its substrates (in vitro). (592 aa)
SOX3Transcription factor SOX-3; Transcription factor required during the formation of the hypothalamo-pituitary axis. May function as a switch in neuronal development. Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation. Required also within the pharyngeal epithelia for craniofacial morphogenesis. Controls a genetic switch in male development. Is necessary for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (By s [...] (446 aa)
PAX2Paired box protein Pax-2; Transcription factor that may have a role in kidney cell differentiation. Has a critical role in the development of the urogenital tract, the eyes, and the CNS. (396 aa)
TBX18T-box transcription factor TBX18; Acts as transcriptional repressor involved in developmental processes of a variety of tissues and organs, including the heart and coronary vessels, the ureter and the vertebral column. Required for embryonic development of the sino atrial node (SAN) head area. (607 aa)
CHD1LChromodomain-helicase-DNA-binding protein 1-like; DNA helicase which plays a role in chromatin-remodeling following DNA damage. Targeted to sites of DNA damage through interaction with poly(ADP-ribose) and functions to regulate chromatin during DNA repair. Able to catalyze nucleosome sliding in an ATP- dependent manner. Helicase activity is strongly stimulated upon poly(ADP-ribose)-binding; Belongs to the SNF2/RAD54 helicase family. (897 aa)
DSTYKDual serine/threonine and tyrosine protein kinase; Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation. Involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death. In the skin, it plays a predominant role in suppressing caspase-dependent apoptosis in response to UV stress in a range of dermal cell types. (929 aa)
RETExtracellular cell-membrane anchored RET cadherin 120 kDa fragment; Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and [...] (1114 aa)
GFRA1GDNF family receptor alpha-1; Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor (By similarity). (465 aa)
SRGAP1SLIT-ROBO Rho GTPase-activating protein 1; GTPase-activating protein for RhoA and Cdc42 small GTPases. Together with CDC42 seems to be involved in the pathway mediating the repulsive signaling of Robo and Slit proteins in neuronal migration. SLIT2, probably through interaction with ROBO1, increases the interaction of SRGAP1 with ROBO1 and inactivates CDC42. (1085 aa)
SMAD4Mothers against decapentaplegic homolog 4; In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac- specific gene expression. Binds to SMAD binding elements (SBEs) (5'- GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By [...] (552 aa)
DACT1Dapper homolog 1; Involved in regulation of intracellular signaling pathways during development. Specifically thought to play a role in canonical and/or non-canonical Wnt signaling pathways through interaction with DSH (Dishevelled) family proteins. The activation/inhibition of Wnt signaling may depend on the phosphorylation status. Proposed to regulate the degradation of CTNNB1/beta-catenin, thereby modulating the transcriptional activation of target genes of the Wnt signaling pathway. Its function in stabilizing CTNNB1 may involve inhibition of GSK3B activity. Promotes the membrane l [...] (836 aa)
EYA2Eyes absent homolog 2; Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5. Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Its function as histone phosphatase may contribute to its function in transcription regulat [...] (538 aa)
SMAD3Mothers against decapentaplegic homolog 3; Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP- 1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and m [...] (425 aa)
SLIT3Slit homolog 3 protein; May act as molecular guidance cue in cellular migration, and function may be mediated by interaction with roundabout homolog receptors. (1530 aa)
SIX5Homeobox protein SIX5; Transcription factor that is thought to be involved in regulation of organogenesis. May be involved in determination and maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the myogenin promoter, and in the IGFBP5 promoter (By similarity). Thought to be regulated by association with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2 and EYA3 (By similarity). (739 aa)
SIX2Homeobox protein SIX2; Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach. During kidney development, maintains cap mesenchyme multipotent nephron progenitor cells in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud and cooperates with WNT9B to promote renewing progenitor cells proliferation. Acts through its interaction with TCF7L2 and OSR1 in a canonical Wnt signaling independent manner preventing transcription of differentiation genes in cap mesenchyme such as WNT4. Al [...] (291 aa)
AGXTAlanine--glyoxylate and serine--pyruvate aminotransferase. (392 aa)
WNT4Protein Wnt-4; Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Plays an important role in the embryonic development of the urogenital tract and the lung. Required for normal mesenchyme to epithelium transition during embryonic kidney development. Required for the formation of early epithelial renal vesicles during kidney development (By similarity). Required for normal formation of the Mullerian duct in females, and normal levels of oocytes in the ovaries. Required for normal down-regulation of 3 beta-hydroxysteroid dehydrogenase in the ovary. Req [...] (351 aa)
FREM2FRAS1-related extracellular matrix protein 2; Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia. Required for epidermal adhesion. Involved in the development of eyelids and the anterior segment of the eyeballs. Belongs to the FRAS1 family. (3169 aa)
LIN7CProtein lin-7 homolog C; Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may funct [...] (197 aa)
PIK3CAPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to v [...] (1068 aa)
TBC1D1TBC1 domain family member 1; May act as a GTPase-activating protein for Rab family protein(s). May play a role in the cell cycle and differentiation of various tissues. Involved in the trafficking and translocation of GLUT4-containing vesicles and insulin-stimulated glucose uptake into cells (By similarity). (1168 aa)
SALL1Sal-like protein 1; Transcriptional repressor involved in organogenesis. (1324 aa)
TGFB1Transforming growth factor beta-1 proprotein; Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively. Transforming growth factor beta-1: Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form fo [...] (390 aa)
WFS1Wolframin; Participates in the regulation of cellular Ca(2+) homeostasis, at least partly, by modulating the filling state of the endoplasmic reticulum Ca(2+) store. (890 aa)
ZBTB24Zinc finger and BTB domain-containing protein 24; May be involved in BMP2-induced transcription. (697 aa)
AQP2Aquaporin-2; Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Plays an essential role in renal water homeostasis. (271 aa)
TGFBR3Transforming growth factor beta receptor type 3; Binds to TGF-beta. Could be involved in capturing and retaining TGF-beta for presentation to the signaling receptors. (851 aa)
BMP4Bone morphogenetic protein 4; Induces cartilage and bone formation. Also acts in mesoderm induction, tooth development, limb formation and fracture repair. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity). (408 aa)
SALL4Sal-like protein 4; Transcription factor with a key role in the maintenance and self-renewal of embryonic and hematopoietic stem cells. (1053 aa)
PIK3CBPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation [...] (1070 aa)
GREM1Gremlin-1; Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner (By similarity). Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro). Acts as inhibitor of monocyte chemotaxis. Can inhibit the growth or viability of normal cells but not transformed cells when is overexpressed (By similarity). Belongs to the DAN family. (184 aa)
FRAS1Fraser extracellular matrix complex subunit 1. (4012 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (22%) [HD]
STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.