STRINGSTRING
DDR2 DDR2 YAP1 YAP1 ILK ILK CCN4 CCN4 TENT5A TENT5A GDF10 GDF10 LTF LTF TWSG1 TWSG1 BAMBI BAMBI BMP4 BMP4 HOXA2 HOXA2 RANBP3L RANBP3L CTHRC1 CTHRC1 SMAD3 SMAD3 SNAI2 SNAI2 NOTCH1 NOTCH1 CLIC1 CLIC1 WDR63 WDR63 ID3 ID3 FERMT2 FERMT2 VEGFC VEGFC IL6 IL6 FBN2 FBN2 WNT10B WNT10B TP63 TP63 TNN TNN CTNNB1 CTNNB1 RASSF2 RASSF2 SMAD6 SMAD6 TWIST2 TWIST2 TOB1 TOB1 FFAR4 FFAR4 TCIRG1 TCIRG1 BMPR1A BMPR1A ATF4 ATF4 CHRD CHRD SUCO SUCO HAND2 HAND2 BMP7 BMP7 SKI SKI LRP3 LRP3 RIOX1 RIOX1 IGF1 IGF1 PTCH1 PTCH1 CITED1 CITED1 TWIST1 TWIST1 NOG NOG RORB RORB UCMA UCMA BMPR2 BMPR2 JUND JUND LIMD1 LIMD1 OSTN OSTN SFRP1 SFRP1 AXIN2 AXIN2 SMOC1 SMOC1 TNF TNF MEF2C MEF2C GLI3 GLI3 SFRP2 SFRP2 ATRAID ATRAID HEMGN HEMGN CCN1 CCN1 BMPR1B BMPR1B HDAC7 HDAC7 SOX11 SOX11 SEMA4D SEMA4D GREM1 GREM1 PRKACA PRKACA FBXO5 FBXO5 SMAD5 SMAD5 REST REST MEN1 MEN1 TNFAIP6 TNFAIP6 NBR1 NBR1 CDK6 CDK6 PRKD1 PRKD1 CRIM1 CRIM1 CTNNBIP1 CTNNBIP1 PPP3CA PPP3CA WWTR1 WWTR1 TMEM119 TMEM119 GDPD2 GDPD2 RUNX2 RUNX2 NPNT NPNT CEBPB CEBPB SOX9 SOX9 SCUBE3 SCUBE3 SMAD1 SMAD1 ZHX3 ZHX3 IL6ST IL6ST HDAC4 HDAC4 ACVR2A ACVR2A BMP6 BMP6 SCUBE2 SCUBE2 JAG1 JAG1 FGF23 FGF23 GLI1 GLI1 NOCT NOCT LRP5 LRP5 FGF2 FGF2 BMP2 BMP2
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.
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colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
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empty nodes:
proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
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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:
DDR2Discoidin domain receptor tyrosine kinase 2. (869 aa)
YAP1Yes associated protein 1. (432 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)
CCN4Cellular communication network factor 4. (368 aa)
TENT5ATerminal nucleotidyltransferase 5A. (413 aa)
GDF10Growth/differentiation factor 10; Growth factor involved in osteogenesis and adipogenesis. Plays an inhibitory role in the process of osteoblast differentiation via SMAD2/3 pathway. Plays an inhibitory role in the process of adipogenesis. (478 aa)
LTFLactotransferrin; Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. Lactoferricin B is an antimicrobial peptide. Inhibits the growth of Gram-negative and Gram-positive bacteria. (708 aa)
TWSG1Twisted gastrulation BMP signaling modulator 1. (223 aa)
BAMBIBMP and activin membrane-bound inhibitor homolog; Negatively regulates TGF-beta signaling. Belongs to the BAMBI family. (260 aa)
BMP4Bone morphogenetic protein 4; Induces cartilage and bone formation. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity). (409 aa)
HOXA2Homeobox protein Hox-A2; Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis; Belongs to the Antp homeobox family. Proboscipedia subfamily. (372 aa)
RANBP3LRAN binding protein 3 like. (463 aa)
CTHRC1Collagen triple helix repeat containing 1. (243 aa)
SMAD3Mothers against decapentaplegic homolog. (425 aa)
SNAI2Zinc finger protein SNAI2; Transcriptional repressor that modulates both activator- dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transcriptional repression of the TJ protein, occludin (OCLN) and subsequent oncogenic transformation of epithelial cells. Represses BRCA2 expression by binding to its E2-box-containing silencer and recruiting CTBP1 and HDAC1 in breast cells. In epidermal keratinocytes, binds to the E-box in ITGA3 promoter and represses its transcription. Involved in the regulation of [...] (268 aa)
NOTCH1Notch receptor 1. (2533 aa)
CLIC1Chloride intracellular channel protein 1; Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions (By similarity). (241 aa)
WDR63WD repeat domain 63. (892 aa)
ID3DNA-binding protein inhibitor ID-3; Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Involved in myogenesis by inhibiting skeletal muscle and cardiac myocyte differentiation and promoting muscle precursor cells proliferation. Inhibits the [...] (119 aa)
FERMT2Fermitin family member 2. (680 aa)
VEGFCVascular endothelial growth factor C; Belongs to the PDGF/VEGF growth factor family. (420 aa)
IL6Interleukin-6; Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasm [...] (208 aa)
FBN2Fibrillin 2. (2912 aa)
WNT10BProtein Wnt; Ligand for members of the frizzled family of seven transmembrane receptors; Belongs to the Wnt family. (391 aa)
TP63Tumor protein 63 (p63); Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. (680 aa)
TNNTenascin N. (1296 aa)
CTNNB1Catenin beta-1; Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion, as component of an [...] (781 aa)
RASSF2Ras association domain family member 2. (326 aa)
SMAD6Mothers against decapentaplegic homolog. (529 aa)
TWIST2Twist family bHLH transcription factor 2. (160 aa)
TOB1Transducer of ERBB2, 1. (341 aa)
FFAR4G protein-coupled receptor 120. (375 aa)
TCIRG1V-type proton ATPase subunit a; Essential component of the vacuolar proton pump (V-ATPase), a multimeric enzyme that catalyzes the translocation of protons across the membranes. Required for assembly and activity of the V-ATPase. (830 aa)
BMPR1AReceptor protein serine/threonine kinase; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (532 aa)
ATF4Cyclic AMP-dependent transcription factor ATF-4; Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to endoplasmic reticulum (ER) stress. In concert with DDIT3/CHOP, activates the transcription of TRIB3 and promotes ER stress-induced neuronal apoptosis [...] (348 aa)
CHRDChordin; Dorsalizing factor. Key developmental protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta family bone morphogenetic proteins (BMPs) and sequestering them in latent complexes. (958 aa)
SUCOSUN domain containing ossification factor. (1253 aa)
HAND2Heart and neural crest derivatives expressed 2. (217 aa)
BMP7Bone morphogenetic protein 7. (431 aa)
SKISKI proto-oncogene. (729 aa)
LRP3LDL receptor related protein 3. (782 aa)
RIOX1Ribosomal oxygenase 1; Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase. Specifically demethylates 'Lys- 4' (H3K4me) and 'Lys-36' (H3K36me) of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' (H3K4me3) and monomethylated H3 'Lys-4' (H3K4me1) residues, while it has weaker activity for dimethylated H3 'Lys-36' (H3K36me2). Also catalyzes the hydroxylation of 60S ribosomal protein L8 on 'His- 216'. Acts as a regulator of osteoblast differentiation via its interaction with SP7/OS [...] (667 aa)
IGF1Insulin-like growth factor I; The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]- 2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation. Ca(2+)-dependent exo [...] (188 aa)
PTCH1SSD domain-containing protein. (1453 aa)
CITED1Cbp/p300-interacting transactivator 1; Transcriptional coactivator of the p300/CBP-mediated transcription complex. Enhances SMAD-mediated transcription by strengthening the functional link between the DNA-binding SMAD transcription factors and the p300/CBP transcription coactivator complex. Stimulates estrogen-dependent transactivation activity mediated by estrogen receptors signaling; stabilizes the interaction of estrogen receptor ESR1 and histone acetyltransferase EP300. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional c [...] (256 aa)
TWIST1Twist family bHLH transcription factor 1. (201 aa)
NOGNoggin; Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite. (232 aa)
RORBRAR related orphan receptor B. (470 aa)
UCMAUncharacterized protein. (136 aa)
BMPR2Receptor protein serine/threonine kinase; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (1038 aa)
JUNDTranscription factor jun-D; Transcription factor binding AP-1 sites. Belongs to the bZIP family. Jun subfamily. (347 aa)
LIMD1LIM domain-containing protein 1; Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts [...] (674 aa)
OSTNOSTN protein. (132 aa)
SFRP1Secreted frizzled-related protein 1; Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP1 decreases intracellular beta-catenin levels (By similarity). Has antiproliferative effects on vascular cells, in vitro and in vivo, and can induce, in vivo, an angiogenic response. In vascular cell cycle, delays the G1 phase and entry into the S phase (By similarity). In kidney development, inhibits tubule formation and bud growth in metane [...] (308 aa)
AXIN2Axin 2. (846 aa)
SMOC1SPARC related modular calcium binding 1. (445 aa)
TNFTumor necrosis factor, membrane form; Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation (By similarity). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces [...] (333 aa)
MEF2CMyocyte-specific enhancer factor 2C; Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Enhances transcriptional activation mediated by SOX18. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex [...] (473 aa)
GLI3GLI family zinc finger 3. (1587 aa)
SFRP2Secreted frizzled-related protein 2. (294 aa)
ATRAIDAll-trans retinoic acid induced differentiation factor. (229 aa)
HEMGNHemogen; Regulates the proliferation and differentiation of hematopoietic cells. Overexpression block the TPA-induced megakaryocytic differentiation in the K562 cell model. May also prevent cell apoptosis through the activation of the nuclear factor-kappa B (NF-kB) (By similarity). (447 aa)
CCN1Cellular communication network factor 1. (463 aa)
BMPR1BSerine/threonine-protein kinase receptor; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (532 aa)
HDAC7Histone deacetylase; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. (1014 aa)
SOX11Transcription factor SOX. (451 aa)
SEMA4DSemaphorin 4D; Belongs to the semaphorin family. (863 aa)
GREM1CTCK domain-containing protein. (240 aa)
PRKACAcAMP-dependent protein kinase catalytic subunit alpha; Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose- mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the [...] (351 aa)
FBXO5F-box protein 5. (448 aa)
SMAD5Mothers against decapentaplegic homolog. (465 aa)
RESTUncharacterized protein. (1004 aa)
MEN1Menin; Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the [...] (610 aa)
TNFAIP6Tumor necrosis factor, alpha-induced protein 6. (280 aa)
NBR1NBR1 autophagy cargo receptor. (986 aa)
CDK6Cyclin dependent kinase 6; Belongs to the protein kinase superfamily. (326 aa)
PRKD1Serine/threonine-protein kinase; Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. (920 aa)
CRIM1Cysteine rich transmembrane BMP regulator 1. (1035 aa)
CTNNBIP1Beta-catenin-interacting protein 1; Prevents the interaction between CTNNB1 and TCF family members, and acts as negative regulator of the Wnt signaling pathway. (81 aa)
PPP3CASerine/threonine-protein phosphatase 2B catalytic subunit alpha isoform; Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Many of the substrates contain a PxIxIT motif and/or a LxVP motif (By similarity). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (By similarity). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to t [...] (527 aa)
WWTR1WW domain containing transcription regulator 1. (412 aa)
TMEM119Transmembrane protein 119. (302 aa)
GDPD2Glycerophosphodiester phosphodiesterase domain containing 2. (539 aa)
RUNX2Runt-related transcription factor; Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'- TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. (518 aa)
NPNTNephronectin. (616 aa)
CEBPBCCAAT/enhancer-binding protein beta; Important transcription factor regulating the expression of genes involved in immune and inflammatory responses. Plays also a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant functions with CEBPA. Has a promitotic effect on many cell types such as hepatocytes and adipo [...] (348 aa)
SOX9SRY-box transcription factor 9. (524 aa)
SCUBE3Signal peptide, CUB domain and EGF like domain containing 3. (1009 aa)
SMAD1Mothers against decapentaplegic homolog 1; Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor- regulated SMAD (R-SMAD). May act synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression; Belongs to the dwarfin/SMAD family. (465 aa)
ZHX3Zinc fingers and homeoboxes 3. (944 aa)
IL6STInterleukin 6 signal transducer. (918 aa)
HDAC4Histone deacetylase; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. (1089 aa)
ACVR2AActivin receptor type-2A; On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin A, activin B and inhibin A. Mediates induction of adipogenesis by GDF6; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (513 aa)
BMP6Bone morphogenetic protein 6. (496 aa)
SCUBE2Signal peptide, CUB domain and EGF like domain containing 2. (1027 aa)
JAG1Delta-like protein; Putative Notch ligand involved in the mediation of Notch signaling. (1218 aa)
FGF23Fibroblast growth factor 23; Belongs to the heparin-binding growth factors family. (245 aa)
GLI1GLI family zinc finger 1. (1105 aa)
NOCTCCR4 carbon catabolite repression 4-like (S. cerevisiae). (427 aa)
LRP5Low-density lipoprotein receptor-related protein; Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Belongs to the LDLR family. (1629 aa)
FGF2Kidney-derived growth factor; Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4. Also acts as an integrin ligand which is required for FGF2 signaling. Binds to integrin ITGAV:ITGB3. Plays an important role in the regulation of cell survival, cell division, cell differentiation and cell migration. Functions as a potent mitogen in vitro. Can induce angiogenesis. Belongs to the heparin-binding growth factors family. (155 aa)
BMP2Bone morphogenetic protein 2. (395 aa)
Your Current Organism:
Bos taurus
NCBI taxonomy Id: 9913
Other names: B. taurus, Bos bovis, Bos primigenius taurus, Bovidae sp. Adi Nefas, bovine, cattle, cow, dairy cow, domestic cattle, domestic cow
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