STRINGSTRING
HES1 HES1 HEY2 HEY2 ANXA4 ANXA4 ADAM17 ADAM17 IL17A IL17A HES5 HES5 ATOH1 ATOH1 RBPJ RBPJ DTX4 DTX4 HNF1B HNF1B HOXD3 HOXD3 KRT19 KRT19 BMP2 BMP2 NEUROD4 NEUROD4 DLK2 DLK2 JAG1 JAG1 MIB1 MIB1 KCNA5 KCNA5 NRIP2 NRIP2 HEYL HEYL TMEM100 TMEM100 DTX3L DTX3L FAT4 FAT4 DLL4 DLL4 MIB2 MIB2 S1PR3 S1PR3 GRIP2 GRIP2 GOT1 GOT1 GMDS GMDS SIX1 SIX1 HES7 HES7 FOXC2 FOXC2 PLN PLN CDH6 CDH6 ITGB1BP1 ITGB1BP1 SNAI2 SNAI2 NOTCH1 NOTCH1 ETV2 ETV2 NR1H4 NR1H4 TBX2 TBX2 NR0B2 NR0B2 DLX1 DLX1 WDR12 WDR12 TP63 TP63 HEY1 HEY1 ASCL1 ASCL1 NFKBIA NFKBIA DTX1 DTX1 ZNF423 ZNF423 CDKN1B CDKN1B PSENEN PSENEN TSPEAR TSPEAR IFT74 IFT74 TIMP4 TIMP4 ANGPT4 ANGPT4 RITA1 RITA1 HES3 HES3 PSEN1 PSEN1 CNTN1 CNTN1 DLX2 DLX2 SUSD5 SUSD5 NOTCH4 NOTCH4 RBM15 RBM15 MAML2 MAML2 NOTCH3 NOTCH3 FOXA1 FOXA1 MAML3 MAML3 MECP2 MECP2 NRARP NRARP TGFBR2 TGFBR2 EPN1 EPN1 CFD CFD ONECUT1 ONECUT1 GSX2 GSX2 PTP4A3 PTP4A3 DTX2 DTX2 ADAM10 ADAM10 PSEN2 PSEN2 SNAI1 SNAI1 APH1B APH1B SORBS2 SORBS2 APP APP ENSBTAP00000062996 ENSBTAP00000062996 NLE1 NLE1 FBXW7 FBXW7 TGFB1 TGFB1 CFAP58 CFAP58 DLL1 DLL1 JAG2 JAG2 CDK6 CDK6 MAML1 MAML1 HP HP APH1A APH1A SOX9 SOX9 NOTCH2 NOTCH2 POFUT1 POFUT1 DTX3 DTX3
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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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query proteins and first shell of interactors
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second shell of interactors
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proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
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Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
protein homology
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HES1Transcription factor HES-1; Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'- CANNTG-3' with low affinity (By similarity). May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage (By similarity). (280 aa)
HEY2Hes related family bHLH transcription factor with YRPW motif 2. (337 aa)
ANXA4Annexin A4; May play a role in alveolar type II cells through interaction with the surfactant protein SFTPA1 (SP-A); Belongs to the annexin family. (319 aa)
ADAM17ADAM metallopeptidase domain 17. (825 aa)
IL17AInterleukin-17A; Ligand for IL17RA and IL17RC. The heterodimer formed by IL17A and IL17F is a ligand for the heterodimeric complex formed by IL17RA and IL17RC. Involved in inducing stromal cells to produce proinflammatory and hematopoietic cytokines. (153 aa)
HES5Hes family bHLH transcription factor 5. (227 aa)
ATOH1Atonal bHLH transcription factor 1. (352 aa)
RBPJRecombining binding protein suppressor of hairless; Transcriptional regulator that plays a central role in Notch signaling, a signaling pathway involved in cell-cell communication that regulates a broad spectrum of cell-fate determinations. Acts as a transcriptional repressor when it is not associated with Notch proteins. When associated with some NICD product of Notch proteins (Notch intracellular domain), it acts as a transcriptional activator that activates transcription of Notch target genes. Probably represses or activates transcription via the recruitment of chromatin remodeling [...] (487 aa)
DTX4Deltex E3 ubiquitin ligase 4. (615 aa)
HNF1BHNF1 homeobox B. (558 aa)
HOXD3Homeobox D3. (434 aa)
KRT19Keratin, type I cytoskeletal 19; Involved in the organization of myofibers. Together with KRT8, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle (By similarity); Belongs to the intermediate filament family. (399 aa)
BMP2Bone morphogenetic protein 2. (395 aa)
NEUROD4Neurogenic differentiation factor. (330 aa)
DLK2Protein delta homolog 2; Regulates adipogenesis. (383 aa)
JAG1Delta-like protein; Putative Notch ligand involved in the mediation of Notch signaling. (1218 aa)
MIB1Mindbomb E3 ubiquitin protein ligase 1. (1006 aa)
KCNA5Potassium voltage-gated channel subfamily A member 5; Belongs to the potassium channel family. (598 aa)
NRIP2Nuclear receptor interacting protein 2. (232 aa)
HEYLHairy/enhancer-of-split related with YRPW motif-like protein; Downstream effector of Notch signaling which may be required for cardiovascular development. Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3'. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6; Belongs to the HEY family. (328 aa)
TMEM100Transmembrane protein 100; Plays a role during embryonic arterial endothelium differentiation and vascular morphogenesis through the ACVRL1 receptor- dependent signaling pathway upon stimulation by bone morphogenetic proteins, such as GDF2/BMP9 and BMP10. Involved in the regulation of nociception, acting as a modulator of the interaction between TRPA1 and TRPV1, two molecular sensors and mediators of pain signals in dorsal root ganglia (DRG) neurons. Mechanistically, it weakens their interaction, thereby releasing the inhibition of TRPA1 by TRPV1 and increasing the single-channel open [...] (134 aa)
DTX3LDeltex E3 ubiquitin ligase 3L. (739 aa)
FAT4FAT atypical cadherin 4. (4982 aa)
DLL4Delta-like protein; Putative Notch ligand involved in the mediation of Notch signaling. (685 aa)
MIB2Mindbomb E3 ubiquitin protein ligase 2. (959 aa)
S1PR3Sphingosine-1-phosphate receptor 3; Belongs to the G-protein coupled receptor 1 family. (378 aa)
GRIP2Glutamate receptor interacting protein 2. (1046 aa)
GOT1Aspartate aminotransferase, cytoplasmic; Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-m [...] (413 aa)
GMDSGDP-mannose 4,6-dehydratase. (372 aa)
SIX1SIX homeobox 1. (284 aa)
HES7Hes family bHLH transcription factor 7. (229 aa)
FOXC2Forkhead box C2. (502 aa)
PLNCardiac phospholamban; Reversibly inhibits the activity of ATP2A2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+). Modulates the contractility of the heart muscle in response to physiological stimuli via its effects on ATP2A2. Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in the heart muscle. The degree of ATP2A2 inhibition depends on the oligomeric state of PLN. ATP2A2 inhibition is alleviated by PLN phosphorylation (By similarity). Belongs to the phospholamban family. (52 aa)
CDH6Cadherin-6; Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types (By similarity). (790 aa)
ITGB1BP1Integrin beta-1-binding protein 1; Key regulator of the integrin-mediated cell-matrix interaction signaling by binding to the ITGB1 cytoplasmic tail and preventing the activation of integrin alpha-5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. Plays a role in cell proliferation, differentiation, spreading, adhesion and migration in the context of mineralization and bone development and angiogenesis. Stimulates cellular proliferation in a fibronectin-dependent manner. Involved in the regulation of beta-1 integrin-containing focal adhesion (FA) site dynamics by controlling [...] (200 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)
ETV2ETS variant 2. (332 aa)
NR1H4Bile acid receptor; Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in wh [...] (482 aa)
TBX2T-box transcription factor 2. (714 aa)
NR0B2Nuclear receptor subfamily 0 group B member 2. (260 aa)
DLX1Distal-less homeobox 1. (255 aa)
WDR12Ribosome biogenesis protein WDR12; Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome. (423 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)
HEY1Hairy/enhancer-of-split related with YRPW motif protein 1; Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3'. Downstream effector of Notch signaling required for cardiovascular development. Specifically required for the Notch-induced endocardial epithelial to mesenchymal transition, which is itself criticial for cardiac valve and septum development. May be required in conjunction with HEY2 to specify arterial cell fate or identity. Promotes maintenance of neuronal precursor cells and glial versus neuronal fate specification. Represses tra [...] (304 aa)
ASCL1Achaete-scute family bHLH transcription factor 1. (219 aa)
NFKBIANuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha. (314 aa)
DTX1Deltex E3 ubiquitin ligase 1. (619 aa)
ZNF423Zinc finger protein 423. (1292 aa)
CDKN1BCyclin dependent kinase inhibitor 1B. (198 aa)
PSENENGamma-secretase subunit PEN-2; Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity. (101 aa)
TSPEARThrombospondin type laminin G domain and EAR repeats. (670 aa)
IFT74Intraflagellar transport 74. (600 aa)
TIMP4Metalloproteinase inhibitor 4; Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor; Belongs to the protease inhibitor I35 (TIMP) family. (224 aa)
ANGPT4Angiopoietin-4; Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis (By similarity). (498 aa)
RITA1RBPJ-interacting and tubulin-associated protein 1; Tubulin-binding protein that acts as a negative regulator of Notch signaling pathway. Shuttles between the cytoplasm and the nucleus and mediates the nuclear export of RBPJ/RBPSUH, thereby preventing the interaction between RBPJ/RBPSUH and NICD product of Notch proteins (Notch intracellular domain), leading to down-regulate Notch-mediated transcription. May play a role in neurogenesis (By similarity). (300 aa)
HES3Hes family bHLH transcription factor 3. (178 aa)
PSEN1Presenilin-1 CTF subunit; Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1; this stabili [...] (478 aa)
CNTN1Contactin-1; Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between axons and myelinating glial cells via its association with CNTNAP1. Participates in oligodendrocytes generation by acting as a ligand of NOTCH1. Its association with NOTCH1 promotes NOTCH1 activation through the released notch intracellular domain (NICD) and subsequent translocation to the nucleus. Interaction with TNR induces a repulsion of neurons and an inhibition of neurit [...] (1018 aa)
DLX2Distal-less homeobox 2. (331 aa)
SUSD5Sushi domain containing 5. (624 aa)
NOTCH4Notch receptor 4. (1989 aa)
RBM15RNA binding motif protein 15. (962 aa)
MAML2Mastermind-like protein 2; Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Potentiates activation by NOTCH3 and NOTCH4 more efficiently than MAML1 or MAML3 (By similarity); Belongs to the mastermind family. (1128 aa)
NOTCH3Notch receptor 3. (2332 aa)
FOXA1Forkhead box A1. (468 aa)
MAML3Mastermind like transcriptional coactivator 3. (666 aa)
MECP2Methyl-CpG-binding protein 2; Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC). (498 aa)
NRARPNOTCH regulated ankyrin repeat protein. (114 aa)
TGFBR2Serine/threonine-protein kinase receptor; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (595 aa)
EPN1Epsin 1. (576 aa)
CFDComplement factor D; Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. Its function is homologous to that of C1s in the classical pathway (By similarity). (259 aa)
ONECUT1One cut domain family member. (465 aa)
GSX2GS homeobox 2. (305 aa)
PTP4A3Protein tyrosine phosphatase type IVA 3; Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II (By similarity). (173 aa)
DTX2Deltex E3 ubiquitin ligase 2. (619 aa)
ADAM10Disintegrin and metalloproteinase domain-containing protein 10; Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (By similarity). Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha- secretase cleavage of amyloid precursor protein (APP). Contributes to the normal cleavage of the cellular prion protein (By similarity). Involve [...] (748 aa)
PSEN2Presenilin-2 CTF subunit; Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). Requires the other members of the gamma- secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. May function in the cytoplasmic partitioning of proteins. The holoprotein functions as a calcium-leak channel that allows the passive movement o [...] (449 aa)
SNAI1Snail family transcriptional repressor 1. (267 aa)
APH1BAph-1 homolog B, gamma-secretase subunit. (257 aa)
SORBS2Uncharacterized protein. (760 aa)
APPGamma-secretase C-terminal fragment 57; Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions (By similarity). Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb (By similarity). Couples to apoptosis-inducing pathways such as those medi [...] (770 aa)
ENSBTAP00000062996Uncharacterized protein. (346 aa)
NLE1Notchless protein homolog 1; Plays a role in regulating Notch activity. Plays a role in regulating the expression of CDKN1A and several members of the Wnt pathway, probably via its effects on Notch activity. Required during embryogenesis for inner mass cell survival (By similarity). (487 aa)
FBXW7F-box/WD repeat-containing protein 7; Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination (By similarity). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1, and probably PSEN1. Acts as a negative regulator of JNK si [...] (706 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 [...] (499 aa)
CFAP58Cilia and flagella associated protein 58. (873 aa)
DLL1Delta-like protein; Putative Notch ligand involved in the mediation of Notch signaling. (784 aa)
JAG2Delta-like protein; Putative Notch ligand involved in the mediation of Notch signaling. (1069 aa)
CDK6Cyclin dependent kinase 6; Belongs to the protein kinase superfamily. (326 aa)
MAML1Mastermind like transcriptional coactivator 1. (1013 aa)
HPHaptoglobin alpha chain; As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pat [...] (390 aa)
APH1AAph-1 homolog A, gamma-secretase subunit. (265 aa)
SOX9SRY-box transcription factor 9. (524 aa)
NOTCH2Notch receptor 2. (2471 aa)
POFUT1Protein O-fucosyltransferase 1a. (391 aa)
DTX3Deltex E3 ubiquitin ligase 3. (383 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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