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ULK4 ULK4 EBF4 EBF4 SUFU SUFU APOB APOB EBF3 EBF3 STK36 STK36 DHH DHH PTCH2 PTCH2 EBF2 EBF2 GLI2 GLI2 SMO SMO IHH IHH SHH SHH GLI1 GLI1 GLI3 GLI3 BMP4 BMP4 NRG2 NRG2 EBF1 EBF1 BMP2 BMP2 CCND1 CCND1 DNAJA3 DNAJA3 CDK4 CDK4 HDAC3 HDAC3 CDK6 CDK6 RBL1 RBL1 RBL2 RBL2
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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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protein of unknown 3D structure
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some 3D structure is known or predicted
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query proteins and first shell of interactors
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white nodes:
second shell of interactors
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Predicted Interactions
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CCND1cyclin D1; Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate [...] (295 aa)
GLI1GLI family zinc finger 1; Acts as a transcriptional activator. May regulate the transcription of specific genes during normal development. May play a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling and thus cell proliferation and differentiation (1106 aa)
APOBapolipoprotein B (including Ag(x) antigen) (4563 aa)
BMP4bone morphogenetic protein 4; Induces cartilage and bone formation. Also act 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)
SMOsmoothened, frizzled family receptor; G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog’s proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7 and GLI3 in the cilia (787 aa)
CDK4cyclin-dependent kinase 4; Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. [...] (303 aa)
RBL2retinoblastoma-like 2 (p130); Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 ’Lys-20’ trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferent [...] (1139 aa)
DNAJA3DnaJ (Hsp40) homolog, subfamily A, member 3; Modulates apoptotic signal transduction or effector structures within the mitochondrial matrix. Affect cytochrome C release from the mitochondria and caspase 3 activation, but not caspase 8 activation. Isoform 1 increases apoptosis triggered by both TNF and the DNA-damaging agent mytomycin C; in sharp contrast, isoform 2 suppresses apoptosis. Can modulate IFN-gamma- mediated transcriptional activity. Isoform 2 may play a role in neuromuscular junction development as an effector of the MUSK signaling pathway (480 aa)
CDK6cyclin-dependent kinase 6; Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cel [...] (326 aa)
DHHdesert hedgehog; Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development (396 aa)
STK36serine/threonine kinase 36; Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors. Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization. GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for this to occur. Required for postnatal development, possibly by regulating the homeostasis of cerebral [...] (1315 aa)
IHHIndian hedgehog; Intercellular signal essential for a variety of patterning events during development. Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. Implicated in endochondral ossification- may regulate the balance between growth and ossification of the developing bones. Induces the expression of parathyroid hormone-related protein (PTHRP) (By similarity) (411 aa)
SHHsonic hedgehog; Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of SMO. Also regulates another target, the gli oncogene. Intercellular signal essential for a variety of patterning events during development- signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Displays both floor plate- [...] (462 aa)
ULK4unc-51-like kinase 4 (C. elegans) (1275 aa)
HDAC3histone deacetylase 3; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Probably participates in the regulation of transcription through its binding to the zinc-finger transcription factor YY1; increases YY1 repression activity. Required [...] (428 aa)
EBF1early B-cell factor 1; Transcriptional activator which recognizes variations of the palindromic sequence 5’-ATTCCCNNGGGAATT-3’ (By similarity) (591 aa)
GLI2GLI family zinc finger 2; Acts as a transcriptional activator. May play a role during embryogenesis. Binds to the DNA sequence 5’-GAACCACCCA-3’ which is part of the TRE-2S regulatory element that augments the Tax-dependent enhancer of human T-cell leukemia virus type 1. Is involved in the smoothened (SHH) signaling pathway (1586 aa)
NRG2neuregulin 2; Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. May also promote the heterodimerization with the EGF receptor (850 aa)
EBF3early B-cell factor 3; Transcriptional activator which recognizes variations of the palindromic sequence 5’-ATTCCCNNGGGAATT-3’ (By similarity) (551 aa)
SUFUsuppressor of fused homolog (Drosophila); Negative regulator in the hedgehog signaling pathway. Down-regulates GLI1-mediated transactivation of target genes. Part of a corepressor complex that acts on DNA-bound GLI1. May also act by linking GLI1 to BTRC and thereby targeting GLI1 to degradation by the proteasome. Sequesters GLI1, GLI2 and GLI3 in the cytoplasm, this effect is overcome by binding of STK36 to both SUFU and a GLI protein. Negative regulator of beta-catenin signaling. Regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) of the full len [...] (484 aa)
PTCH2patched 2; May have a role in epidermal development. May act as a receptor for Sonic hedgehog (SHH) (1203 aa)
RBL1retinoblastoma-like 1 (p107); Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 ’Lys-20’ trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation. Forms a complex with [...] (1068 aa)
BMP2bone morphogenetic protein 2; Induces cartilage and bone formation (396 aa)
EBF4early B-cell factor 4; Transcriptional factor which recognizes variations of the palindromic sequence 5’-ATTCCCNNGGGAATT-3’ (By similarity) (598 aa)
GLI3GLI family zinc finger 3; Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. In concert with TRPS1, plays a role in regulatin [...] (1580 aa)
EBF2early B-cell factor 2; Transcription factor that, in osteoblasts, activates the decoy receptor for RANKL, TNFRSF11B, which in turn regulates osteoclast differentiation. Acts in synergy with the Wnt- responsive LEF1/CTNNB1 pathway. Recognizes variations of the palindromic sequence 5’-ATTCCCNNGGGAATT-3’ (By similarity) (575 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo, Homo sapiens, human, man
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