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  • 11.0 [archived version]
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NPAS4 NPAS4 SIM1 SIM1 PJA1 PJA1 PJA2 PJA2 SIM2 SIM2 USP9X USP9X ARNT2 ARNT2 TRAF4 TRAF4 TOLLIP TOLLIP IRAK1 IRAK1 AATF AATF XIAP XIAP NGFR NGFR DLX5 DLX5 CHUK CHUK MAGED1 MAGED1 ROR2 ROR2 MSX2 MSX2 UNC5A UNC5A TFG TFG DLX4 DLX4 BARD1 BARD1 RNF8 RNF8 BRCA2 BRCA2 NREP NREP PCNA PCNA
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
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
some 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 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:
NGFRTumor necrosis factor receptor superfamily member 16; Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Low affinity receptor which can bind to NGF, BDNF, NT-3, and NT-4. Can mediate cell survival as well as cell death of neural cells. Necessary for the circadian oscillation of the clock genes ARNTL/BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SC [...] (427 aa)
DLX5Homeobox protein DLX-5; Transcriptional factor involved in bone development. Acts as an immediate early BMP-responsive transcriptional activator essential for osteoblast differentiation. Stimulates ALPL promoter activity in a RUNX2-independent manner during osteoblast differentiation. Stimulates SP7 promoter activity during osteoblast differentiation. Promotes cell proliferation by up-regulating MYC promoter activity. Involved as a positive regulator of both chondrogenesis and chondrocyte hypertrophy in the endochondral skeleton. Binds to the homeodomain-response element of the ALPL an [...] (289 aa)
MSX2Homeobox protein MSX-2; Acts as a transcriptional regulator in bone development. Represses the ALPL promoter activity and antogonizes the stimulatory effect of DLX5 on ALPL expression during osteoblast differentiation. Probable morphogenetic role. May play a role in limb-pattern formation. In osteoblasts, suppresses transcription driven by the osteocalcin FGF response element (OCFRE). Binds to the homeodomain-response element of the ALPL promoter; NKL subclass homeoboxes and pseudogenes (267 aa)
DLX4Homeobox protein DLX-4; May play a role in determining the production of hemoglobin S. May act as a repressor. During embryonic development, plays a role in palatogenesis; Belongs to the distal-less homeobox family (240 aa)
TFGProtein TFG; Plays a role in the normal dynamic function of the endoplasmic reticulum (ER) and its associated microtubules (400 aa)
BARD1BRCA1-associated RING domain protein 1; E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of ’Lys-6’-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II [...] (777 aa)
TRAF4TNF receptor-associated factor 4; Adapter protein and signal transducer that links members of the tumor necrosis factor receptor (TNFR) family to different signaling pathways. Plays a role in the activation of NF-kappa-B and JNK, and in the regulation of cell survival and apoptosis. Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract (By similarity). Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions (470 aa)
SIM2Single-minded homolog 2; Transcription factor that may be a master gene of CNS development in cooperation with Arnt. It may have pleiotropic effects in the tissues expressed during development; Basic helix-loop-helix proteins (667 aa)
ARNT2Aryl hydrocarbon receptor nuclear translocator 2; Transcription factor that plays a role in the development of the hypothalamo-pituitary axis, postnatal brain growth, and visual and renal function. Specifically recognizes the xenobiotic response element (XRE); Basic helix-loop-helix proteins (717 aa)
NPAS4Neuronal PAS domain-containing protein 4; Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hyppocampus (By similarity). Plays a key role in the structural and functional plasticity of neurons (By similarity). Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons [...] (802 aa)
TOLLIPToll-interacting protein; Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and kinase activity. Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin- ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates; C2 domain containing (274 aa)
USP9XProbable ubiquitin carboxyl-terminal hydrolase FAF-X; Deubiquitinase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin. Essential component of TGF-beta/BMP signaling cascade. Regulates chromosome alignment and segregation in mitosis by regulating the localization of BIRC5/survivin to mitotic centromeres. Specifically hydrolyzes both ’Lys-29’- and ’Lys-33’-linked polyubiquitins chains. Spec [...] (2570 aa)
UNC5ANetrin receptor UNC5A; Receptor for netrin required for axon guidance. Functions in the netrin signaling pathway and promotes neurite outgrowth in response to NTN1. Mediates axon repulsion of neuronal growth cones in the developing nervous system in response to netrin. Axon repulsion in growth cones may be mediated by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand; I-set domain containing (842 aa)
PJA2E3 ubiquitin-protein ligase Praja-2; Has E2-dependent E3 ubiquitin-protein ligase activity. Responsible for ubiquitination of cAMP-dependent protein kinase type I and type II-alpha/beta regulatory subunits and for targeting them for proteasomal degradation. Essential for PKA- mediated long-term memory processes; Ring finger proteins (708 aa)
PJA1E3 ubiquitin-protein ligase Praja-1; Has E2-dependent E3 ubiquitin-protein ligase activity. Ubiquitinates MAGED1 antigen leading to its subsequent degradation by proteasome (By similarity). May be involved in protein sorting; Ring finger proteins (643 aa)
SIM1Single-minded homolog 1; Transcriptional factor that may have pleiotropic effects during embryogenesis and in the adult; Basic helix-loop-helix proteins (766 aa)
IRAK1Interleukin-1 receptor-associated kinase 1; Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor- signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiqui [...] (712 aa)
CHUKInhibitor of nuclear factor kappa-B kinase subunit alpha; Serine kinase that plays an essential role in the NF- kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into [...] (745 aa)
XIAPE3 ubiquitin-protein ligase XIAP; Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligas [...] (497 aa)
RNF8E3 ubiquitin-protein ligase RNF8; E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles- by mediating the ’Lys-63’- linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing ’Lys-48’-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the ’Lys-63’-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP5 [...] (485 aa)
MAGED1Melanoma-associated antigen D1; Involved in the apoptotic response after nerve growth factor (NGF) binding in neuronal cells. Inhibits cell cycle progression, and facilitates NGFR-mediated apoptosis. May act as a regulator of the function of DLX family members. May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3-substrate complex. Plays a role in the circadian rhythm regulation. May act as RORA co-regulator, modulating the expression [...] (834 aa)
ROR2Tyrosine-protein kinase transmembrane receptor ROR2; Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development (By similarity). Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation. In contrast, has also been shown to have very little tyrosine kinase activity in vitro. May act as a receptor for wnt ligand WNT5A which may result in the inhibition of WNT3A-mediated signaling; I-set domain containing (943 aa)
PCNAProliferating cell nuclear antigen; Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase’s processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3’- 5’ exonuclease and 3’-phosphodiesterase, but not apurinic- apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA re [...] (261 aa)
BRCA2Breast cancer type 2 susceptibility protein; Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. B [...] (3418 aa)
NREPNeuronal regeneration-related protein; May have roles in neural function. Ectopic expression augments motility of gliomas. Promotes also axonal regeneration (By similarity). May also have functions in cellular differentiation (By similarity). Induces differentiation of fibroblast into myofibroblast and myofibroblast ameboid migration. Increases retinoic-acid regulation of lipid-droplet biogenesis (By similarity). Down-regulates the expression of TGFB1 and TGFB2 but not of TGFB3 (By similarity). May play a role in the regulation of alveolar generation (112 aa)
AATFProtein AATF; May function as a general inhibitor of the histone deacetylase HDAC1. Binding to the pocket region of RB1 may displace HDAC1 from RB1/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Conversely, displacement of HDAC1 from SP1 bound to the CDKN1A promoter leads to increased expression of this CDK inhibitor and blocks cell cycle progression. Also antagonizes PAWR mediated induction of aberrant amyloid peptide production in Alzheimer disease (presenile and senile dementia), although the molecular basis for this phenomenon has not been desc [...] (560 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo sapiens, human, man
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