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NEDD8 NEDD8 VPS35L VPS35L UBE2M UBE2M DCUN1D5 DCUN1D5 WSB1 WSB1 COMMD9 COMMD9 COMMD4 COMMD4 RNF7 RNF7 COMMD10 COMMD10 COMMD7 COMMD7 DCUN1D1 DCUN1D1 SOCS5 SOCS5 COMMD1 COMMD1 VPS26C VPS26C DCUN1D3 DCUN1D3 ELOA2 ELOA2 SENP8 SENP8 KCTD6 KCTD6 COMMD6 COMMD6 NAE1 NAE1 UBA3 UBA3 CCDC22 CCDC22 CCDC93 CCDC93 COMMD3 COMMD3 COMMD8 COMMD8 BTBD6 BTBD6 CUL5 CUL5 SOCS6 SOCS6 DCUN1D4 DCUN1D4 COMMD5 COMMD5 CISH CISH DCUN1D2 DCUN1D2 COMMD2 COMMD2 SPSB2 SPSB2 CAND1 CAND1 ASB2 ASB2 SPSB3 SPSB3 LRRC41 LRRC41 ELOC ELOC UBE2F UBE2F VPS29 VPS29 SOCS2 SOCS2 SOCS1 SOCS1 SOCS7 SOCS7
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query proteins and first shell of interactors
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proteins of unknown 3D structure
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NEDD8NEDD8; Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins. (81 aa)
VPS35LVPS35 endosomal protein sorting factor-like; Acts as component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1). The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes. In the endosomes, drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numero [...] (1052 aa)
UBE2MNEDD8-conjugating enzyme Ubc12; Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation; Belongs to the ubiquitin-conjugating enzyme family. UBC12 subfamily. (183 aa)
DCUN1D5DCN1-like protein 5; Defective in cullin neddylation 1 domain containing 5. (237 aa)
WSB1WD repeat and SOCS box-containing protein 1; Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes type II iodothyronine deiodinase/DIO2. Confers constitutive instability to HIPK2 through proteasomal degradation. (421 aa)
COMMD9COMM domain-containing protein 9; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride- sensitive sodium channel (ENaC) subunits. (198 aa)
COMMD4COMM domain-containing protein 4; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Down-regulates activation of NF- kappa-B. (199 aa)
RNF7RING-box protein 2; Probable component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (By similarity). Through the RING- type zinc finger, seems to recruit the E2 ubiquitination enzyme to the complex and brings it into close proximity to the substrat [...] (113 aa)
COMMD10COMM domain-containing protein 10; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. (202 aa)
COMMD7COMM domain-containing protein 7; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Associates with the NF-kappa-B complex and suppresses its transcriptional activity. (200 aa)
DCUN1D1DCN1-like protein 1; Part of an E3 ubiquitin ligase complex for neddylation. Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes. Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity. Acts also [...] (259 aa)
SOCS5Suppressor of cytokine signaling 5; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5- SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Inhibits for instance EGF signaling by mediating the degradation of the EGF receptor/EGFR. Involved in the regulation of T- helper cell differentiation by inhibiting of the IL4 signaling pathway which promotes diff [...] (536 aa)
COMMD1COMM domain-containing protein 1; Proposed scaffold protein that is implicated in diverse physiological processes and whose function may be in part linked to its ability to regulate ubiquitination of specific cellular proteins. Can modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by displacing CAND1; in vitro promotes CRL E3 activity and dissociates CAND1 from CUL1 and CUL2. Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity. Involved in the regulation of membrane expression and ubiquitin [...] (190 aa)
VPS26CVacuolar protein sorting-associated protein 26C; Acts as component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1). The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes. In the endosomes, drives the retriever and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of nu [...] (297 aa)
DCUN1D3DCN1-like protein 3; Antagonizes DCUN1D1-mediated CUL1 neddylation by sequestering CUL1 at the cell membrane. When overexpressed in transformed cells, may promote mesenchymal to epithelial-like changes and inhibit colony formation in soft agar. (304 aa)
ELOA2Elongin-A2; SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A2 is transcriptionally active but its transcription activity is not enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex). (753 aa)
SENP8Sentrin-specific protease 8; Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53. (212 aa)
KCTD6BTB/POZ domain-containing protein KCTD6; Probable substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex mediating the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes the ubiquitination of HDAC1; the function seems to depend on KCTD11:KCTD6 oligomerization. Can function as antagonist of the Hedgehog pathway by affecting the nuclear transfer of transcription factor GLI1; the function probably occurs via HDAC1 down-regulation, keeping GLI1 acetylated and inactive. Inhibits cell growth and tumorigenicity of medulloblastom [...] (237 aa)
COMMD6COMM domain-containing protein 6; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Down-regulates activation of NF- kappa-B. Inhibits TNF-induced NFKB1 activation. (98 aa)
NAE1NEDD8-activating enzyme E1 regulatory subunit; Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation. (537 aa)
UBA3NEDD8-activating enzyme E1 catalytic subunit; Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down- regulates steroid receptor activity. Necessary for cell cycle progression. (463 aa)
CCDC22Coiled-coil domain-containing protein 22; Involved in regulation of NF-kappa-B signaling. Promotes ubiquitination of I-kappa-B-kinase subunit IKBKB and its subsequent proteasomal degradation leading to NF-kappa-B activation; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex. May down-regulate NF-kappa-B activity via association with COMMD1 and involving a CUL2-dependent E3 ubiquitin ligase complex. Regulates the cellular localization of COMM domain-containing proteins, such as COMMD1 and COMMD10. Component of the CCC complex, which is inv [...] (627 aa)
CCDC93Coiled-coil domain-containing protein 93; Component of the CCC complex, which is involved in the regulation of endosomal recycling of surface proteins, including integrins, signaling receptor and channels. The CCC complex associates with SNX17, retriever and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGA5:ITGB1. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and coop [...] (631 aa)
COMMD3COMM domain-containing protein 3; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride- sensitive sodium channel (ENaC) subunits. (195 aa)
COMMD8COMM domain-containing protein 8; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. (183 aa)
BTBD6BTB/POZ domain-containing protein 6; Adapter protein for the cul3 E3 ubiquitin-protein ligase complex (By similarity). Involved in late neuronal development and muscle formation (By similarity). (485 aa)
CUL5Cullin-5; Core component of multiple SCF-like ECS (Elongin-Cullin 2/5- SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAK2. Seems to be involved in proteosomal degradation of p53/TP53 stimulate [...] (780 aa)
SOCS6Suppressor of cytokine signaling 6; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5- SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Regulates KIT degradation by ubiquitination of the tyrosine-phosphorylated receptor. (535 aa)
DCUN1D4DCN1-like protein 4; Defective in cullin neddylation 1 domain containing 4. (336 aa)
COMMD5COMM domain-containing protein 5; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Negatively regulates cell proliferation. Negatively regulates cell cycle G2/M phase transition probably by transactivating p21/CDKN1A through the p53/TP53-independent signaling pathway. Involved in kidney proximal tubule morphogenesis (By similarity). Down-regulates activation of NF-kappa-B. (224 aa)
CISHCytokine-inducible SH2-containing protein; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasom [...] (275 aa)
DCUN1D2DCN1-like protein 2; Potently stimulates the neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes from the NEDD8-conjugating E2 enzyme UBC12. Neddylation of cullins play an essential role in the regulation of SCF-type complexes activity. (259 aa)
COMMD2COMM domain-containing protein 2; May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF- kappa-B. (199 aa)
SPSB2SPRY domain-containing SOCS box protein 2; Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2. Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5. (263 aa)
CAND1Cullin-associated NEDD8-dissociated protein 1; Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate- recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar [...] (1230 aa)
ASB2Ankyrin repeat and SOCS box protein 2; Substrate-recognition component of a SCF-like ECS (Elongin- Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. [Isoform 2]: Involved in myogenic differentiation and targets filamin FLNB for proteasomal degradation but not filamin FLNA. (635 aa)
SPSB3SPRY domain-containing SOCS box protein 3; May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. (355 aa)
LRRC41Leucine-rich repeat-containing protein 41; Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. (812 aa)
ELOCElongin-C; SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex). In embryonic stem cells, the elongin BC complex is recruited by EPOP to Polycomb group (PcG) target genes in order generate genomic region that display both active and repressive chromatin properties, an important featur [...] (112 aa)
UBE2FNEDD8-conjugating enzyme UBE2F; Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX2, but not RBX1, suggests that the RBX2-UBE2F complex neddylates specific target proteins, such as CUL5. (185 aa)
VPS29Vacuolar protein sorting-associated protein 29; Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans- Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for carg [...] (214 aa)
SOCS2Suppressor of cytokine signaling 2; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. (198 aa)
SOCS1Suppressor of cytokine signaling 1; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS1 is involved in negative regulation of cytokines that signal through the JAK/STAT3 pathway. Through binding to JAKs, inhibits their kinase activity. In vitro, also suppresses Tec protein-tyrosine activity. Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival (By similarity). Probable substrate recognition component of an [...] (211 aa)
SOCS7Suppressor of cytokine signaling 7; Regulates signaling cascades probably through protein ubiquitination and/or sequestration. Functions in insulin signaling and glucose homeostasis through IRS1 ubiquitination and subsequent proteasomal degradation. Inhibits also prolactin, growth hormone and leptin signaling by preventing STAT3 and STAT5 activation, sequestering them in the cytoplasm and reducing their binding to DNA. May be a substrate recognition component of a SCF-like E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of ta [...] (581 aa)
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Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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