ID:RBX1_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase RBX1; EC=6.3.2.-; AltName: Full=Protein ZYP; AltName: Full=RING finger protein 75; AltName: Full=RING-box protein 1; Short=Rbx1; AltName: Full=Regulator of cullins 1; FUNCTION: E3 ubiquitin ligase component of multiple cullin-RING- based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair. The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme, like CDC34, to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2. Part of a SCF-like complex consisting of CUL7, RBX1, SKP1 and FBXW8. Part of CBC(VHL) complexes with elongin BC complex (TCEB1 and TCEB2), CUL2 or CUL5 and VHL. Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Part of multisubunit E3 ubiquitin ligase complexes with elongin BC complex (TCEB1 and TCEB2), CUL2 and MED8; elongin BC complex (TCEB1 and TCEB2), CUL5 and MUF1. Part of multisubunit complexes with elongin BC complex (TCEB1 and TCEB2), elongin A/TCEB3 or SOCS1 or WSB1 and CUL5. Interacts directly with CUL1 and probably also with CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7. Probably interacts with CDC34. Interacts with COPS6. Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1. Part of an E3 ligase complex composed of RBX1, DDB1, DDB2 and CUL4A or CUL4B. Interacts with UBE2M. Part of a SCF complex consisting of CUL1, FBXO3, RBX1 and SKP1; this complex interacts with PML via FBXO3. Interacts with human adenovirus early E1A protein; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBW7) complex. Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF. INTERACTION: Q13616:CUL1; NbExp=12; IntAct=EBI-398523, EBI-359390; Q93034:CUL5; NbExp=3; IntAct=EBI-398523, EBI-1057139; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. TISSUE SPECIFICITY: Widely expressed. DOMAIN: The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion. SIMILARITY: Belongs to the RING-box family. SIMILARITY: Contains 1 RING-type zinc finger. SEQUENCE CAUTION: Sequence=AAH17370.2; Type=Erroneous initiation; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RBX1ID42075ch22q13.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P62877
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004842 ubiquitin-protein transferase activity GO:0005515 protein binding GO:0008134 transcription factor binding GO:0008270 zinc ion binding GO:0016740 transferase activity GO:0019788 NEDD8 transferase activity GO:0031625 ubiquitin protein ligase binding GO:0034450 ubiquitin-ubiquitin ligase activity GO:0044877 macromolecular complex binding GO:0046872 metal ion binding GO:0061630 ubiquitin protein ligase activity GO:0097602 cullin family protein binding
Biological Process: GO:0000165 MAPK cascade GO:0000209 protein polyubiquitination GO:0000715 nucleotide-excision repair, DNA damage recognition GO:0006281 DNA repair GO:0006283 transcription-coupled nucleotide-excision repair GO:0006293 nucleotide-excision repair, preincision complex stabilization GO:0006294 nucleotide-excision repair, preincision complex assembly GO:0006296 nucleotide-excision repair, DNA incision, 5'-to lesion GO:0006513 protein monoubiquitination GO:0006974 cellular response to DNA damage stimulus GO:0010265 SCF complex assembly GO:0010972 negative regulation of G2/M transition of mitotic cell cycle GO:0016032 viral process GO:0016055 Wnt signaling pathway GO:0016567 protein ubiquitination GO:0030163 protein catabolic process GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0033683 nucleotide-excision repair, DNA incision GO:0042769 DNA damage response, detection of DNA damage GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043687 post-translational protein modification GO:0045116 protein neddylation GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0070498 interleukin-1-mediated signaling pathway GO:0070911 global genome nucleotide-excision repair GO:0090090 negative regulation of canonical Wnt signaling pathway
AK301758 - Homo sapiens cDNA FLJ60363 complete cds, weakly similar to Probable peptidase YER078C (EC 3.4.-.-). BC017370 - Homo sapiens ring-box 1, mRNA (cDNA clone IMAGE:4065797), partial cds. CR456560 - Homo sapiens RBX1 full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.RBX1). AK315722 - Homo sapiens cDNA, FLJ96824, Homo sapiens ring-box 1 (RBX1), mRNA. AF140598 - Homo sapiens ring-box protein 1 (RBX1) mRNA, complete cds. BC001466 - Homo sapiens ring-box 1, mRNA (cDNA clone MGC:1481 IMAGE:3138751), complete cds. CU674722 - Synthetic construct Homo sapiens gateway clone IMAGE:100017907 5' read RBX1 mRNA. AB590096 - Synthetic construct DNA, clone: pFN21AE1496, Homo sapiens RBX1 gene for ring-box 1, without stop codon, in Flexi system. CU013160 - Homo sapiens RBX1, mRNA (cDNA clone IMAGE:100000513), complete cds, with stop codon, in Gateway system. CU013448 - Homo sapiens RBX1, mRNA (cDNA clone IMAGE:100000417), complete cds, without stop codon, in Gateway system. KJ892885 - Synthetic construct Homo sapiens clone ccsbBroadEn_02279 RBX1 gene, encodes complete protein. AF142059 - Homo sapiens RING finger protein (ROC1) mRNA, complete cds. AF085906 - Homo sapiens full length insert cDNA clone YQ60A05. AY099360 - Homo sapiens ZYP protein mRNA, partial cds. AK090764 - Homo sapiens cDNA FLJ33445 fis, clone BRALZ2000263.
Biochemical and Signaling Pathways
BioCyc Knowledge Library PWY-7511 - protein ubiquitination PWY-7899 - protein NEDDylation
BioCarta from NCI Cancer Genome Anatomy Project h_p27Pathway - Regulation of p27 Phosphorylation during Cell Cycle Progression h_eradPathway - ER�associated degradation (ERAD) Pathway
Reactome (by CSHL, EBI, and GO)
Protein P62877 (Reactome details) participates in the following event(s):
R-HSA-8854052 Formation of the SCF-FBXL7 complex R-HSA-180555 Association of APOBEC3G:Vif with the Cul5-SCF complex R-HSA-209125 SCF Beta-TrCP complex binds to NFKB p50:p65: phospho IKBA complex R-HSA-1370500 PRLR binds SCF beta-TrCP complex R-HSA-2130279 Association of beta-catenin with the RBX1:SCF(beta-TrCP1) ubiquitin ligase complex R-HSA-1504213 DVL is bound by the CUL3:KLHL12:RBX1 ubiquitin ligase complex R-HSA-8853496 SCF:FBXL7 binds AURKA R-HSA-8956031 NEDD8:AcM-UBE2M binds CUL9:RBX1 ubiquitin ligase complex R-HSA-8956050 NEDD8-CUL9:RBX1 binds CUL7:CCDC8:OBSL1 R-HSA-8956025 AcM-UBE2M transfers NEDD8 to CUL9:RBX1 R-HSA-8956099 VHL:EloB,C:NEDD8-CUL2:RBX1 complex binds UBXN7 R-HSA-8956103 VHL:EloB,C:NEDD8-CUL2:RBX1 complex binds hydroxyprolyl-HIF-alpha R-HSA-8955245 CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus R-HSA-1234169 Nuclear VHL:EloB,C:CUL2:RBX1 binds hydroxyprolyl-HIF-alpha R-HSA-1912385 Phosphorylated NICD1 binds FBXW7 R-NUL-2064853 FBXW7 binds phosphorylated NICD1 R-HSA-1852623 Ubiquitination of NICD1 by FBWX7 R-NUL-2064883 FBXW7 mediates ubiquitination of phosphorylated NICD1 R-HSA-9008478 FBXW7 binds RUNX2 and GSK3B R-HSA-5635855 phosphorylated GLI proteins bind SPOP:CUL3:RBX1 R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER R-HSA-8939688 SCF(SKP2) complex binds RUNX2 R-HSA-8939706 SCF(SKP2) polyubiquitinates RUNX2 R-HSA-180540 Multi-ubiquitination of APOBEC3G R-HSA-209063 Beta-TrCP ubiquitinates NFKB p50:p65:phospho IKBA complex R-HSA-2130286 Multi-ubiquitination of phospho-beta-catenin by RBX1:SCF(beta-TrCP1) R-HSA-5610742 SCF(beta-TrCP) ubiquitinates p-GLI1 R-HSA-5610745 SCF(beta-TrCP) ubiquitinates p-GLI2 R-HSA-5610746 SCF(beta-TrCP) ubiquitinates p-GLI3 R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-1234183 Cytosolic VHL:EloB,C:CUL2:RBX1 binds hydroxyprolyl-HIF-alpha R-HSA-8955241 CAND1 binds cytosolic CRL E3 ubiquitin ligases R-HSA-8952620 NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex R-HSA-8956200 MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex R-HSA-1504190 DVL is ubiquitinated by CUL3:KLHL12:RBX1 R-HSA-5658424 KBTBD7:CUL3:RBX1 ubiquitinates NF1 R-HSA-8854041 SCF-FBXL7 ubiquitinates AURKA R-HSA-8854051 SCF-FBXL18 ubiquitinates FBXL7 R-HSA-8952618 AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex R-HSA-8956026 CUL9:RBX1 ubiquitinates BIRC5 R-HSA-8956106 VHL:EloB,C:NEDD8-CUL2:RBX1 complex ubiquitinylates HIF-alpha R-HSA-8955285 COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex R-HSA-8952639 NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex R-HSA-8956045 COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex R-HSA-1234172 Nuclear VBC complex ubiquitinylates HIF-alpha R-HSA-9008479 FBXW7 polyubiquitinates RUNX2 R-HSA-5635856 SPOP:CUL3:RBX1 ubiquitinates GLI2,3 R-HSA-5652005 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA R-HSA-5652009 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA R-HSA-6782943 UV-DDB ubiquitinates XPC R-HSA-5691006 XPC:RAD23:CETN2 and UV-DDB bind distorted dsDNA site R-HSA-5696664 PARP1 or PARP2 binds DDB2 at GG-NER site R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site R-HSA-5690990 5'- incision of DNA by ERCC1:ERCC4 in GG-NER R-HSA-6790487 RNF111 ubiquitinates SUMOylated XPC R-HSA-6790454 SUMOylation of XPC R-HSA-5689317 Formation of the pre-incision complex in GG-NER R-HSA-6781867 ERCC8:DDB1:CUL4:RBX1 ubiquitinates ERCC6 and RNA Pol II R-HSA-6781833 ERCC8 (CSA) binds stalled RNA Pol II R-HSA-6782004 Assembly of the pre-incision complex in TC-NER R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site R-HSA-6782204 5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER R-HSA-68946 Phosphorylated Orc1 is ubiquitinated while still associated with chromatin R-HSA-8952638 AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-1234163 Cytosolic VBC complex ubiquitinylates hydroxyprolyl-HIF-alpha R-HSA-1234173 Cytosolic PHD2,3 hydroxylates proline residues on HIF3A R-HSA-1234177 Cytosolic PHD2,3 hydroxylates proline residues on HIF1A R-HSA-1234179 Cytosolic PHD2,3 hydroxylates proline residues on EPAS1 (HIF2A) R-HSA-8955289 COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes R-HSA-8956040 COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes R-HSA-5696655 PARP1 or PARP2 PARylates DDB2 and autoPARylates R-HSA-5690996 ERCC2 and ERCC3 DNA helicases form an open bubble structure in damaged DNA R-HSA-5691000 TFIIH binds GG-NER site to form a verification complex R-HSA-5690991 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER R-HSA-6782069 UVSSA:USP7 deubiquitinates ERCC6 R-HSA-6782131 RNA Pol II backtracking in TC-NER R-HSA-6782138 ERCC5 and RPA bind TC-NER site R-HSA-5696670 CHD1L is recruited to GG-NER site R-HSA-5689861 Recruitment of XPA and release of CAK R-HSA-6782141 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis R-HSA-180585 Vif-mediated degradation of APOBEC3G R-HSA-9020702 Interleukin-1 signaling R-HSA-1170546 Prolactin receptor signaling R-HSA-195253 Degradation of beta-catenin by the destruction complex R-HSA-4641258 Degradation of DVL R-HSA-8951664 Neddylation R-HSA-9010553 Regulation of expression of SLITs and ROBOs R-HSA-69275 G2/M Transition R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-2644607 Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling R-HSA-8939902 Regulation of RUNX2 expression and activity R-HSA-5632684 Hedgehog 'on' state R-HSA-5696400 Dual Incision in GG-NER R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-162909 Host Interactions of HIV factors R-HSA-446652 Interleukin-1 family signaling R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-195721 Signaling by WNT R-HSA-5610780 Degradation of GLI1 by the proteasome R-HSA-5610783 Degradation of GLI2 by the proteasome R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-5658442 Regulation of RAS by GAPs R-HSA-597592 Post-translational protein modification R-HSA-376176 Signaling by ROBO receptors R-HSA-453274 Mitotic G2-G2/M phases R-HSA-1234174 Regulation of Hypoxia-inducible Factor (HIF) by oxygen R-HSA-1980143 Signaling by NOTCH1 R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-2644605 FBXW7 Mutants and NOTCH1 in Cancer R-HSA-8878166 Transcriptional regulation by RUNX2 R-HSA-5358351 Signaling by Hedgehog R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex R-HSA-5696394 DNA Damage Recognition in GG-NER R-HSA-5696395 Formation of Incision Complex in GG-NER R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-6781823 Formation of TC-NER Pre-Incision Complex R-HSA-6782135 Dual incision in TC-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-5696398 Nucleotide Excision Repair R-HSA-68949 Orc1 removal from chromatin R-HSA-162906 HIV Infection R-HSA-449147 Signaling by Interleukins R-HSA-168256 Immune System R-HSA-162582 Signal Transduction R-HSA-5610787 Hedgehog 'off' state R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-5673001 RAF/MAP kinase cascade R-HSA-392499 Metabolism of proteins R-HSA-422475 Axon guidance R-HSA-69278 Cell Cycle (Mitotic) R-HSA-2262749 Cellular response to hypoxia R-HSA-157118 Signaling by NOTCH R-HSA-2644603 Signaling by NOTCH1 in Cancer R-HSA-212436 Generic Transcription Pathway R-HSA-73893 DNA Damage Bypass R-HSA-73894 DNA Repair R-HSA-69052 Switching of origins to a post-replicative state R-HSA-5663205 Infectious disease R-HSA-1280218 Adaptive Immune System R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-1266738 Developmental Biology R-HSA-1640170 Cell Cycle R-HSA-2262752 Cellular responses to stress R-HSA-5663202 Diseases of signal transduction R-HSA-73857 RNA Polymerase II Transcription R-HSA-69239 Synthesis of DNA R-HSA-1643685 Disease R-HSA-5683057 MAPK family signaling cascades R-HSA-8953897 Cellular responses to external stimuli R-HSA-74160 Gene expression (Transcription) R-HSA-69242 S Phase R-HSA-69306 DNA Replication
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
