P62877 · RBX1_HUMAN

  • Protein
    E3 ubiquitin-protein ligase RBX1
  • Gene
    RBX1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase (CRLs) 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 (PubMed:10230407, PubMed:10579999, PubMed:11961546, PubMed:15983046, PubMed:16678110, PubMed:19112177, PubMed:19679664, PubMed:22748924, PubMed:23455478, PubMed:27565346, PubMed:29769719, PubMed:33417871).
CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (PubMed:27565346).
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. Core component of the Cul7-RING(FBXW8) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:35982156).
Recruits the E2 ubiquitin-conjugating enzyme 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. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and CUL3, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A (PubMed:19920177).

Catalytic activity

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.
    EC:2.3.2.27 (UniProtKB | ENZYME | Rhea)
  • S-[NEDD8-protein]-yl-[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]-L-lysine = [E2 NEDD8-conjugating enzyme]-L-cysteine + N6-[NEDD8-protein]-yl-[cullin]-L-lysine.
    EC:2.3.2.32 (UniProtKB | ENZYME | Rhea)

Pathway

Protein modification; protein ubiquitination.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site42Zn2+ 1 (UniProtKB | ChEBI)
Binding site45Zn2+ 1 (UniProtKB | ChEBI)
Binding site53Zn2+ 2 (UniProtKB | ChEBI)
Binding site56Zn2+ 2 (UniProtKB | ChEBI)
Binding site68Zn2+ 2 (UniProtKB | ChEBI)
Binding site75Zn2+ 3 (UniProtKB | ChEBI)
Binding site77Zn2+ 3 (UniProtKB | ChEBI)
Binding site80Zn2+ 1 (UniProtKB | ChEBI)
Binding site82Zn2+ 2 (UniProtKB | ChEBI)
Binding site83Zn2+ 1 (UniProtKB | ChEBI)
Binding site94Zn2+ 3 (UniProtKB | ChEBI)
Binding site97Zn2+ 3 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular ComponentCul2-RING ubiquitin ligase complex
Cellular ComponentCul3-RING ubiquitin ligase complex
Cellular ComponentCul4A-RING E3 ubiquitin ligase complex
Cellular ComponentCul4B-RING E3 ubiquitin ligase complex
Cellular ComponentCul5-RING ubiquitin ligase complex
Cellular ComponentCul7-RING ubiquitin ligase complex
Cellular Componentcullin-RING ubiquitin ligase complex
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentnucleoplasm
Cellular Componentnucleus
Cellular ComponentSCF ubiquitin ligase complex
Molecular Functioncullin family protein binding
Molecular Functionmolecular adaptor activity
Molecular FunctionNEDD8 ligase activity
Molecular FunctionNEDD8 transferase activity
Molecular FunctionRNA polymerase II-specific DNA-binding transcription factor binding
Molecular Functionubiquitin protein ligase activity
Molecular Functionubiquitin protein ligase binding
Molecular Functionubiquitin-ubiquitin ligase activity
Molecular Functionzinc ion binding
Biological Processcellular response to amino acid stimulus
Biological Processcellular response to chemical stress
Biological Processcellular response to UV
Biological ProcessDNA damage response
Biological ProcessDNA repair
Biological ProcessMAPK cascade
Biological Processnegative regulation of canonical Wnt signaling pathway
Biological Processnegative regulation of response to oxidative stress
Biological Processnegative regulation of type I interferon production
Biological Processpositive regulation of canonical NF-kappaB signal transduction
Biological Processpositive regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Processpositive regulation of protein autoubiquitination
Biological Processpositive regulation of protein catabolic process
Biological Processpositive regulation of TORC1 signaling
Biological Processpost-translational protein modification
Biological Processproteasome-mediated ubiquitin-dependent protein catabolic process
Biological Processprotein K48-linked ubiquitination
Biological Processprotein monoubiquitination
Biological Processprotein neddylation
Biological Processprotein polyubiquitination
Biological Processprotein ubiquitination
Biological Processregulation of cellular response to insulin stimulus
Biological ProcessSCF-dependent proteasomal ubiquitin-dependent protein catabolic process
Biological Processspermatogenesis
Biological ProcessT cell activation
Biological Processubiquitin-dependent protein catabolic process
Biological Processubiquitin-dependent protein catabolic process via the C-end degron rule pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    E3 ubiquitin-protein ligase RBX1
  • EC number
  • Alternative names
    • E3 ubiquitin-protein transferase RBX1
    • Protein ZYP
    • RING finger protein 75
    • RING-box protein 1 (Rbx1)
    • Regulator of cullins 1 (ROC1
      )
  • Cleaved into 1 chains

Gene names

    • Name
      RBX1
    • Synonyms
      RNF75, ROC1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P62877
  • Secondary accessions
    • B2RDY1
    • Q8N6Z8
    • Q9D1S2
    • Q9WUK9
    • Q9Y254

Proteomes

Organism-specific databases

Disease & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis53Strong reduction in ligase activity; when associated with A-56.
Mutagenesis56Strong reduction in ligase activity; when associated with A-53.
Mutagenesis75Strong reduction in ligase activity; when associated with A-77.
Mutagenesis77Strong reduction in ligase activity; when associated with A-75.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 49 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
Initiator methionine1UniProtRemoved; alternate
Modified residue1UniProtN-acetylmethionine
ChainPRO_00004232641-108UniProtE3 ubiquitin-protein ligase RBX1
Modified residue2UniProtN-acetylalanine; in E3 ubiquitin-protein ligase RBX1, N-terminally processed
ChainPRO_00000560132-108UniProtE3 ubiquitin-protein ligase RBX1, N-terminally processed
Modified residue9UniProtPhosphothreonine
Modified residue (large scale data)9PRIDEPhosphothreonine
Modified residue (large scale data)13PRIDEPhosphothreonine
Modified residue (large scale data)15PRIDEPhosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2 (PubMed:10230406, PubMed:11961546).
Part of CBC(VHL) complexes with elongin BC complex (ELOB and ELOC), CUL2 or CUL5 and VHL (PubMed:10213691).
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 (PubMed:12732143).
Part of multisubunit E3 ubiquitin ligase complexes with elongin BC complex (ELOB and ELOC), CUL2 and MED8; elongin BC complex (ELOB and ELOC), CUL5 and MUF1 (PubMed:11384984, PubMed:12149480).
Part of multisubunit complexes with elongin BC complex (ELOB and ELOC), SOCS1 or WSB1 and CUL5. Part of a multisubunit ubiquitin ligase complex consisting of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5 (PubMed:19920177).
Interacts directly with CUL1 and probably also with CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7 (PubMed:10230407, PubMed:12481031).
Interacts with CDC34 (PubMed:22748924).
Interacts with GLMN. GLMN competes for the binding site of the E2 ubiquitin-conjugating enzyme CDC34 and disrupts CDC34 binding (PubMed:22748924).
Interacts with COPS6 (PubMed:11337588).
Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1 (PubMed:14739464).
Part of an E3 ligase complex composed of RBX1, DDB1, DDB2 and CUL4A or CUL4B (PubMed:16678110).
Interacts with UBE2M (PubMed:19250909).
Part of a SCF complex consisting of CUL1, FBXO3, RBX1 and SKP1; this complex interacts with PML via FBXO3 (PubMed:18809579).
Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF (PubMed:20596027).
Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and CDC34 (PubMed:19112177).
Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein (PubMed:15983046).
Part of the BCR(ENC1) complex containing ENC1 (PubMed:15983046).
Part of the BCR(GAN) complex containing GAN (PubMed:15983046).
Part of the BCR(KLHL41) complex containing KLHL41 (PubMed:15983046).
Part of the BCR(KEAP1) complex containing KEAP1 (PubMed:15983046).
Interacts with SESN1 and SESN2 (PubMed:23274085).
Interacts with NOTCH2 (PubMed:29149593).
Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1 (PubMed:23455478).
Interacts with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5 (PubMed:24192928, PubMed:25349211, PubMed:26906416).
Component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin ligase complex, also named Cul3-RING ubiquitin ligase complex CUL3(KBTBD6/7), composed of CUL3, RBX1, KBTBD6 and KBTBD7 (PubMed:25684205).
Component of the ECS(LRR1) complex with the substrate recognition component LRR1 (PubMed:34700328).
Component of the BCR(KBTBD4) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD4 and RBX1 (PubMed:33417871).
Component of the Cul7-RING(FBXW8) complex consisting of CUL7, RBX1, SKP1 and FBXW8; within the complex interacts with CUL7 (PubMed:12481031, PubMed:35982156).
(Microbial infection) Interacts with human adenovirus 5 protein E1A; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBW7) complex.

Binary interactions

View interactors in UniProtKB
View CPX-2214 in Complex Portal

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for zinc finger.

TypeIDPosition(s)Description
Zinc finger53-98RING-type

Domain

The RING-type zinc finger domain is essential for ubiquitin ligase activity (PubMed:10230407).
It coordinates an additional third zinc ion (PubMed:11961546, PubMed:22748924).

Sequence similarities

Belongs to the RING-box family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    108
  • Mass (Da)
    12,274
  • Last updated
    2004-08-16 v1
  • Checksum
    30FC5ADF66096C0E
MAAAMDVDTPSGTNSGAGKKRFEVKKWNAVALWAWDIVVDNCAICRNHIMDLCIECQANQASATSEECTVAWGVCNHAFHFHCISRWLKTRQVCPLDNREWEFQKYGH

Sequence caution

The sequence AAH17370.2 differs from that shown. Reason: Erroneous initiation Extended N-terminus.

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict18in Ref. 9; AAM21718

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF142059
EMBL· GenBank· DDBJ
AAD30146.1
EMBL· GenBank· DDBJ
mRNA
AF140598
EMBL· GenBank· DDBJ
AAD29715.1
EMBL· GenBank· DDBJ
mRNA
CR456560
EMBL· GenBank· DDBJ
CAG30446.1
EMBL· GenBank· DDBJ
mRNA
AK315722
EMBL· GenBank· DDBJ
BAG38078.1
EMBL· GenBank· DDBJ
mRNA
AL080242
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471095
EMBL· GenBank· DDBJ
EAW60403.1
EMBL· GenBank· DDBJ
Genomic DNA
BC001466
EMBL· GenBank· DDBJ
AAH01466.1
EMBL· GenBank· DDBJ
mRNA
BC017370
EMBL· GenBank· DDBJ
AAH17370.2
EMBL· GenBank· DDBJ
mRNA Different initiation
AY099360
EMBL· GenBank· DDBJ
AAM21718.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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