Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

E3 ubiquitin-protein ligase RBX1

Gene

RBX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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. 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. 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.9 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication
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.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi42Zinc 11 Publication1
Metal bindingi45Zinc 11 Publication1
Metal bindingi53Zinc 21 Publication1
Metal bindingi56Zinc 21 Publication1
Metal bindingi68Zinc 21 Publication1
Metal bindingi75Zinc 31 Publication1
Metal bindingi77Zinc 3; via pros nitrogen1 Publication1
Metal bindingi80Zinc 1; via pros nitrogen1 Publication1
Metal bindingi82Zinc 21 Publication1
Metal bindingi83Zinc 11 Publication1
Metal bindingi94Zinc 31 Publication1
Metal bindingi97Zinc 31 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri53 – 98RING-typePROSITE-ProRule annotationAdd BLAST46

GO - Molecular functioni

  • cullin family protein binding Source: MGI
  • NEDD8 transferase activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: MGI
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: Reactome
  • ubiquitin-ubiquitin ligase activity Source: MGI
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processDNA damage, DNA repair, Host-virus interaction, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex
R-HSA-1170546 Prolactin receptor signaling
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-180585 Vif-mediated degradation of APOBEC3G
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2644607 Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-4641258 Degradation of DVL
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-5632684 Hedgehog 'on' state
R-HSA-5658442 Regulation of RAS by GAPs
R-HSA-5696394 DNA Damage Recognition in GG-NER
R-HSA-5696395 Formation of Incision Complex in GG-NER
R-HSA-5696400 Dual Incision in GG-NER
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135 Dual incision in TC-NER
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-68949 Orc1 removal from chromatin
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-8951664 Neddylation
R-HSA-9010553 Regulation of expression of SLITs and ROBOs
R-HSA-9020702 Interleukin-1 signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiP62877
SIGNORiP62877
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RBX1 (EC:2.3.2.271 Publication, EC:2.3.2.321 Publication)
Alternative name(s):
E3 ubiquitin-protein transferase RBX1Curated
Protein ZYP
RING finger protein 75
RING-box protein 1
Short name:
Rbx1
Regulator of cullins 1
Cleaved into the following chain:
Alternative name(s):
E3 ubiquitin-protein transferase RBX1, N-terminally processedCurated
Gene namesi
Name:RBX1
Synonyms:RNF75, ROC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100387.8
HGNCiHGNC:9928 RBX1
MIMi603814 gene
neXtProtiNX_P62877

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi53C → A: Strong reduction in ligase activity; when associated with A-56. 1 Publication1
Mutagenesisi56C → A: Strong reduction in ligase activity; when associated with A-53. 1 Publication1
Mutagenesisi75C → A: Strong reduction in ligase activity; when associated with A-77. 1 Publication1
Mutagenesisi77H → A: Strong reduction in ligase activity; when associated with A-75. 1 Publication1

Organism-specific databases

DisGeNETi9978
OpenTargetsiENSG00000100387
PharmGKBiPA34299

Chemistry databases

ChEMBLiCHEMBL3833061

Polymorphism and mutation databases

BioMutaiRBX1
DMDMi51338609

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004232641 – 108E3 ubiquitin-protein ligase RBX1Add BLAST108
Initiator methionineiRemoved; alternateCombined sources1 Publication
ChainiPRO_00000560132 – 108E3 ubiquitin-protein ligase RBX1, N-terminally processedAdd BLAST107

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei2N-acetylalanine; in E3 ubiquitin-protein ligase RBX1, N-terminally processedCombined sources1 Publication1
Modified residuei9PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP62877
MaxQBiP62877
PaxDbiP62877
PeptideAtlasiP62877
PRIDEiP62877
TopDownProteomicsiP62877

PTM databases

iPTMnetiP62877
PhosphoSitePlusiP62877

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSG00000100387
CleanExiHS_RBX1
GenevisibleiP62877 HS

Organism-specific databases

HPAiHPA003038

Interactioni

Subunit structurei

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 (ELOB and ELOC), 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 (ELOB and ELOC), CUL2 and MED8; elongin BC complex (ELOB and ELOC), CUL5 and MUF1. Part of multisubunit complexes with elongin BC complex (ELOB and ELOC), elongin A/ELOA 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 5 E1A protein; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBW7) complex (PubMed:19679664). Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF. Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and CDC34. Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein. Part of the BCR(ENC1) complex containing ENC1. Part of the BCR(GAN) complex containing GAN. Part of the BCR(KLHL41) complex containing KLHL41. Part of the BCR(KEAP1) complex containing KEAP1. Interacts with DCUN1D3. Interacts with SESN1 and SESN2 (PubMed:23274085). Interacts with NOTCH2 (PubMed:29149593).20 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cullin family protein binding Source: MGI
  • transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115301, 184 interactors
CORUMiP62877
DIPiDIP-17014N
IntActiP62877, 75 interactors
MINTiP62877
STRINGi9606.ENSP00000216225

Structurei

Secondary structure

1108
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi21 – 37Combined sources17
Beta strandi39 – 41Combined sources3
Beta strandi43 – 45Combined sources3
Turni49 – 54Combined sources6
Helixi56 – 59Combined sources4
Turni63 – 67Combined sources5
Beta strandi70 – 73Combined sources4
Beta strandi74 – 76Combined sources3
Beta strandi78 – 80Combined sources3
Helixi81 – 88Combined sources8
Beta strandi90 – 93Combined sources4
Beta strandi95 – 97Combined sources3
Beta strandi103 – 105Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LDJX-ray3.00B19-108[»]
1LDKX-ray3.10C19-108[»]
1U6GX-ray3.10B1-108[»]
2HYEX-ray3.10D1-108[»]
2LGVNMR-A12-108[»]
3DPLX-ray2.60R5-108[»]
3DQVX-ray3.00R/Y5-108[»]
3RTRX-ray3.21B/D/F/H5-108[»]
4F52X-ray3.00B/D5-108[»]
4P5OX-ray3.11B/D5-108[»]
5N4WX-ray3.90R1-102[»]
ProteinModelPortaliP62877
SMRiP62877
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62877

Family & Domainsi

Domaini

The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion.

Sequence similaritiesi

Belongs to the RING-box family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri53 – 98RING-typePROSITE-ProRule annotationAdd BLAST46

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2930 Eukaryota
COG5194 LUCA
GeneTreeiENSGT00390000017058
HOGENOMiHOG000171951
HOVERGENiHBG001507
InParanoidiP62877
KOiK03868
OMAiNHIMEPC
OrthoDBiEOG091G0TA5
PhylomeDBiP62877
TreeFamiTF105503

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR024766 Znf_RING_H2
PfamiView protein in Pfam
PF12678 zf-rbx1, 1 hit
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P62877-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAMDVDTP SGTNSGAGKK RFEVKKWNAV ALWAWDIVVD NCAICRNHIM
60 70 80 90 100
DLCIECQANQ ASATSEECTV AWGVCNHAFH FHCISRWLKT RQVCPLDNRE

WEFQKYGH
Length:108
Mass (Da):12,274
Last modified:August 16, 2004 - v1
Checksum:i30FC5ADF66096C0E
GO

Sequence cautioni

The sequence AAH17370 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18G → S in AAM21718 (PubMed:10643962).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF142059 mRNA Translation: AAD30146.1
AF140598 mRNA Translation: AAD29715.1
CR456560 mRNA Translation: CAG30446.1
AK315722 mRNA Translation: BAG38078.1
AL080242 Genomic DNA No translation available.
CH471095 Genomic DNA Translation: EAW60403.1
BC001466 mRNA Translation: AAH01466.1
BC017370 mRNA Translation: AAH17370.2 Different initiation.
AY099360 mRNA Translation: AAM21718.1
CCDSiCCDS14009.1
PIRiT51146
RefSeqiNP_055063.1, NM_014248.3
UniGeneiHs.474949

Genome annotation databases

EnsembliENST00000216225; ENSP00000216225; ENSG00000100387
GeneIDi9978
KEGGihsa:9978
UCSCiuc003azk.4 human

Similar proteinsi

Entry informationi

Entry nameiRBX1_HUMAN
AccessioniPrimary (citable) accession number: P62877
Secondary accession number(s): B2RDY1
, Q8N6Z8, Q9D1S2, Q9WUK9, Q9Y254
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: May 23, 2018
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Cookie policy

We would like to use anonymized google analytics cookies to gather statistics on how uniprot.org is used in aggregate. Learn more

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health