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Protein

Cullin-2

Gene

CUL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). May serve as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF).4 Publications

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.

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • cell cycle arrest Source: ProtInc
  • G1/S transition of mitotic cell cycle Source: ProtInc
  • intrinsic apoptotic signaling pathway Source: ProtInc
  • negative regulation of cell proliferation Source: ProtInc
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000108094-MONOMER.
ReactomeiR-HSA-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ13617.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-2
Short name:
CUL-2
Gene namesi
Name:CUL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:2552. CUL2.

Subcellular locationi

GO - Cellular componenti

  • Cul2-RING ubiquitin ligase complex Source: UniProtKB
  • cytosol Source: Reactome
  • nucleolus Source: Ensembl
  • nucleoplasm Source: HPA
  • VCB complex Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi621K → R: No effect on conjugation with NEDD8. 1 Publication1
Mutagenesisi689K → R: Loss of conjugation with NEDD8. 1 Publication1
Mutagenesisi719K → R: No effect on conjugation with NEDD8. 1 Publication1

Organism-specific databases

DisGeNETi8453.
OpenTargetsiENSG00000108094.
PharmGKBiPA27048.

Polymorphism and mutation databases

BioMutaiCUL2.
DMDMi19863260.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001197901 – 745Cullin-2Add BLAST745

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei393N6-acetyllysineCombined sources1
Modified residuei661PhosphothreonineCombined sources1
Cross-linki689Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)2 Publications

Post-translational modificationi

Neddylated; which enhances the ubiquitination activity of ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes. CBC(VHL) complex formation seems to promote neddylation. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity).By similarity2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13617.
MaxQBiQ13617.
PaxDbiQ13617.
PeptideAtlasiQ13617.
PRIDEiQ13617.

PTM databases

iPTMnetiQ13617.
PhosphoSitePlusiQ13617.
SwissPalmiQ13617.

Expressioni

Gene expression databases

BgeeiENSG00000108094.
CleanExiHS_CUL2.
ExpressionAtlasiQ13617. baseline and differential.
GenevisibleiQ13617. HS.

Organism-specific databases

HPAiCAB002677.
HPA024578.

Interactioni

Subunit structurei

Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL2, Elongin BC (TCEB1 and TCEB2), RBX1 and a variable substrate-specific adapter. Component of the ECS(VHL) or CBC(VHL) complex containing VHL. Component of the ECS(MED8) complex with the probable substrate recognition component MED8. Component of the ECS(LRR1) complex with the probable substrate recognition component LRR1. Component of a probable ECS E3 ubiquitin-protein ligase complex containing CUL2, RBX1, TCEB1, TCEB2 and FEM1B. Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC. Part of an E3 ubiquitin-protein ligase complex including ZYG11BL, CUL2 and Elongin BC. Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1. Interacts with COPS2, and MED8. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 and CUL2. Interacts with KLHDC10; which may be an E3 ubiquitin ligase complex substrate recognition component. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346).11 Publications
(Microbial infection) Interacts with human respiratory syncytial virus (HRSV) protein NS1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CAND1Q86VP63EBI-456179,EBI-456077
COMMD1Q8N6686EBI-456179,EBI-1550112
RBX1P628775EBI-456179,EBI-398523
TCEB1Q153696EBI-456179,EBI-301231
VHLP403379EBI-456179,EBI-301246
vifP125045EBI-456179,EBI-779991From a different organism.

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114031. 472 interactors.
DIPiDIP-31612N.
IntActiQ13617. 49 interactors.
MINTiMINT-1523339.
STRINGi9606.ENSP00000444856.

Structurei

Secondary structure

1745
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 25Combined sources16
Helixi32 – 47Combined sources16
Beta strandi49 – 51Combined sources3
Helixi54 – 77Combined sources24
Helixi85 – 104Combined sources20
Helixi106 – 112Combined sources7
Helixi139 – 156Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WQOX-ray3.20D1-163[»]
ProteinModelPortaliQ13617.
SMRiQ13617.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2284. Eukaryota.
COG5647. LUCA.
GeneTreeiENSGT00760000119212.
HOGENOMiHOG000176713.
HOVERGENiHBG106177.
InParanoidiQ13617.
KOiK03870.
OMAiMPTQFVE.
OrthoDBiEOG091G024O.
PhylomeDBiQ13617.
TreeFamiTF101152.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTiSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEiPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13617-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP
60 70 80 90 100
EPLGERLYTE TKIFLENHVR HLHKRVLESE EQVLVMYHRY WEEYSKGADY
110 120 130 140 150
MDCLYRYLNT QFIKKNKLTE ADLQYGYGGV DMNEPLMEIG ELALDMWRKL
160 170 180 190 200
MVEPLQAILI RMLLREIKND RGGEDPNQKV IHGVINSFVH VEQYKKKFPL
210 220 230 240 250
KFYQEIFESP FLTETGEYYK QEASNLLQES NCSQYMEKVL GRLKDEEIRC
260 270 280 290 300
RKYLHPSSYT KVIHECQQRM VADHLQFLHA ECHNIIRQEK KNDMANMYVL
310 320 330 340 350
LRAVSTGLPH MIQELQNHIH DEGLRATSNL TQENMPTLFV ESVLEVHGKF
360 370 380 390 400
VQLINTVLNG DQHFMSALDK ALTSVVNYRE PKSVCKAPEL LAKYCDNLLK
410 420 430 440 450
KSAKGMTENE VEDRLTSFIT VFKYIDDKDV FQKFYARMLA KRLIHGLSMS
460 470 480 490 500
MDSEEAMINK LKQACGYEFT SKLHRMYTDM SVSADLNNKF NNFIKNQDTV
510 520 530 540 550
IDLGISFQIY VLQAGAWPLT QAPSSTFAIP QELEKSVQMF ELFYSQHFSG
560 570 580 590 600
RKLTWLHYLC TGEVKMNYLG KPYVAMVTTY QMAVLLAFNN SETVSYKELQ
610 620 630 640 650
DSTQMNEKEL TKTIKSLLDV KMINHDSEKE DIDAESSFSL NMNFSSKRTK
660 670 680 690 700
FKITTSMQKD TPQEMEQTRS AVDEDRKMYL QAAIVRIMKA RKVLRHNALI
710 720 730 740
QEVISQSRAR FNPSISMIKK CIEVLIDKQY IERSQASADE YSYVA
Length:745
Mass (Da):86,983
Last modified:August 14, 2001 - v2
Checksum:i30647248F671AB0E
GO
Isoform 2 (identifier: Q13617-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MYRVTWSTFWLRFQHYTCTM

Note: No experimental confirmation available.
Show »
Length:764
Mass (Da):89,492
Checksum:i11890883B1EA53A4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20T → I in BAH13294 (PubMed:14702039).Curated1
Sequence conflicti95 – 98SKGA → IRHE in AAC50545 (PubMed:8681378).Curated4
Sequence conflicti681Q → H in AAC50545 (PubMed:8681378).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011374109N → S.2 PublicationsCorresponds to variant rs1131503dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0444981M → MYRVTWSTFWLRFQHYTCTM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83410 mRNA. Translation: AAC51190.1.
AF126404 mRNA. Translation: AAD23581.1.
AK095217 mRNA. Translation: BAG53007.1.
AK300491 mRNA. Translation: BAH13294.1.
AL392046 Genomic DNA. Translation: CAI13163.1.
CH471072 Genomic DNA. Translation: EAW85924.1.
CH471072 Genomic DNA. Translation: EAW85925.1.
CH471072 Genomic DNA. Translation: EAW85926.1.
CH471072 Genomic DNA. Translation: EAW85927.1.
CH471072 Genomic DNA. Translation: EAW85928.1.
BC009591 mRNA. Translation: AAH09591.1.
BC110901 mRNA. Translation: AAI10902.1.
U58088 mRNA. Translation: AAC50545.1.
CCDSiCCDS55709.1. [Q13617-2]
CCDS7179.1. [Q13617-1]
RefSeqiNP_001185706.1. NM_001198777.1. [Q13617-1]
NP_001185707.1. NM_001198778.1. [Q13617-2]
NP_001185708.1. NM_001198779.1.
NP_003582.2. NM_003591.3. [Q13617-1]
XP_011518049.1. XM_011519747.1. [Q13617-1]
UniGeneiHs.82919.

Genome annotation databases

EnsembliENST00000374748; ENSP00000363880; ENSG00000108094. [Q13617-1]
ENST00000374749; ENSP00000363881; ENSG00000108094. [Q13617-1]
ENST00000374751; ENSP00000363883; ENSG00000108094. [Q13617-1]
ENST00000421317; ENSP00000414095; ENSG00000108094. [Q13617-2]
GeneIDi8453.
KEGGihsa:8453.
UCSCiuc001ixv.4. human. [Q13617-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83410 mRNA. Translation: AAC51190.1.
AF126404 mRNA. Translation: AAD23581.1.
AK095217 mRNA. Translation: BAG53007.1.
AK300491 mRNA. Translation: BAH13294.1.
AL392046 Genomic DNA. Translation: CAI13163.1.
CH471072 Genomic DNA. Translation: EAW85924.1.
CH471072 Genomic DNA. Translation: EAW85925.1.
CH471072 Genomic DNA. Translation: EAW85926.1.
CH471072 Genomic DNA. Translation: EAW85927.1.
CH471072 Genomic DNA. Translation: EAW85928.1.
BC009591 mRNA. Translation: AAH09591.1.
BC110901 mRNA. Translation: AAI10902.1.
U58088 mRNA. Translation: AAC50545.1.
CCDSiCCDS55709.1. [Q13617-2]
CCDS7179.1. [Q13617-1]
RefSeqiNP_001185706.1. NM_001198777.1. [Q13617-1]
NP_001185707.1. NM_001198778.1. [Q13617-2]
NP_001185708.1. NM_001198779.1.
NP_003582.2. NM_003591.3. [Q13617-1]
XP_011518049.1. XM_011519747.1. [Q13617-1]
UniGeneiHs.82919.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WQOX-ray3.20D1-163[»]
ProteinModelPortaliQ13617.
SMRiQ13617.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114031. 472 interactors.
DIPiDIP-31612N.
IntActiQ13617. 49 interactors.
MINTiMINT-1523339.
STRINGi9606.ENSP00000444856.

PTM databases

iPTMnetiQ13617.
PhosphoSitePlusiQ13617.
SwissPalmiQ13617.

Polymorphism and mutation databases

BioMutaiCUL2.
DMDMi19863260.

Proteomic databases

EPDiQ13617.
MaxQBiQ13617.
PaxDbiQ13617.
PeptideAtlasiQ13617.
PRIDEiQ13617.

Protocols and materials databases

DNASUi8453.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374748; ENSP00000363880; ENSG00000108094. [Q13617-1]
ENST00000374749; ENSP00000363881; ENSG00000108094. [Q13617-1]
ENST00000374751; ENSP00000363883; ENSG00000108094. [Q13617-1]
ENST00000421317; ENSP00000414095; ENSG00000108094. [Q13617-2]
GeneIDi8453.
KEGGihsa:8453.
UCSCiuc001ixv.4. human. [Q13617-1]

Organism-specific databases

CTDi8453.
DisGeNETi8453.
GeneCardsiCUL2.
HGNCiHGNC:2552. CUL2.
HPAiCAB002677.
HPA024578.
MIMi603135. gene.
neXtProtiNX_Q13617.
OpenTargetsiENSG00000108094.
PharmGKBiPA27048.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2284. Eukaryota.
COG5647. LUCA.
GeneTreeiENSGT00760000119212.
HOGENOMiHOG000176713.
HOVERGENiHBG106177.
InParanoidiQ13617.
KOiK03870.
OMAiMPTQFVE.
OrthoDBiEOG091G024O.
PhylomeDBiQ13617.
TreeFamiTF101152.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000108094-MONOMER.
ReactomeiR-HSA-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ13617.

Miscellaneous databases

ChiTaRSiCUL2. human.
GeneWikiiCUL2.
GenomeRNAii8453.
PROiQ13617.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108094.
CleanExiHS_CUL2.
ExpressionAtlasiQ13617. baseline and differential.
GenevisibleiQ13617. HS.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTiSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEiPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCUL2_HUMAN
AccessioniPrimary (citable) accession number: Q13617
Secondary accession number(s): B3KT95
, B7Z6K8, D3DRY6, G3V1S2, O00200, Q5T2B6, Q9UNF9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: August 14, 2001
Last modified: November 30, 2016
This is version 160 of the entry and version 2 of the sequence. [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, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.