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Protein

Cullin-2

Gene

Cul2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (By similarity). 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 (By similarity). The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF) (By similarity).By similarity

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

GO - Biological processi

  • protein catabolic process Source: MGI
  • protein ubiquitination Source: UniProtKB-UniPathway
  • ubiquitin-dependent protein catabolic process Source: InterPro

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-MMU-8951664 Neddylation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-2
Short name:
CUL-2
Gene namesi
Name:Cul2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:1918995 Cul2

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001197911 – 745Cullin-2Add BLAST745

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei393N6-acetyllysineCombined sources1
Modified residuei661PhosphothreonineBy similarity1
Cross-linki689Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)By similarity

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 (By similarity). Deneddylated via its interaction with the COP9 signalosome (CSN) complex.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9D4H8
PaxDbiQ9D4H8
PeptideAtlasiQ9D4H8
PRIDEiQ9D4H8

PTM databases

iPTMnetiQ9D4H8
PhosphoSitePlusiQ9D4H8

Expressioni

Gene expression databases

BgeeiENSMUSG00000024231
CleanExiMM_CUL2
ExpressionAtlasiQ9D4H8 baseline and differential
GenevisibleiQ9D4H8 MM

Interactioni

Subunit structurei

Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL2, Elongin BC (ELOB and ELOC), 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, ELOB, ELOC 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, ELOB 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 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi214895, 7 interactors
CORUMiQ9D4H8
IntActiQ9D4H8, 7 interactors
MINTiQ9D4H8
STRINGi10090.ENSMUSP00000125403

Structurei

3D structure databases

ProteinModelPortaliQ9D4H8
SMRiQ9D4H8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2284 Eukaryota
COG5647 LUCA
GeneTreeiENSGT00760000119212
HOGENOMiHOG000176713
HOVERGENiHBG106177
InParanoidiQ9D4H8
KOiK03870
OMAiMPTQFVE
OrthoDBiEOG091G024O
PhylomeDBiQ9D4H8
TreeFamiTF101152

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR016157 Cullin_CS
IPR016158 Cullin_homology
IPR036317 Cullin_homology_sf
IPR001373 Cullin_N
IPR019559 Cullin_neddylation_domain
IPR016159 Cullin_repeat-like_dom_sf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00888 Cullin, 1 hit
PF10557 Cullin_Nedd8, 1 hit
SMARTiView protein in SMART
SM00182 CULLIN, 1 hit
SM00884 Cullin_Nedd8, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF74788 SSF74788, 1 hit
SSF75632 SSF75632, 1 hit
PROSITEiView protein in PROSITE
PS01256 CULLIN_1, 1 hit
PS50069 CULLIN_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9D4H8-1) [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
EPLGERLYAE TKIFLESHVR HLYKRVLESE EQVLVMYHRY WEEYSKGADY
110 120 130 140 150
MDCLYRYLNT QYIKKNKLTE ADIQYGYGGV DMNEPLMEIG ELALDMWRKL
160 170 180 190 200
MVEPLQNILI RMLLREIKND RGGEDPNQKV IHGVINSFVH VEQYKKKFPL
210 220 230 240 250
KFYQGIFVSP FLTETGEYYK QEASNLLQES NCSQYMEKVL GRLKDEEIRC
260 270 280 290 300
RKYLHPSSYT KVIHECQQRM VADHLQFLHS ECHSIIQQER KNDMANMYVL
310 320 330 340 350
LRAVSSGLPH MIEELQKHIH DEGLRATSNL TQEHMPTLFV ESVLEVHGKF
360 370 380 390 400
VQLINTVLNG DQHFMSALDK ALTSVVNYRE PKSVCKAPEL LAKYCDNLLK
410 420 430 440 450
KSAKGMTENE VEDKLTSFIT VFKYIDDKDV FQKFYARMLA KRLIHGLSMS
460 470 480 490 500
MDSEEAMINK LKQACGYEFT SKLHRMYTDM SVSADLNNKF NNFIRNQDTV
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 NMSFSSKRTK
660 670 680 690 700
FKITTSMQKD TPQELEQTRS AVDEDRKMYL QAAIVRIMKA RKVLRHNALI
710 720 730 740
QEVISQSRAR FNPSISMIKK CIEVLIDKQY IERSQASADE YSYVA
Length:745
Mass (Da):86,877
Last modified:November 7, 2003 - v2
Checksum:i311C05CC262692E0
GO
Isoform 2 (identifier: Q9D4H8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     664-702: Missing.

Show »
Length:706
Mass (Da):82,271
Checksum:iDDF5F2945896FA3D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti612K → R in BAB30283 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008823664 – 702Missing in isoform 2. 2 PublicationsAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK016520 mRNA Translation: BAB30283.1
AK160597 mRNA Translation: BAE35903.1
BC026779 mRNA Translation: AAH26779.1
BC027428 mRNA Translation: AAH27428.1
BC025902 mRNA Translation: AAH25902.1
CCDSiCCDS29032.2 [Q9D4H8-1]
RefSeqiNP_083678.2, NM_029402.3 [Q9D4H8-1]
XP_006526337.1, XM_006526274.3 [Q9D4H8-1]
XP_006526338.1, XM_006526275.3 [Q9D4H8-1]
UniGeneiMm.291707
Mm.443148

Genome annotation databases

EnsembliENSMUST00000025073; ENSMUSP00000025073; ENSMUSG00000024231 [Q9D4H8-2]
ENSMUST00000162301; ENSMUSP00000125403; ENSMUSG00000024231 [Q9D4H8-1]
GeneIDi71745
KEGGimmu:71745
UCSCiuc008dxz.2 mouse [Q9D4H8-2]
uc008dya.2 mouse [Q9D4H8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCUL2_MOUSE
AccessioniPrimary (citable) accession number: Q9D4H8
Secondary accession number(s): Q3TUR8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: November 7, 2003
Last modified: April 25, 2018
This is version 141 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

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