CUL2_PONAB
ID CUL2_PONAB Reviewed; 745 AA.
AC Q5RCF3;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 96.
DE RecName: Full=Cullin-2;
DE Short=CUL-2;
GN Name=CUL2;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Core component of multiple cullin-RING-based ECS (ElonginB/C-
CC CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which
CC mediate the ubiquitination of target proteins. CUL2 may serve as a
CC rigid scaffold in the complex and may contribute to catalysis through
CC positioning of the substrate and the ubiquitin-conjugating enzyme. The
CC E3 ubiquitin-protein ligase activity of the complex is dependent on the
CC neddylation of the cullin subunit and is inhibited by the association
CC of the deneddylated cullin subunit with TIP120A/CAND1. The functional
CC specificity of the ECS complex depends on the substrate recognition
CC component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible
CC factor (HIF). A number of ECS complexes (containing either KLHDC2,
CC KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition
CC component) are part of the DesCEND (destruction via C-end degrons)
CC pathway, which recognizes a C-degron located at the extreme C terminus
CC of target proteins, leading to their ubiquitination and degradation.
CC ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination
CC of target proteins. {ECO:0000250|UniProtKB:Q13617}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q13617}.
CC -!- SUBUNIT: Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein)
CC E3 ubiquitin-protein ligase complexes formed of CUL2, Elongin BC (ELOB
CC and ELOC), RBX1 and a variable substrate-specific adapter. Component of
CC the ECS(VHL) or CBC(VHL) complex containing VHL. Component of the
CC ECS(MED8) complex with the probable substrate recognition component
CC MED8. Component of multiple ECS complexes part of the DesCEND
CC (destruction via C-end degrons) pathway, which contain either KLHDC2,
CC KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition
CC component. Component of the ECS(LRR1) complex with the probable
CC substrate recognition component LRR1. Component of a probable ECS E3
CC ubiquitin-protein ligase complex containing CUL2, RBX1, ELOB, ELOC and
CC FEM1B. Part of an E3 ubiquitin-protein ligase complex including ZYG11B,
CC CUL2 and Elongin BC. Part of an E3 ubiquitin-protein ligase complex
CC including ZER1, CUL2 and Elongin BC. Interacts with RBX1, RNF7, FEM1B
CC and TIP120A/CAND1. Found in a complex composed of LIMD1, VHL,
CC EGLN1/PHD2, ELOB and CUL2. Interacts (when neddylated) with ARIH1;
CC leading to activate the E3 ligase activity of ARIH1. Interacts
CC (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and
CC DCUN1D5; these interactions promote the cullin neddylation. Component
CC of VCB (elongins BC/CUL2/VHL) complex that contains at least DCUN1D1,
CC CUL2 and VHL; this complex triggers CUL2 neddylation and consequently
CC cullin ring ligase (CRL) substrates polyubiquitylation.
CC {ECO:0000250|UniProtKB:Q13617}.
CC -!- PTM: Neddylated; which enhances the ubiquitination activity of ECS
CC (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase
CC complexes. CBC(VHL) complex formation seems to promote neddylation.
CC Deneddylated via its interaction with the COP9 signalosome (CSN)
CC complex (By similarity). {ECO:0000250|UniProtKB:Q13617}.
CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00330}.
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DR EMBL; CR858317; CAH90554.1; -; mRNA.
DR RefSeq; NP_001127301.1; NM_001133829.1.
DR RefSeq; XP_009235163.1; XM_009236888.1.
DR RefSeq; XP_009235164.1; XM_009236889.1.
DR AlphaFoldDB; Q5RCF3; -.
DR SMR; Q5RCF3; -.
DR STRING; 9601.ENSPPYP00000022294; -.
DR Ensembl; ENSPPYT00000045229; ENSPPYP00000038250; ENSPPYG00000019905.
DR GeneID; 100174361; -.
DR KEGG; pon:100174361; -.
DR CTD; 8453; -.
DR eggNOG; KOG2284; Eukaryota.
DR GeneTree; ENSGT00940000154926; -.
DR HOGENOM; CLU_004747_6_1_1; -.
DR InParanoid; Q5RCF3; -.
DR OMA; WRLYMIE; -.
DR OrthoDB; 1040292at2759; -.
DR TreeFam; TF101152; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001595; Chromosome 10.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IEA:InterPro.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR045093; Cullin.
DR InterPro; IPR016157; Cullin_CS.
DR InterPro; IPR016158; Cullin_homology.
DR InterPro; IPR036317; Cullin_homology_sf.
DR InterPro; IPR001373; Cullin_N.
DR InterPro; IPR019559; Cullin_neddylation_domain.
DR InterPro; IPR016159; Cullin_repeat-like_dom_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11932; PTHR11932; 1.
DR Pfam; PF00888; Cullin; 1.
DR Pfam; PF10557; Cullin_Nedd8; 1.
DR SMART; SM00182; CULLIN; 1.
DR SMART; SM00884; Cullin_Nedd8; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF74788; SSF74788; 1.
DR SUPFAM; SSF75632; SSF75632; 1.
DR PROSITE; PS01256; CULLIN_1; 1.
DR PROSITE; PS50069; CULLIN_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Isopeptide bond; Phosphoprotein; Reference proteome;
KW Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..745
FT /note="Cullin-2"
FT /id="PRO_0000119792"
FT MOD_RES 393
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13617"
FT MOD_RES 661
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13617"
FT CROSSLNK 689
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in NEDD8)"
FT /evidence="ECO:0000250|UniProtKB:Q13616"
SQ SEQUENCE 745 AA; 86983 MW; 30647248F671AB0E CRC64;
MSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP EPLGERLYTE
TKIFLENHVR HLHKRVLESE EQVLVMYHRY WEEYSKGADY MDCLYRYLNT QFIKKNKLTE
ADLQYGYGGV DMNEPLMEIG ELALDMWRKL MVEPLQAILI RMLLREIKND RGGEDPNQKV
IHGVINSFVH VEQYKKKFPL KFYQEIFESP FLTETGEYYK QEASNLLQES NCSQYMEKVL
GRLKDEEIRC RKYLHPSSYT KVIHECQQRM VADHLQFLHA ECHNIIRQEK KNDMANMYVL
LRAVSTGLPH MIQELQNHIH DEGLRATSNL TQENMPTLFV ESVLEVHGKF VQLINTVLNG
DQHFMSALDK ALTSVVNYRE PKSVCKAPEL LAKYCDNLLK KSAKGMTENE VEDRLTSFIT
VFKYIDDKDV FQKFYARMLA KRLIHGLSMS MDSEEAMINK LKQACGYEFT SKLHRMYTDM
SVSADLNNKF NNFIKNQDTV IDLGISFQIY VLQAGAWPLT QAPSSTFAIP QELEKSVQMF
ELFYSQHFSG RKLTWLHYLC TGEVKMNYLG KPYVAMVTTY QMAVLLAFNN SETVSYKELQ
DSTQMNEKEL TKTIKSLLDV KMINHDSEKE DIDAESSFSL NMNFSSKRTK FKITTSMQKD
TPQEMEQTRS AVDEDRKMYL QAAIVRIMKA RKVLRHNALI QEVISQSRAR FNPSISMIKK
CIEVLIDKQY IERSQASADE YSYVA
