[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). DOI=10.1074/jbc.273.38.24289; PubMed=9733711 [NCBI, ExPASy, EBI, Israel, Japan] Du M., Sansores-Garcia L., Zu Z., Wu K.K.; "Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family."; J. Biol. Chem. 273:24289-24292(1998).
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). TISSUE=Brain; DOI=10.1093/dnares/5.3.169; PubMed=9734811 [NCBI, ExPASy, EBI, Israel, Japan] Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.; "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."; DNA Res. 5:169-176(1998).
[3]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). TISSUE=Colon carcinoma; PubMed=9663463 [NCBI, ExPASy, EBI, Israel, Japan] Michel J.J., Xiong Y.; "Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A."; Cell Growth Differ. 9:435-449(1998).
[4]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). TISSUE=Testis; Xu M., Huang X.Y., Yin L.L., Xu Z.Y., Lu L., Zhou Z.M., Sha J.H.; "Cloning and characterization of a new isoform of CUL3 gene in testis."; Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). TISSUE=Ovary, Skin, and Uterus; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[6]	NUCLEOTIDE SEQUENCE [MRNA] OF 192-768. DOI=10.1016/S0092-8674(00)81267-2; PubMed=8681378 [NCBI, ExPASy, EBI, Israel, Japan] Kipreos E.T., Lander L.E., Wing J.P., He W.W., Hedgecock E.M.; "cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family."; Cell 85:829-839(1996).
[7]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 398-768. TISSUE=Brain; Yu W., Sarginson J., Gibbs R.A.; Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
[8]	ALTERNATIVE SPLICING (ISOFORMS 1 AND 3), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CYCE, AND NEDDYLATION. DOI=10.1101/gad.13.18.2375; PubMed=10500095 [NCBI, ExPASy, EBI, Israel, Japan] Singer J.D., Gurian-West M., Clurman B., Roberts J.M.; "Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells."; Genes Dev. 13:2375-2387(1999).
[9]	FUNCTION. DOI=10.1016/S0014-5793(01)02343-2; PubMed=11311237 [NCBI, ExPASy, EBI, Israel, Japan] Maeda I., Ohta T., Koizumi H., Fukuda M.; "In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3."; FEBS Lett. 494:181-185(2001).
[10]	NEDDYLATION. DOI=10.1038/sj.onc.1203093; PubMed=10597293 [NCBI, ExPASy, EBI, Israel, Japan] Hori T., Osaka F., Chiba T., Miyamoto C., Okabayashi K., Shimbara N., Kato S., Tanaka K.; "Covalent modification of all members of human cullin family proteins by NEDD8."; Oncogene 18:6829-6834(1999).
[11]	INTERACTION WITH RBX1 AND RNF7. DOI=10.1016/S1097-2765(00)80482-7; PubMed=10230407 [NCBI, ExPASy, EBI, Israel, Japan] Ohta T., Michel J.J., Schottelius A.J., Xiong Y.; "ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity."; Mol. Cell 3:535-541(1999).
[12]	INTERACTION WITH TIP120A. DOI=10.1074/jbc.M213070200; PubMed=12609982 [NCBI, ExPASy, EBI, Israel, Japan] Min K.-W., Hwang J.-W., Lee J.-S., Park Y., Tamura T.-A., Yoon J.-B.; "TIP120A associates with cullins and modulates ubiquitin ligase activity."; J. Biol. Chem. 278:15905-15910(2003).
[13]	INTERACTION WITH GAN; ZBTB16; KLHL9; KLHL13; KLHL211; KLHL3; KLHL15; KLHL20; C16ORF44; GMCL1L; BTBD1 AND SPOP. DOI=10.1038/ncb1056; PubMed=14528312 [NCBI, ExPASy, EBI, Israel, Japan] Furukawa M., He Y.J., Borchers C., Xiong Y.; "Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases."; Nat. Cell Biol. 5:1001-1007(2003).
[14]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-737, AND MASS SPECTROMETRY. TISSUE=Epithelium; DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan] Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.; "Large-scale characterization of HeLa cell nuclear phosphoproteins."; Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[15]	IDENTIFICATION IN THE BCR(KBTBD10) COMPLEX, IDENTIFICATION IN THE BCR(ENC1) COMPLEX, AND IDENTIFICATION IN A COMPLEX WITH RBX1 AND GAN. DOI=10.1074/jbc.M501279200; PubMed=15983046 [NCBI, ExPASy, EBI, Israel, Japan] Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M.; "Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway."; J. Biol. Chem. 280:30091-30099(2005).
[16]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-58, AND MASS SPECTROMETRY. DOI=10.1038/nbt1046; PubMed=15592455 [NCBI, ExPASy, EBI, Israel, Japan] Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.; "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; Nat. Biotechnol. 23:94-101(2005).
[17]	IDENTIFICATION IN A COMPLEX WITH SPOP AND BMI1, IDENTIFICATION IN A COMPLEX WITH SPOP AND H2AFY, AND FUNCTION. DOI=10.1073/pnas.0408918102; PubMed=15897469 [NCBI, ExPASy, EBI, Israel, Japan] Hernandez-Munoz I., Lund A.H., van der Stoop P., Boutsma E., Muijrers I., Verhoeven E., Nusinow D.A., Panning B., Marahrens Y., van Lohuizen M.; "Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase."; Proc. Natl. Acad. Sci. U.S.A. 102:7635-7640(2005).
[18]	IDENTIFICATION IN THE BCR(SPOP) COMPLEX, INTERACTION WITH SPOP, AND FUNCTION IN UBIQUITINATION OF DAXX. DOI=10.1074/jbc.M600204200; PubMed=16524876 [NCBI, ExPASy, EBI, Israel, Japan] Kwon J.E., La M., Oh K.H., Oh Y.M., Kim G.R., Seol J.H., Baek S.H., Chiba T., Tanaka K., Bang O.S., Joe C.O., Chung C.H.; "BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase."; J. Biol. Chem. 281:12664-12672(2006).
[19]	FUNCTION, AND INTERACTION WITH KLHL9 AND KLHL13. DOI=10.1016/j.devcel.2007.03.019; PubMed=17543862 [NCBI, ExPASy, EBI, Israel, Japan] Sumara I., Quadroni M., Frei C., Olma M.H., Sumara G., Ricci R., Peter M.; "A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells."; Dev. Cell 12:887-900(2007).
[20]	SELF-ASSOCIATION. DOI=10.1016/j.cellsig.2006.12.002; PubMed=17254749 [NCBI, ExPASy, EBI, Israel, Japan] Chew E.H., Poobalasingam T., Hawkey C.J., Hagen T.; "Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells -- evidence for cullin dimerization."; Cell. Signal. 19:1071-1080(2007).
[21]	BCR COMPLEX HOMODIMERIZATION. DOI=10.1091/mbc.E06-06-0542; PubMed=17192413 [NCBI, ExPASy, EBI, Israel, Japan] Wimuttisuk W., Singer J.D.; "The Cullin3 ubiquitin ligase functions as a Nedd8-bound heterodimer."; Mol. Biol. Cell 18:899-909(2007).
[22]	IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. Colinge J., Superti-Furga G., Bennett K.L.; Submitted (OCT-2008) to UniProtKB.

Comments

FUNCTION: Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein 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 BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition.
PATHWAY: Protein modification; protein ubiquitination .
SUBUNIT: Forms neddylation-dependent homodimers. Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein acting as both, adapter to cullin and substrate recognition subunit. The BCR complex may be active as a heterodimeric complex, in which NEDD8, covalently attached to one CUL3 molecule, binds to the C-terminus of a second CUL3 molecule. Interacts with RBX1, RNF7, CYCE and TIP120A/CAND1. Part of the BCR(SPOP) containing SPOP. Part of the probable BCR(KLHL9-KLHL13) complex with BTB domain proteins KLHL9 and KLHL13. Part of the BCR(KBTBD10) complex containing KBTBD10. Part of the BCR(ENC1) complex containing ENC1. Part of a complex consisting of BMI1/PCGF4, CUL3 and SPOP. Part of a complex consisting of H2AFY, CUL3 and SPOP. Interacts with KLHL9, KLHL13, GAN, ZBTB16, KLHL21, KLHL3, KLHL15, KLHL20, C16orf44, GMCL1L, BTBD1. Part of a complex that contains CUL3, RBX1 and GAN.
INTERACTION:
Q86VP6:CAND1; NbExp=1; IntAct=EBI-456129, EBI-456077;
SUBCELLULAR LOCATION: Nucleus. Golgi apparatus.

ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing.

Name	1
Synonyms	Cul-3 Long
Isoform ID	Q13618-1
This is the isoform sequence displayed in this entry.

Name	2
Isoform ID	Q13618-2
Features which should be applied to build the isoform sequence: VSP_008824.

Name	3
Synonyms	Cul-3 Short
Isoform ID	Q13618-3
Features which should be applied to build the isoform sequence: VSP_008825.

TISSUE SPECIFICITY: Widely expressed.
PTM: Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-protein ligase activity of the BCR complex. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.
SIMILARITY: Belongs to the cullin family.
SEQUENCE CAUTION:
- Sequence=AAC28621.1; Type=Frameshift; Positions=452;
- Sequence=AAC36682.1; Type=Frameshift; Positions=159, 179;

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AF064087; AAC36304.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB014517; BAA31592.2; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF062537; AAC36682.1; ALT_FRAME; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY337761; AAQ01660.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC031844; AAH31844.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC039598; AAH39598.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC092409; AAH92409.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U58089; AAC50546.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF052147; AAC28621.1; ALT_FRAME; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00014312; -.
IPI00382458; -.
IPI00382459; -.

RefSeq

NP_003581.1; -.

UniGene

Hs.372286

3D structure databases

ModBase

Q13618.

Protein-protein interaction databases

IntAct

Q13618; 5.

PTM databases

PhosphoSite

Q13618; -.

Enzyme and pathway databases

Pathway_Interaction_DB

aurora_b_pathway; Aurora B signaling.

Organism-specific databases

GC02M225043; -.

HIX0002888; -.

HGNC:2553; CUL3.

CAB002678; -.

603136; gene. [NCBI / EBI]

PharmGKB

PA27049; -.

HUGE

KIAA0617.

Gene expression databases

Q13618; -.

Q13618; -.

HS_CUL3; -.

ENSG00000036257; Homo sapiens.

Ontologies

GO:0031461;	Cellular component: cullin-RING ubiquitin ligase complex (inferred from electronic annotation from InterPro).
GO:0005794;	Cellular component: Golgi apparatus (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005634;	Cellular component: nucleus (inferred from electronic annotation from UniProtKB-SubCell).
GO:0031625;	Molecular function: ubiquitin protein ligase binding (inferred from electronic annotation from InterPro).
GO:0007050;	Biological process: cell cycle arrest (traceable author statement from ProtInc).
GO:0008054;	Biological process: cyclin catabolic process (inferred from direct assay from MGI).
GO:0000082;	Biological process: G1/S transition of mitotic cell cycle (traceable author statement from ProtInc).
GO:0008629;	Biological process: induction of apoptosis by intracellular signals (traceable author statement from ProtInc).
GO:0008284;	Biological process: positive regulation of cell proliferation (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR016157; Cullin_CS.
IPR016158; Cullin_homology.
IPR001373; Cullin_N.
IPR019559; Cullin_neddylation_domain.
IPR011991; Wing_hlx_DNA_bd.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 2.

Pfam

PF00888; Cullin; 1.
PF10557; Cullin_Nedd8; 1.
Pfam graphical view of domain structure.

SMART

SM00182; CULLIN; 1.
SMART graphical view of domain structure.

PROSITE

PS01256; CULLIN_1; 1.
PS50069; CULLIN_2; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

Q13618; -.

Genome annotation databases

Ensembl

ENSG00000036257; Homo sapiens. [Contig view]

GeneID

8452; -.

KEGG

hsa:8452; -.

Phylogenomic databases

HOGENOM

Q13618; -.

HOVERGEN

Q13618; -.

OMA

Q13618; EREYLQR.

Other

31630; -.

CUL3; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; Golgi apparatus; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; Ubl conjugation; Ubl conjugation pathway.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 768`	`768`	`Cullin-3.`	`PRO_0000119793`
`MOD_RES`	`58 58`		`Phosphotyrosine.`
`MOD_RES`	`450 450`		`Phosphoserine (By similarity).`
`MOD_RES`	`737 737`		`Phosphoserine.`
`CROSSLNK`	`712 712`		`Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) (By similarity).`
`VAR_SEQ`	`1 24`		`Missing (in isoform 2).`	`VSP_008824`
`VAR_SEQ`	`23 88`		`Missing (in isoform 3).`	`VSP_008825`
`VARIANT`	`13 13`	`1`	`D -> H (in dbSNP:rs2969802 [NCBI]).`	`VAR_017194`
`VARIANT`	`184 184`	`1`	`R -> S (in dbSNP:rs17480168 [NCBI]).`	`VAR_048839`
`VARIANT`	`567 567`	`1`	`V -> I (in dbSNP:rs3738952 [NCBI]).`	`VAR_017195`
`CONFLICT`	`13 13`		`D -> G (in Ref. 3; AAC36682).`
`CONFLICT`	`179 179`		`D -> S (in Ref. 3).`
`CONFLICT`	`397 397`		`K -> T (in Ref. 4; AAQ01660).`
`CONFLICT`	`481 481`		`N -> T (in Ref. 4; AAQ01660).`
`CONFLICT`	`609 609`		`E -> G (in Ref. 5; AAH31844).`
`CONFLICT`	`666 666`		`T -> I (in Ref. 4; AAQ01660).`

Sequence information

Length: 768 AA [This is the length of the unprocessed precursor]

Molecular weight: 88930 Da [This is the MW of the unprocessed precursor]

CRC64: A1A02022480BF099 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MSNLSKGTGS RKDTKMRIRA FPMTMDEKYV NSIWDLLKNA IQEIQRKNNS GLSFEELYRN 

        70         80         90        100        110        120 
AYTMVLHKHG EKLYTGLREV VTEHLINKVR EDVLNSLNNN FLQTLNQAWN DHQTAMVMIR 

       130        140        150        160        170        180 
DILMYMDRVY VQQNNVENVY NLGLIIFRDQ VVRYGCIRDH LRQTLLDMIA RERKGEVVDR 

       190        200        210        220        230        240 
GAIRNACQML MILGLEGRSV YEEDFEAPFL EMSAEFFQME SQKFLAENSA SVYIKKVEAR 

       250        260        270        280        290        300 
INEEIERVMH CLDKSTEEPI VKVVERELIS KHMKTIVEME NSGLVHMLKN GKTEDLGCMY 

       310        320        330        340        350        360 
KLFSRVPNGL KTMCECMSSY LREQGKALVS EEGEGKNPVD YIQGLLDLKS RFDRFLLESF 

       370        380        390        400        410        420 
NNDRLFKQTI AGDFEYFLNL NSRSPEYLSL FIDDKLKKGV KGLTEQEVET ILDKAMVLFR 

       430        440        450        460        470        480 
FMQEKDVFER YYKQHLARRL LTNKSVSDDS EKNMISKLKT ECGCQFTSKL EGMFRDMSIS 

       490        500        510        520        530        540 
NTTMDEFRQH LQATGVSLGG VDLTVRVLTT GYWPTQSATP KCNIPPAPRH AFEIFRRFYL 

       550        560        570        580        590        600 
AKHSGRQLTL QHHMGSADLN ATFYGPVKKE DGSEVGVGGA QVTGSNTRKH ILQVSTFQMT 

       610        620        630        640        650        660 
ILMLFNNREK YTFEEIQQET DIPERELVRA LQSLACGKPT QRVLTKEPKS KEIENGHIFT 

       670        680        690        700        710        720 
VNDQFTSKLH RVKIQTVAAK QGESDPERKE TRQKVDDDRK HEIEAAIVRI MKSRKKMQHN 

       730        740        750        760 
VLVAEVTQQL KARFLPSPVV IKKRIEGLIE REYLARTPED RKVYTYVA

Q13618 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools