Q13618 (CUL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cullin-3
Short name=CUL-3

Gene names

Name:	CUL3
Synonyms:	KIAA0617

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	768 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (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 substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. Ref.11 Ref.12 Ref.17 Ref.18 Ref.19 Ref.20 Ref.24 Ref.26 Ref.28 Ref.29
Pathway	Protein modification; protein ubiquitination.
Subunit structure	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, and of BCR containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL. Part of the probable BCR(KLHL9-KLHL13) complex with BTB domain proteins KLHL9 and KLHL13. Part of the BCR(KLHL41) complex containing KLHL41. Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1. Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 Probable. 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 BRMS1, CUL3 and SPOP. Part of a complex consisting of H2AFY, CUL3 and SPOP. Component of the BCR(KLHL42) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL42. Interacts with KLHL42 (via the BTB domain). Interacts with KATNA1; the interaction is enhanced by KLHL42. Interacts with KCTD5, KLHL9, KLHL11, KLHL13, GAN, ZBTB16, KLHL21, KLHL3, KLHL15, KLHL20, KLHL36, GMCL1P1, BTBD1. Part of a complex that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with KLHL17; the interaction regulates surface GRIK2 expression. Interacts with KCTD7. Part of the BCR(GAN) complex containing GAN. Part of the BCR(KEAP1) complex containing KEAP1. Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30
Subcellular location	Nucleus. Golgi apparatus Ref.11 Ref.26.
Tissue specificity	Widely expressed.
Post-translational modification	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.
Involvement in disease	Pseudohypoaldosteronism 2E (PHA2E) [MIM:614496]: An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.31
Sequence similarities	Belongs to the cullin family.
Sequence caution	The sequence AAC28621.1 differs from that shown. Reason: Frameshift at position 452. The sequence AAC36682.1 differs from that shown. Reason: Frameshift at positions 159 and 179. The sequence BAA31592.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	ER-Golgi transport Transport Ubl conjugation pathway
Cellular component	Golgi apparatus Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	COPII vesicle coating Inferred from mutant phenotype Ref.28. Source: UniProtKB G1/S transition of mitotic cell cycle Traceable author statement Ref.9. Source: ProtInc Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara cell cycle arrest Traceable author statement Ref.9. Source: ProtInc cell migration Inferred from mutant phenotype PubMed 19782033. Source: UniProtKB cyclin catabolic process Inferred from direct assay Ref.11. Source: MGI cytokinesis Inferred from mutant phenotype Ref.20PubMed 19995937. Source: UniProtKB embryonic cleavage Inferred from sequence or structural similarity. Source: UniProtKB gastrulation Inferred from electronic annotation. Source: Compara integrin-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB intrinsic apoptotic signaling pathway Traceable author statement Ref.9. Source: ProtInc mitotic anaphase Inferred from mutant phenotype Ref.20. Source: UniProtKB negative regulation of Rho protein signal transduction Inferred from mutant phenotype PubMed 19782033. Source: UniProtKB positive regulation of cell proliferation Traceable author statement Ref.1. Source: ProtInc positive regulation of cytokinesis Inferred from mutant phenotype Ref.24. Source: UniProtKB protein monoubiquitination Inferred from direct assay Ref.28. Source: UniProtKB protein polyubiquitination Inferred from direct assay Ref.24. Source: UniProtKB stem cell division Inferred from sequence or structural similarity. Source: UniProtKB stress fiber assembly Inferred from mutant phenotype PubMed 19782033. Source: UniProtKB trophectodermal cellular morphogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	Cul3-RING ubiquitin ligase complex Inferred from direct assay Ref.17Ref.20Ref.24PubMed 19782033PubMed 19995937PubMed 20389280Ref.28. Source: UniProtKB Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell polar microtubule Inferred from direct assay PubMed 19995937. Source: UniProtKB
Molecular_function	POZ domain binding Inferred from direct assay Ref.24. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAND1	Q86VP6	2	EBI-456129,EBI-456077
CASP8	Q14790	6	EBI-456129,EBI-78060
HSP90AB1	P08238	2	EBI-456129,EBI-352572
SPOP	O43791	2	EBI-456129,EBI-743549
TNFSF10	P50591	2	EBI-456129,EBI-495373

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13618-1)

Also known as: Cul-3 Long;

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.

Isoform 2 (identifier: Q13618-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.

Isoform 3 (identifier: Q13618-3)

Also known as: Cul-3 Short;

The sequence of this isoform differs from the canonical sequence as follows:
     23-88: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 768

768

Cullin-3

PRO_0000119793

Amino acid modifications

Modified residue

450

1

Phosphoserine By similarity

Cross-link

712

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) By similarity

Natural variations

Alternative sequence

1 – 24

24

Missing in isoform 2.

VSP_008824

Alternative sequence

23 – 88

66

Missing in isoform 3.

VSP_008825

Natural variant

13

1

D → H.
Corresponds to variant rs2969802 [ dbSNP | Ensembl ].

VAR_017194

Natural variant

184

1

R → S.
Corresponds to variant rs17480168 [ dbSNP | Ensembl ].

VAR_048839

Natural variant

413

1

D → G in PHA2E. Ref.31

VAR_067532

Natural variant

459

1

K → R in PHA2E. Ref.31

VAR_067533

Natural variant

567

1

V → I.
Corresponds to variant rs3738952 [ dbSNP | Ensembl ].

VAR_017195

Experimental info

Sequence conflict

13

1

D → G in AAC36682. Ref.3

Sequence conflict

397

1

K → T in AAQ01660. Ref.4

Sequence conflict

481

1

N → T in AAQ01660. Ref.4

Sequence conflict

609

1

E → G in AAH31844. Ref.8

Sequence conflict

666

1

T → I in AAQ01660. Ref.4

Secondary structure

1

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768

Helix Strand Turn

Details...

Helix

26 – 45

20

Helix

49 – 51

3

Helix

54 – 66

13

Helix

70 – 87

18

Helix

89 – 94

6

Turn

95 – 98

4

Helix

101 – 122

22

Helix

124 – 129

6

Helix

132 – 134

3

Helix

139 – 150

12

Turn

151 – 153

3

Helix

155 – 173

19

Helix

180 – 192

13

Beta strand

195 – 198

4

Helix

199 – 204

6

Helix

206 – 227

22

Helix

230 – 251

22

Helix

254 – 256

3

Helix

257 – 268

12

Turn

269 – 272

4

Helix

273 – 277

5

Turn

280 – 282

3

Helix

284 – 287

4

Turn

288 – 291

4

Helix

293 – 303

11

Helix

309 – 323

15

Helix

339 – 358

20

Helix

364 – 380

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Cul-3 Long) [UniParc]. Last modified January 24, 2001. Version 2. Checksum: A1A02022480BF099	FASTA	768	88,930
	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
	Isoform 2 [UniParc]. Checksum: AD845C2516117B9F	FASTA	744	86,234
	10 20 30 40 50 60 MDEKYVNSIW DLLKNAIQEI QRKNNSGLSF EELYRNAYTM VLHKHGEKLY TGLREVVTEH 70 80 90 100 110 120 LINKVREDVL NSLNNNFLQT LNQAWNDHQT AMVMIRDILM YMDRVYVQQN NVENVYNLGL 130 140 150 160 170 180 IIFRDQVVRY GCIRDHLRQT LLDMIARERK GEVVDRGAIR NACQMLMILG LEGRSVYEED 190 200 210 220 230 240 FEAPFLEMSA EFFQMESQKF LAENSASVYI KKVEARINEE IERVMHCLDK STEEPIVKVV 250 260 270 280 290 300 ERELISKHMK TIVEMENSGL VHMLKNGKTE DLGCMYKLFS RVPNGLKTMC ECMSSYLREQ 310 320 330 340 350 360 GKALVSEEGE GKNPVDYIQG LLDLKSRFDR FLLESFNNDR LFKQTIAGDF EYFLNLNSRS 370 380 390 400 410 420 PEYLSLFIDD KLKKGVKGLT EQEVETILDK AMVLFRFMQE KDVFERYYKQ HLARRLLTNK 430 440 450 460 470 480 SVSDDSEKNM ISKLKTECGC QFTSKLEGMF RDMSISNTTM DEFRQHLQAT GVSLGGVDLT 490 500 510 520 530 540 VRVLTTGYWP TQSATPKCNI PPAPRHAFEI FRRFYLAKHS GRQLTLQHHM GSADLNATFY 550 560 570 580 590 600 GPVKKEDGSE VGVGGAQVTG SNTRKHILQV STFQMTILML FNNREKYTFE EIQQETDIPE 610 620 630 640 650 660 RELVRALQSL ACGKPTQRVL TKEPKSKEIE NGHIFTVNDQ FTSKLHRVKI QTVAAKQGES 670 680 690 700 710 720 DPERKETRQK VDDDRKHEIE AAIVRIMKSR KKMQHNVLVA EVTQQLKARF LPSPVVIKKR 730 740 IEGLIEREYL ARTPEDRKVY TYVA
	Isoform 3 (Cul-3 Short) [UniParc]. Checksum: 2CDE8E7AF43C898A	FASTA	702	81,093
	10 20 30 40 50 60 MSNLSKGTGS RKDTKMRIRA FPVREDVLNS LNNNFLQTLN QAWNDHQTAM VMIRDILMYM 70 80 90 100 110 120 DRVYVQQNNV ENVYNLGLII FRDQVVRYGC IRDHLRQTLL DMIARERKGE VVDRGAIRNA 130 140 150 160 170 180 CQMLMILGLE GRSVYEEDFE APFLEMSAEF FQMESQKFLA ENSASVYIKK VEARINEEIE 190 200 210 220 230 240 RVMHCLDKST EEPIVKVVER ELISKHMKTI VEMENSGLVH MLKNGKTEDL GCMYKLFSRV 250 260 270 280 290 300 PNGLKTMCEC MSSYLREQGK ALVSEEGEGK NPVDYIQGLL DLKSRFDRFL LESFNNDRLF 310 320 330 340 350 360 KQTIAGDFEY FLNLNSRSPE YLSLFIDDKL KKGVKGLTEQ EVETILDKAM VLFRFMQEKD 370 380 390 400 410 420 VFERYYKQHL ARRLLTNKSV SDDSEKNMIS KLKTECGCQF TSKLEGMFRD MSISNTTMDE 430 440 450 460 470 480 FRQHLQATGV SLGGVDLTVR VLTTGYWPTQ SATPKCNIPP APRHAFEIFR RFYLAKHSGR 490 500 510 520 530 540 QLTLQHHMGS ADLNATFYGP VKKEDGSEVG VGGAQVTGSN TRKHILQVST FQMTILMLFN 550 560 570 580 590 600 NREKYTFEEI QQETDIPERE LVRALQSLAC GKPTQRVLTK EPKSKEIENG HIFTVNDQFT 610 620 630 640 650 660 SKLHRVKIQT VAAKQGESDP ERKETRQKVD DDRKHEIEAA IVRIMKSRKK MQHNVLVAEV 670 680 690 700 TQQLKARFLP SPVVIKKRIE GLIEREYLAR TPEDRKVYTY VA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family." Du M., Sansores-Garcia L., Zu Z., Wu K.K. J. Biol. Chem. 273:24289-24292(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"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." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A." Michel J.J., Xiong Y. Cell Growth Differ. 9:435-449(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Colon carcinoma.
[4]	"Cloning and characterization of a new isoform of CUL3 gene in testis." Xu M., Huang X.Y., Yin L.L., Xu Z.Y., Lu L., Zhou Z.M., Sha J.H. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Testis.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Ovary, Skin and Uterus.
[9]	"cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family." Kipreos E.T., Lander L.E., Wing J.P., He W.W., Hedgecock E.M. Cell 85:829-839(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 192-768.
[10]	Yu W., Sarginson J., Gibbs R.A. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 398-768. Tissue: Brain.
[11]	"Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells." Singer J.D., Gurian-West M., Clurman B., Roberts J.M. Genes Dev. 13:2375-2387(1999) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS 1 AND 3), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CYCE, NEDDYLATION.
[12]	"In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3." Maeda I., Ohta T., Koizumi H., Fukuda M. FEBS Lett. 494:181-185(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"Covalent modification of all members of human cullin family proteins by NEDD8." Hori T., Osaka F., Chiba T., Miyamoto C., Okabayashi K., Shimbara N., Kato S., Tanaka K. Oncogene 18:6829-6834(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NEDDYLATION.
[14]	"ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity." Ohta T., Michel J.J., Schottelius A.J., Xiong Y. Mol. Cell 3:535-541(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RBX1 AND RNF7.
[15]	"TIP120A associates with cullins and modulates ubiquitin ligase activity." Min K.-W., Hwang J.-W., Lee J.-S., Park Y., Tamura T.-A., Yoon J.-B. J. Biol. Chem. 278:15905-15910(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TIP120A.
[16]	"Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases." Furukawa M., He Y.J., Borchers C., Xiong Y. Nat. Cell Biol. 5:1001-1007(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GAN; ZBTB16; KLHL9; KLHL13; KLHL211; KLHL3; KLHL15; KLHL20; KLHL36; GMCL1P1; BTBD1 AND SPOP.
[17]	"Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway." Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M. J. Biol. Chem. 280:30091-30099(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN THE BCR(KLHL41) COMPLEX, IDENTIFICATION IN THE BCR(ENC1) COMPLEX, IDENTIFICATION IN THE BCR(KEAP1) COMPLEX, IDENTIFICATION IN THE BCR(GAN) COMPLEX.
[18]	"Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase." 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. Proc. Natl. Acad. Sci. U.S.A. 102:7635-7640(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH SPOP AND BMI1, IDENTIFICATION IN A COMPLEX WITH SPOP AND H2AFY, FUNCTION.
[19]	"BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase." 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. J. Biol. Chem. 281:12664-12672(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE BCR(SPOP) COMPLEX, INTERACTION WITH SPOP, FUNCTION IN UBIQUITINATION OF DAXX.
[20]	"A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells." Sumara I., Quadroni M., Frei C., Olma M.H., Sumara G., Ricci R., Peter M. Dev. Cell 12:887-900(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH KLHL9 AND KLHL13.
[21]	"Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells -- evidence for cullin dimerization." Chew E.H., Poobalasingam T., Hawkey C.J., Hagen T. Cell. Signal. 19:1071-1080(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SELF-ASSOCIATION.
[22]	"The Cullin3 ubiquitin ligase functions as a Nedd8-bound heterodimer." Wimuttisuk W., Singer J.D. Mol. Biol. Cell 18:899-909(2007) [PubMed] [Europe PMC] [Abstract] Cited for: BCR COMPLEX HOMODIMERIZATION.
[23]	"KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases." Bayon Y., Trinidad A.G., de la Puerta M.L., Del Carmen Rodriguez M., Bogetz J., Rojas A., De Pereda J.M., Rahmouni S., Williams S., Matsuzawa S., Reed J.C., Crespo M.S., Mustelin T., Alonso A. FEBS J. 275:3900-3910(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCTD5.
[24]	"The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells." Cummings C.M., Bentley C.A., Perdue S.A., Baas P.W., Singer J.D. J. Biol. Chem. 284:11663-11675(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE BCR(KLHL42) COMPLEX, FUNCTION IN UBIQUITINATION OF KATNA1, INTERACTION WITH KATNA1 AND KLHL42.
[25]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]	"Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-SPOP E3 ubiquitin ligase complex." Kim B., Nam H.J., Pyo K.E., Jang M.J., Kim I.S., Kim D., Boo K., Lee S.H., Yoon J.B., Baek S.H., Kim J.H. Biochem. Biophys. Res. Commun. 415:720-726(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH SPOP AND BRMS1.
[27]	"A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin-proteasome system." Staropoli J.F., Karaa A., Lim E.T., Kirby A., Elbalalesy N., Romansky S.G., Leydiker K.B., Coppel S.H., Barone R., Xin W., MacDonald M.E., Abdenur J.E., Daly M.J., Sims K.B., Cotman S.L. Am. J. Hum. Genet. 91:202-208(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCTD7.
[28]	"Ubiquitin-dependent regulation of COPII coat size and function." Jin L., Pahuja K.B., Wickliffe K.E., Gorur A., Baumgartel C., Schekman R., Rape M. Nature 482:495-500(2012) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE BCR(KLHL12) COMPLEX, FUNCTION.
[29]	"Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase." Errington W.J., Khan M.Q., Bueler S.A., Rubinstein J.L., Chakrabartty A., Prive G.G. Structure 20:1141-1153(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 20-381 IN COMPLEX WITH SPOP, FUNCTION, IDENTIFICATION IN UBIQUITIN LIGASE COMPLEXES WITH SPOP AND SPOPL, SUBUNIT.
[30]	"Structural basis for Cul3 assembly with the BTB-Kelch family of E3 ubiquitin ligases." Canning P., Cooper C.D., Krojer T., Murray J.W., Pike A.C., Chaikuad A., Keates T., Thangaratnarajah C., Hojzan V., Marsden B.D., Gileadi O., Knapp S., von Delft F., Bullock A.N. J. Biol. Chem. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-388 IN COMPLEX WITH KLHL11, INTERACTION WITH KLHL11.
[31]	"Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities." Boyden L.M., Choi M., Choate K.A., Nelson-Williams C.J., Farhi A., Toka H.R., Tikhonova I.R., Bjornson R., Mane S.M., Colussi G., Lebel M., Gordon R.D., Semmekrot B.A., Poujol A., Valimaki M.J., De Ferrari M.E., Sanjad S.A., Gutkin M. , Karet F.E., Tucci J.R., Stockigt J.R., Keppler-Noreuil K.M., Porter C.C., Anand S.K., Whiteford M.L., Davis I.D., Dewar S.B., Bettinelli A., Fadrowski J.J., Belsha C.W., Hunley T.E., Nelson R.D., Trachtman H., Cole T.R., Pinsk M., Bockenhauer D., Shenoy M., Vaidyanathan P., Foreman J.W., Rasoulpour M., Thameem F., Al-Shahrouri H.Z., Radhakrishnan J., Gharavi A.G., Goilav B., Lifton R.P. Nature 482:98-102(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PHA2E GLY-413 AND ARG-459.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF064087 mRNA. Translation: AAC36304.1.
AB014517 mRNA. Translation: BAA31592.2. Different initiation.
AF062537 mRNA. Translation: AAC36682.1. Frameshift.
AY337761 mRNA. Translation: AAQ01660.1.
AK291151 mRNA. Translation: BAF83840.1.
AC073052 Genomic DNA. No translation available.
AC092679 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW70828.1.
BC031844 mRNA. Translation: AAH31844.1.
BC039598 mRNA. Translation: AAH39598.1.
BC092409 mRNA. Translation: AAH92409.1.
U58089 mRNA. Translation: AAC50546.1.
AF052147 mRNA. Translation: AAC28621.1. Frameshift.

IPI

IPI00014312.
IPI00382458.
IPI00382459.

RefSeq

NP_001244126.1. NM_001257197.1.
NP_001244127.1. NM_001257198.1.
NP_003581.1. NM_003590.4.

UniGene

Hs.372286.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4AP2	X-ray	2.80	B	1-388	[»]
4APF	X-ray	3.10	B	23-388	[»]
4EOZ	X-ray	2.40	B/D	20-381	[»]
4HXI	X-ray	3.51	B	20-381	[»]

ProteinModelPortal

Q13618.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31611N.

IntAct

Q13618. 32 interactions.

STRING

9606.ENSP00000264414.

PTM databases

PhosphoSite

Q13618.

Polymorphism databases

DMDM

12643396.

Proteomic databases

PaxDb

Q13618.

PRIDE

Q13618.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264414; ENSP00000264414; ENSG00000036257.
ENST00000344951; ENSP00000343601; ENSG00000036257.
ENST00000409096; ENSP00000387200; ENSG00000036257.
ENST00000409777; ENSP00000386525; ENSG00000036257.

GeneID

8452.

KEGG

hsa:8452.

UCSC

uc002vny.2. human.
uc010zls.1. human.

Organism-specific databases

CTD

8452.

GeneCards

GC02M225298.

HGNC

HGNC:2553. CUL3.

HPA

CAB002678.

MIM

603136. gene.
614496. phenotype.

neXtProt

NX_Q13618.

Orphanet

300530. Pseudohypoaldosteronism type 2E.

PharmGKB

PA27049.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5647.

HOVERGEN

HBG003619.

InParanoid

Q13618.

KO

K03869.

OMA

ATFYGPI.

OrthoDB

EOG4JWVCW.

PhylomeDB

Q13618.

Enzyme and pathway databases

Pathway_Interaction_DB

aurora_b_pathway. Aurora B signaling.

Reactome

REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q13618.

Bgee

Q13618.

CleanEx

HS_CUL3.

Genevestigator

Q13618.

GermOnline

ENSG00000036257. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 2 hits.

InterPro

IPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]

SMART

SM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]

SUPFAM

SSF75632. Cullin_homology. 1 hit.
SSF74788. Cullin_repeat-like. 1 hit.

PROSITE

PS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

CUL3. human.

GenomeRNAi

8452.

NextBio

31630.

SOURCE

Search...

Entry information

Entry name

CUL3_HUMAN

Accession

Primary (citable) accession number: Q13618
Secondary accession number(s): A8K536 , B8ZZC3, O75415, Q569L3, Q9UBI8, Q9UET7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 24, 2001
Last modified:	May 1, 2013
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.