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Q13618 (CUL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cullin-3

Short name=CUL-3
Gene names
Name:CUL3
Synonyms:KIAA0617
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length768 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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; by mediating ubiquitination of WNK4. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1). 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. In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Ref.11 Ref.12 Ref.17 Ref.18 Ref.19 Ref.20 Ref.24 Ref.25 Ref.26 Ref.28 Ref.30 Ref.31 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37

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. Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL21 and RBX1. Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1. Component of the BCR(KLHL25) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL25 and RBX1. 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, 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. Interacts with KLHL10 By similarity. Interacts with KAT5 and ATF2. Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.39

Subcellular location

Nucleus. Golgi apparatus Ref.11 Ref.28.

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.40

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 processER-Golgi transport
Transport
Ubl conjugation pathway
   Cellular componentGolgi apparatus
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   PTMAcetylation
Isopeptide bond
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processCOPII vesicle coating

Inferred from mutant phenotype Ref.31. Source: UniProtKB

ER to Golgi vesicle-mediated transport

Inferred from direct assay Ref.31. Source: UniProtKB

G1/S transition of mitotic cell cycle

Traceable author statement Ref.9. Source: ProtInc

Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

anaphase

Inferred from mutant phenotype Ref.26. Source: UniProtKB

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.20Ref.26. Source: UniProtKB

embryonic cleavage

Inferred from sequence or structural similarity. Source: UniProtKB

gastrulation

Inferred from electronic annotation. Source: Ensembl

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.25. Source: UniProtKB

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.25PubMed 19782033PubMed 20389280. Source: UniProtKB

protein monoubiquitination

Inferred from direct assay Ref.31. Source: UniProtKB

protein polyubiquitination

Inferred from direct assay Ref.25. Source: UniProtKB

protein ubiquitination

Inferred from direct assay Ref.20PubMed 19782033Ref.26PubMed 20389280. 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: Ensembl

   Cellular_componentCul3-RING ubiquitin ligase complex

Inferred from direct assay Ref.17Ref.20PubMed 19158078Ref.25PubMed 19782033Ref.26PubMed 20389280Ref.31Ref.30Ref.34Ref.35Ref.36. Source: UniProtKB

Golgi membrane

Inferred from mutant phenotype Ref.31. Source: GOC

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

polar microtubule

Inferred from direct assay Ref.26. Source: UniProtKB

   Molecular_functionPOZ domain binding

Inferred from direct assay Ref.25. Source: UniProtKB

Complete GO annotation...

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.32
Chain2 – 768767Cullin-3
PRO_0000119793

Amino acid modifications

Modified residue21N-acetylserine Ref.32
Cross-link712Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) By similarity

Natural variations

Alternative sequence1 – 2424Missing in isoform 2.
VSP_008824
Alternative sequence23 – 8866Missing in isoform 3.
VSP_008825
Natural variant131D → H.
Corresponds to variant rs2969802 [ dbSNP | Ensembl ].
VAR_017194
Natural variant1841R → S.
Corresponds to variant rs17480168 [ dbSNP | Ensembl ].
VAR_048839
Natural variant4131D → G in PHA2E. Ref.40
VAR_067532
Natural variant4591K → R in PHA2E. Ref.40
VAR_067533
Natural variant5671V → I.
Corresponds to variant rs3738952 [ dbSNP | Ensembl ].
VAR_017195

Experimental info

Sequence conflict131D → G in AAC36682. Ref.3
Sequence conflict3971K → T in AAQ01660. Ref.4
Sequence conflict4811N → T in AAQ01660. Ref.4
Sequence conflict6091E → G in AAH31844. Ref.8
Sequence conflict6661T → I in AAQ01660. Ref.4

Secondary structure

.................................................. 768
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Cul-3 Long) [UniParc].

Last modified January 24, 2001. Version 2.
Checksum: A1A02022480BF099

FASTA76888,930
        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 

« Hide

Isoform 2 [UniParc].

Checksum: AD845C2516117B9F
Show »

FASTA74486,234
Isoform 3 (Cul-3 Short) [UniParc].

Checksum: 2CDE8E7AF43C898A
Show »

FASTA70281,093

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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; KLHL21; 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]"Regulation of TIP60 by ATF2 modulates ATM activation."
Bhoumik A., Singha N., O'Connell M.J., Ronai Z.A.
J. Biol. Chem. 283:17605-17614(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ATF2 AND KAT5.
[25]"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.
[26]"The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midzone microtubules in anaphase and is required for cytokinesis."
Maerki S., Olma M.H., Staubli T., Steigemann P., Gerlich D.W., Quadroni M., Sumara I., Peter M.
J. Cell Biol. 187:791-800(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE BCR(KLHL21) COMPLEX, FUNCTION.
[27]"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].
[28]"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.
[29]"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.
[30]"Translational homeostasis via the mRNA cap-binding protein, eIF4E."
Yanagiya A., Suyama E., Adachi H., Svitkin Y.V., Aza-Blanc P., Imataka H., Mikami S., Martineau Y., Ronai Z.A., Sonenberg N.
Mol. Cell 46:847-858(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE BCR(KLHL25) COMPLEX, FUNCTION.
[31]"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.
[32]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[33]"The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction."
Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A., Macartney T.J., Wood N.T., Alessi D.R., Kurz T.
Biochem. J. 451:111-122(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH KLHL3.
[34]"Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension."
Wakabayashi M., Mori T., Isobe K., Sohara E., Susa K., Araki Y., Chiga M., Kikuchi E., Nomura N., Mori Y., Matsuo H., Murata T., Nomura S., Asano T., Kawaguchi H., Nonoyama S., Rai T., Sasaki S., Uchida S.
Cell Rep. 3:858-868(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE BCR(KLHL3) COMPLEX.
[35]"Ubiquitylation-dependent localization of PLK1 in mitosis."
Beck J., Maerki S., Posch M., Metzger T., Persaud A., Scheel H., Hofmann K., Rotin D., Pedrioli P., Swedlow J.R., Peter M., Sumara I.
Nat. Cell Biol. 15:430-439(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE BCR(KLHL22) COMPLEX, FUNCTION.
[36]"Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4."
Shibata S., Zhang J., Puthumana J., Stone K.L., Lifton R.P.
Proc. Natl. Acad. Sci. U.S.A. 110:7838-7843(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE BCR(KLHL3) COMPLEX.
[37]"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.
[38]"Crystal structure of KLHL3 in complex with Cullin3."
Ji A.X., Prive G.G.
PLoS ONE 8:E60445-E60445(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.51 ANGSTROMS) OF 20-381 IN COMPLEX WITH KLHL3.
[39]"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. 288:7803-7814(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-388 IN COMPLEX WITH KLHL11, INTERACTION WITH KLHL11.
[40]"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. expand/collapse author list , 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.
RefSeqNP_001244126.1. NM_001257197.1.
NP_001244127.1. NM_001257198.1.
NP_003581.1. NM_003590.4.
UniGeneHs.372286.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4AP2X-ray2.80B1-388[»]
4APFX-ray3.10B23-388[»]
4EOZX-ray2.40B/D20-381[»]
4HXIX-ray3.51B20-381[»]
ProteinModelPortalQ13618.
SMRQ13618. Positions 17-768.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114030. 1151 interactions.
DIPDIP-31611N.
IntActQ13618. 38 interactions.
MINTMINT-3028280.
STRING9606.ENSP00000264414.

PTM databases

PhosphoSiteQ13618.

Polymorphism databases

DMDM12643396.

Proteomic databases

PaxDbQ13618.
PRIDEQ13618.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264414; ENSP00000264414; ENSG00000036257. [Q13618-1]
ENST00000344951; ENSP00000343601; ENSG00000036257. [Q13618-3]
ENST00000409096; ENSP00000387200; ENSG00000036257. [Q13618-2]
ENST00000409777; ENSP00000386525; ENSG00000036257. [Q13618-2]
GeneID8452.
KEGGhsa:8452.
UCSCuc002vny.3. human. [Q13618-1]
uc010zls.2. human. [Q13618-3]

Organism-specific databases

CTD8452.
GeneCardsGC02M225298.
HGNCHGNC:2553. CUL3.
HPACAB002678.
MIM603136. gene.
614496. phenotype.
neXtProtNX_Q13618.
Orphanet300530. Pseudohypoaldosteronism type 2E.
PharmGKBPA27049.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5647.
HOVERGENHBG003619.
InParanoidQ13618.
KOK03869.
OMAIHTKNAS.
OrthoDBEOG7C5M7H.
PhylomeDBQ13618.
TreeFamTF105858.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ13618.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ13618.
BgeeQ13618.
CleanExHS_CUL3.
GenevestigatorQ13618.

Family and domain databases

Gene3D1.10.10.10. 2 hits.
InterProIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMSSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCUL3. human.
GeneWikiCUL3.
GenomeRNAi8452.
NextBio31630.
PROQ13618.
SOURCESearch...

Entry information

Entry nameCUL3_HUMAN
AccessionPrimary (citable) accession number: Q13618
Secondary accession number(s): A8K536 expand/collapse secondary AC list , B8ZZC3, O75415, Q569L3, Q9UBI8, Q9UET7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 24, 2001
Last modified: April 16, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM