CUL3_HUMAN
ID CUL3_HUMAN Reviewed; 768 AA.
AC Q13618; A8K536; B8ZZC3; O75415; Q569L3; Q9UBI8; Q9UET7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Cullin-3 {ECO:0000305};
DE Short=CUL-3;
GN Name=CUL3 {ECO:0000312|HGNC:HGNC:2553}; Synonyms=KIAA0617;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9733711; DOI=10.1074/jbc.273.38.24289;
RA Du M., Sansores-Garcia L., Zu Z., Wu K.K.;
RT "Cloning and expression analysis of a novel salicylate suppressible gene,
RT Hs-CUL-3, a member of cullin/Cdc53 family.";
RL J. Biol. Chem. 273:24289-24292(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Colon carcinoma;
RX PubMed=9663463;
RA Michel J.J., Xiong Y.;
RT "Human CUL-1, but not other cullin family members, selectively interacts
RT with SKP1 to form a complex with SKP2 and cyclin A.";
RL Cell Growth Differ. 9:435-449(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RA Xu M., Huang X.Y., Yin L.L., Xu Z.Y., Lu L., Zhou Z.M., Sha J.H.;
RT "Cloning and characterization of a new isoform of CUL3 gene in testis.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary, Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 192-768.
RX PubMed=8681378; DOI=10.1016/s0092-8674(00)81267-2;
RA Kipreos E.T., Lander L.E., Wing J.P., He W.W., Hedgecock E.M.;
RT "cul-1 is required for cell cycle exit in C. elegans and identifies a novel
RT gene family.";
RL Cell 85:829-839(1996).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 398-768.
RC TISSUE=Brain;
RA Yu W., Sarginson J., Gibbs R.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 3), FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH CYCE, AND NEDDYLATION.
RX PubMed=10500095; DOI=10.1101/gad.13.18.2375;
RA Singer J.D., Gurian-West M., Clurman B., Roberts J.M.;
RT "Cullin-3 targets cyclin E for ubiquitination and controls S phase in
RT mammalian cells.";
RL Genes Dev. 13:2375-2387(1999).
RN [12]
RP FUNCTION.
RX PubMed=11311237; DOI=10.1016/s0014-5793(01)02343-2;
RA Maeda I., Ohta T., Koizumi H., Fukuda M.;
RT "In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3.";
RL FEBS Lett. 494:181-185(2001).
RN [13]
RP NEDDYLATION.
RX PubMed=10597293; DOI=10.1038/sj.onc.1203093;
RA Hori T., Osaka F., Chiba T., Miyamoto C., Okabayashi K., Shimbara N.,
RA Kato S., Tanaka K.;
RT "Covalent modification of all members of human cullin family proteins by
RT NEDD8.";
RL Oncogene 18:6829-6834(1999).
RN [14]
RP INTERACTION WITH RBX1 AND RNF7.
RX PubMed=10230407; DOI=10.1016/s1097-2765(00)80482-7;
RA Ohta T., Michel J.J., Schottelius A.J., Xiong Y.;
RT "ROC1, a homolog of APC11, represents a family of cullin partners with an
RT associated ubiquitin ligase activity.";
RL Mol. Cell 3:535-541(1999).
RN [15]
RP INTERACTION WITH TIP120A.
RX PubMed=12609982; DOI=10.1074/jbc.m213070200;
RA Min K.-W., Hwang J.-W., Lee J.-S., Park Y., Tamura T.-A., Yoon J.-B.;
RT "TIP120A associates with cullins and modulates ubiquitin ligase activity.";
RL J. Biol. Chem. 278:15905-15910(2003).
RN [16]
RP INTERACTION WITH GAN; ZBTB16; KLHL9; KLHL13; KLHL21; KLHL3; KLHL15; KLHL20;
RP KLHL36; GMCL2; BTBD1 AND SPOP.
RX PubMed=14528312; DOI=10.1038/ncb1056;
RA Furukawa M., He Y.J., Borchers C., Xiong Y.;
RT "Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin
RT ligases.";
RL Nat. Cell Biol. 5:1001-1007(2003).
RN [17]
RP FUNCTION, IDENTIFICATION IN THE BCR(KLHL41) COMPLEX, IDENTIFICATION IN THE
RP BCR(ENC1) COMPLEX, IDENTIFICATION IN THE BCR(KEAP1) COMPLEX, AND
RP IDENTIFICATION IN THE BCR(GAN) COMPLEX.
RX PubMed=15983046; DOI=10.1074/jbc.m501279200;
RA Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M.;
RT "Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3,
RT targets Keap1 for degradation by a proteasome-independent pathway.";
RL J. Biol. Chem. 280:30091-30099(2005).
RN [18]
RP IDENTIFICATION IN A COMPLEX WITH SPOP AND BMI1, IDENTIFICATION IN A COMPLEX
RP WITH SPOP AND MACROH2A1, AND FUNCTION.
RX PubMed=15897469; DOI=10.1073/pnas.0408918102;
RA Hernandez-Munoz I., Lund A.H., van der Stoop P., Boutsma E., Muijrers I.,
RA Verhoeven E., Nusinow D.A., Panning B., Marahrens Y., van Lohuizen M.;
RT "Stable X chromosome inactivation involves the PRC1 Polycomb complex and
RT requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:7635-7640(2005).
RN [19]
RP IDENTIFICATION IN THE BCR(SPOP) COMPLEX, INTERACTION WITH SPOP, AND
RP FUNCTION IN UBIQUITINATION OF DAXX.
RX PubMed=16524876; DOI=10.1074/jbc.m600204200;
RA Kwon J.E., La M., Oh K.H., Oh Y.M., Kim G.R., Seol J.H., Baek S.H.,
RA Chiba T., Tanaka K., Bang O.S., Joe C.O., Chung C.H.;
RT "BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor
RT of Daxx for ubiquitination by Cul3-based ubiquitin ligase.";
RL J. Biol. Chem. 281:12664-12672(2006).
RN [20]
RP FUNCTION OF THE BCR(KEAP1) COMPLEX, AND IDENTIFICATION IN THE BCR(KEAP1)
RP COMPLEX.
RX PubMed=15601839; DOI=10.1128/mcb.25.1.162-171.2005;
RA Furukawa M., Xiong Y.;
RT "BTB protein Keap1 targets antioxidant transcription factor Nrf2 for
RT ubiquitination by the Cullin 3-Roc1 ligase.";
RL Mol. Cell. Biol. 25:162-171(2005).
RN [21]
RP FUNCTION, AND INTERACTION WITH KLHL9 AND KLHL13.
RX PubMed=17543862; DOI=10.1016/j.devcel.2007.03.019;
RA Sumara I., Quadroni M., Frei C., Olma M.H., Sumara G., Ricci R., Peter M.;
RT "A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes,
RT regulating mitotic progression and completion of cytokinesis in human
RT cells.";
RL Dev. Cell 12:887-900(2007).
RN [22]
RP SELF-ASSOCIATION.
RX PubMed=17254749; DOI=10.1016/j.cellsig.2006.12.002;
RA Chew E.H., Poobalasingam T., Hawkey C.J., Hagen T.;
RT "Characterization of cullin-based E3 ubiquitin ligases in intact mammalian
RT cells -- evidence for cullin dimerization.";
RL Cell. Signal. 19:1071-1080(2007).
RN [23]
RP BCR COMPLEX HOMODIMERIZATION.
RX PubMed=17192413; DOI=10.1091/mbc.e06-06-0542;
RA Wimuttisuk W., Singer J.D.;
RT "The Cullin3 ubiquitin ligase functions as a Nedd8-bound heterodimer.";
RL Mol. Biol. Cell 18:899-909(2007).
RN [24]
RP INTERACTION WITH KCTD5.
RX PubMed=18573101; DOI=10.1111/j.1742-4658.2008.06537.x;
RA Bayon Y., Trinidad A.G., de la Puerta M.L., Del Carmen Rodriguez M.,
RA Bogetz J., Rojas A., De Pereda J.M., Rahmouni S., Williams S.,
RA Matsuzawa S., Reed J.C., Crespo M.S., Mustelin T., Alonso A.;
RT "KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases.";
RL FEBS J. 275:3900-3910(2008).
RN [25]
RP FUNCTION, AND INTERACTION WITH ATF2 AND KAT5.
RX PubMed=18397884; DOI=10.1074/jbc.m802030200;
RA Bhoumik A., Singha N., O'Connell M.J., Ronai Z.A.;
RT "Regulation of TIP60 by ATF2 modulates ATM activation.";
RL J. Biol. Chem. 283:17605-17614(2008).
RN [26]
RP FUNCTION OF THE BCR(KEAP1) COMPLEX.
RX PubMed=16006525; DOI=10.1073/pnas.0502402102;
RA Eggler A.L., Liu G., Pezzuto J.M., van Breemen R.B., Mesecar A.D.;
RT "Modifying specific cysteines of the electrophile-sensing human Keap1
RT protein is insufficient to disrupt binding to the Nrf2 domain Neh2.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10070-10075(2005).
RN [27]
RP IDENTIFICATION IN THE BCR(KLHL42) COMPLEX, FUNCTION IN UBIQUITINATION OF
RP KATNA1, AND INTERACTION WITH KATNA1 AND KLHL42.
RX PubMed=19261606; DOI=10.1074/jbc.m809374200;
RA Cummings C.M., Bentley C.A., Perdue S.A., Baas P.W., Singer J.D.;
RT "The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal
RT mitosis in mammalian cells.";
RL J. Biol. Chem. 284:11663-11675(2009).
RN [28]
RP IDENTIFICATION IN THE BCR(KLHL21) COMPLEX, AND FUNCTION.
RX PubMed=19995937; DOI=10.1083/jcb.200906117;
RA Maerki S., Olma M.H., Staubli T., Steigemann P., Gerlich D.W., Quadroni M.,
RA Sumara I., Peter M.;
RT "The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midzone
RT microtubules in anaphase and is required for cytokinesis.";
RL J. Cell Biol. 187:791-800(2009).
RN [29]
RP FUNCTION, AND IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE
RP COMPLEX.
RX PubMed=20389280; DOI=10.1038/emboj.2010.62;
RA Lee Y.R., Yuan W.C., Ho H.C., Chen C.H., Shih H.M., Chen R.H.;
RT "The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to
RT control interferon responses.";
RL EMBO J. 29:1748-1761(2010).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [31]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN A COMPLEX WITH SPOP
RP AND BRMS1.
RX PubMed=22085717; DOI=10.1016/j.bbrc.2011.10.154;
RA Kim B., Nam H.J., Pyo K.E., Jang M.J., Kim I.S., Kim D., Boo K., Lee S.H.,
RA Yoon J.B., Baek S.H., Kim J.H.;
RT "Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-
RT SPOP E3 ubiquitin ligase complex.";
RL Biochem. Biophys. Res. Commun. 415:720-726(2011).
RN [32]
RP FUNCTION, AND IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE
RP COMPLEX.
RX PubMed=21840486; DOI=10.1016/j.ccr.2011.07.008;
RA Yuan W.C., Lee Y.R., Huang S.F., Lin Y.M., Chen T.Y., Chung H.C.,
RA Tsai C.H., Chen H.Y., Chiang C.T., Lai C.K., Lu L.T., Chen C.H., Gu D.L.,
RA Pu Y.S., Jou Y.S., Lu K.P., Hsiao P.W., Shih H.M., Chen R.H.;
RT "A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to
RT potentiate HIF-1 signaling and prostate cancer progression.";
RL Cancer Cell 20:214-228(2011).
RN [33]
RP FUNCTION, AND IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE
RP COMPLEX.
RX PubMed=21670212; DOI=10.1083/jcb.201103015;
RA Lin M.Y., Lin Y.M., Kao T.C., Chuang H.H., Chen R.H.;
RT "PDZ-RhoGEF ubiquitination by Cullin3-KLHL20 controls neurotrophin-induced
RT neurite outgrowth.";
RL J. Cell Biol. 193:985-994(2011).
RN [34]
RP INTERACTION WITH KCTD7.
RX PubMed=22748208; DOI=10.1016/j.ajhg.2012.05.023;
RA Staropoli J.F., Karaa A., Lim E.T., Kirby A., Elbalalesy N., Romansky S.G.,
RA Leydiker K.B., Coppel S.H., Barone R., Xin W., MacDonald M.E.,
RA Abdenur J.E., Daly M.J., Sims K.B., Cotman S.L.;
RT "A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the
RT ubiquitin-proteasome system.";
RL Am. J. Hum. Genet. 91:202-208(2012).
RN [35]
RP FUNCTION, INTERACTION WITH AURKA AND KLHL18, AND SUBCELLULAR LOCATION.
RX PubMed=23213400; DOI=10.1242/bio.2011018;
RA Moghe S., Jiang F., Miura Y., Cerny R.L., Tsai M.Y., Furukawa M.;
RT "The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-
RT A.";
RL Biol. Open 1:82-91(2012).
RN [36]
RP INTERACTION WITH PPP2R5B.
RX PubMed=23135275; DOI=10.1074/jbc.m112.420281;
RA Oberg E.A., Nifoussi S.K., Gingras A.C., Strack S.;
RT "Selective proteasomal degradation of the B'beta subunit of protein
RT phosphatase 2A by the E3 ubiquitin ligase adaptor Kelch-like 15.";
RL J. Biol. Chem. 287:43378-43389(2012).
RN [37]
RP IDENTIFICATION IN THE BCR(KLHL25) COMPLEX, AND FUNCTION.
RX PubMed=22578813; DOI=10.1016/j.molcel.2012.04.004;
RA Yanagiya A., Suyama E., Adachi H., Svitkin Y.V., Aza-Blanc P., Imataka H.,
RA Mikami S., Martineau Y., Ronai Z.A., Sonenberg N.;
RT "Translational homeostasis via the mRNA cap-binding protein, eIF4E.";
RL Mol. Cell 46:847-858(2012).
RN [38]
RP IDENTIFICATION IN THE BCR(KLHL12) COMPLEX, AND FUNCTION.
RX PubMed=22358839; DOI=10.1038/nature10822;
RA Jin L., Pahuja K.B., Wickliffe K.E., Gorur A., Baumgartel C., Schekman R.,
RA Rape M.;
RT "Ubiquitin-dependent regulation of COPII coat size and function.";
RL Nature 482:495-500(2012).
RN [39]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [40]
RP FUNCTION, AND INTERACTION WITH KLHL3.
RX PubMed=23387299; DOI=10.1042/bj20121903;
RA Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A.,
RA Macartney T.J., Wood N.T., Alessi D.R., Kurz T.;
RT "The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome
RT interacts with and ubiquitylates WNK isoforms: disease-causing mutations in
RT KLHL3 and WNK4 disrupt interaction.";
RL Biochem. J. 451:111-122(2013).
RN [41]
RP FUNCTION, AND IDENTIFICATION IN THE BCR(KLHL3) COMPLEX.
RX PubMed=23453970; DOI=10.1016/j.celrep.2013.02.024;
RA Wakabayashi M., Mori T., Isobe K., Sohara E., Susa K., Araki Y., Chiga M.,
RA Kikuchi E., Nomura N., Mori Y., Matsuo H., Murata T., Nomura S., Asano T.,
RA Kawaguchi H., Nonoyama S., Rai T., Sasaki S., Uchida S.;
RT "Impaired KLHL3-mediated ubiquitination of WNK4 causes human
RT hypertension.";
RL Cell Rep. 3:858-868(2013).
RN [42]
RP INTERACTION WITH ARIH1, AND NEDDYLATION.
RX PubMed=24076655; DOI=10.1038/emboj.2013.209;
RA Kelsall I.R., Duda D.M., Olszewski J.L., Hofmann K., Knebel A.,
RA Langevin F., Wood N., Wightman M., Schulman B.A., Alpi A.F.;
RT "TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-
RT RING ligase complexes.";
RL EMBO J. 32:2848-2860(2013).
RN [43]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-585, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [44]
RP IDENTIFICATION IN THE BCR(KLHL22) COMPLEX, AND FUNCTION.
RX PubMed=23455478; DOI=10.1038/ncb2695;
RA Beck J., Maerki S., Posch M., Metzger T., Persaud A., Scheel H.,
RA Hofmann K., Rotin D., Pedrioli P., Swedlow J.R., Peter M., Sumara I.;
RT "Ubiquitylation-dependent localization of PLK1 in mitosis.";
RL Nat. Cell Biol. 15:430-439(2013).
RN [45]
RP INTERACTION WITH COPS9.
RX PubMed=23776465; DOI=10.1371/journal.pone.0065285;
RA Ebina M., Tsuruta F., Katoh M.C., Kigoshi Y., Someya A., Chiba T.;
RT "Myeloma overexpressed 2 (Myeov2) regulates L11 subnuclear localization
RT through Nedd8 modification.";
RL PLoS ONE 8:E65285-E65285(2013).
RN [46]
RP FUNCTION, AND IDENTIFICATION IN THE BCR(KLHL3) COMPLEX.
RX PubMed=23576762; DOI=10.1073/pnas.1304592110;
RA Shibata S., Zhang J., Puthumana J., Stone K.L., Lifton R.P.;
RT "Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via
RT ubiquitination and degradation of WNK4.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:7838-7843(2013).
RN [47]
RP INTERACTION WITH DCUN1D1; DCUN1D2; DCUN1D3; DCUN1D4 AND DCUN1D5.
RX PubMed=23201271; DOI=10.1016/j.str.2012.10.013;
RA Monda J.K., Scott D.C., Miller D.J., Lydeard J., King D., Harper J.W.,
RA Bennett E.J., Schulman B.A.;
RT "Structural conservation of distinctive N-terminal acetylation-dependent
RT interactions across a family of mammalian NEDD8 ligation enzymes.";
RL Structure 21:42-53(2013).
RN [48]
RP INTERACTION WITH DCUN1D5.
RX PubMed=24192928; DOI=10.1158/1078-0432.ccr-13-1252;
RA Bommelje C.C., Weeda V.B., Huang G., Shah K., Bains S., Buss E., Shaha M.,
RA Goenen M., Ghossein R., Ramanathan S.Y., Singh B.;
RT "Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylation E3 activity
RT and nuclear localization.";
RL Clin. Cancer Res. 20:372-381(2014).
RN [49]
RP INTERACTION WITH DCUN1D3.
RX PubMed=25349211; DOI=10.1074/jbc.m114.585505;
RA Huang G., Stock C., Bommelje C.C., Weeda V.B., Shah K., Bains S., Buss E.,
RA Shaha M., Rechler W., Ramanathan S.Y., Singh B.;
RT "SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of
RT SCCRO (DCUN1D1).";
RL J. Biol. Chem. 289:34728-34742(2014).
RN [50]
RP FUNCTION, AND IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE
RP COMPLEX.
RX PubMed=24768539; DOI=10.1016/j.molcel.2014.03.035;
RA Yuan W.C., Lee Y.R., Lin S.Y., Chang L.Y., Tan Y.P., Hung C.C., Kuo J.C.,
RA Liu C.H., Lin M.Y., Xu M., Chen Z.J., Chen R.H.;
RT "K33-linked polyubiquitination of coronin 7 by Cul3-KLHL20 ubiquitin E3
RT ligase regulates protein trafficking.";
RL Mol. Cell 54:586-600(2014).
RN [51]
RP INTERACTION WITH KCTD17, IDENTIFICATION IN THE BCR(KCTD17) E3 UBIQUITIN
RP LIGASE COMPLEX, AND FUNCTION.
RX PubMed=25270598; DOI=10.1038/ncomms6081;
RA Kasahara K., Kawakami Y., Kiyono T., Yonemura S., Kawamura Y., Era S.,
RA Matsuzaki F., Goshima N., Inagaki M.;
RT "Ubiquitin-proteasome system controls ciliogenesis at the initial step of
RT axoneme extension.";
RL Nat. Commun. 5:5081-5081(2014).
RN [52]
RP FUNCTION, AND SUBUNIT.
RX PubMed=25684205; DOI=10.1016/j.molcel.2014.12.040;
RA Genau H.M., Huber J., Baschieri F., Akutsu M., Doetsch V., Farhan H.,
RA Rogov V., Behrends C.;
RT "CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to
RT spatially restrict TIAM1-RAC1 signaling.";
RL Mol. Cell 57:995-1010(2015).
RN [53]
RP FUNCTION, AND INTERACTION WITH KBTBD8.
RX PubMed=26399832; DOI=10.1038/nature14978;
RA Werner A., Iwasaki S., McGourty C.A., Medina-Ruiz S., Teerikorpi N.,
RA Fedrigo I., Ingolia N.T., Rape M.;
RT "Cell-fate determination by ubiquitin-dependent regulation of
RT translation.";
RL Nature 525:523-527(2015).
RN [54]
RP FUNCTION.
RX PubMed=27716508; DOI=10.1016/j.cell.2016.09.026;
RA McGourty C.A., Akopian D., Walsh C., Gorur A., Werner A., Schekman R.,
RA Bautista D., Rape M.;
RT "Regulation of the CUL3 ubiquitin ligase by a calcium-dependent co-
RT adaptor.";
RL Cell 167:525-538(2016).
RN [55]
RP FUNCTION, INTERACTION WITH ARIH1, AND NEDDYLATION.
RX PubMed=27565346; DOI=10.1016/j.cell.2016.07.027;
RA Scott D.C., Rhee D.Y., Duda D.M., Kelsall I.R., Olszewski J.L., Paulo J.A.,
RA de Jong A., Ovaa H., Alpi A.F., Harper J.W., Schulman B.A.;
RT "Two distinct types of E3 ligases work in unison to regulate substrate
RT ubiquitylation.";
RL Cell 166:1198-1214(2016).
RN [56]
RP INTERACTION WITH DCUN1D1; DCUN1D2; DCUN1D3; DCUN1D4 AND DCUN1D5.
RX PubMed=26906416; DOI=10.1242/jcs.181784;
RA Keuss M.J., Thomas Y., Mcarthur R., Wood N.T., Knebel A., Kurz T.;
RT "Characterization of the mammalian family of DCN-type NEDD8 E3 ligases.";
RL J. Cell Sci. 129:1441-1454(2016).
RN [57]
RP INTERACTION WITH KLHL15 AND RBBP8, AND NEDDYLATION.
RX PubMed=27561354; DOI=10.1038/ncomms12628;
RA Ferretti L.P., Himmels S.F., Trenner A., Walker C., von Aesch C.,
RA Eggenschwiler A., Murina O., Enchev R.I., Peter M., Freire R., Porro A.,
RA Sartori A.A.;
RT "Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-
RT tune DNA-end resection.";
RL Nat. Commun. 7:12628-12628(2016).
RN [58]
RP FUNCTION, IDENTIFICATION IN THE BCR(KLHL24) COMPLEX, AND INTERACTION WITH
RP KLHL24.
RX PubMed=27798626; DOI=10.1038/ng.3701;
RA Lin Z., Li S., Feng C., Yang S., Wang H., Ma D., Zhang J., Gou M., Bu D.,
RA Zhang T., Kong X., Wang X., Sarig O., Ren Y., Dai L., Liu H., Zhang J.,
RA Li F., Hu Y., Padalon-Brauch G., Vodo D., Zhou F., Chen T., Deng H.,
RA Sprecher E., Yang Y., Tan X.;
RT "Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14
RT and human skin fragility.";
RL Nat. Genet. 48:1508-1516(2016).
RN [59]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=28395323; DOI=10.1095/biolreprod.116.143479;
RA Jumeau F., Chalmel F., Fernandez-Gomez F.J., Carpentier C., Obriot H.,
RA Tardivel M., Caillet-Boudin M.L., Rigot J.M., Rives N., Buee L.,
RA Sergeant N., Mitchell V.;
RT "Defining the human sperm microtubulome: an integrated genomics approach.";
RL Biol. Reprod. 96:93-106(2017).
RN [60]
RP INTERACTION WITH RHOBTB2.
RX PubMed=29276004; DOI=10.1016/j.ajhg.2017.11.008;
RG Deciphering Developmental Disorders Study;
RA Straub J., Konrad E.D.H., Gruener J., Toutain A., Bok L.A., Cho M.T.,
RA Crawford H.P., Dubbs H., Douglas G., Jobling R., Johnson D., Krock B.,
RA Mikati M.A., Nesbitt A., Nicolai J., Phillips M., Poduri A.,
RA Ortiz-Gonzalez X.R., Powis Z., Santani A., Smith L., Stegmann A.P.A.,
RA Stumpel C., Vreeburg M., Fliedner A., Gregor A., Sticht H., Zweier C.;
RT "Missense variants in RHOBTB2 cause a developmental and epileptic
RT encephalopathy in humans, and altered levels cause neurological defects in
RT Drosophila.";
RL Am. J. Hum. Genet. 102:44-57(2018).
RN [61]
RP FUNCTION.
RX PubMed=29769719; DOI=10.1038/s41586-018-0128-9;
RA Chen J., Ou Y., Yang Y., Li W., Xu Y., Xie Y., Liu Y.;
RT "KLHL22 activates amino-acid-dependent mTORC1 signalling to promote
RT tumorigenesis and ageing.";
RL Nature 557:585-589(2018).
RN [62]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 20-381 IN COMPLEX WITH SPOP,
RP FUNCTION, IDENTIFICATION IN UBIQUITIN LIGASE COMPLEXES WITH SPOP AND SPOPL,
RP AND SUBUNIT.
RX PubMed=22632832; DOI=10.1016/j.str.2012.04.009;
RA Errington W.J., Khan M.Q., Bueler S.A., Rubinstein J.L., Chakrabartty A.,
RA Prive G.G.;
RT "Adaptor protein self-assembly drives the control of a cullin-RING
RT ubiquitin ligase.";
RL Structure 20:1141-1153(2012).
RN [63]
RP X-RAY CRYSTALLOGRAPHY (3.51 ANGSTROMS) OF 20-381 IN COMPLEX WITH KLHL3.
RX PubMed=23573258; DOI=10.1371/journal.pone.0060445;
RA Ji A.X., Prive G.G.;
RT "Crystal structure of KLHL3 in complex with Cullin3.";
RL PLoS ONE 8:E60445-E60445(2013).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-388 IN COMPLEX WITH KLHL11, AND
RP INTERACTION WITH KLHL11.
RX PubMed=23349464; DOI=10.1074/jbc.m112.437996;
RA Canning P., Cooper C.D., Krojer T., Murray J.W., Pike A.C., Chaikuad A.,
RA Keates T., Thangaratnarajah C., Hojzan V., Marsden B.D., Gileadi O.,
RA Knapp S., von Delft F., Bullock A.N.;
RT "Structural basis for Cul3 assembly with the BTB-Kelch family of E3
RT ubiquitin ligases.";
RL J. Biol. Chem. 288:7803-7814(2013).
RN [65]
RP VARIANTS PHA2E GLY-413 AND ARG-459.
RX PubMed=22266938; DOI=10.1038/nature10814;
RA Boyden L.M., Choi M., Choate K.A., Nelson-Williams C.J., Farhi A.,
RA Toka H.R., Tikhonova I.R., Bjornson R., Mane S.M., Colussi G., Lebel M.,
RA Gordon R.D., Semmekrot B.A., Poujol A., Valimaki M.J., De Ferrari M.E.,
RA Sanjad S.A., Gutkin M., Karet F.E., Tucci J.R., Stockigt J.R.,
RA Keppler-Noreuil K.M., Porter C.C., Anand S.K., Whiteford M.L., Davis I.D.,
RA Dewar S.B., Bettinelli A., Fadrowski J.J., Belsha C.W., Hunley T.E.,
RA Nelson R.D., Trachtman H., Cole T.R., Pinsk M., Bockenhauer D., Shenoy M.,
RA Vaidyanathan P., Foreman J.W., Rasoulpour M., Thameem F.,
RA Al-Shahrouri H.Z., Radhakrishnan J., Gharavi A.G., Goilav B., Lifton R.P.;
RT "Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte
RT abnormalities.";
RL Nature 482:98-102(2012).
RN [66]
RP VARIANT ARG-719.
RX PubMed=25969726; DOI=10.1186/s13229-015-0017-0;
RA Codina-Sola M., Rodriguez-Santiago B., Homs A., Santoyo J., Rigau M.,
RA Aznar-Lain G., Del Campo M., Gener B., Gabau E., Botella M.P.,
RA Gutierrez-Arumi A., Antinolo G., Perez-Jurado L.A., Cusco I.;
RT "Integrated analysis of whole-exome sequencing and transcriptome profiling
RT in males with autism spectrum disorders.";
RL Mol. Autism 6:21-21(2015).
RN [67]
RP VARIANT NEDAUS ALA-285, CHARACTERIZATION OF VARIANT NEDAUS ALA-285, AND
RP INTERACTION WITH KEAP1.
RX PubMed=32341456; DOI=10.1038/s10038-020-0758-2;
RA Nakashima M., Kato M., Matsukura M., Kira R., Ngu L.H., Lichtenbelt K.D.,
RA van Gassen K.L.I., Mitsuhashi S., Saitsu H., Matsumoto N.;
RT "De novo variants in CUL3 are associated with global developmental delays
RT with or without infantile spasms.";
RL J. Hum. Genet. 65:727-734(2020).
RN [68]
RP VARIANT NEDAUS 587-THR--ALA-768 DEL.
RX PubMed=33097317; DOI=10.1016/j.braindev.2020.09.015;
RA Iwafuchi S., Kikuchi A., Endo W., Inui T., Aihara Y., Satou K., Kaname T.,
RA Kure S.;
RT "A novel stop-gain CUL3 mutation in a Japanese patient with autism spectrum
RT disorder.";
RL Brain Dev. 43:303-307(2021).
CC -!- FUNCTION: Core component of multiple cullin-RING-based BCR (BTB-CUL3-
CC RBX1) E3 ubiquitin-protein ligase complexes which mediate the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins. BCR complexes and ARIH1 collaborate in tandem to mediate
CC ubiquitination of target proteins (PubMed:27565346). As a scaffold
CC protein may contribute to catalysis through positioning of the
CC substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-
CC protein ligase activity of the complex is dependent on the neddylation
CC of the cullin subunit and is inhibited by the association of the
CC deneddylated cullin subunit with TIP120A/CAND1. The functional
CC specificity of the BCR complex depends on the BTB domain-containing
CC protein as the substrate recognition component. BCR(KLHL42) is involved
CC in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of
CC BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a
CC cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase
CC complex containing homodimeric SPOPL or the heterodimer formed by SPOP
CC and SPOPL; these complexes have lower ubiquitin ligase activity.
CC BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic
CC chromosomes and thereby coordinates faithful mitotic progression and
CC completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi
CC transport by regulating the size of COPII coats, thereby playing a key
CC role in collagen export, which is required for embryonic stem (ES)
CC cells division: BCR(KLHL12) acts by mediating monoubiquitination of
CC SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3)
CC acts as a regulator of ion transport in the distal nephron; by
CC mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970,
CC PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is
CC involved in interferon response and anterograde Golgi to endosome
CC transport: it mediates both ubiquitination leading to degradation and
CC 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21840486,
CC PubMed:21670212, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase
CC complex regulates localization of the chromosomal passenger complex
CC (CPC) from chromosomes to the spindle midzone in anaphase and mediates
CC the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22)
CC ubiquitin ligase complex mediates monoubiquitination of PLK1, leading
CC to PLK1 dissociation from phosphoreceptor proteins and subsequent
CC removal from kinetochores, allowing silencing of the spindle assembly
CC checkpoint (SAC) and chromosome segregation (PubMed:23455478). The
CC BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino
CC acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation
CC of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1
CC complex-mediated inhibition of the TORC1 pathway (PubMed:29769719). The
CC BCR(KLHL25) ubiquitin ligase complex is involved in translational
CC homeostasis by mediating ubiquitination and subsequent degradation of
CC hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KBTBD8)
CC complex acts by mediating monoubiquitination of NOLC1 and TCOF1,
CC leading to remodel the translational program of differentiating cells
CC in favor of neural crest specification (PubMed:26399832). Involved in
CC ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in
CC regulation of G1/S transition. Involved in the ubiquitination of KEAP1,
CC ENC1 and KLHL41 (PubMed:15983046). In concert with ATF2 and RBX1,
CC promotes degradation of KAT5 thereby attenuating its ability to
CC acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex
CC mediates ubiquitination and degradation of TCHP, a down-regulator of
CC cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The
CC BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of
CC KRT14, controls KRT14 levels during keratinocytes differentiation, and
CC is essential for skin integrity (PubMed:27798626). The BCR(KLHL18) E3
CC ubiquitin ligase complex mediates the ubiquitination of AURKA leading
CC to its activation at the centrosome which is required for initiating
CC mitotic entry (PubMed:23213400). The BCR(KEAP1) E3 ubiquitin ligase
CC complex acts as a key sensor of oxidative and electrophilic stress by
CC mediating ubiquitination and degradation of NFE2L2/NRF2, a
CC transcription factor regulating expression of many cytoprotective genes
CC (PubMed:15601839, PubMed:16006525). As part of the CUL3(KBTBD6/7) E3
CC ubiquitin ligase complex functions mediates 'Lys-48' ubiquitination and
CC proteasomal degradation of TIAM1 (PubMed:25684205). By controlling the
CC ubiquitination of that RAC1 guanine exchange factors (GEF), regulates
CC RAC1 signal transduction and downstream biological processes including
CC the organization of the cytoskeleton, cell migration and cell
CC proliferation (PubMed:25684205). {ECO:0000269|PubMed:10500095,
CC ECO:0000269|PubMed:11311237, ECO:0000269|PubMed:15601839,
CC ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046,
CC ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:16524876,
CC ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:18397884,
CC ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937,
CC ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212,
CC ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717,
CC ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813,
CC ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:23213400,
CC ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970,
CC ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23576762,
CC ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598,
CC ECO:0000269|PubMed:25684205, ECO:0000269|PubMed:26399832,
CC ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27716508,
CC ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:29769719}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Forms neddylation-dependent homodimers. Component of multiple
CC BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of
CC CUL3, RBX1 and a variable BTB domain-containing protein acting as both,
CC adapter to cullin and substrate recognition subunit. The BCR complex
CC may be active as a heterodimeric complex, in which NEDD8, covalently
CC attached to one CUL3 molecule, binds to the C-terminus of a second CUL3
CC molecule. Interacts with RBX1, RNF7, CYCE and TIP120A/CAND1
CC (PubMed:10500095, PubMed:10230407, PubMed:12609982). Part of the
CC BCR(SPOP) containing SPOP, and of BCR containing homodimeric SPOPL or
CC the heterodimer formed by SPOP and SPOPL. Part of the probable
CC BCR(KLHL9-KLHL13) complex with BTB domain proteins KLHL9 and KLHL13.
CC Part of the BCR(KLHL41) complex containing KLHL41. Component of the
CC BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and
CC KLHL12 and RBX1. Component of the BCR(KLHL3) E3 ubiquitin ligase
CC complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable). Part
CC of the BCR(ENC1) complex containing ENC1. Part of a complex consisting
CC of BMI1/PCGF4, CUL3 and SPOP. Part of a complex consisting of BRMS1,
CC CUL3 and SPOP. Component of the BCR(KLHL21) E3 ubiquitin ligase
CC complex, at least composed of CUL3, KLHL21 and RBX1. Component of the
CC BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3,
CC KLHL22 and RBX1. Component of the BCR(KLHL25) E3 ubiquitin ligase
CC complex, at least composed of CUL3, KLHL25 and RBX1. Part of a complex
CC consisting of MACROH2A1, CUL3 and SPOP. Component of the BCR(KLHL42) E3
CC ubiquitin ligase complex, at least composed of CUL3 and KLHL42.
CC Interacts with KLHL42 (via the BTB domain). Interacts with KATNA1; the
CC interaction is enhanced by KLHL42. Component of the BCR(KBTBD8) E3
CC ubiquitin ligase complex, at least composed of CUL3, KBTBD8 and RBX1
CC (PubMed:26399832). Interacts with KCTD5, KLHL9, KLHL11, KLHL13, GAN,
CC ZBTB16, KLHL3, KLHL15, KLHL20, KLHL36, GMCL2, BTBD1. Part of a complex
CC that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with
CC KLHL17; the interaction regulates surface GRIK2 expression. Interacts
CC with KCTD7. Part of the BCR(GAN) complex containing GAN. Part of the
CC BCR(KEAP1) complex containing KEAP1 (PubMed:15983046, PubMed:15601839,
CC PubMed:32341456). Interacts with KLHL10 (By similarity). Interacts with
CC KAT5 and ATF2. Interacts with KCTD17 in the BCR(KCTD17) E3 ubiquitin
CC ligase complex, at least composed of CUL3, KCTD17 and RBX1
CC (PubMed:25270598). Interacts (when neddylated) with ARIH1; leading to
CC activate the E3 ligase activity of ARIH1 (PubMed:24076655,
CC PubMed:27565346). Interacts with COPS9 isoform 2 (PubMed:23776465).
CC Interacts with PPP2R5B; this interaction is indirect and mediated
CC through KLHL15-binding and leads to PPP2R5B proteasomal degradation
CC (PubMed:23135275). Interacts with RBBP8/CtIP; this interaction is
CC indirect and mediated through KLHL15-binding and leads to RBBP8
CC proteasomal degradation (PubMed:27561354). Interacts with KLHL24 in the
CC BCR(KLHL24) E3 ubiquitin ligase complex, composed of CUL3, RBX1 and
CC KLHL24 (PubMed:27798626). Interacts with RHOBTB2 (PubMed:29276004).
CC Interacts with AURKA and KLHL18 (via BTB domain) (PubMed:23213400).
CC Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4
CC and DCUN1D5; these interactions promote the cullin neddylation
CC (PubMed:24192928, PubMed:26906416, PubMed:23201271, PubMed:25349211).
CC Component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin ligase complex, also
CC named Cul3-RING ubiquitin ligase complex CUL3(KBTBD6/7), composed of
CC CUL3, RBX1, KBTBD6 and KBTBD7 (PubMed:25684205).
CC {ECO:0000250|UniProtKB:Q9JLV5, ECO:0000269|PubMed:10230407,
CC ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:12609982,
CC ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:15601839,
CC ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046,
CC ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862,
CC ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:18573101,
CC ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937,
CC ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212,
CC ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717,
CC ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813,
CC ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:22748208,
CC ECO:0000269|PubMed:23135275, ECO:0000269|PubMed:23201271,
CC ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:23349464,
CC ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970,
CC ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23573258,
CC ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:23776465,
CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:24192928,
CC ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598,
CC ECO:0000269|PubMed:25349211, ECO:0000269|PubMed:25684205,
CC ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:26906416,
CC ECO:0000269|PubMed:27561354, ECO:0000269|PubMed:27565346,
CC ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:29276004,
CC ECO:0000269|PubMed:32341456, ECO:0000305}.
CC -!- INTERACTION:
CC Q13618; Q969K4: ABTB1; NbExp=5; IntAct=EBI-456129, EBI-7223971;
CC Q13618; O00154: ACOT7; NbExp=2; IntAct=EBI-456129, EBI-948905;
CC Q13618; Q9H0C5: BTBD1; NbExp=7; IntAct=EBI-456129, EBI-935503;
CC Q13618; Q9BSF8: BTBD10; NbExp=4; IntAct=EBI-456129, EBI-720180;
CC Q13618; Q9BX70: BTBD2; NbExp=7; IntAct=EBI-456129, EBI-710091;
CC Q13618; Q9Y2F9: BTBD3; NbExp=3; IntAct=EBI-456129, EBI-311155;
CC Q13618; Q96KE9-2: BTBD6; NbExp=3; IntAct=EBI-456129, EBI-12012762;
CC Q13618; Q86VP6: CAND1; NbExp=6; IntAct=EBI-456129, EBI-456077;
CC Q13618; Q14790: CASP8; NbExp=6; IntAct=EBI-456129, EBI-78060;
CC Q13618; O60826: CCDC22; NbExp=2; IntAct=EBI-456129, EBI-3943153;
CC Q13618; Q8IWE4: DCUN1D3; NbExp=2; IntAct=EBI-456129, EBI-15794102;
CC Q13618; Q15369: ELOC; NbExp=3; IntAct=EBI-456129, EBI-301231;
CC Q13618; Q53SE7: FLJ13057; NbExp=3; IntAct=EBI-456129, EBI-10172181;
CC Q13618; Q96IK5: GMCL1; NbExp=5; IntAct=EBI-456129, EBI-2548508;
CC Q13618; P08238: HSP90AB1; NbExp=3; IntAct=EBI-456129, EBI-352572;
CC Q13618; P42858: HTT; NbExp=3; IntAct=EBI-456129, EBI-466029;
CC Q13618; Q9H3F6: KCTD10; NbExp=6; IntAct=EBI-456129, EBI-2505886;
CC Q13618; Q8WZ19: KCTD13; NbExp=7; IntAct=EBI-456129, EBI-742916;
CC Q13618; Q8NC69: KCTD6; NbExp=11; IntAct=EBI-456129, EBI-2511344;
CC Q13618; Q96MP8-2: KCTD7; NbExp=3; IntAct=EBI-456129, EBI-11954971;
CC Q13618; Q7L273: KCTD9; NbExp=10; IntAct=EBI-456129, EBI-4397613;
CC Q13618; Q14145: KEAP1; NbExp=5; IntAct=EBI-456129, EBI-751001;
CC Q13618; Q53G59: KLHL12; NbExp=12; IntAct=EBI-456129, EBI-740929;
CC Q13618; Q9P2N7: KLHL13; NbExp=7; IntAct=EBI-456129, EBI-1996321;
CC Q13618; O95198: KLHL2; NbExp=5; IntAct=EBI-456129, EBI-746999;
CC Q13618; Q9Y2M5: KLHL20; NbExp=6; IntAct=EBI-456129, EBI-714379;
CC Q13618; Q8N4I8: KLHL3; NbExp=3; IntAct=EBI-456129, EBI-10230467;
CC Q13618; Q9UH77: KLHL3; NbExp=7; IntAct=EBI-456129, EBI-8524663;
CC Q13618; Q96PQ7: KLHL5; NbExp=4; IntAct=EBI-456129, EBI-2692595;
CC Q13618; Q8IXQ5: KLHL7; NbExp=9; IntAct=EBI-456129, EBI-6153160;
CC Q13618; Q8TBC3: SHKBP1; NbExp=6; IntAct=EBI-456129, EBI-724292;
CC Q13618; O43791: SPOP; NbExp=2; IntAct=EBI-456129, EBI-743549;
CC Q13618; Q13829: TNFAIP1; NbExp=4; IntAct=EBI-456129, EBI-2505861;
CC Q13618; P50591: TNFSF10; NbExp=2; IntAct=EBI-456129, EBI-495373;
CC Q13618; O94888: UBXN7; NbExp=6; IntAct=EBI-456129, EBI-1993627;
CC Q13618; Q9H898: ZMAT4; NbExp=3; IntAct=EBI-456129, EBI-2548542;
CC Q13618; Q9H898-2: ZMAT4; NbExp=3; IntAct=EBI-456129, EBI-11529334;
CC Q13618-1; Q8IWE4: DCUN1D3; NbExp=3; IntAct=EBI-15794202, EBI-15794102;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10500095,
CC ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:23213400}. Golgi
CC apparatus {ECO:0000269|PubMed:10500095}. Cell projection, cilium,
CC flagellum {ECO:0000269|PubMed:28395323}. Cytoplasm, cytoskeleton,
CC spindle {ECO:0000269|PubMed:23213400}. Cytoplasm. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:23213400}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000269|PubMed:23213400}. Note=Detected along the length of the
CC sperm flagellum and in the cytoplasm of the germ cells
CC (PubMed:28395323). Predominantly found in the nucleus in interphase
CC cells, found at the centrosome at late G2 or prophase, starts
CC accumulating at the spindle poles in prometaphase and stays on the
CC spindle poles and the mitotic spindle at metaphase (PubMed:23213400).
CC {ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:28395323}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Cul-3 Long;
CC IsoId=Q13618-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13618-2; Sequence=VSP_008824;
CC Name=3; Synonyms=Cul-3 Short;
CC IsoId=Q13618-3; Sequence=VSP_008825;
CC -!- TISSUE SPECIFICITY: Brain, spermatozoa, and testis (at protein level).
CC Widely expressed. {ECO:0000269|PubMed:28395323}.
CC -!- PTM: Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-
CC protein ligase activity of the BCR complex. Deneddylated via its
CC interaction with the COP9 signalosome (CSN) complex.
CC {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:10597293,
CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346}.
CC -!- DISEASE: Pseudohypoaldosteronism 2E (PHA2E) [MIM:614496]: An autosomal
CC dominant disorder characterized by severe hypertension, hyperkalemia,
CC hyperchloremia, hyperchloremic metabolic acidosis, and correction of
CC physiologic abnormalities by thiazide diuretics.
CC {ECO:0000269|PubMed:22266938}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neurodevelopmental disorder with or without autism or seizures
CC (NEDAUS) [MIM:619239]: An autosomal dominant disorder manifesting in
CC infancy and characterized by global developmental delay, variably
CC impaired intellectual development, and speech delay. Some patients have
CC seizures, others have autistic features or behavioral abnormalities.
CC Additional variable features include cardiac defects, failure to
CC thrive, or brain imaging anomalies. {ECO:0000269|PubMed:32341456,
CC ECO:0000269|PubMed:33097317}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00330}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC28621.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAC36682.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA31592.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AF064087; AAC36304.1; -; mRNA.
DR EMBL; AB014517; BAA31592.2; ALT_INIT; mRNA.
DR EMBL; AF062537; AAC36682.1; ALT_FRAME; mRNA.
DR EMBL; AY337761; AAQ01660.1; -; mRNA.
DR EMBL; AK291151; BAF83840.1; -; mRNA.
DR EMBL; AC073052; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092679; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471063; EAW70828.1; -; Genomic_DNA.
DR EMBL; BC031844; AAH31844.1; -; mRNA.
DR EMBL; BC039598; AAH39598.1; -; mRNA.
DR EMBL; BC092409; AAH92409.1; -; mRNA.
DR EMBL; U58089; AAC50546.1; -; mRNA.
DR EMBL; AF052147; AAC28621.1; ALT_FRAME; mRNA.
DR CCDS; CCDS2462.1; -. [Q13618-1]
DR CCDS; CCDS58751.1; -. [Q13618-3]
DR RefSeq; NP_001244126.1; NM_001257197.1. [Q13618-3]
DR RefSeq; NP_001244127.1; NM_001257198.1.
DR RefSeq; NP_003581.1; NM_003590.4. [Q13618-1]
DR PDB; 2MYL; NMR; -; A=49-68.
DR PDB; 2MYM; NMR; -; A=49-68.
DR PDB; 4AP2; X-ray; 2.80 A; B=1-388.
DR PDB; 4APF; X-ray; 3.10 A; B=23-388.
DR PDB; 4EOZ; X-ray; 2.40 A; B/D=20-381.
DR PDB; 4HXI; X-ray; 3.51 A; B=20-381.
DR PDB; 5NLB; X-ray; 3.45 A; B=26-381.
DR PDB; 6I2M; X-ray; 2.30 A; B=23-388.
DR PDBsum; 2MYL; -.
DR PDBsum; 2MYM; -.
DR PDBsum; 4AP2; -.
DR PDBsum; 4APF; -.
DR PDBsum; 4EOZ; -.
DR PDBsum; 4HXI; -.
DR PDBsum; 5NLB; -.
DR PDBsum; 6I2M; -.
DR AlphaFoldDB; Q13618; -.
DR SMR; Q13618; -.
DR BioGRID; 114030; 1298.
DR CORUM; Q13618; -.
DR DIP; DIP-31611N; -.
DR IntAct; Q13618; 1057.
DR MINT; Q13618; -.
DR STRING; 9606.ENSP00000264414; -.
DR iPTMnet; Q13618; -.
DR PhosphoSitePlus; Q13618; -.
DR BioMuta; CUL3; -.
DR DMDM; 12643396; -.
DR EPD; Q13618; -.
DR jPOST; Q13618; -.
DR MassIVE; Q13618; -.
DR MaxQB; Q13618; -.
DR PaxDb; Q13618; -.
DR PeptideAtlas; Q13618; -.
DR PRIDE; Q13618; -.
DR ProteomicsDB; 59606; -. [Q13618-1]
DR ProteomicsDB; 59607; -. [Q13618-2]
DR ProteomicsDB; 59608; -. [Q13618-3]
DR Antibodypedia; 3632; 411 antibodies from 40 providers.
DR DNASU; 8452; -.
DR Ensembl; ENST00000264414.9; ENSP00000264414.4; ENSG00000036257.14. [Q13618-1]
DR Ensembl; ENST00000344951.8; ENSP00000343601.4; ENSG00000036257.14. [Q13618-3]
DR Ensembl; ENST00000409096.5; ENSP00000387200.1; ENSG00000036257.14. [Q13618-2]
DR Ensembl; ENST00000409777.5; ENSP00000386525.1; ENSG00000036257.14. [Q13618-2]
DR GeneID; 8452; -.
DR KEGG; hsa:8452; -.
DR MANE-Select; ENST00000264414.9; ENSP00000264414.4; NM_003590.5; NP_003581.1.
DR UCSC; uc002vny.4; human. [Q13618-1]
DR CTD; 8452; -.
DR DisGeNET; 8452; -.
DR GeneCards; CUL3; -.
DR GeneReviews; CUL3; -.
DR HGNC; HGNC:2553; CUL3.
DR HPA; ENSG00000036257; Tissue enhanced (testis).
DR MalaCards; CUL3; -.
DR MIM; 603136; gene.
DR MIM; 614496; phenotype.
DR MIM; 619239; phenotype.
DR neXtProt; NX_Q13618; -.
DR OpenTargets; ENSG00000036257; -.
DR Orphanet; 300530; Pseudohypoaldosteronism type 2E.
DR PharmGKB; PA27049; -.
DR VEuPathDB; HostDB:ENSG00000036257; -.
DR eggNOG; KOG2166; Eukaryota.
DR GeneTree; ENSGT00940000155066; -.
DR HOGENOM; CLU_004747_7_1_1; -.
DR InParanoid; Q13618; -.
DR OMA; MFKDMTI; -.
DR OrthoDB; 1040292at2759; -.
DR PhylomeDB; Q13618; -.
DR TreeFam; TF105858; -.
DR PathwayCommons; Q13618; -.
DR Reactome; R-HSA-4641258; Degradation of DVL.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9013418; RHOBTB2 GTPase cycle.
DR Reactome; R-HSA-9013422; RHOBTB1 GTPase cycle.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR Reactome; R-HSA-9706019; RHOBTB3 ATPase cycle.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q13618; -.
DR SIGNOR; Q13618; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 8452; 518 hits in 1155 CRISPR screens.
DR ChiTaRS; CUL3; human.
DR GeneWiki; CUL3; -.
DR GenomeRNAi; 8452; -.
DR Pharos; Q13618; Tbio.
DR PRO; PR:Q13618; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q13618; protein.
DR Bgee; ENSG00000036257; Expressed in sperm and 203 other tissues.
DR ExpressionAtlas; Q13618; baseline and differential.
DR Genevisible; Q13618; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005827; C:polar microtubule; IDA:UniProtKB.
DR GO; GO:0036126; C:sperm flagellum; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0005112; F:Notch binding; IPI:MGI.
DR GO; GO:0031208; F:POZ domain binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent catabolic process; IDA:MGI.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW.
DR GO; GO:0048208; P:COPII vesicle coating; IMP:UniProtKB.
DR GO; GO:0040016; P:embryonic cleavage; ISS:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IDA:UniProtKB.
DR GO; GO:0044346; P:fibroblast apoptotic process; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0007369; P:gastrulation; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:ProtInc.
DR GO; GO:0072576; P:liver morphogenesis; IEA:Ensembl.
DR GO; GO:0007080; P:mitotic metaphase plate congression; IMP:UniProtKB.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0071630; P:nuclear protein quality control by the ubiquitin-proteasome system; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:1901992; P:positive regulation of mitotic cell cycle phase transition; IMP:UniProtKB.
DR GO; GO:0045842; P:positive regulation of mitotic metaphase/anaphase transition; IMP:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IGI:BHF-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IGI:BHF-UCL.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0017145; P:stem cell division; ISS:UniProtKB.
DR GO; GO:0043149; P:stress fiber assembly; IMP:UniProtKB.
DR GO; GO:0001831; P:trophectodermal cellular morphogenesis; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Autism spectrum disorder;
KW Cell cycle; Cell division; Cell projection; Cilium;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Disease variant;
KW Epilepsy; ER-Golgi transport; Flagellum; Golgi apparatus;
KW Intellectual disability; Isopeptide bond; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Transport; Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..768
FT /note="Cullin-3"
FT /id="PRO_0000119793"
FT REGION 2..41
FT /note="Interaction with KLHL18"
FT /evidence="ECO:0000269|PubMed:23213400"
FT REGION 677..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 682..698
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 585
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 712
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in NEDD8)"
FT /evidence="ECO:0000250|UniProtKB:Q13616"
FT VAR_SEQ 1..24
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_008824"
FT VAR_SEQ 23..88
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_008825"
FT VARIANT 13
FT /note="D -> H (in dbSNP:rs2969802)"
FT /id="VAR_017194"
FT VARIANT 184
FT /note="R -> S (in dbSNP:rs17480168)"
FT /id="VAR_048839"
FT VARIANT 285
FT /note="V -> A (in NEDAUS; decreases interaction with KEAP1;
FT dbSNP:rs1343840421)"
FT /evidence="ECO:0000269|PubMed:32341456"
FT /id="VAR_085407"
FT VARIANT 413
FT /note="D -> G (in PHA2E; dbSNP:rs199469656)"
FT /evidence="ECO:0000269|PubMed:22266938"
FT /id="VAR_067532"
FT VARIANT 459
FT /note="K -> R (in PHA2E; dbSNP:rs199469658)"
FT /evidence="ECO:0000269|PubMed:22266938"
FT /id="VAR_067533"
FT VARIANT 567
FT /note="V -> I (in dbSNP:rs3738952)"
FT /id="VAR_017195"
FT VARIANT 587..768
FT /note="Missing (in NEDAUS)"
FT /evidence="ECO:0000269|PubMed:33097317"
FT /id="VAR_085408"
FT VARIANT 719
FT /note="H -> R (found in a patient with autism spectrum
FT disorder; unknown pathological significance;
FT dbSNP:rs763087632)"
FT /evidence="ECO:0000269|PubMed:25969726"
FT /id="VAR_078688"
FT CONFLICT 13
FT /note="D -> G (in Ref. 3; AAC36682)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="K -> T (in Ref. 4; AAQ01660)"
FT /evidence="ECO:0000305"
FT CONFLICT 481
FT /note="N -> T (in Ref. 4; AAQ01660)"
FT /evidence="ECO:0000305"
FT CONFLICT 609
FT /note="E -> G (in Ref. 8; AAH31844)"
FT /evidence="ECO:0000305"
FT CONFLICT 666
FT /note="T -> I (in Ref. 4; AAQ01660)"
FT /evidence="ECO:0000305"
FT HELIX 26..45
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 54..66
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 70..87
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:6I2M"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 101..122
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 124..128
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 130..133
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 139..150
FT /evidence="ECO:0007829|PDB:6I2M"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 155..174
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 180..192
FT /evidence="ECO:0007829|PDB:6I2M"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 199..204
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 206..227
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 230..251
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 257..268
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 273..277
FT /evidence="ECO:0007829|PDB:6I2M"
FT TURN 280..282
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 284..290
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 293..303
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 309..327
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 345..358
FT /evidence="ECO:0007829|PDB:6I2M"
FT HELIX 364..380
FT /evidence="ECO:0007829|PDB:6I2M"
SQ SEQUENCE 768 AA; 88930 MW; A1A02022480BF099 CRC64;
MSNLSKGTGS RKDTKMRIRA FPMTMDEKYV NSIWDLLKNA IQEIQRKNNS GLSFEELYRN
AYTMVLHKHG EKLYTGLREV VTEHLINKVR EDVLNSLNNN FLQTLNQAWN DHQTAMVMIR
DILMYMDRVY VQQNNVENVY NLGLIIFRDQ VVRYGCIRDH LRQTLLDMIA RERKGEVVDR
GAIRNACQML MILGLEGRSV YEEDFEAPFL EMSAEFFQME SQKFLAENSA SVYIKKVEAR
INEEIERVMH CLDKSTEEPI VKVVERELIS KHMKTIVEME NSGLVHMLKN GKTEDLGCMY
KLFSRVPNGL KTMCECMSSY LREQGKALVS EEGEGKNPVD YIQGLLDLKS RFDRFLLESF
NNDRLFKQTI AGDFEYFLNL NSRSPEYLSL FIDDKLKKGV KGLTEQEVET ILDKAMVLFR
FMQEKDVFER YYKQHLARRL LTNKSVSDDS EKNMISKLKT ECGCQFTSKL EGMFRDMSIS
NTTMDEFRQH LQATGVSLGG VDLTVRVLTT GYWPTQSATP KCNIPPAPRH AFEIFRRFYL
AKHSGRQLTL QHHMGSADLN ATFYGPVKKE DGSEVGVGGA QVTGSNTRKH ILQVSTFQMT
ILMLFNNREK YTFEEIQQET DIPERELVRA LQSLACGKPT QRVLTKEPKS KEIENGHIFT
VNDQFTSKLH RVKIQTVAAK QGESDPERKE TRQKVDDDRK HEIEAAIVRI MKSRKKMQHN
VLVAEVTQQL KARFLPSPVV IKKRIEGLIE REYLARTPED RKVYTYVA
