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   27-MAR-2024, entry version 225.
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   FUNCTION, PATHWAY, AND IDENTIFICATION IN THE BCR(KLHL25) UBIQUITIN LIGASE
RP   COMPLEX.
RX   PubMed=27664236; DOI=10.1101/gad.283283.116;
RA   Zhang C., Liu J., Huang G., Zhao Y., Yue X., Wu H., Li J., Zhu J., Shen Z.,
RA   Haffty B.G., Hu W., Feng Z.;
RT   "Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit
RT   lipid synthesis and tumor progression.";
RL   Genes Dev. 30:1956-1970(2016).
RN   [57]
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   [58]
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   [59]
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   [60]
RP   IDENTIFICATION IN BCR(KBTBD2) E3 UBIQUITIN LIGASE COMPLEX.
RX   PubMed=27708159; DOI=10.1073/pnas.1614467113;
RA   Zhang Z., Turer E., Li X., Zhan X., Choi M., Tang M., Press A., Smith S.R.,
RA   Divoux A., Moresco E.M., Beutler B.;
RT   "Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2
RT   deficiency in mice.";
RL   Proc. Natl. Acad. Sci. U.S.A. 113:E6418-E6426(2016).
RN   [61]
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   [62]
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   [63]
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   [64]
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   [65]
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   [66]
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   [67]
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   [68]
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   [69]
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   [70]
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(KLHL25)
CC       ubiquitin ligase complex is also involved in lipid synthesis by
CC       mediating ubiquitination and degradation of ACLY (PubMed:27664236). The
CC       BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and
CC       TCOF1, leading to remodel the translational program of differentiating
CC       cells in favor of neural crest specification (PubMed:26399832).
CC       Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus
CC       involved in regulation of G1/S transition. Involved in the
CC       ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046). In concert
CC       with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating
CC       its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin
CC       ligase complex mediates ubiquitination and degradation of TCHP, a down-
CC       regulator of cilium assembly, thereby inducing ciliogenesis
CC       (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates
CC       ubiquitination of KRT14, controls KRT14 levels during keratinocytes
CC       differentiation, and is essential for skin integrity (PubMed:27798626).
CC       The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination
CC       of AURKA leading to its activation at the centrosome which is required
CC       for initiating mitotic entry (PubMed:23213400). The BCR(KEAP1) E3
CC       ubiquitin ligase complex acts as a key sensor of oxidative and
CC       electrophilic stress by mediating ubiquitination and degradation of
CC       NFE2L2/NRF2, a transcription factor regulating expression of many
CC       cytoprotective genes (PubMed:15601839, PubMed:16006525). As part of the
CC       CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions mediates 'Lys-48'
CC       ubiquitination and proteasomal degradation of TIAM1 (PubMed:25684205).
CC       By controlling the ubiquitination of that RAC1 guanine exchange factors
CC       (GEF), regulates RAC1 signal transduction and downstream biological
CC       processes including the organization of the cytoskeleton, cell
CC       migration and cell proliferation (PubMed:25684205).
CC       {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:11311237,
CC       ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:15897469,
CC       ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525,
CC       ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862,
CC       ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19261606,
CC       ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:20389280,
CC       ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486,
CC       ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22358839,
CC       ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22632832,
CC       ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:23387299,
CC       ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23455478,
CC       ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:24768539,
CC       ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:25684205,
CC       ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:27565346,
CC       ECO:0000269|PubMed:27664236, ECO:0000269|PubMed:27716508,
CC       ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:29769719}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000269|PubMed:27664236}.
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 (PubMed:22578813,
CC       PubMed:27664236). Part of a complex consisting of MACROH2A1, CUL3 and
CC       SPOP. Component of the BCR(KLHL42) E3 ubiquitin ligase complex, at
CC       least composed of CUL3 and KLHL42. Interacts with KLHL42 (via the BTB
CC       domain). Interacts with KATNA1; the interaction is enhanced by KLHL42.
CC       Component of the BCR(KBTBD8) E3 ubiquitin ligase complex, at least
CC       composed of CUL3, KBTBD8 and RBX1 (PubMed:26399832). Interacts with
CC       KCTD5, KLHL9, KLHL11, KLHL13, GAN, ZBTB16, KLHL3, KLHL15, KLHL20,
CC       KLHL36, GMCL2, BTBD1. Part of a complex that contains CUL3, RBX1 and
CC       GAN. Interacts (via BTB domain) with KLHL17; the interaction regulates
CC       surface GRIK2 expression. Interacts with KCTD7. Part of the BCR(GAN)
CC       complex containing GAN. Part of the BCR(KEAP1) complex containing KEAP1
CC       (PubMed:15983046, PubMed:15601839, PubMed:32341456). Interacts with
CC       KLHL10 (By similarity). Interacts with KAT5 and ATF2. Interacts with
CC       KCTD17 in the BCR(KCTD17) E3 ubiquitin ligase complex, at least
CC       composed of CUL3, KCTD17 and RBX1 (PubMed:25270598). Interacts (when
CC       neddylated) with ARIH1; leading to activate the E3 ligase activity of
CC       ARIH1 (PubMed:24076655, PubMed:27565346). Interacts with COPS9 isoform
CC       2 (PubMed:23776465). Interacts with PPP2R5B; this interaction is
CC       indirect and mediated through KLHL15-binding and leads to PPP2R5B
CC       proteasomal degradation (PubMed:23135275). Interacts with RBBP8/CtIP;
CC       this interaction is indirect and mediated through KLHL15-binding and
CC       leads to RBBP8 proteasomal degradation (PubMed:27561354). Interacts
CC       with KLHL24 in the BCR(KLHL24) E3 ubiquitin ligase complex, composed of
CC       CUL3, RBX1 and KLHL24 (PubMed:27798626). Interacts with RHOBTB2
CC       (PubMed:29276004). Interacts with AURKA and KLHL18 (via BTB domain)
CC       (PubMed:23213400). Interacts (unneddylated form) with DCUN1D1, DCUN1D2,
CC       DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin
CC       neddylation (PubMed:24192928, PubMed:26906416, PubMed:23201271,
CC       PubMed:25349211). Component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin
CC       ligase complex, also named Cul3-RING ubiquitin ligase complex
CC       CUL3(KBTBD6/7), composed of CUL3, RBX1, KBTBD6 and KBTBD7
CC       (PubMed:25684205). Component of the BCR(KBTBD2) E3 ubiquitin ligase
CC       complex, at least composed of CUL3, KBTBD2 and RBX1. Interacts with
CC       KBTBD2 (via the BTB domain) (PubMed:27708159).
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:27664236, ECO:0000269|PubMed:27708159,
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=9; IntAct=EBI-456129, EBI-935503;
CC       Q13618; Q9BSF8: BTBD10; NbExp=5; IntAct=EBI-456129, EBI-720180;
CC       Q13618; Q9BX70: BTBD2; NbExp=9; 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=8; 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; Q8NFY9: KBTBD8; NbExp=4; IntAct=EBI-456129, EBI-21328977;
CC       Q13618; Q9H3F6: KCTD10; NbExp=7; IntAct=EBI-456129, EBI-2505886;
CC       Q13618; Q8WZ19: KCTD13; NbExp=8; 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=24; IntAct=EBI-456129, EBI-740929;
CC       Q13618; Q9P2N7: KLHL13; NbExp=15; IntAct=EBI-456129, EBI-1996321;
CC       Q13618; O95198: KLHL2; NbExp=7; IntAct=EBI-456129, EBI-746999;
CC       Q13618; Q9Y2M5: KLHL20; NbExp=8; 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=8; IntAct=EBI-456129, EBI-2692595;
CC       Q13618; Q8IXQ5: KLHL7; NbExp=12; IntAct=EBI-456129, EBI-6153160;
CC       Q13618; Q9P2G9: KLHL8; NbExp=7; IntAct=EBI-456129, EBI-949008;
CC       Q13618; Q9P2J3: KLHL9; NbExp=12; IntAct=EBI-456129, EBI-2510152;
CC       Q13618; P62877: RBX1; NbExp=4; IntAct=EBI-456129, EBI-398523;
CC       Q13618; Q8TBC3: SHKBP1; NbExp=7; IntAct=EBI-456129, EBI-724292;
CC       Q13618; O43791: SPOP; NbExp=2; IntAct=EBI-456129, EBI-743549;
CC       Q13618; Q13829: TNFAIP1; NbExp=5; 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};
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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   PDB; 8GQ6; EM; 3.96 A; C/F=1-768.
DR   PDB; 8H33; EM; 7.86 A; C/F/H/I=1-768.
DR   PDB; 8H34; EM; 7.99 A; C/F/H/I/M/O=1-768.
DR   PDB; 8H35; EM; 7.41 A; C/F/H/I/M/O/T/V=1-768.
DR   PDB; 8H36; EM; 4.60 A; C/F=1-768.
DR   PDB; 8H37; EM; 7.52 A; C/F/M/O=1-768.
DR   PDB; 8H38; EM; 4.25 A; L=1-768.
DR   PDB; 8H3A; EM; 7.51 A; L=1-768.
DR   PDB; 8H3F; EM; 6.73 A; L=1-768.
DR   PDB; 8H3Q; EM; 3.76 A; C=1-768.
DR   PDB; 8H3R; EM; 6.36 A; C/F=1-768.
DR   PDB; 8I79; EM; 2.80 A; B/C/E/H/J=22-388.
DR   PDB; 8U80; EM; 3.60 A; C1/C2/C3/C4/C5=1-381.
DR   PDB; 8U81; EM; 3.82 A; C1/C2/C3/C4/C5=1-381.
DR   PDB; 8U82; EM; 3.84 A; C1/C2/C3/C4/C5=2-381.
DR   PDB; 8U83; EM; 3.98 A; C1/C2/C3/C4/C5=1-381.
DR   PDB; 8U84; EM; 3.88 A; C1/C2/C3/C4/C5=1-381.
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   PDBsum; 8GQ6; -.
DR   PDBsum; 8H33; -.
DR   PDBsum; 8H34; -.
DR   PDBsum; 8H35; -.
DR   PDBsum; 8H36; -.
DR   PDBsum; 8H37; -.
DR   PDBsum; 8H38; -.
DR   PDBsum; 8H3A; -.
DR   PDBsum; 8H3F; -.
DR   PDBsum; 8H3Q; -.
DR   PDBsum; 8H3R; -.
DR   PDBsum; 8I79; -.
DR   PDBsum; 8U80; -.
DR   PDBsum; 8U81; -.
DR   PDBsum; 8U82; -.
DR   PDBsum; 8U83; -.
DR   PDBsum; 8U84; -.
DR   AlphaFoldDB; Q13618; -.
DR   EMDB; EMD-3317; -.
DR   EMDB; EMD-34199; -.
DR   EMDB; EMD-34449; -.
DR   EMDB; EMD-34450; -.
DR   EMDB; EMD-34451; -.
DR   EMDB; EMD-34452; -.
DR   EMDB; EMD-34453; -.
DR   EMDB; EMD-34455; -.
DR   EMDB; EMD-34462; -.
DR   EMDB; EMD-34467; -.
DR   EMDB; EMD-34473; -.
DR   EMDB; EMD-34474; -.
DR   EMDB; EMD-35212; -.
DR   EMDB; EMD-41994; -.
DR   EMDB; EMD-41996; -.
DR   EMDB; EMD-41997; -.
DR   EMDB; EMD-42000; -.
DR   EMDB; EMD-42001; -.
DR   EMDB; EMD-42004; -.
DR   EMDB; EMD-42008; -.
DR   SMR; Q13618; -.
DR   BioGRID; 114030; 2669.
DR   ComplexPortal; CPX-8007; CRL3 E3 ubiquitin ligase complex, KLHL1 variant.
DR   ComplexPortal; CPX-8025; CRL3 E3 ubiquitin ligase complex, KLHL2 variant.
DR   ComplexPortal; CPX-8041; CRL3 E3 ubiquitin ligase complex, KLHL3 variant.
DR   ComplexPortal; CPX-8061; CRL3 E3 ubiquitin ligase complex, KLHL4 variant.
DR   ComplexPortal; CPX-8063; CRL3 E3 ubiquitin ligase complex, KLHL5 variant.
DR   ComplexPortal; CPX-8064; CRL3 E3 ubiquitin ligase complex, KLHL6 variant.
DR   ComplexPortal; CPX-8083; CRL3 E3 ubiquitin ligase complex, KLHL9 variant.
DR   ComplexPortal; CPX-8084; CRL3 E3 ubiquitin ligase complex, KLHL7 variant.
DR   ComplexPortal; CPX-8085; CRL3 E3 ubiquitin ligase complex, KLHL8 variant.
DR   ComplexPortal; CPX-8087; CRL3 E3 ubiquitin ligase complex, KLHL10 variant.
DR   ComplexPortal; CPX-8088; CRL3 E3 ubiquitin ligase complex, KLHL11 variant.
DR   ComplexPortal; CPX-8089; CRL3 E3 ubiquitin ligase complex, KLHL12 variant.
DR   ComplexPortal; CPX-8090; CRL3 E3 ubiquitin ligase complex, KLHL13 variant.
DR   ComplexPortal; CPX-8091; CRL3 E3 ubiquitin ligase complex, KLHL14 variant.
DR   ComplexPortal; CPX-8097; CRL3 E3 ubiquitin ligase complex, KLHL15 variant.
DR   ComplexPortal; CPX-8102; CRL3 E3 ubiquitin ligase complex, KLHL16 variant.
DR   ComplexPortal; CPX-8103; CRL3 E3 ubiquitin ligase complex, KLHL17 variant.
DR   ComplexPortal; CPX-8106; CRL3 E3 ubiquitin ligase complex, KLHL18 variant.
DR   ComplexPortal; CPX-8107; CRL3 E3 ubiquitin ligase complex, KEAP1 variant.
DR   ComplexPortal; CPX-8109; CRL3 E3 ubiquitin ligase complex, KLHL20 variant.
DR   ComplexPortal; CPX-8110; CRL3 E3 ubiquitin ligase complex, KLHL21 variant.
DR   ComplexPortal; CPX-8122; CRL3 E3 ubiquitin ligase complex, KLHL22 variant.
DR   ComplexPortal; CPX-8123; CRL3 E3 ubiquitin ligase complex, KLHL23 variant.
DR   ComplexPortal; CPX-8125; CRL3 E3 ubiquitin ligase complex, KLHL24 variant.
DR   ComplexPortal; CPX-8126; CRL3 E3 ubiquitin ligase complex, KLHL25 variant.
DR   ComplexPortal; CPX-8130; CRL3 E3 ubiquitin ligase complex, KLHL26 variant.
DR   ComplexPortal; CPX-8131; CRL3 E3 ubiquitin ligase complex, IPP variant.
DR   ComplexPortal; CPX-8135; CRL3 E3 ubiquitin ligase complex, KLHL28 variant.
DR   ComplexPortal; CPX-8147; CRL3 E3 ubiquitin ligase complex, KLHL29 variant.
DR   ComplexPortal; CPX-8150; CRL3 E3 ubiquitin ligase complex, KLHL30 variant.
DR   ComplexPortal; CPX-8151; CRL3 E3 ubiquitin ligase complex, KLHL31 variant.
DR   ComplexPortal; CPX-8201; CRL3 E3 ubiquitin ligase complex, KLHL32 variant.
DR   ComplexPortal; CPX-8202; CRL3 E3 ubiquitin ligase complex, KLHL34 variant.
DR   ComplexPortal; CPX-8221; CRL3 E3 ubiquitin ligase complex, KLHL35 variant.
DR   ComplexPortal; CPX-8222; CRL3 E3 ubiquitin ligase complex, KLHL36 variant.
DR   ComplexPortal; CPX-8241; CRL3 E3 ubiquitin ligase complex, ENC1 variant.
DR   ComplexPortal; CPX-8242; CRL3 E3 ubiquitin ligase complex, KLHL38 variant.
DR   ComplexPortal; CPX-8261; CRL3 E3 ubiquitin ligase complex, KLHL40 variant.
DR   ComplexPortal; CPX-8262; CRL3 E3 ubiquitin ligase complex, KLHL41 variant.
DR   ComplexPortal; CPX-8263; CRL3 E3 ubiquitin ligase complex, KLHL42 variant.
DR   CORUM; Q13618; -.
DR   DIP; DIP-31611N; -.
DR   IntAct; Q13618; 1072.
DR   MINT; Q13618; -.
DR   STRING; 9606.ENSP00000264414; -.
DR   GlyGen; Q13618; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q13618; -.
DR   PhosphoSitePlus; Q13618; -.
DR   SwissPalm; Q13618; -.
DR   BioMuta; CUL3; -.
DR   DMDM; 12643396; -.
DR   EPD; Q13618; -.
DR   jPOST; Q13618; -.
DR   MassIVE; Q13618; -.
DR   MaxQB; Q13618; -.
DR   PaxDb; 9606-ENSP00000264414; -.
DR   PeptideAtlas; Q13618; -.
DR   ProteomicsDB; 59606; -. [Q13618-1]
DR   ProteomicsDB; 59607; -. [Q13618-2]
DR   ProteomicsDB; 59608; -. [Q13618-3]
DR   Pumba; Q13618; -.
DR   Antibodypedia; 3632; 476 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   AGR; HGNC:2553; -.
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; 21270at2759; -.
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; 550 hits in 1242 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 205 other cell types or tissues.
DR   ExpressionAtlas; Q13618; baseline and differential.
DR   GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR   GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
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:0098978; C:glutamatergic synapse; IEA:Ensembl.
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:0098794; C:postsynapse; IEA:GOC.
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:0160072; F:ubiquitin ligase complex scaffold activity; IDA:UniProt.
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:0071230; P:cellular response to amino acid stimulus; IDA:UniProt.
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 chromosome alignment; 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:0032480; P:negative regulation of type I interferon production; IDA:UniProt.
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:1904263; P:positive regulation of TORC1 signaling; IDA:UniProt.
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:0140252; P:regulation protein catabolic process at postsynapse; IEA:Ensembl.
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; 1.20.1310.10; Cullin Repeats; 4.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 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; CULLIN; 1.
DR   PANTHER; PTHR11932:SF168; CULLIN-3; 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; SSF75632; Cullin homology domain; 1.
DR   SUPFAM; SSF74788; Cullin repeat-like; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS01256; CULLIN_1; 1.
DR   PROSITE; PS50069; CULLIN_2; 1.
DR   Genevisible; Q13618; HS.
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; uncertain significance; 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
//