CUL2_HUMAN
ID CUL2_HUMAN Reviewed; 745 AA.
AC Q13617; B3KT95; B7Z6K8; D3DRY6; G3V1S2; O00200; Q5T2B6; Q9UNF9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Cullin-2;
DE Short=CUL-2;
GN Name=CUL2;
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), VARIANT SER-109, IDENTIFICATION IN
RP COMPLEX WITH VHL AND ELONGIN BC, AND FUNCTION.
RC TISSUE=Kidney;
RX PubMed=9122164; DOI=10.1073/pnas.94.6.2156;
RA Pause A., Lee S., Worrel R., Chen D.Y.T., Burgess W.H., Linehan W.M.,
RA Klausner R.D.;
RT "The von Hippel-Lindau tumor-suppressor gene product forms a stable complex
RT with human CUL-2, a member of the Cdc53 family of proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2156-2161(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-109, MUTAGENESIS OF
RP LYS-621; LYS-689 AND LYS-719, AND NEDDYLATION AT LYS-689.
RC TISSUE=Brain;
RX PubMed=10092517; DOI=10.1006/bbrc.1999.0339;
RA Wada H., Yeh E.T.H., Kamitani T.;
RT "Identification of NEDD8-conjugation site in human cullin-2.";
RL Biochem. Biophys. Res. Commun. 257:100-105(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Prostate;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 95-745.
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 [8]
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 [9]
RP FUNCTION, AND IDENTIFICATION IN CBC(VHL) COMPLEX.
RX PubMed=10973499; DOI=10.1073/pnas.190332597;
RA Kamura T., Sato S., Iwai K., Czyzyk-Krzeska M., Conaway R.C., Conaway J.W.;
RT "Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-
RT Lindau (VHL) tumor suppressor complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:10430-10435(2000).
RN [10]
RP IDENTIFICATION IN COMPLEX WITH VHL; ELONGIN BC AND RBX1, AND FUNCTION.
RX PubMed=11384984; DOI=10.1074/jbc.m103093200;
RA Kamura T., Burian D., Yan Q., Schmidt S.L., Lane W.S., Querido E.,
RA Branton P.E., Shilatifard A., Conaway R.C., Conaway J.W.;
RT "Muf1, a novel elongin BC-interacting leucine-rich repeat protein that can
RT assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase.";
RL J. Biol. Chem. 276:29748-29753(2001).
RN [11]
RP IDENTIFICATION IN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX WITH MED8.
RX PubMed=12149480; DOI=10.1073/pnas.162424199;
RA Brower C.S., Sato S., Tomomori-Sato C., Kamura T., Pause A., Stearman R.,
RA Klausner R.D., Malik S., Lane W.S., Sorokina I., Roeder R.G., Conaway J.W.,
RA Conaway R.C.;
RT "Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that
RT can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10353-10358(2002).
RN [12]
RP FUNCTION, AND 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 [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 LRR1 AND FEM1B.
RX PubMed=15601820; DOI=10.1101/gad.1252404;
RA Kamura T., Maenaka K., Kotoshiba S., Matsumoto M., Kohda D., Conaway R.C.,
RA Conaway J.W., Nakayama K.I.;
RT "VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1
RT and Cul5-Rbx2 modules of ubiquitin ligases.";
RL Genes Dev. 18:3055-3065(2004).
RN [15]
RP IDENTIFICATION IN COMPLEX WITH ELOC AND ZYG11B, AND IDENTIFICATION IN
RP COMPLEX WITH ELOB; ELOC AND ZER1.
RX PubMed=17304241; DOI=10.1038/sj.embor.7400895;
RA Vasudevan S., Starostina N.G., Kipreos E.T.;
RT "The Caenorhabditis elegans cell-cycle regulator ZYG-11 defines a conserved
RT family of CUL-2 complex components.";
RL EMBO Rep. 8:279-286(2007).
RN [16]
RP INTERACTION WITH HRSV VIRUS PROTEIN NS1 (MICROBIAL INFECTION).
RX PubMed=17251292; DOI=10.1128/jvi.02303-06;
RA Elliott J., Lynch O.T., Suessmuth Y., Qian P., Boyd C.R., Burrows J.F.,
RA Buick R., Stevenson N.J., Touzelet O., Gadina M., Power U.F.,
RA Johnston J.A.;
RT "Respiratory syncytial virus NS1 protein degrades STAT2 by using the
RT Elongin-Cullin E3 ligase.";
RL J. Virol. 81:3428-3436(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-661, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-393, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [19]
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 [20]
RP INTERACTS WITH KLHDC10.
RX PubMed=23102700; DOI=10.1016/j.molcel.2012.09.018;
RA Sekine Y., Hatanaka R., Watanabe T., Sono N., Iemura S., Natsume T.,
RA Kuranaga E., Miura M., Takeda K., Ichijo H.;
RT "The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1
RT activation by suppressing PP5.";
RL Mol. Cell 48:692-704(2012).
RN [21]
RP IDENTIFICATION IN A COMPLEX WITH LIMD1; EGLN1/PHD2; VHL AND ELOB.
RX PubMed=22286099; DOI=10.1038/ncb2424;
RA Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., Feng Y.,
RA Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., Ingvarsson S.,
RA Ratcliffe P.J., Longmore G.D., Sharp T.V.;
RT "The LIMD1 protein bridges an association between the prolyl hydroxylases
RT and VHL to repress HIF-1 activity.";
RL Nat. Cell Biol. 14:201-208(2012).
RN [22]
RP FUNCTION, 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-661, 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 [24]
RP INTERACTION WITH DCUN1D1, AND COMPONENT OF VCB COMPLEX.
RX PubMed=23401859; DOI=10.1128/mcb.01342-12;
RA Heir P., Sufan R.I., Greer S.N., Poon B.P., Lee J.E., Ohh M.;
RT "DCNL1 functions as a substrate sensor and activator of cullin 2-RING
RT ligase.";
RL Mol. Cell. Biol. 33:1621-1631(2013).
RN [25]
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 [26]
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 [27]
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 [28]
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 [29]
RP FUNCTION, AND PATHWAY.
RX PubMed=26138980; DOI=10.1126/science.aab0515;
RA Lin H.C., Ho S.C., Chen Y.Y., Khoo K.H., Hsu P.H., Yen H.C.;
RT "SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced
RT by failed UGA/Sec decoding.";
RL Science 349:91-95(2015).
RN [30]
RP FUNCTION, PATHWAY, AND IDENTIFICATION IN A CRL2 E3 UBIQUITIN-PROTEIN LIGASE
RP COMPLEX.
RX PubMed=29779948; DOI=10.1016/j.cell.2018.04.028;
RA Koren I., Timms R.T., Kula T., Xu Q., Li M.Z., Elledge S.J.;
RT "The eukaryotic proteome is shaped by E3 ubiquitin ligases targeting C-
RT terminal degrons.";
RL Cell 173:1622-1635(2018).
RN [31]
RP FUNCTION, PATHWAY, AND IDENTIFICATION IN A CRL2 E3 UBIQUITIN-PROTEIN LIGASE
RP COMPLEX.
RX PubMed=29775578; DOI=10.1016/j.molcel.2018.04.006;
RA Lin H.C., Yeh C.W., Chen Y.F., Lee T.T., Hsieh P.Y., Rusnac D.V., Lin S.Y.,
RA Elledge S.J., Zheng N., Yen H.S.;
RT "C-terminal end-directed protein elimination by CRL2 ubiquitin ligases.";
RL Mol. Cell 70:602-613(2018).
CC -!- FUNCTION: Core component of multiple cullin-RING-based ECS (ElonginB/C-
CC CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which
CC mediate the ubiquitination of target proteins (PubMed:11384984,
CC PubMed:26138980, PubMed:29779948, PubMed:29775578). CUL2 may serve as a
CC rigid scaffold in the complex and may contribute to catalysis through
CC positioning of the substrate and the ubiquitin-conjugating enzyme
CC (PubMed:9122164, PubMed:10973499, PubMed:11384984, PubMed:12609982,
CC PubMed:24076655). The E3 ubiquitin-protein ligase activity of the
CC complex is dependent on the neddylation of the cullin subunit and is
CC inhibited by the association of the deneddylated cullin subunit with
CC TIP120A/CAND1 (PubMed:12609982, PubMed:24076655, PubMed:27565346). The
CC functional specificity of the ECS complex depends on the substrate
CC recognition component (PubMed:9122164, PubMed:10973499,
CC PubMed:26138980, PubMed:29779948, PubMed:29775578). ECS(VHL) mediates
CC the ubiquitination of hypoxia-inducible factor (HIF) (PubMed:9122164,
CC PubMed:10973499). A number of ECS complexes (containing either KLHDC2,
CC KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition
CC component) are part of the DesCEND (destruction via C-end degrons)
CC pathway, which recognizes a C-degron located at the extreme C terminus
CC of target proteins, leading to their ubiquitination and degradation
CC (PubMed:26138980, PubMed:29779948, PubMed:29775578). ECS complexes and
CC ARIH1 collaborate in tandem to mediate ubiquitination of target
CC proteins (PubMed:27565346). {ECO:0000269|PubMed:10973499,
CC ECO:0000269|PubMed:11384984, ECO:0000269|PubMed:12609982,
CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:26138980,
CC ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:29775578,
CC ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:9122164}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:26138980, ECO:0000269|PubMed:29775578,
CC ECO:0000269|PubMed:29779948}.
CC -!- SUBUNIT: Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein)
CC E3 ubiquitin-protein ligase complexes formed of CUL2, Elongin BC (ELOB
CC and ELOC), RBX1 and a variable substrate-specific adapter
CC (PubMed:9122164, PubMed:10973499, PubMed:11384984, PubMed:26138980,
CC PubMed:29779948, PubMed:29775578). Component of the ECS(VHL) or
CC CBC(VHL) complex containing VHL (PubMed:9122164, PubMed:10973499,
CC PubMed:11384984). Component of the ECS(MED8) complex with the probable
CC substrate recognition component MED8 (PubMed:12149480). Component of
CC multiple ECS complexes part of the DesCEND (destruction via C-end
CC degrons) pathway, which contain either KLHDC2, KLHDC3, KLHDC10, APPBP2,
CC FEM1A, FEM1B or FEM1C as substrate-recognition component
CC (PubMed:23102700, PubMed:26138980, PubMed:29779948, PubMed:29775578).
CC Component of the ECS(LRR1) complex with the probable substrate
CC recognition component LRR1 (PubMed:15601820). Component of a probable
CC ECS E3 ubiquitin-protein ligase complex containing CUL2, RBX1, ELOB,
CC ELOC and FEM1B (PubMed:15601820). Part of an E3 ubiquitin-protein
CC ligase complex including ZYG11B, CUL2 and Elongin BC (PubMed:17304241).
CC Part of an E3 ubiquitin-protein ligase complex including ZER1, CUL2 and
CC Elongin BC (PubMed:17304241). Interacts with RBX1, RNF7, FEM1B and
CC TIP120A/CAND1 (PubMed:10230407, PubMed:12609982). Found in a complex
CC composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2 (PubMed:22286099).
CC Interacts (when neddylated) with ARIH1; leading to activate the E3
CC ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346). Interacts
CC (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and
CC DCUN1D5; these interactions promote the cullin neddylation
CC (PubMed:23401859, PubMed:23201271, PubMed:24192928, PubMed:26906416).
CC Component of VCB (elongins BC/CUL2/VHL) complex that contains at least
CC DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and
CC consequently cullin ring ligase (CRL) substrates polyubiquitylation
CC (PubMed:23401859). {ECO:0000269|PubMed:10230407,
CC ECO:0000269|PubMed:10973499, ECO:0000269|PubMed:11384984,
CC ECO:0000269|PubMed:12149480, ECO:0000269|PubMed:12609982,
CC ECO:0000269|PubMed:15601820, ECO:0000269|PubMed:17304241,
CC ECO:0000269|PubMed:22286099, ECO:0000269|PubMed:23102700,
CC ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:23401859,
CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:24192928,
CC ECO:0000269|PubMed:26138980, ECO:0000269|PubMed:26906416,
CC ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:29775578,
CC ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:9122164}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human respiratory
CC syncytial virus (HRSV) protein NS1. {ECO:0000269|PubMed:17251292}.
CC -!- INTERACTION:
CC Q13617; Q86VP6: CAND1; NbExp=3; IntAct=EBI-456179, EBI-456077;
CC Q13617; Q8N668: COMMD1; NbExp=6; IntAct=EBI-456179, EBI-1550112;
CC Q13617; Q15369: ELOC; NbExp=10; IntAct=EBI-456179, EBI-301231;
CC Q13617; P08238: HSP90AB1; NbExp=2; IntAct=EBI-456179, EBI-352572;
CC Q13617; Q9BQ90: KLHDC3; NbExp=8; IntAct=EBI-456179, EBI-1055396;
CC Q13617; Q15048: LRRC14; NbExp=6; IntAct=EBI-456179, EBI-2510124;
CC Q13617; P62877: RBX1; NbExp=8; IntAct=EBI-456179, EBI-398523;
CC Q13617; O94888: UBXN7; NbExp=20; IntAct=EBI-456179, EBI-1993627;
CC Q13617; P40337: VHL; NbExp=16; IntAct=EBI-456179, EBI-301246;
CC Q13617; Q9C0D3: ZYG11B; NbExp=4; IntAct=EBI-456179, EBI-1811414;
CC Q13617; P12504: vif; Xeno; NbExp=6; IntAct=EBI-456179, EBI-779991;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13617-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13617-2; Sequence=VSP_044498;
CC -!- PTM: Neddylated; which enhances the ubiquitination activity of ECS
CC (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase
CC complexes. CBC(VHL) complex formation seems to promote neddylation.
CC Deneddylated via its interaction with the COP9 signalosome (CSN)
CC complex (By similarity). {ECO:0000250|UniProtKB:Q9D4H8,
CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346}.
CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00330}.
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DR EMBL; U83410; AAC51190.1; -; mRNA.
DR EMBL; AF126404; AAD23581.1; -; mRNA.
DR EMBL; AK095217; BAG53007.1; -; mRNA.
DR EMBL; AK300491; BAH13294.1; -; mRNA.
DR EMBL; AL392046; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471072; EAW85924.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW85925.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW85926.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW85927.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW85928.1; -; Genomic_DNA.
DR EMBL; BC009591; AAH09591.1; -; mRNA.
DR EMBL; BC110901; AAI10902.1; -; mRNA.
DR EMBL; U58088; AAC50545.1; -; mRNA.
DR CCDS; CCDS55709.1; -. [Q13617-2]
DR CCDS; CCDS7179.1; -. [Q13617-1]
DR RefSeq; NP_001185706.1; NM_001198777.1. [Q13617-1]
DR RefSeq; NP_001185707.1; NM_001198778.1. [Q13617-2]
DR RefSeq; NP_001185708.1; NM_001198779.1.
DR RefSeq; NP_003582.2; NM_003591.3. [Q13617-1]
DR RefSeq; XP_011518049.1; XM_011519747.1. [Q13617-1]
DR PDB; 4WQO; X-ray; 3.20 A; D=1-163.
DR PDB; 5N4W; X-ray; 3.90 A; A=1-745.
DR PDB; 6R6H; EM; 8.40 A; O=1-745.
DR PDB; 6R7F; EM; 8.20 A; O=1-745.
DR PDB; 6R7H; EM; 8.80 A; O=1-654.
DR PDB; 6R7I; EM; 5.90 A; O=1-745.
DR PDB; 6R7N; EM; 6.50 A; O=1-745.
DR PDB; 7PLO; EM; 2.80 A; S=1-745.
DR PDBsum; 4WQO; -.
DR PDBsum; 5N4W; -.
DR PDBsum; 6R6H; -.
DR PDBsum; 6R7F; -.
DR PDBsum; 6R7H; -.
DR PDBsum; 6R7I; -.
DR PDBsum; 6R7N; -.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; Q13617; -.
DR SMR; Q13617; -.
DR BioGRID; 114031; 549.
DR CORUM; Q13617; -.
DR DIP; DIP-31612N; -.
DR IntAct; Q13617; 381.
DR MINT; Q13617; -.
DR STRING; 9606.ENSP00000444856; -.
DR GlyGen; Q13617; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13617; -.
DR MetOSite; Q13617; -.
DR PhosphoSitePlus; Q13617; -.
DR SwissPalm; Q13617; -.
DR BioMuta; CUL2; -.
DR DMDM; 19863260; -.
DR EPD; Q13617; -.
DR jPOST; Q13617; -.
DR MassIVE; Q13617; -.
DR MaxQB; Q13617; -.
DR PaxDb; Q13617; -.
DR PeptideAtlas; Q13617; -.
DR PRIDE; Q13617; -.
DR ProteomicsDB; 32423; -.
DR ProteomicsDB; 59605; -. [Q13617-1]
DR Antibodypedia; 3631; 502 antibodies from 42 providers.
DR DNASU; 8453; -.
DR Ensembl; ENST00000374748.5; ENSP00000363880.1; ENSG00000108094.17. [Q13617-1]
DR Ensembl; ENST00000374749.8; ENSP00000363881.3; ENSG00000108094.17. [Q13617-1]
DR Ensembl; ENST00000374751.7; ENSP00000363883.3; ENSG00000108094.17. [Q13617-1]
DR Ensembl; ENST00000421317.5; ENSP00000414095.2; ENSG00000108094.17. [Q13617-2]
DR Ensembl; ENST00000673636.2; ENSP00000501215.1; ENSG00000108094.17. [Q13617-1]
DR Ensembl; ENST00000690393.1; ENSP00000510691.1; ENSG00000108094.17. [Q13617-1]
DR Ensembl; ENST00000691974.1; ENSP00000508908.1; ENSG00000108094.17. [Q13617-1]
DR GeneID; 8453; -.
DR KEGG; hsa:8453; -.
DR MANE-Select; ENST00000374749.8; ENSP00000363881.3; NM_003591.4; NP_003582.2.
DR UCSC; uc001ixv.4; human. [Q13617-1]
DR CTD; 8453; -.
DR DisGeNET; 8453; -.
DR GeneCards; CUL2; -.
DR HGNC; HGNC:2552; CUL2.
DR HPA; ENSG00000108094; Low tissue specificity.
DR MIM; 603135; gene.
DR neXtProt; NX_Q13617; -.
DR OpenTargets; ENSG00000108094; -.
DR PharmGKB; PA27048; -.
DR VEuPathDB; HostDB:ENSG00000108094; -.
DR eggNOG; KOG2284; Eukaryota.
DR GeneTree; ENSGT00940000154926; -.
DR HOGENOM; CLU_004747_6_1_1; -.
DR InParanoid; Q13617; -.
DR OrthoDB; 1040292at2759; -.
DR PhylomeDB; Q13617; -.
DR TreeFam; TF101152; -.
DR BRENDA; 2.3.2.32; 2681.
DR PathwayCommons; Q13617; -.
DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q13617; -.
DR SIGNOR; Q13617; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 8453; 454 hits in 1144 CRISPR screens.
DR ChiTaRS; CUL2; human.
DR GeneWiki; CUL2; -.
DR GenomeRNAi; 8453; -.
DR Pharos; Q13617; Tbio.
DR PRO; PR:Q13617; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q13617; protein.
DR Bgee; ENSG00000108094; Expressed in sperm and 196 other tissues.
DR ExpressionAtlas; Q13617; baseline and differential.
DR Genevisible; Q13617; HS.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0030891; C:VCB complex; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:ProtInc.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
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; Host-virus interaction;
KW Isopeptide bond; Phosphoprotein; Reference proteome; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..745
FT /note="Cullin-2"
FT /id="PRO_0000119790"
FT MOD_RES 393
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 661
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 689
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in NEDD8)"
FT /evidence="ECO:0000269|PubMed:10092517,
FT ECO:0000269|PubMed:10597293"
FT VAR_SEQ 1
FT /note="M -> MYRVTWSTFWLRFQHYTCTM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044498"
FT VARIANT 109
FT /note="N -> S"
FT /evidence="ECO:0000269|PubMed:10092517,
FT ECO:0000269|PubMed:9122164"
FT /id="VAR_011374"
FT MUTAGEN 621
FT /note="K->R: No effect on conjugation with NEDD8."
FT /evidence="ECO:0000269|PubMed:10092517"
FT MUTAGEN 689
FT /note="K->R: Loss of conjugation with NEDD8."
FT /evidence="ECO:0000269|PubMed:10092517"
FT MUTAGEN 719
FT /note="K->R: No effect on conjugation with NEDD8."
FT /evidence="ECO:0000269|PubMed:10092517"
FT CONFLICT 20
FT /note="T -> I (in Ref. 3; BAH13294)"
FT /evidence="ECO:0000305"
FT CONFLICT 95..98
FT /note="SKGA -> IRHE (in Ref. 7; AAC50545)"
FT /evidence="ECO:0000305"
FT CONFLICT 681
FT /note="Q -> H (in Ref. 7; AAC50545)"
FT /evidence="ECO:0000305"
FT HELIX 10..25
FT /evidence="ECO:0007829|PDB:4WQO"
FT HELIX 32..47
FT /evidence="ECO:0007829|PDB:4WQO"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:4WQO"
FT HELIX 54..77
FT /evidence="ECO:0007829|PDB:4WQO"
FT HELIX 85..104
FT /evidence="ECO:0007829|PDB:4WQO"
FT HELIX 106..112
FT /evidence="ECO:0007829|PDB:4WQO"
FT HELIX 139..156
FT /evidence="ECO:0007829|PDB:4WQO"
SQ SEQUENCE 745 AA; 86983 MW; 30647248F671AB0E CRC64;
MSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP EPLGERLYTE
TKIFLENHVR HLHKRVLESE EQVLVMYHRY WEEYSKGADY MDCLYRYLNT QFIKKNKLTE
ADLQYGYGGV DMNEPLMEIG ELALDMWRKL MVEPLQAILI RMLLREIKND RGGEDPNQKV
IHGVINSFVH VEQYKKKFPL KFYQEIFESP FLTETGEYYK QEASNLLQES NCSQYMEKVL
GRLKDEEIRC RKYLHPSSYT KVIHECQQRM VADHLQFLHA ECHNIIRQEK KNDMANMYVL
LRAVSTGLPH MIQELQNHIH DEGLRATSNL TQENMPTLFV ESVLEVHGKF VQLINTVLNG
DQHFMSALDK ALTSVVNYRE PKSVCKAPEL LAKYCDNLLK KSAKGMTENE VEDRLTSFIT
VFKYIDDKDV FQKFYARMLA KRLIHGLSMS MDSEEAMINK LKQACGYEFT SKLHRMYTDM
SVSADLNNKF NNFIKNQDTV IDLGISFQIY VLQAGAWPLT QAPSSTFAIP QELEKSVQMF
ELFYSQHFSG RKLTWLHYLC TGEVKMNYLG KPYVAMVTTY QMAVLLAFNN SETVSYKELQ
DSTQMNEKEL TKTIKSLLDV KMINHDSEKE DIDAESSFSL NMNFSSKRTK FKITTSMQKD
TPQEMEQTRS AVDEDRKMYL QAAIVRIMKA RKVLRHNALI QEVISQSRAR FNPSISMIKK
CIEVLIDKQY IERSQASADE YSYVA
