ID CUL2_MOUSE Reviewed; 745 AA. AC Q9D4H8; Q3TUR8; DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 07-NOV-2003, sequence version 2. DT 07-APR-2021, entry version 158. DE RecName: Full=Cullin-2; DE Short=CUL-2; GN Name=Cul2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6J; TISSUE=Testis; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6J, and Czech II; TISSUE=Mammary tumor; 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 [3] RP INTERACTION WITH COPS2. RX PubMed=11967155; DOI=10.1016/s0960-9822(02)00791-1; RA Yang X., Menon S., Lykke-Andersen K., Tsuge T., Xiao D., Wang X., RA Rodriguez-Suarez R.J., Zhang H., Wei N.; RT "The COP9 signalosome inhibits p27(kip1) degradation and impedes G1-S phase RT progression via deneddylation of SCF Cul1."; RL Curr. Biol. 12:667-672(2002). RN [4] RP INTERACTION 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 [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, RC Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [6] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-393, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). 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. ECS complexes and ARIH1 CC collaborate in tandem to mediate ubiquitination of target proteins (By CC similarity). May serve as a rigid scaffold in the complex and may CC contribute to catalysis through positioning of the substrate and the CC ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity CC of the complex is dependent on the neddylation of the cullin subunit CC and is inhibited by the association of the deneddylated cullin subunit CC with TIP120A/CAND1 (By similarity). The functional specificity of the CC ECS complex depends on the substrate recognition component. ECS(VHL) CC mediates the ubiquitination of hypoxia-inducible factor (HIF) (By CC similarity). {ECO:0000250|UniProtKB:Q13617}. CC -!- PATHWAY: Protein modification; protein ubiquitination. 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. Component of CC the ECS(VHL) or CBC(VHL) complex containing VHL. Component of the CC ECS(MED8) complex with the probable substrate recognition component CC MED8. Component of the ECS(LRR1) complex with the probable substrate CC recognition component LRR1. Component of a probable ECS E3 ubiquitin- CC protein ligase complex containing CUL2, RBX1, ELOB, ELOC and FEM1B. CC Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 CC and Elongin BC. Part of an E3 ubiquitin-protein ligase complex CC including ZER1, CUL2 and Elongin BC. Interacts with RBX1, RNF7, FEM1B CC and TIP120A/CAND1. Interacts with COPS2, and MED8. Found in a complex CC composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with CC KLHDC10; which may be an E3 ubiquitin ligase complex substrate CC recognition component. Interacts (when neddylated) with ARIH1; leading CC to activate the E3 ligase activity of ARIH1. Interacts (unneddylated CC form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these CC interactions promote the cullin neddylation. Component of VCB (elongins CC BC/CUL2/VHL) complex that contains at least DCUN1D1, CUL2 and VHL; this CC complex triggers CUL2 neddylation and consequently cullin ring ligase CC (CRL) substrates polyubiquitylation. {ECO:0000250|UniProtKB:Q13617}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9D4H8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9D4H8-2; Sequence=VSP_008823; 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 (By CC similarity). Deneddylated via its interaction with the COP9 signalosome CC (CSN) complex. {ECO:0000250|UniProtKB:Q13617}. CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE- CC ProRule:PRU00330}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK016520; BAB30283.1; -; mRNA. DR EMBL; AK160597; BAE35903.1; -; mRNA. DR EMBL; BC026779; AAH26779.1; -; mRNA. DR EMBL; BC027428; AAH27428.1; -; mRNA. DR EMBL; BC025902; AAH25902.1; -; mRNA. DR CCDS; CCDS29032.2; -. [Q9D4H8-1] DR RefSeq; NP_083678.2; NM_029402.3. [Q9D4H8-1] DR RefSeq; XP_006526337.1; XM_006526274.3. DR RefSeq; XP_006526338.1; XM_006526275.3. [Q9D4H8-1] DR SMR; Q9D4H8; -. DR BioGRID; 214895; 40. DR IntAct; Q9D4H8; 7. DR MINT; Q9D4H8; -. DR STRING; 10090.ENSMUSP00000125403; -. DR iPTMnet; Q9D4H8; -. DR PhosphoSitePlus; Q9D4H8; -. DR EPD; Q9D4H8; -. DR jPOST; Q9D4H8; -. DR PaxDb; Q9D4H8; -. DR PeptideAtlas; Q9D4H8; -. DR PRIDE; Q9D4H8; -. DR ProteomicsDB; 279209; -. [Q9D4H8-1] DR ProteomicsDB; 279210; -. [Q9D4H8-2] DR Antibodypedia; 3631; 481 antibodies. DR Ensembl; ENSMUST00000025073; ENSMUSP00000025073; ENSMUSG00000024231. [Q9D4H8-2] DR Ensembl; ENSMUST00000162301; ENSMUSP00000125403; ENSMUSG00000024231. [Q9D4H8-1] DR GeneID; 71745; -. DR KEGG; mmu:71745; -. DR UCSC; uc008dxz.2; mouse. [Q9D4H8-2] DR UCSC; uc008dya.2; mouse. [Q9D4H8-1] DR CTD; 8453; -. DR MGI; MGI:1918995; Cul2. DR eggNOG; KOG2284; Eukaryota. DR GeneTree; ENSGT00940000154926; -. DR HOGENOM; CLU_004747_6_1_1; -. DR InParanoid; Q9D4H8; -. DR OMA; FEGPMLE; -. DR OrthoDB; 1040292at2759; -. DR PhylomeDB; Q9D4H8; -. DR TreeFam; TF101152; -. DR Reactome; R-MMU-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha. DR Reactome; R-MMU-8951664; Neddylation. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 71745; 21 hits in 52 CRISPR screens. DR ChiTaRS; Cul2; mouse. DR PRO; PR:Q9D4H8; -. DR Proteomes; UP000000589; Chromosome 18. DR RNAct; Q9D4H8; protein. DR Bgee; ENSMUSG00000024231; Expressed in epiblast (generic) and 310 other tissues. DR ExpressionAtlas; Q9D4H8; baseline and differential. DR Genevisible; Q9D4H8; MM. DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:MGI. DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central. DR GO; GO:0005730; C:nucleolus; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central. DR GO; GO:0030891; C:VCB complex; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central. DR GO; GO:0030163; P:protein catabolic process; IMP:MGI. 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; 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 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 Acetylation; Alternative splicing; Isopeptide bond; Phosphoprotein; KW Reference proteome; Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..745 FT /note="Cullin-2" FT /id="PRO_0000119791" FT MOD_RES 393 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 661 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q13617" FT CROSSLNK 689 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in NEDD8)" FT /evidence="ECO:0000250|UniProtKB:Q13616" FT VAR_SEQ 664..702 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16141072" FT /id="VSP_008823" FT CONFLICT 612 FT /note="K -> R (in Ref. 1; BAB30283)" FT /evidence="ECO:0000305" SQ SEQUENCE 745 AA; 86877 MW; 311C05CC262692E0 CRC64; MSLKPRVVDF DETWNKLLTT IKAVVMLEYV ERATWNDRFS DIYALCVAYP EPLGERLYAE TKIFLESHVR HLYKRVLESE EQVLVMYHRY WEEYSKGADY MDCLYRYLNT QYIKKNKLTE ADIQYGYGGV DMNEPLMEIG ELALDMWRKL MVEPLQNILI RMLLREIKND RGGEDPNQKV IHGVINSFVH VEQYKKKFPL KFYQGIFVSP FLTETGEYYK QEASNLLQES NCSQYMEKVL GRLKDEEIRC RKYLHPSSYT KVIHECQQRM VADHLQFLHS ECHSIIQQER KNDMANMYVL LRAVSSGLPH MIEELQKHIH DEGLRATSNL TQEHMPTLFV ESVLEVHGKF VQLINTVLNG DQHFMSALDK ALTSVVNYRE PKSVCKAPEL LAKYCDNLLK KSAKGMTENE VEDKLTSFIT VFKYIDDKDV FQKFYARMLA KRLIHGLSMS MDSEEAMINK LKQACGYEFT SKLHRMYTDM SVSADLNNKF NNFIRNQDTV IDLGISFQIY VLQAGAWPLT QAPSSTFAIP QELEKSVQMF ELFYSQHFSG RKLTWLHYLC TGEVKMNYLG KPYVAMVTTY QMAVLLAFNN SETVSYKELQ DSTQMNEKEL TKTIKSLLDV KMINHDSEKE DIDAESSFSL NMSFSSKRTK FKITTSMQKD TPQELEQTRS AVDEDRKMYL QAAIVRIMKA RKVLRHNALI QEVISQSRAR FNPSISMIKK CIEVLIDKQY IERSQASADE YSYVA //