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 13-FEB-2019, entry version 147. DE RecName: Full=Cullin-2; DE Short=CUL-2; GN Name=Cul2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA 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 RT project: 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 RT phase 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., RA Stearman R., Klausner R.D., Malik S., Lane W.S., Sorokina I., RA Roeder R.G., Conaway J.W., Conaway R.C.; RT "Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein RT that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin RT 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, RC Pancreas, 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 RT expression."; RL Cell 143:1174-1189(2010). RN [6] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-393, AND IDENTIFICATION BY RP MASS 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., RA Zhang Y., 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 CC (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase CC complexes, which mediate the ubiquitination of target proteins. CC ECS complexes and ARIH1 collaborate in tandem to mediate CC ubiquitination of target proteins (By similarity). May serve as a CC rigid scaffold in the complex and may contribute to catalysis CC through positioning of the substrate and the ubiquitin-conjugating CC enzyme. The E3 ubiquitin-protein ligase activity of the complex is CC dependent on the neddylation of the cullin subunit and is CC inhibited by the association of the deneddylated cullin subunit CC with TIP120A/CAND1 (By similarity). The functional specificity of CC the ECS complex depends on the substrate recognition component. CC ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor CC (HIF) (By similarity). {ECO:0000250|UniProtKB:Q13617}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box CC protein) E3 ubiquitin-protein ligase complexes formed of CUL2, CC Elongin BC (ELOB and ELOC), RBX1 and a variable substrate-specific CC adapter. Component of the ECS(VHL) or CBC(VHL) complex containing CC VHL. Component of the ECS(MED8) complex with the probable CC substrate recognition component MED8. Component of the ECS(LRR1) CC complex with the probable substrate recognition component LRR1. CC Component of a probable ECS E3 ubiquitin-protein ligase complex CC containing CUL2, RBX1, ELOB, ELOC and FEM1B. Part of an E3 CC ubiquitin-protein ligase complex including ZYG11B, CUL2 and CC Elongin BC. Part of an E3 ubiquitin-protein ligase complex CC including ZYG11BL, CUL2 and Elongin BC. Interacts with RBX1, RNF7, CC FEM1B and TIP120A/CAND1. Interacts with COPS2, and MED8. Found in CC a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. CC Interacts with KLHDC10; which may be an E3 ubiquitin ligase CC complex substrate recognition component. Interacts (when CC neddylated) with ARIH1; leading to activate the E3 ligase activity CC of ARIH1 (By similarity). {ECO:0000250|UniProtKB:Q13617, CC ECO:0000269|PubMed:11967155, ECO:0000269|PubMed:12149480}. 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 CC (By similarity). Deneddylated via its interaction with the COP9 CC signalosome (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 UniGene; Mm.291707; -. DR UniGene; Mm.443148; -. DR ProteinModelPortal; Q9D4H8; -. DR SMR; Q9D4H8; -. DR BioGrid; 214895; 7. DR IntAct; Q9D4H8; 7. DR MINT; Q9D4H8; -. DR STRING; 10090.ENSMUSP00000125403; -. DR iPTMnet; Q9D4H8; -. DR PhosphoSitePlus; Q9D4H8; -. DR EPD; Q9D4H8; -. DR PaxDb; Q9D4H8; -. DR PeptideAtlas; Q9D4H8; -. DR PRIDE; Q9D4H8; -. 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 eggNOG; COG5647; LUCA. DR GeneTree; ENSGT00940000154926; -. DR HOGENOM; HOG000176713; -. DR HOVERGEN; HBG106177; -. DR InParanoid; Q9D4H8; -. DR KO; K03870; -. DR OMA; MPTQFVE; -. DR OrthoDB; 1377709at2759; -. 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 PRO; PR:Q9D4H8; -. DR Proteomes; UP000000589; Chromosome 18. DR Bgee; ENSMUSG00000024231; Expressed in 295 organ(s), highest expression level in embryo. 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:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR GO; GO:0030163; P:protein catabolic process; IMP:MGI. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR GO; GO:0006511; P: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; Complete proteome; Isopeptide bond; KW Phosphoprotein; Reference proteome; Ubl conjugation; KW Ubl conjugation pathway. FT CHAIN 1 745 Cullin-2. FT /FTId=PRO_0000119791. FT MOD_RES 393 393 N6-acetyllysine. FT {ECO:0000244|PubMed:23806337}. FT MOD_RES 661 661 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q13617}. FT CROSSLNK 689 689 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in NEDD8). FT {ECO:0000250|UniProtKB:Q13616}. FT VAR_SEQ 664 702 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16141072}. FT /FTId=VSP_008823. FT CONFLICT 612 612 K -> R (in Ref. 1; BAB30283). FT {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 //