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 03-APR-2013, entry version 96. 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; Sciurognathi; 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284 AND TYR-394, AND RP MASS SPECTROMETRY. RC TISSUE=Liver; RX PubMed=17203969; DOI=10.1021/pr0604155; RA Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R.; RT "Protein phosphorylation and expression profiling by Yin-yang RT multidimensional liquid chromatography (Yin-yang MDLC) mass RT spectrometry."; RL J. Proteome Res. 6:250-262(2007). 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 May serve as a rigid scaffold in the complex and may contribute to CC catalysis through positioning of the substrate and the ubiquitin- CC conjugating enzyme. The E3 ubiquitin-protein ligase activity of CC the complex is dependent on the neddylation of the cullin subunit CC and is inhibited by the association of the deneddylated cullin CC subunit with TIP120A/CAND1 (By similarity). The functional CC specificity of the ECS complex depends on the substrate CC recognition component. ECS(VHL) mediates the ubiquitination of CC hypoxia-inducible factor (HIF) (By similarity). 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 (TCEB1 and TCEB2), RBX1 and a variable substrate- CC specific adapter. Component of the ECS(VHL) or CBC(VHL) complex CC containing VHL. Component of the ECS(MED8) complex with the CC probable substrate recognition component MED8 (By similarity). CC Component of the ECS(LRR1) complex with the probable substrate CC recognition component LRR1. Component of a probable ECS E3 CC ubiquitin-protein ligase complex containing CUL2, RBX1, TCEB1, CC TCEB2 and FEM1B. Part of an E3 ubiquitin-protein ligase complex CC including ZYG11B, CUL2 and Elongin BC. Part of an E3 ubiquitin- CC protein ligase complex including ZYG11BL, CUL2 and Elongin BC. CC Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1 (By CC similarity). Interacts with COPS2, and MED8. Found in a complex CC composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2 (By CC similarity). 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: CBC(VHL) complex formation seems to promote neddylation. CC Deneddylated via its interaction with the COP9 signalosome (CSN) CC complex. CC -!- SIMILARITY: Belongs to the cullin family. 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 IPI; IPI00387216; -. DR IPI; IPI00387217; -. DR RefSeq; NP_083678.2; NM_029402.3. DR UniGene; Mm.291707; -. DR UniGene; Mm.443148; -. DR ProteinModelPortal; Q9D4H8; -. DR SMR; Q9D4H8; 10-745. DR IntAct; Q9D4H8; 4. DR PhosphoSite; Q9D4H8; -. DR PaxDb; Q9D4H8; -. DR PRIDE; Q9D4H8; -. DR Ensembl; ENSMUST00000025073; ENSMUSP00000025073; ENSMUSG00000024231. DR Ensembl; ENSMUST00000162301; ENSMUSP00000125403; ENSMUSG00000024231. DR GeneID; 71745; -. DR KEGG; mmu:71745; -. DR UCSC; uc008dxz.2; mouse. DR CTD; 8453; -. DR MGI; MGI:1918995; Cul2. DR eggNOG; COG5647; -. DR GeneTree; ENSGT00550000074299; -. DR HOGENOM; HOG000176713; -. DR HOVERGEN; HBG106177; -. DR InParanoid; Q9D4H8; -. DR KO; K03870; -. DR OMA; VMLDYVE; -. DR OrthoDB; EOG4Z0B51; -. DR UniPathway; UPA00143; -. DR NextBio; 334387; -. DR ArrayExpress; Q9D4H8; -. DR Bgee; Q9D4H8; -. DR CleanEx; MM_CUL2; -. DR Genevestigator; Q9D4H8; -. DR GermOnline; ENSMUSG00000024231; Mus musculus. DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IEA:Compara. DR GO; GO:0030163; P:protein catabolic process; IMP:MGI. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. DR Gene3D; 1.10.10.10; -; 2. DR InterPro; IPR016157; Cullin_CS. DR InterPro; IPR016158; Cullin_homology. DR InterPro; IPR001373; Cullin_N. DR InterPro; IPR019559; Cullin_neddylation_domain. DR InterPro; IPR016159; Cullin_repeat-like_dom. DR InterPro; IPR011991; WHTH_trsnscrt_rep_DNA-bd_dom. 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; 1. DR SUPFAM; SSF74788; Cullin_repeat-like; 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 284 284 Phosphoserine. FT MOD_RES 393 393 N6-acetyllysine (By similarity). FT MOD_RES 394 394 Phosphotyrosine. FT MOD_RES 661 661 Phosphothreonine (By similarity). FT CROSSLNK 689 689 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in NEDD8) (By FT similarity). FT VAR_SEQ 664 702 Missing (in isoform 2). FT /FTId=VSP_008823. FT CONFLICT 612 612 K -> R (in Ref. 1; BAB30283). 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 //