ID CUL5_HUMAN Reviewed; 780 AA. AC Q93034; A8K960; O14766; Q9BZC6; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 27-MAR-2024, entry version 205. DE RecName: Full=Cullin-5 {ECO:0000305}; DE Short=CUL-5 {ECO:0000305}; DE AltName: Full=Vasopressin-activated calcium-mobilizing receptor 1 {ECO:0000303|PubMed:9037604}; DE Short=VACM-1 {ECO:0000303|PubMed:9037604}; GN Name=CUL5 {ECO:0000303|PubMed:10230407, ECO:0000312|HGNC:HGNC:2556}; GN Synonyms=VACM1 {ECO:0000303|PubMed:9037604}; 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], AND FUNCTION. RX PubMed=9037604; DOI=10.1101/gr.7.1.71; RA Byrd P.J., Stankovic T., McConville C.M., Smith A.D., Cooper P.R., RA Taylor A.M.R.; RT "Identification and analysis of expression of human VACM-1, a cullin gene RT family member located on chromosome 11q22-23."; RL Genome Res. 7:71-75(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Longo K.A., North W.G., Du J., Fay M.J.; RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Testis; RA Kanaya K., Kamitani T.; RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; 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 [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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; 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 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 [8] 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 [9] RP FUNCTION, IDENTIFICATION IN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX WITH RP LRRC41, IDENTIFICATION IN A COMPLEX WITH ELOA, IDENTIFICATION IN A COMPLEX RP WITH SOCS1, AND IDENTIFICATION IN A COMPLEX WITH WSB1. 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 [10] RP FUNCTION (MICROBIAL INFECTION), IDENTIFICATION IN COMPLEX WITH HUMAN RP ADENOVIRUS 5 PROTEINS E1B-55K AND E4-ORF6 (MICROBIAL INFECTION), AND RP NEDDYLATION. RX PubMed=12186903; DOI=10.1128/jvi.76.18.9194-9206.2002; RA Harada J.N., Shevchenko A., Shevchenko A., Pallas D.C., Berk A.J.; RT "Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to RT ubiquitination machinery."; RL J. Virol. 76:9194-9206(2002). RN [11] RP INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION). RX PubMed=15574592; DOI=10.1101/gad.1249904; RA Mehle A., Goncalves J., Santa-Marta M., McPike M., Gabuzda D.; RT "Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif- RT Cul5 complex that promotes APOBEC3G degradation."; RL Genes Dev. 18:2861-2866(2004). RN [12] RP FUNCTION, IDENTIFICATION IN THE ECS(LRRC41) COMPLEX, IDENTIFICATION IN THE RP ECS(SOCS3) COMPLEX, IDENTIFICATION IN THE ECS(SPSB1) COMPLEX, RP IDENTIFICATION IN THE ECS(SPSB2) COMPLEX, IDENTIFICATION IN THE ECS(SPSB4) RP COMPLEX, IDENTIFICATION IN THE ECS(RAB40C) COMPLEX, IDENTIFICATION IN THE RP ECS(WSB1) COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION RP WITH LRRC41; SOCS3; SPSB1; SPSB2; SPSB4; WSB1 AND RAB40C. 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 [13] RP INTERACTION WITH ASB1; ASB2; ASB6; ASB7 AND ASB12. RX PubMed=16325183; DOI=10.1016/j.febslet.2005.11.016; RA Kohroki J., Nishiyama T., Nakamura T., Masuho Y.; RT "ASB proteins interact with cullin5 and Rbx2 to form E3 ubiquitin ligase RT complexes."; RL FEBS Lett. 579:6796-6802(2005). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210, 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 [15] RP FUNCTION, AND IDENTIFICATION IN COMPLEX WITH ELOA; ELOB; ELOC AND RBX1. RX PubMed=19920177; DOI=10.1073/pnas.0907052106; RA Harreman M., Taschner M., Sigurdsson S., Anindya R., Reid J., Somesh B., RA Kong S.E., Banks C.A., Conaway R.C., Conaway J.W., Svejstrup J.Q.; RT "Distinct ubiquitin ligases act sequentially for RNA polymerase II RT polyubiquitylation."; RL Proc. Natl. Acad. Sci. U.S.A. 106:20705-20710(2009). RN [16] 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 [17] RP INTERACTION WITH ASB2. RX PubMed=21119685; DOI=10.1038/cr.2010.165; RA Nie L., Zhao Y., Wu W., Yang Y.Z., Wang H.C., Sun X.H.; RT "Notch-induced Asb2 expression promotes protein ubiquitination by forming RT non-canonical E3 ligase complexes."; RL Cell Res. 21:754-769(2011). RN [18] RP INTERACTION WITH NOS2. RX PubMed=21199876; DOI=10.1074/jbc.m110.190678; RA Nishiya T., Matsumoto K., Maekawa S., Kajita E., Horinouchi T., RA Fujimuro M., Ogasawara K., Uehara T., Miwa S.; RT "Regulation of inducible nitric-oxide synthase by the SPRY domain- and SOCS RT box-containing proteins."; RL J. Biol. Chem. 286:9009-9019(2011). RN [19] RP INTERACTION WITH HERPES VIRUS 8 PROTEIN LANA1 (MICROBIAL INFECTION). RX PubMed=21697472; DOI=10.1128/jvi.00733-11; RA Li X., Liang D., Lin X., Robertson E.S., Lan K.; RT "Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear RT antigen reduces interleukin-8 expression in endothelial cells and impairs RT neutrophil chemotaxis by degrading nuclear p65."; RL J. Virol. 85:8606-8615(2011). RN [20] RP INTERACTION WITH ARIH2, 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-34, 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 [22] 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 [23] RP INTERACTION WITH MOLLUSCUM CONTAGIOSUM VIRUS PROTEIN MC132 (MICROBIAL RP INFECTION). RX PubMed=26041281; DOI=10.1128/jvi.00799-15; RA Brady G., Haas D.A., Farrell P.J., Pichlmair A., Bowie A.G.; RT "Poxvirus protein MC132 from molluscum contagiosum virus inhibits NF-B RT activation by targeting p65 for degradation."; RL J. Virol. 89:8406-8415(2015). RN [24] 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 [25] RP INTERACTION WITH ERCC6 AND ELOA. RX PubMed=28292928; DOI=10.1074/jbc.c117.777946; RA Weems J.C., Slaughter B.D., Unruh J.R., Boeing S., Hall S.M., McLaird M.B., RA Yasukawa T., Aso T., Svejstrup J.Q., Conaway J.W., Conaway R.C.; RT "Cockayne syndrome B protein regulates recruitment of the Elongin A RT ubiquitin ligase to sites of DNA damage."; RL J. Biol. Chem. 292:6431-6437(2017). RN [26] RP FUNCTION, PATHWAY, AND IDENTIFICATION IN A E3 UBIQUITIN-PROTEIN LIGASE RP COMPLEX CONTAINING KLHDC1. RX PubMed=32200094; DOI=10.1016/j.isci.2020.100970; RA Okumura F., Fujiki Y., Oki N., Osaki K., Nishikimi A., Fukui Y., RA Nakatsukasa K., Kamura T.; RT "Cul5-type ubiquitin ligase KLHDC1 contributes to the elimination of RT truncated SELENOS produced by failed UGA/Sec decoding."; RL IScience 23:100970-100970(2020). RN [27] RP IDENTIFICATION IN A E3 UBIQUITIN-PROTEIN LIGASE COMPLEX CONTAINING PCMTD1. RX PubMed=35486881; DOI=10.1021/acs.biochem.2c00130; RA Warmack R.A., Pang E.Z., Peluso E., Lowenson J.D., Ong J.Y., Torres J.Z., RA Clarke S.G.; RT "Human Protein-l-isoaspartate O-Methyltransferase Domain-Containing Protein RT 1 (PCMTD1) Associates with Cullin-RING Ligase Proteins."; RL Biochemistry 61:879-894(2022). RN [28] RP SUBCELLULAR LOCATION. RX PubMed=35633597; DOI=10.1016/j.dnarep.2022.103343; RA Herlihy A.E., Boeing S., Weems J.C., Walker J., Dirac-Svejstrup A.B., RA Lehner M.H., Conaway R.C., Conaway J.W., Svejstrup J.Q.; RT "UBAP2/UBAP2L regulate UV-induced ubiquitylation of RNA polymerase II and RT are the human orthologues of yeast Def1."; RL DNA Repair 115:103343-103343(2022). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 401-780 IN COMPLEX WITH NEDD8 AND RP RBX1, AND NEDDYLATION AT LYS-724. RX PubMed=18805092; DOI=10.1016/j.cell.2008.07.022; RA Duda D.M., Borg L.A., Scott D.C., Hunt H.W., Hammel M., Schulman B.A.; RT "Structural insights into NEDD8 activation of cullin-RING ligases: RT conformational control of conjugation."; RL Cell 134:995-1006(2008). CC -!- FUNCTION: Core component of multiple SCF-like ECS (Elongin-Cullin 2/5- CC SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate CC the ubiquitination and subsequent proteasomal degradation of target CC proteins (PubMed:11384984, PubMed:15601820). As a scaffold protein may CC contribute to catalysis through positioning of the substrate and the CC ubiquitin-conjugating enzyme (PubMed:11384984, PubMed:15601820). The CC functional specificity of the E3 ubiquitin-protein ligase complex CC depends on the variable substrate recognition component CC (PubMed:11384984, PubMed:15601820). ECS(SOCS1) seems to direct CC ubiquitination of JAK2 (PubMed:11384984). ECS(KLHDC1) complex is part CC of the DesCEND (destruction via C-end degrons) pathway and mediates CC ubiquitination and degradation of truncated SELENOS selenoprotein CC produced by failed UGA/Sec decoding, which ends with a glycine CC (PubMed:32200094). As part of a multisubunit complex composed of CC elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; CC polyubiquitinates monoubiquitinated POLR2A (PubMed:19920177). May form CC a cell surface vasopressin receptor (PubMed:9037604). CC {ECO:0000269|PubMed:11384984, ECO:0000269|PubMed:15601820, CC ECO:0000269|PubMed:19920177, ECO:0000269|PubMed:32200094, CC ECO:0000269|PubMed:9037604}. CC -!- FUNCTION: (Microbial infection) Seems to be involved in proteasomal CC degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. CC {ECO:0000269|PubMed:12186903}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:11384984, ECO:0000269|PubMed:15601820, CC ECO:0000269|PubMed:32200094}. CC -!- SUBUNIT: Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) CC E3 ubiquitin-protein ligase complexes formed of CUL5, Elongin BC (ELOB CC and ELOC), RBX2 and a variable SOCS box domain-containing protein as CC substrate-specific recognition component (PubMed:11384984, CC PubMed:15601820). Component of the probable ECS(LRRC41) complex with CC the substrate recognition component LRRC41 (PubMed:11384984). Component CC of the probable ECS(SOCS1) complex with the substrate recognition CC component SOCS1 (PubMed:11384984). Component of the probable ECS(WSB1) CC complex with the substrate recognition subunit WSB1 (PubMed:15601820). CC Component of the probable ECS(SOCS3) complex with the substrate CC recognition component SOCS3 (PubMed:15601820). Component of the CC probable ECS(SPSB1) complex with the substrate recognition component CC SPSB1 (PubMed:15601820). Component of the probable ECS(SPSB2) complex CC with the substrate recognition component SPSB2 (PubMed:15601820). CC Component of the probable ECS(SPSB4) complex with the substrate CC recognition component SPSB4 (PubMed:15601820). Component of the CC probable ECS(RAB40C) complex with the substrate recognition subunit CC RAB40C (PubMed:15601820). Component of the probable ECS(KLHDC1) complex CC with the substrate recognition component KLHDC1 (PubMed:32200094). May CC also form complexes containing CUL5, elongin BC complex (ELOB and CC ELOC), RBX1 and ELOA (PubMed:11384984, PubMed:19920177). May also form CC complexes containing CUL5, Elongin BC (ELOB and ELOC), RBX1 and VHL CC (PubMed:10230407, PubMed:18805092). Interacts with RNF7/RBX2, LRRC41, CC SOCS3, SPSB1, SPSB2, SPSB4 and RAB40C (PubMed:15601820). Interacts with CC ASB1, ASB2, ASB6, ASB7 and ASB12 (PubMed:16325183, PubMed:21119685). CC Interacts (when neddylated) with ARIH2; leading to activate the E3 CC ligase activity of ARIH1 (PubMed:24076655). Interacts with NOS2 in the CC presence of SPSB1 or SPSB2 or SPSB4 (PubMed:21199876). Interacts with CC ERCC6; the interaction is induced by DNA damaging agents or inhibitors CC of RNA polymerase II elongation (PubMed:28292928). Interacts with ELOA CC (via the BC-box) (PubMed:28292928). Interacts (unneddylated form) with CC DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions CC promote the cullin neddylation (PubMed:23201271, PubMed:26906416). CC Component of the probable ECS(PCMTD1) complex with the substrate CC recognition subunit PCMTD1 (PubMed:35486881). CC {ECO:0000269|PubMed:10230407, ECO:0000269|PubMed:11384984, CC ECO:0000269|PubMed:15601820, ECO:0000269|PubMed:16325183, CC ECO:0000269|PubMed:18805092, ECO:0000269|PubMed:19920177, CC ECO:0000269|PubMed:21199876, ECO:0000269|PubMed:23201271, CC ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:26906416, CC ECO:0000269|PubMed:28292928, ECO:0000269|PubMed:32200094, CC ECO:0000269|PubMed:35486881}. CC -!- SUBUNIT: (Microbial infection) Interacts (via the substrate recognition CC component) with HIV-1 Vif. {ECO:0000269|PubMed:12186903}. CC -!- SUBUNIT: (Microbial infection) Interacts (via the substrate recognition CC component) with human adenovirus 5 proteins E1B-55K and E4-orf6. CC {ECO:0000269|PubMed:12186903}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8 protein CC LANA1; this interaction promotes the degradation of NF-kappa-B CC component RELA. {ECO:0000269|PubMed:21697472}. CC -!- SUBUNIT: (Microbial infection) Interacts with molluscum contagiosum CC virus protein MC132; this interaction promotes the degradation of NF- CC kappa-B component RELA. {ECO:0000269|PubMed:26041281}. CC -!- INTERACTION: CC Q93034; O95376: ARIH2; NbExp=12; IntAct=EBI-1057139, EBI-711158; CC Q93034; Q9Y576: ASB1; NbExp=6; IntAct=EBI-1057139, EBI-2323092; CC Q93034; Q96Q27-2: ASB2; NbExp=3; IntAct=EBI-1057139, EBI-28950233; CC Q93034; Q9NWX5: ASB6; NbExp=9; IntAct=EBI-1057139, EBI-6425205; CC Q93034; Q9H672: ASB7; NbExp=3; IntAct=EBI-1057139, EBI-3916346; CC Q93034; Q9NPC3: CCNB1IP1; NbExp=3; IntAct=EBI-1057139, EBI-745269; CC Q93034; O95273: CCNDBP1; NbExp=4; IntAct=EBI-1057139, EBI-748961; CC Q93034; Q9Y2V7: COG6; NbExp=3; IntAct=EBI-1057139, EBI-3866319; CC Q93034; P04626: ERBB2; NbExp=2; IntAct=EBI-1057139, EBI-641062; CC Q93034; Q08379: GOLGA2; NbExp=3; IntAct=EBI-1057139, EBI-618309; CC Q93034; P42858: HTT; NbExp=10; IntAct=EBI-1057139, EBI-466029; CC Q93034; Q5T7N3: KANK4; NbExp=3; IntAct=EBI-1057139, EBI-9355810; CC Q93034; P62877: RBX1; NbExp=3; IntAct=EBI-1057139, EBI-398523; CC Q93034; Q9UBF6: RNF7; NbExp=8; IntAct=EBI-1057139, EBI-398632; CC Q93034; O14508: SOCS2; NbExp=9; IntAct=EBI-1057139, EBI-617737; CC Q93034; O41974: GAMMAHV.ORF73; Xeno; NbExp=2; IntAct=EBI-1057139, EBI-6933128; CC Q93034; P12504: vif; Xeno; NbExp=11; IntAct=EBI-1057139, EBI-779991; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:35633597}. CC Note=Localizes to sites of DNA damage in a UBAP2 and UBAP2L-dependent CC manner. {ECO:0000269|PubMed:35633597}. CC -!- PTM: Neddylated; which enhances the ubiquitination activity of SCF and CC prevents binding of the inhibitor CAND1. Deneddylated via its CC interaction with the COP9 signalosome (CSN). CC {ECO:0000269|PubMed:10597293, ECO:0000269|PubMed:12186903, CC ECO:0000269|PubMed:18805092, ECO:0000269|PubMed:24076655}. 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; X81882; CAA57465.1; -; mRNA. DR EMBL; AF017061; AAB70253.1; -; mRNA. DR EMBL; AF327710; AAK07472.1; -; mRNA. DR EMBL; AK292575; BAF85264.1; -; mRNA. DR EMBL; CH471065; EAW67102.1; -; Genomic_DNA. DR EMBL; BC063306; AAH63306.1; -; mRNA. DR CCDS; CCDS31668.1; -. DR RefSeq; NP_003469.2; NM_003478.4. DR PDB; 3DPL; X-ray; 2.60 A; C=401-780. DR PDB; 3DQV; X-ray; 3.00 A; C/D=401-780. DR PDB; 4JGH; X-ray; 3.00 A; D=10-386. DR PDB; 4N9F; X-ray; 3.30 A; 3/9/C/I/O/U/V/f/l/r/w/x=12-321. DR PDB; 6V9I; EM; 5.20 A; C=2-780. DR PDB; 7ONI; EM; 3.40 A; C=1-780. DR PDB; 8EI2; X-ray; 2.80 A; A=1-386. DR PDB; 8FVJ; EM; 3.54 A; 2/7=12-320. DR PDBsum; 3DPL; -. DR PDBsum; 3DQV; -. DR PDBsum; 4JGH; -. DR PDBsum; 4N9F; -. DR PDBsum; 6V9I; -. DR PDBsum; 7ONI; -. DR PDBsum; 8EI2; -. DR PDBsum; 8FVJ; -. DR AlphaFoldDB; Q93034; -. DR EMDB; EMD-12995; -. DR EMDB; EMD-27885; -. DR EMDB; EMD-29489; -. DR EMDB; EMD-29490; -. DR SMR; Q93034; -. DR BioGRID; 113743; 561. DR CORUM; Q93034; -. DR DIP; DIP-43696N; -. DR IntAct; Q93034; 374. DR MINT; Q93034; -. DR STRING; 9606.ENSP00000376808; -. DR GlyGen; Q93034; 1 site, 2 O-linked glycans (1 site). DR iPTMnet; Q93034; -. DR PhosphoSitePlus; Q93034; -. DR BioMuta; CUL5; -. DR DMDM; 14917099; -. DR EPD; Q93034; -. DR jPOST; Q93034; -. DR MassIVE; Q93034; -. DR MaxQB; Q93034; -. DR PaxDb; 9606-ENSP00000376808; -. DR PeptideAtlas; Q93034; -. DR ProteomicsDB; 75673; -. DR Pumba; Q93034; -. DR Antibodypedia; 990; 266 antibodies from 36 providers. DR DNASU; 8065; -. DR Ensembl; ENST00000393094.7; ENSP00000376808.2; ENSG00000166266.14. DR Ensembl; ENST00000531427.5; ENSP00000435376.1; ENSG00000166266.14. DR GeneID; 8065; -. DR KEGG; hsa:8065; -. DR MANE-Select; ENST00000393094.7; ENSP00000376808.2; NM_003478.6; NP_003469.2. DR UCSC; uc001pjv.4; human. DR AGR; HGNC:2556; -. DR DisGeNET; 8065; -. DR GeneCards; CUL5; -. DR HGNC; HGNC:2556; CUL5. DR HPA; ENSG00000166266; Low tissue specificity. DR MIM; 601741; gene. DR neXtProt; NX_Q93034; -. DR OpenTargets; ENSG00000166266; -. DR PharmGKB; PA27052; -. DR VEuPathDB; HostDB:ENSG00000166266; -. DR eggNOG; KOG2285; Eukaryota. DR GeneTree; ENSGT00940000156648; -. DR HOGENOM; CLU_004747_5_0_1; -. DR InParanoid; Q93034; -. DR OMA; FNILTCR; -. DR OrthoDB; 5474206at2759; -. DR PhylomeDB; Q93034; -. DR TreeFam; TF105874; -. DR PathwayCommons; Q93034; -. DR Reactome; R-HSA-180585; Vif-mediated degradation of APOBEC3G. DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q93034; -. DR SIGNOR; Q93034; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 8065; 48 hits in 1213 CRISPR screens. DR ChiTaRS; CUL5; human. DR EvolutionaryTrace; Q93034; -. DR GeneWiki; CUL5; -. DR GenomeRNAi; 8065; -. DR Pharos; Q93034; Tbio. DR PRO; PR:Q93034; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q93034; Protein. DR Bgee; ENSG00000166266; Expressed in secondary oocyte and 221 other cell types or tissues. DR ExpressionAtlas; Q93034; baseline and differential. DR GO; GO:0031466; C:Cul5-RING ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central. DR GO; GO:0090734; C:site of DNA damage; IDA:UniProtKB. DR GO; GO:0005262; F:calcium channel activity; TAS:ProtInc. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:Reactome. DR GO; GO:0038128; P:ERBB2 signaling pathway; TAS:Reactome. 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; 1.20.1310.10; Cullin Repeats; 4. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR IDEAL; IID00519; -. 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:SF76; CULLIN-5; 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; Q93034; HS. PE 1: Evidence at protein level; KW 3D-structure; Host-virus interaction; Isopeptide bond; Nucleus; KW Phosphoprotein; Receptor; Reference proteome; Ubl conjugation; KW Ubl conjugation pathway. FT CHAIN 1..780 FT /note="Cullin-5" FT /id="PRO_0000119797" FT MOD_RES 34 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 210 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT CROSSLNK 724 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in NEDD8)" FT /evidence="ECO:0000269|PubMed:18805092" FT CONFLICT 9 FT /note="N -> D (in Ref. 2; AAB70253)" FT /evidence="ECO:0000305" FT CONFLICT 12 FT /note="S -> F (in Ref. 2; AAB70253)" FT /evidence="ECO:0000305" FT CONFLICT 16 FT /note="E -> G (in Ref. 2; AAB70253)" FT /evidence="ECO:0000305" FT CONFLICT 32..34 FT /note="QES -> RDF (in Ref. 2; AAB70253)" FT /evidence="ECO:0000305" FT CONFLICT 38 FT /note="Q -> R (in Ref. 2; AAB70253)" FT /evidence="ECO:0000305" FT CONFLICT 50..52 FT /note="VCL -> FCF (in Ref. 2; AAB70253)" FT /evidence="ECO:0000305" FT CONFLICT 68 FT /note="D -> DF (in Ref. 2; AAB70253)" FT /evidence="ECO:0000305" FT CONFLICT 224 FT /note="Q -> P (in Ref. 1; CAA57465)" FT /evidence="ECO:0000305" FT CONFLICT 648 FT /note="L -> F (in Ref. 1; CAA57465)" FT /evidence="ECO:0000305" FT CONFLICT 651 FT /note="E -> D (in Ref. 1; CAA57465)" FT /evidence="ECO:0000305" FT HELIX 15..30 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 37..53 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 57..81 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 86..103 FT /evidence="ECO:0007829|PDB:4JGH" FT TURN 104..108 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 112..115 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 134..146 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 148..167 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 175..186 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 196..199 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 202..224 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 227..248 FT /evidence="ECO:0007829|PDB:4JGH" FT STRAND 252..254 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 257..269 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 271..273 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 274..277 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 278..280 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 281..286 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 290..300 FT /evidence="ECO:0007829|PDB:4JGH" FT TURN 304..306 FT /evidence="ECO:0007829|PDB:4N9F" FT HELIX 310..333 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 337..357 FT /evidence="ECO:0007829|PDB:4JGH" FT TURN 358..361 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 363..377 FT /evidence="ECO:0007829|PDB:4JGH" FT HELIX 405..416 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 417..419 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 420..423 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 427..438 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 439..443 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 447..463 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 470..482 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 487..513 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 523..525 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 526..532 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 533..536 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 549..552 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 555..563 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 566..573 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 575..577 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 579..585 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 590..596 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 597..603 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 604..606 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 607..609 FT /evidence="ECO:0007829|PDB:7ONI" FT HELIX 616..623 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 627..638 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 647..652 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 657..659 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 665..668 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 674..687 FT /evidence="ECO:0007829|PDB:3DPL" FT TURN 690..693 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 697..723 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 726..729 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 731..741 FT /evidence="ECO:0007829|PDB:3DPL" FT TURN 742..745 FT /evidence="ECO:0007829|PDB:3DPL" FT HELIX 750..762 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 765..769 FT /evidence="ECO:0007829|PDB:3DPL" FT STRAND 772..778 FT /evidence="ECO:0007829|PDB:3DPL" SQ SEQUENCE 780 AA; 90955 MW; 57463CB4ED76E303 CRC64; MATSNLLKNK GSLQFEDKWD FMRPIVLKLL RQESVTKQQW FDLFSDVHAV CLWDDKGPAK IHQALKEDIL EFIKQAQARV LSHQDDTALL KAYIVEWRKF FTQCDILPKP FCQLEITLMG KQGSNKKSNV EDSIVRKLML DTWNESIFSN IKNRLQDSAM KLVHAERLGE AFDSQLVIGV RESYVNLCSN PEDKLQIYRD NFEKAYLDST ERFYRTQAPS YLQQNGVQNY MKYADAKLKE EEKRALRYLE TRRECNSVEA LMECCVNALV TSFKETILAE CQGMIKRNET EKLHLMFSLM DKVPNGIEPM LKDLEEHIIS AGLADMVAAA ETITTDSEKY VEQLLTLFNR FSKLVKEAFQ DDPRFLTARD KAYKAVVNDA TIFKLELPLK QKGVGLKTQP ESKCPELLAN YCDMLLRKTP LSKKLTSEEI EAKLKEVLLV LKYVQNKDVF MRYHKAHLTR RLILDISADS EIEENMVEWL REVGMPADYV NKLARMFQDI KVSEDLNQAF KEMHKNNKLA LPADSVNIKI LNAGAWSRSS EKVFVSLPTE LEDLIPEVEE FYKKNHSGRK LHWHHLMSNG IITFKNEVGQ YDLEVTTFQL AVLFAWNQRP REKISFENLK LATELPDAEL RRTLWSLVAF PKLKRQVLLY EPQVNSPKDF TEGTLFSVNQ EFSLIKNAKV QKRGKINLIG RLQLTTERMR EEENEGIVQL RILRTQEAII QIMKMRKKIS NAQLQTELVE ILKNMFLPQK KMIKEQIEWL IEHKYIRRDE SDINTFIYMA //