ID CUL5_MOUSE Reviewed; 780 AA. AC Q9D5V5; Q8BMQ6; Q8BV53; Q8C098; DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 24-JUL-2024, entry version 170. DE RecName: Full=Cullin-5 {ECO:0000305}; DE Short=CUL-5 {ECO:0000305}; GN Name=Cul5 {ECO:0000303|PubMed:23806657, ECO:0000312|MGI:MGI:1922967}; 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]. RC STRAIN=C57BL/6J; RC TISSUE=Brain, Medulla oblongata, Ovary, Testis, and Uterus; 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]. RC TISSUE=Olfactory epithelium; 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 FUNCTION, PATHWAY, AND IDENTIFICATION IN VARIOUS ECS(SOCS7) COMPLEXES. RX PubMed=17974915; DOI=10.1101/gad.1604207; RA Feng L., Allen N.S., Simo S., Cooper J.A.; RT "Cullin 5 regulates Dab1 protein levels and neuron positioning during RT cortical development."; RL Genes Dev. 21:2717-2730(2007). RN [4] 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 [5] RP FUNCTION, PATHWAY, AND IDENTIFICATION IN THE ECS(SOCS7) COMPLEX. RX PubMed=24210661; DOI=10.1016/j.devcel.2013.09.022; RA Simo S., Cooper J.A.; RT "Rbx2 regulates neuronal migration through different cullin 5-RING ligase RT adaptors."; RL Dev. Cell 27:399-411(2013). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 1-384, FUNCTION, AND PATHWAY. RX PubMed=23806657; DOI=10.1016/j.jmb.2013.06.015; RA Muniz J.R., Guo K., Kershaw N.J., Ayinampudi V., von Delft F., Babon J.J., RA Bullock A.N.; RT "Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 RT ubiquitin ligases."; RL J. Mol. Biol. 425:3166-3177(2013). CC -!- FUNCTION: Core component of multiple cullin-5-RING E3 ubiquitin-protein CC ligase complexes (ECS complexes, also named CRL5 complexes), which CC mediate the ubiquitination and subsequent proteasomal degradation of CC target proteins (PubMed:17974915, PubMed:23806657, PubMed:24210661). CC Acts a scaffold protein that contributes to catalysis through CC positioning of the substrate and the ubiquitin-conjugating enzyme (By CC similarity). The functional specificity of the E3 ubiquitin-protein CC ligase complex depends on the variable SOCS box-containing substrate CC recognition component (By similarity). Acts as a key regulator of CC neuron positioning during cortex development: component of various CC SOCS-containing ECS complexes, such as the ECS(SOCS7) complex, that CC regulate reelin signaling by mediating ubiquitination and degradation CC of DAB1 (PubMed:17974915, PubMed:24210661). ECS(SOCS1) seems to direct CC ubiquitination of JAK2 (By similarity). The ECS(SOCS2) complex mediates CC the ubiquitination and subsequent proteasomal degradation of CC phosphorylated EPOR and GHR (By similarity). The ECS(SPSB3) complex CC catalyzes ubiquitination of nuclear CGAS (By similarity). ECS(KLHDC1) CC complex is part of the DesCEND (destruction via C-end degrons) pathway CC and mediates ubiquitination and degradation of truncated SELENOS CC selenoprotein produced by failed UGA/Sec decoding, which ends with a CC glycine (By similarity). The ECS(ASB9) complex mediates ubiquitination CC and degradation of CKB (By similarity). As part of some ECS complex, CC promotes 'Lys-11'-linked ubiquitination and degradation of BTRC (By CC similarity). As part of a multisubunit ECS complex, polyubiquitinates CC monoubiquitinated POLR2A. May form a cell surface vasopressin receptor CC (By similarity). {ECO:0000250|UniProtKB:Q93034, CC ECO:0000269|PubMed:17974915, ECO:0000269|PubMed:23806657, CC ECO:0000269|PubMed:24210661}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:17974915, ECO:0000269|PubMed:23806657, CC ECO:0000269|PubMed:24210661}. CC -!- SUBUNIT: Component of multiple cullin-5-RING E3 ubiquitin-protein CC ligase complexes (ECS complexes, also named CRL5 complexes) formed of CC CUL5, Elongin BC (ELOB and ELOC), RNF7/RBX2 and a variable SOCS box CC domain-containing protein as substrate-specific recognition component CC (PubMed:17974915, PubMed:23806657, PubMed:24210661). CUL5-containing CC ECS complexes specifically contain RNF7/RBX2, and not RBX1, as CC catalytic subunit (By similarity). Component of the ECS(ASB2) complex CC with the substrate recognition component ASB2 (By similarity). CC Component of the ECS(ASB6) complex with the substrate recognition CC component ASB6 (By similarity). Component of the ECS(ASB7) complex with CC the substrate recognition component ASB7 (By similarity). Component of CC the ECS(ASB9) complex with the substrate recognition component ASB9 (By CC similarity). Component of the ECS(ASB11) complex with the substrate CC recognition component ASB11 (By similarity). Component of the CC ECS(ASB12) complex with the substrate recognition component ASB12 (By CC similarity). Component of the ECS(LRRC41) complex with the substrate CC recognition component LRRC41 (By similarity). Component of the CC ECS(SOCS1) complex with the substrate recognition component SOCS1 (By CC similarity). Component of the ECS(SOCS2) complex with the substrate CC recognition component SOCS2 (By similarity). Component of the ECS(WSB1) CC complex with the substrate recognition subunit WSB1 (By similarity). CC Component of the ECS(SOCS3) complex with the substrate recognition CC component SOCS3 (By similarity). Component of the ECS(SOCS7) complex CC with the substrate recognition component SOCS7 (PubMed:24210661). CC Component of the ECS(SPSB1) complex with the substrate recognition CC component SPSB1 (By similarity). Component of the ECS(SPSB3) complex CC with the substrate recognition component SPSB3 (By similarity). CC Component of the ECS(SPSB2) complex with the substrate recognition CC component SPSB2 (By similarity). Component of the ECS(SPSB4) complex CC with the substrate recognition component SPSB4 (By similarity). CC Component of the ECS(RAB40C) complex with the substrate recognition CC subunit RAB40C (By similarity). Component of the ECS(KLHDC1) complex CC with the substrate recognition component KLHDC1 (By similarity). CC Component of the ECS(PCMTD1) complex with the substrate recognition CC subunit PCMTD1 (By similarity). May also form complexes containing RBX1 CC and ELOA or VHL; additional evidence is however required to confirm CC this result in vivo (By similarity). Interacts (when neddylated) with CC ARIH2; leading to activate the E3 ligase activity of ARIH2 (By CC similarity). Interacts with ERCC6; the interaction is induced by DNA CC damaging agents or inhibitors of RNA polymerase II elongation (By CC similarity). Interacts with ELOA (via the BC-box) (By similarity). CC Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 CC and DCUN1D5; these interactions promote the cullin neddylation (By CC similarity). {ECO:0000250|UniProtKB:Q93034, CC ECO:0000269|PubMed:17974915, ECO:0000269|PubMed:23806657, CC ECO:0000269|PubMed:24210661}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q93034}. CC Note=Localizes to sites of DNA damage in a UBAP2 and UBAP2L-dependent CC manner. {ECO:0000250|UniProtKB:Q93034}. CC -!- PTM: Neddylated; which enhances the ubiquitination activity of ECS CC complexes and prevents binding of the inhibitor CAND1. Deneddylated via CC its interaction with the COP9 signalosome (CSN). CC {ECO:0000250|UniProtKB:Q93034}. 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; AK014894; BAB29609.1; -; mRNA. DR EMBL; AK030306; BAC26889.1; -; mRNA. DR EMBL; AK031955; BAC27621.1; -; mRNA. DR EMBL; AK046030; BAC32575.1; -; mRNA. DR EMBL; AK080305; BAC37872.1; -; mRNA. DR EMBL; BC075710; AAH75710.1; -; mRNA. DR CCDS; CCDS40638.2; -. DR RefSeq; NP_001155090.1; NM_001161618.1. DR RefSeq; NP_082083.2; NM_027807.3. DR PDB; 2WZK; X-ray; 2.05 A; A=1-384. DR PDBsum; 2WZK; -. DR AlphaFoldDB; Q9D5V5; -. DR SMR; Q9D5V5; -. DR BioGRID; 217689; 54. DR CORUM; Q9D5V5; -. DR IntAct; Q9D5V5; 3. DR MINT; Q9D5V5; -. DR STRING; 10090.ENSMUSP00000034529; -. DR GlyGen; Q9D5V5; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9D5V5; -. DR PhosphoSitePlus; Q9D5V5; -. DR SwissPalm; Q9D5V5; -. DR PaxDb; 10090-ENSMUSP00000034529; -. DR ProteomicsDB; 284062; -. DR Pumba; Q9D5V5; -. DR DNASU; 75717; -. DR GeneID; 75717; -. DR KEGG; mmu:75717; -. DR UCSC; uc009pmj.1; mouse. DR AGR; MGI:1922967; -. DR CTD; 8065; -. DR MGI; MGI:1922967; Cul5. DR eggNOG; KOG2285; Eukaryota. DR InParanoid; Q9D5V5; -. DR OrthoDB; 5474206at2759; -. DR PhylomeDB; Q9D5V5; -. DR Reactome; R-MMU-8863795; Downregulation of ERBB2 signaling. DR Reactome; R-MMU-8951664; Neddylation. DR Reactome; R-MMU-9705462; Inactivation of CSF3 (G-CSF) signaling. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 75717; 10 hits in 78 CRISPR screens. DR ChiTaRS; Cul5; mouse. DR EvolutionaryTrace; Q9D5V5; -. DR PRO; PR:Q9D5V5; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; Q9D5V5; Protein. DR GO; GO:0031466; C:Cul5-RING ubiquitin ligase complex; ISO:MGI. 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; ISS:UniProtKB. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central. DR GO; GO:0021799; P:cerebral cortex radially oriented cell migration; IMP:MGI. DR GO; GO:0016567; P:protein ubiquitination; IGI:MGI. DR GO; GO:0021942; P:radial glia guided migration of Purkinje cell; IMP:MGI. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISO:MGI. 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 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. PE 1: Evidence at protein level; KW 3D-structure; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; KW Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..780 FT /note="Cullin-5" FT /id="PRO_0000119798" FT MOD_RES 34 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q93034" FT MOD_RES 210 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q93034" FT CROSSLNK 724 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in NEDD8)" FT /evidence="ECO:0000250|UniProtKB:Q13616" FT CONFLICT 573 FT /note="W -> C (in Ref. 1; BAC27621)" FT /evidence="ECO:0000305" FT HELIX 15..31 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 37..53 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 57..81 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 86..103 FT /evidence="ECO:0007829|PDB:2WZK" FT TURN 104..108 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 112..115 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 134..146 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 148..167 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 175..186 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 196..200 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 202..248 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 257..269 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 271..273 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 274..278 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 281..286 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 290..300 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 308..329 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 330..332 FT /evidence="ECO:0007829|PDB:2WZK" FT TURN 333..335 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 337..359 FT /evidence="ECO:0007829|PDB:2WZK" FT HELIX 363..382 FT /evidence="ECO:0007829|PDB:2WZK" SQ SEQUENCE 780 AA; 90974 MW; C6EE7A1AF1038C0D CRC64; MATSNLLKNK GSLQFEDKWD FMHPIVLKLL RQESVTKQQW FDLFSDVHAV CLWDDKGSSK IHQALKEDIL EFIKQAQARV LSHQDDTALL KAYIVEWRKF FTQCDILPKP FCQLEVTLLG KQSSNKKSNM 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 DPQVNSPKDF TEGTLFSVNQ DFSLIKNAKV QKRGKINLIG RLQLTTERMR EEENEGIVQL RILRTQEAII QIMKMRKKIS NAQLQTELVE ILKNMFLPQK KMIKEQMEWL IEHRYIRRDE ADINTFIYMA //