ID  Q8VE73;
PN  Cullin-7;
GN  Cul7;
OS  10090;
SL  Nucleus Position: SL-0198;
SL  Comments: Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Golgi apparatus {ECO:0000250}. Note=Colocalizes with FBXW8 at the Golgi apparatus in neurons; localization to Golgi is mediated by OBSL1. During mitosis, localizes to the mitotic apparatus. CCDC8 is required for centrosomal location (By similarity). {ECO:0000250}.
DR  UNIPROT: Q8VE73;
DR  UNIPROT: Q3UHY3;
DR  UNIPROT: Q497I2;
DR  UNIPROT: Q6A0D6;
DR  UNIPROT: Q6PB63;
DR  UNIPROT: Q8R3W4;
DR  UNIPROT: Q9CVD5;
DR  Pfam: PF03256;
DR  Pfam: PF11515;
DR  Pfam: PF00888;
DR  PROSITE: PS01256;
DR  PROSITE: PS50069;
DR  PROSITE: PS51284;
DE  Function: Core component of the 3M and Cul7-RING(FBXW8) complexes, which mediates the ubiquitination of target proteins. Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer. Interaction with CUL9 is required to inhibit CUL9 activity and ubiquitination of BIRC5. Core component of a Cul7-RING ubiquitin- protein ligase with FBXW8, which mediates ubiquitination and consequent degradation of target proteins such as GORASP1, IRS1 and MAP4K1/HPK1. Ubiquitination of GORASP1 regulates Golgi morphogenesis and dendrite patterning in brain. Mediates ubiquitination and degradation of IRS1 in a mTOR-dependent manner: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2). The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradation, thereby affecting cell proliferation and differentiation. Acts as a regulator in trophoblast cell epithelial- mesenchymal transition and placental development. Does not promote polyubiquitination and proteasomal degradation of p53/TP53. While the Cul7-RING(FBXW8) and the 3M complexes are associated and involved in common processes, CUL7 and the Cul7-RING(FBXW8) complex may be have additional functions (By similarity). Probably plays a role in the degradation of proteins involved in endothelial proliferation and/or differentiation. {ECO:0000250, ECO:0000269|PubMed:12904573}.
DE  Reference Proteome: Yes;
GO  GO:1990393;
GO  GO:0005813;
GO  GO:0031467;
GO  GO:0031461;
GO  GO:0005737;
GO  GO:0005794;
GO  GO:0048471;
GO  GO:0031625;
GO  GO:0001837;
GO  GO:0007030;
GO  GO:0000226;
GO  GO:0000281;
GO  GO:0001890;
GO  GO:0050775;
GO  GO:0016567;
GO  GO:0045601;
GO  GO:0007088;
GO  GO:0006511;
GO  GO:0001570;
TP  Membrane Topology: Unknown; Source: UniProt - Sequence Analysis;
SQ  MVGELRYREFRVPLGPGLHAYPDELIRQRVGHNGHPEYQIRWLILRRGDDGDRDSTVDCKAEHILLWMSDDEIYANCHKM
SQ  LGENGQVIAPSRESTEAGALDKSVLGEMETDVKSLIQRALRQLEECVGTVPPAPLLHTVHVLSAYASIEPLTGIFKDRRV
SQ  VNLLMHMLSSPDYQIRWSAGRMIQALSSHDAGTRTQILLSLSQQEAIEKHLDFDSRCALLALFAQATLTEHPMSFEGVQL
SQ  PQVPGRLLFSLVKRYLHVTFLLDRLNGDAGDQGAQNNFIPEELNVGRGRLELEFSMAMGTLISELVQAMRWDGASSRPES
SQ  SSSSTFQPRPAQFRPYTQRFRRSRRFRPRASFASFNTYALYVRDTLRPGMRVRMLENYEEIAAGDEGQFRQSNDGVPPAQ
SQ  VLWDSTGHTYWVHWHMLEILGFEEDIEDVIDIEELQELGANGALSIVPPSQRWKPITQLFAEPYVVPEEEDREESENLTQ
SQ  AEWWELLFFIRQLSEAERLHIVDLLQDHLEEERVLDYDMLPELTVPVDLAQDLLLSLPQQLEDSALRDLFSCSVYRKYGP
SQ  EVLVGHLSYPFVPGAQPNLFGANEESEAKDPPLQSASPALQRLVESLGPEGEVLVELEQALGSEAPQETEVKSCLLQLQE
SQ  QPQPFLALMRSLDTSASNKTLHLTVLRILMQLVNFPEALLLPWHEAMDACVTCLRSPNTDREVLQELIFFLHRLTTTSRD
SQ  YAVILNQLGARDAISKVLEKHRGKLELAQELRDMVSKCEKHAHLYRKLTTNILGGCIQMVLGQIEDHRRTHRPIQIPFFD
SQ  VFLRYLCQGSSEEMKKNRYWEKVEVSSNPQRASRLTDRNPKTYWESSGRAGSHFITLHMRPGVIIRQLTLLVAGEDSSYM
SQ  PAWVVVCGGNSIKSVNKELNTVNVMPSASRVTLLENLTRFWPIIQIRIKRCQQGGINTRIRGLEVLGPKPTFWPVFREQL
SQ  CRHTRLFYMVRAQAWSQDIAEDRRSLLHLSSRLNGALRHEQNFAERFLPDMEAAQALSKTCWEALVSPLVQNITSPDEDS
SQ  TSSLGWLLDQYLGCREAAYNPQSRAAAFSSRVRRLTHLLVHVEPREAAPPVVAIPRSKGRNRIHDWSYLITRGLPSSIMK
SQ  NLTRCWRSVVEEQMNKFLTASWKDDDFVPRYCERYYVLQKSSSELFGPRAAFLLAMRNGCADAVLRLPFLRAAHVSEQFA
SQ  RHIDQRIQGSRMGGARGMEMLAQLQRCLESVLIFSPLEIATTFEHYYQHYMADRLLSVGSSWLEGAVLEQIGPCFPSRLP
SQ  QQMLQSLNVSEELQRQFHVYQLQQLDQELLKLEDTEKKIQVAHEDSGREDKSKKEEAIGEAAAVAMAEEEDQGKKEEGEE
SQ  EGEGEDEEEERYYKGTMPEVCVLVVTPRFWPVASVCQMLNPATCLPAYLRGTINHYTNFYSKSQSRSSLEKEPQRRLQWT
SQ  WQGRAEVQFGGQILHVSTVQMWLLLHLNNQKEVSVESLQAISELPPDVLHRAIGPLTSSRGPLDLQEQKNVPGGVLKIRD
SQ  DSEEPRPRRGNVWLIPPQTYLQAEAEEGRNMEKRRNLLNCLVVRILKAHGDEGLHVDRLVYLVLEAWEKGPCPARGLVSS
SQ  LGRGATCRSSDVLSCILHLLVKGTLRRHDDRPQVLYYAVPVTVMEPHMESLNPGSAGPNPPLTFHTLQIRSRGVPYASCT
SQ  DNHTFSTFR
//