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MGP004019

UniProt Annotations

Entry Information
Gene Namecullin 7
Protein EntryCUL7_HUMAN
UniProt IDQ14999
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q14999-1; Sequence=Displayed; Name=2; IsoId=Q14999-2; Sequence=VSP_046105, VSP_046106; Note=No experimental confirmation available.;
Developmental StageHighly expressed in invasive placental villi during first trimester. {ECO:0000269|PubMed:20139075}.
Disease3M syndrome 1 (3M1) [MIM:273750]: An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies. {ECO:0000269|PubMed:16142236, ECO:0000269|PubMed:17675530, ECO:0000269|PubMed:23018678}. Note=The disease is caused by mutations affecting the gene represented in this entry.
FunctionCore 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 (PubMed:24793695). Interaction with CUL9 is required to inhibit CUL9 activity and ubiquitination of BIRC5 (PubMed:24793696). 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 (PubMed:21572988, PubMed:24362026). Ubiquitination of GORASP1 regulates Golgi morphogenesis and dendrite patterning in brain (PubMed:21572988). 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) (PubMed:18498745). The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradatation, thereby affecting cell proliferation and differentiation (PubMed:24362026). Acts as a regulator in trophoblast cell epithelial-mesenchymal transition and placental development (PubMed:20139075). Does not promote polyubiquitination and proteasomal degradation of p53/TP53 (PubMed:16547496, PubMed:17332328). 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. {ECO:0000269|PubMed:16547496, ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:20139075, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}.
InteractionP04637:TP53; NbExp=4; IntAct=EBI-308606, EBI-366083;
PathwayProtein modification; protein ubiquitination.
PtmAccording to a report, may not be neddylated despite the conserved consensus site for neddylation at Lys-1576. {ECO:0000269|PubMed:17332328}.
Sequence CautionSequence=BAA07551.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the cullin family. {ECO:0000255|PROSITE- ProRule:PRU00330}.
SimilarityContains 1 DOC domain. {ECO:0000255|PROSITE- ProRule:PRU00614}.
Subcellular LocationCytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, perinuclear region. Golgi apparatus. Note=Colocalizes with FBXW8 at the Golgi apparatus in neurons; localization to Golgi is mediated by OBSL1. During mitosis, localizes to the mitotic apparatus (PubMed:24793695). CCDC8 is required for centrosomal location (PubMed:24793695). {ECO:0000269|PubMed:24793695}.
SubunitComponent of the 3M complex, composed of core components CUL7, CCDC8 and OBSL1. Part of a Cul7-RING complex consisting of CUL7, RBX1, SKP1 and FBXW8. Interacts with a complex of SKP1 and FBXW8, but not with SKP1 alone. Interacts with CUL9; leading to inhibit CUL9 activity. Interacts with FBXW8; interaction is mutually exclusive of binding to CUL9 or p53/TP53. Interacts with p53/TP53; the interaction preferentially involves tetrameric and dimeric p53/TP53. The CUL7-CUL9 heterodimer seems to interact specifically with p53/TP53. Interacts with CUL1; the interactions seems to be mediated by FBXW8. Interacts with SV40 Large T antigen; this interaction seems to inhibit CUL7. Interacts with OBSL1. {ECO:0000269|PubMed:12481031, ECO:0000269|PubMed:12904573, ECO:0000269|PubMed:15964813, ECO:0000269|PubMed:16140746, ECO:0000269|PubMed:16547496, ECO:0000269|PubMed:17298945, ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:21737058, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}.
Tissue SpecificityHighly expressed in fetal kidney and adult skeletal muscle. Also abundant in fetal brain, as well as in adult pancreas, kidney, placenta and heart. Detected in trophoblasts, lymphoblasts, osteoblasts, chondrocytes and skin fibroblasts. {ECO:0000269|PubMed:16142236}.
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