Reviewed,
UniProtKB/Swiss-Prot Q14999 (CUL7_HUMAN)
Last modified
November 25, 2008.
Version 81.
History...
Clusters with 100%,
90%,
50% identity |
Documents (8) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Cullin-7 Short name=CUL-7 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1698 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Component of a probable SCF-like E3 ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteosomal degradation of target proteins. Probably plays a role in the degradation of proteins involved in endothelial proliferation and/or differentiation By similarity. Seems not to promote polyubiquitination and proteosomal degradation of TP53. In vitro, complexes of CUL7 with either PARC or FBXW8 or TP53 contain E3 ubiquitin-protein ligase activity. |
| Pathway | |
| Subunit structure | Part of a SCF-like complex consisting of CUL7, RBX1, SKP1, FBXW8 and GLMN isoform 1. Interacts with a complex of SKP1 and FBXW8, but not with SKP1 alone. Interacts with PARC. Interacts with FBXW8; interaction is mutually exclusive of binding to PARC or TP53. Interacts with TP53; the interaction preferentially involves tetrameric and dimeric TP53. The CUL7-PARC heterodimer seems to interact specifically with TP53. Interacts with CUL1; the interactions seems to be mediated by FBXW8 By similarity. |
| Subcellular location | |
| Tissue specificity | Highly 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. |
| Involvement in disease | Defects in CUL7 are the cause of 3M syndrome [MIM:273750]. 3M syndrome is 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. |
| Sequence similarities | Belongs to the cullin family. Contains 1 DOC domain. |
Ontologies
Keywords | |
|---|---|
| Biological process | Ubl conjugation pathway |
| Cellular component | Cytoplasm |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation |
| PTM | Phosphoprotein Ubl conjugation |
| Technical term | 3D-structure |
Gene Ontology (GO) | |
| Biological process | regulation of mitotic metaphase/anaphase transition Inferred from electronic annotation. Source: InterPro ubiquitin-dependent protein catabolic processInferred from electronic annotation. Source: InterPro vasculogenesisInferred from sequence or structural similarity. Source: UniProtKB |
| Cellular component | anaphase-promoting complex Ref.4 Non-traceable author statement. Source: UniProtKB cullin-RING ubiquitin ligase complexInferred from electronic annotation. Source: InterPro cytoplasmInferred from electronic annotation. Source: UniProtKB-KW |
| Molecular function | ubiquitin protein ligase binding Inferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| ABL1 | P00519 | 1 | EBI-308606,EBI-375543 | |
| TP53 | P04637 | 1 | EBI-308606,EBI-366083 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||
Molecule processing | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1698 | 1698 | Cullin-7 | PRO_0000119802 | |||||||||||||||||||
Regions | |||||||||||||||||||||||
| Domain | 814 – 993 | 180 | DOC | ||||||||||||||||||||
| Region | 360 – 460 | 101 | Interaction with TP53 | ||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||
| Modified residue | 329 | 1 | Phosphoserine | ||||||||||||||||||||
| Modified residue | 339 | 1 | Phosphoserine | ||||||||||||||||||||
| Cross-link | 1576 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) By similarity | |||||||||||||||||||||
Natural variations | |||||||||||||||||||||||
| Natural variant | 813 | 1 | Q → R: dbSNP rs9381231. | VAR_026121 | |||||||||||||||||||
| Natural variant | 1014 | 1 | L → R in 3M syndrome. | VAR_026122 | |||||||||||||||||||
| Natural variant | 1246 | 1 | Q → G in 3M syndrome; requires 2 nucleotide substitutions. | VAR_026123 | |||||||||||||||||||
| Natural variant | 1464 | 1 | H → P in 3M syndrome; impairs the ability to interact with RBX1, thus hampers the assembly of polyubiquitin chains. | VAR_026124 | |||||||||||||||||||
Secondary structure | |||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||
| Helix | 360 – 362 | 3 | |||||||||||||||||||||
| Beta strand | 363 – 366 | 4 | |||||||||||||||||||||
| Helix | 367 – 376 | 10 | |||||||||||||||||||||
| Beta strand | 382 – 385 | 4 | |||||||||||||||||||||
| Beta strand | 397 – 403 | 7 | |||||||||||||||||||||
| Beta strand | 407 – 414 | 8 | |||||||||||||||||||||
| Turn | 415 – 418 | 4 | |||||||||||||||||||||
| Beta strand | 419 – 424 | 6 | |||||||||||||||||||||
| Helix | 425 – 427 | 3 | |||||||||||||||||||||
| Beta strand | 428 – 430 | 3 | |||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1." Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., Kawarabayasi Y., Ishikawa K., Tabata S. DNA Res. 1:223-229(1994) [PubMed: 7584044] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-813. Tissue: Bone marrow. |
| [2] | "The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. Beck S.Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-813. Tissue: Eye. |
| [4] | "CUL7: a DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex." Dias D.C., Dolios G., Wang R., Pan Z.Q. Proc. Natl. Acad. Sci. U.S.A. 99:16601-16606(2002) [PubMed: 12481031] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH SKP1A; FBXW8 AND RBX1. |
| [5] | "Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis." Arai T., Kasper J.S., Skaar J.R., Ali S.H., Takahashi C., DeCaprio J.A. Proc. Natl. Acad. Sci. U.S.A. 100:9855-9860(2003) [PubMed: 12904573] [Abstract] Cited for: INTERACTION WITH RBX1, IDENTIFICATION IN A COMPLEX WITH SKP1; FBXW8; RBX1 AND GLMN. |
| [6] | "Cytoplasmic localized ubiquitin ligase cullin 7 binds to p53 and promotes cell growth by antagonizing p53 function." Andrews P., He Y.J., Xiong Y. Oncogene 25:4534-4548(2006) [PubMed: 16547496] [Abstract] Cited for: FUNCTION, INTERACTION WITH RBX1 AND TP53, SUBCELLULAR LOCATION. |
| [7] | "PARC and CUL7 form atypical cullin RING ligase complexes." Skaar J.R., Florens L., Tsutsumi T., Arai T., Tron A., Swanson S.K., Washburn M.P., DeCaprio J.A. Cancer Res. 67:2006-2014(2007) [PubMed: 17332328] [Abstract] Cited for: FUNCTION, INTERACTION WITH PARC; SKP1A; FBXW8; RBX1 AND TP53. |
| [8] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329 AND SER-339, MASS SPECTROMETRY. |
| [9] | "The conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain of p53." Kaustov L., Lukin J., Lemak A., Duan S., Ho M., Doherty R., Penn L.Z., Arrowsmith C.H. J. Biol. Chem. 282:11300-11307(2007) [PubMed: 17298945] [Abstract] Cited for: STRUCTURE BY NMR OF 360-460, INTERACTION WITH TP53. |
| [10] | "Identification of mutations in CUL7 in 3-M syndrome." Huber C., Dias-Santagata D., Glaser A., O'Sullivan J., Brauner R., Wu K., Xu X., Pearce K., Wang R., Giovannucci Uzielli M.L., Dagoneau N., Chemaitilly W., Superti-Furga A., Dos Santos H., Megarbane A., Morin G., Gillessen-Kaesbach G., Hennekam R.C.M. Cormier-Daire V.Nat. Genet. 37:1119-1124(2005) [PubMed: 16142236] [Abstract] Cited for: VARIANTS 3M SYNDROME ARG-1014; GLY-1246 AND PRO-1464, TISSUE SPECIFICITY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D38548 mRNA. Translation: BAA07551.2. Different initiation. AL355385, AL136304 Genomic DNA. Translation: CAI13779.1. AL136304, AL355385 Genomic DNA. Translation: CAI19793.1. BC033647 mRNA. Translation: AAH33647.1. | |||||||||||||
| RefSeq | NP_055595.2. | ||||||||||||
| UniGene | Hs.520136 | ||||||||||||
3D structure databases | |||||||||||||
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| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | Q14999. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q14999. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000044090. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 9820. | ||||||||||||
| KEGG | hsa:9820. | ||||||||||||
Organism-specific databases | |||||||||||||
| H-InvDB | HIX0005893. | ||||||||||||
| HGNC | HGNC:21024. CUL7. | ||||||||||||
| HPA | CAB015449. | ||||||||||||
| MIM | 273750. phenotype. 609577. gene. | ||||||||||||
| Orphanet | 2616. 3M syndrome. | ||||||||||||
| PharmGKB | PA134897835. | ||||||||||||
| HUGE | Search... | ||||||||||||
| GenAtlas | Search... | ||||||||||||
| GeneCards | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOGENOM | Q14999. | ||||||||||||
| HOVERGEN | Q14999. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q14999. | ||||||||||||
| CleanEx | HS_CUL7. | ||||||||||||
| GermOnline | ENSG00000044090. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR016157. Cullin_CS. IPR016158. Cullin_homology. IPR001373. Cullin_N. [Graphical view] | ||||||||||||
| Pfam | PF00888. Cullin. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS01256. CULLIN_1. False negative. PS50069. CULLIN_2. 1 hit. PS51284. DOC. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 36986. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | CUL7_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q14999 Secondary accession number(s): Q5T654 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| UniProtKB secondary accession numbers Index of UniProtKB secondary accession numbers |
| SIMILARITY comments Index of protein domains and families |

Clusters with


