Q14999 (CUL7_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 126.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Cullin-7 Short name=CUL-7 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| 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. |
| 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 proteasomal 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 proteasomal degradation of TP53. In vitro, complexes of CUL7 with either CUL9 or FBXW8 or TP53 contain E3 ubiquitin-protein ligase activity. In complex with FBXW8, mediates ubiquitination and consequent degradation of GORASP1, acting as a component of the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. Ref.8 Ref.9 Ref.14 |
| 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 CUL9. Interacts with FBXW8; interaction is mutually exclusive of binding to CUL9 or TP53. Interacts with TP53; the interaction preferentially involves tetrameric and dimeric TP53. The CUL7-CUL9 heterodimer seems to interact specifically with TP53. Interacts with CUL1; the interactions seems to be mediated by FBXW8 By similarity. Interacts with SV40 Large T antigen; this interaction seems to inhibit CUL7. Component of a SCF-like complex composed of SV40 Large T antigen, CUL7, SKP1, RBX1, and FBXW8. Interacts with OBSL1. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.12 Ref.14 Ref.15 |
| Subcellular location | Cytoplasm. Cytoplasm › perinuclear region. Golgi apparatus. Note: Co-localizes with FBXW8 at the Golgi apparatus in neurons; localization to Golgi is mediated by OBSL1. Ref.8 Ref.14 |
| 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. Ref.16 |
| Post-translational modification | According to a report, may not be neddylated despite the conserved consensus site for neddylation at Lys-1576 (Ref.9). |
| Involvement in disease | 3M 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. |
| Sequence similarities | Belongs to the cullin family. Contains 1 DOC domain. |
| Sequence caution | The sequence BAA07551.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| TP53 | P04637 | 3 | EBI-308606,EBI-366083 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q14999-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q14999-2) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MSRGFWLAEPLAGTGPHPAPVAADSRGCSSVPRRHAPSRLSVSTPSRGPGARM 194-194: G → GEGQCGEEGKAGEGLGRLRDSQDTVAGASDLIR | ||||||
| Note: No experimental confirmation available. |
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 | 339 | 1 | Phosphoserine Ref.10 | ||||||||||||||||||||
| Cross-link | 1576 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) Potential | |||||||||||||||||||||
Natural variations | |||||||||||||||||||||||
| Alternative sequence | 1 | 1 | M → MSRGFWLAEPLAGTGPHPAP VAADSRGCSSVPRRHAPSRL SVSTPSRGPGARM in isoform 2. | VSP_046105 | |||||||||||||||||||
| Alternative sequence | 194 | 1 | G → GEGQCGEEGKAGEGLGRLRD SQDTVAGASDLIR in isoform 2. | VSP_046106 | |||||||||||||||||||
| Natural variant | 616 | 1 | S → G. Corresponds to variant rs7774330 [ dbSNP | Ensembl ]. | VAR_048841 | |||||||||||||||||||
| Natural variant | 813 | 1 | Q → R. Ref.1 Ref.2 Ref.4 Corresponds to variant rs9381231 [ dbSNP | Ensembl ]. | VAR_026121 | |||||||||||||||||||
| Natural variant | 852 | 1 | R → Q. Corresponds to variant rs34574340 [ dbSNP | Ensembl ]. | VAR_048842 | |||||||||||||||||||
| Natural variant | 1014 | 1 | L → R in 3M1. Ref.16 | VAR_026122 | |||||||||||||||||||
| Natural variant | 1246 | 1 | Q → G in 3M1; requires 2 nucleotide substitutions. Ref.16 | VAR_026123 | |||||||||||||||||||
| Natural variant | 1246 | 1 | Q → H. Corresponds to variant rs36071170 [ dbSNP | Ensembl ]. | VAR_048843 | |||||||||||||||||||
| Natural variant | 1464 | 1 | H → P in 3M1; impairs the ability to interact with RBX1, thus hampers the assembly of polyubiquitin chains. Ref.16 | 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
| ||||||||||||||||||||||||
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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-813. Tissue: Bone marrow. |
| [2] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ARG-813. Tissue: Testis. |
| [3] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-813. Tissue: Eye. |
| [5] | "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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH SKP1; FBXW8 AND RBX1. |
| [6] | "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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RBX1, IDENTIFICATION IN A COMPLEX WITH SKP1; FBXW8; RBX1 AND GLMN. |
| [7] | "Simian virus 40 large T antigen's association with the CUL7 SCF complex contributes to cellular transformation." Kasper J.S., Kuwabara H., Arai T., Ali S.H., DeCaprio J.A. J. Virol. 79:11685-11692(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SV40 LARGE ANTIGEN, IDENTIFICATION IN A SFC(CUL7)-LIKE COMPLEX. |
| [8] | "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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RBX1 AND TP53, SUBCELLULAR LOCATION. |
| [9] | "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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CUL9; SKP1; FBXW8; RBX1 AND TP53, LACK OF NEDDYLATION. |
| [10] | "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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [11] | "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma. |
| [12] | "Exome sequencing identifies CCDC8 mutations in 3-M syndrome, Suggesting that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human Growth." Hanson D., Murray P.G., O'Sullivan J., Urquhart J., Daly S., Bhaskar S.S., Biesecker L.G., Skae M., Smith C., Cole T., Kirk J., Chandler K., Kingston H., Donnai D., Clayton P.E., Black G.C. Am. J. Hum. Genet. 89:148-153(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH OBSL1. |
| [13] | "Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| [14] | "An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi morphology and dendrite patterning." Litterman N., Ikeuchi Y., Gallardo G., O'Connell B.C., Sowa M.E., Gygi S.P., Harper J.W., Bonni A. PLoS Biol. 9:E1001060-E1001060(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FBXW8 AND OBSL1, SUBCELLULAR LOCATION. |
| [15] | "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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 360-460, INTERACTION WITH TP53. |
| [16] | "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] [Europe PMC] [Abstract] Cited for: VARIANTS 3M1 ARG-1014; GLY-1246 AND PRO-1464, TISSUE SPECIFICITY. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | D38548 mRNA. Translation: BAA07551.2. Different initiation. AK302668 mRNA. Translation: BAG63902.1. AL355385, AL136304 Genomic DNA. Translation: CAI13779.1. AL136304, AL355385 Genomic DNA. Translation: CAI19793.1. BC033647 mRNA. Translation: AAH33647.1. | ||||||||||||
| IPI | IPI00001690. IPI00955011. | ||||||||||||
| RefSeq | NP_001161842.1. NM_001168370.1. NP_055595.2. NM_014780.4. | ||||||||||||
| UniGene | Hs.520136. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| ProteinModelPortal | Q14999. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | Q14999. 6 interactions. | ||||||||||||
| STRING | 9606.ENSP00000265348. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q14999. | ||||||||||||
Polymorphism databases | |||||||||||||
| DMDM | 160370003. | ||||||||||||
Proteomic databases | |||||||||||||
| PaxDb | Q14999. | ||||||||||||
| PRIDE | Q14999. | ||||||||||||
Protocols and materials databases | |||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000265348; ENSP00000265348; ENSG00000044090. ENST00000535468; ENSP00000438788; ENSG00000044090. | ||||||||||||
| GeneID | 9820. | ||||||||||||
| KEGG | hsa:9820. | ||||||||||||
| UCSC | uc003otq.3. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 9820. | ||||||||||||
| GeneCards | GC06M043053. | ||||||||||||
| HGNC | HGNC:21024. CUL7. | ||||||||||||
| HPA | CAB015449. HPA030095. HPA030096. | ||||||||||||
| MIM | 273750. phenotype. 609577. gene. | ||||||||||||
| neXtProt | NX_Q14999. | ||||||||||||
| Orphanet | 2616. 3M syndrome. | ||||||||||||
| PharmGKB | PA134897835. | ||||||||||||
| HUGE | Search... | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | NOG48148. | ||||||||||||
| HOGENOM | HOG000024831. | ||||||||||||
| HOVERGEN | HBG103792. | ||||||||||||
| InParanoid | Q14999. | ||||||||||||
| KO | K10613. | ||||||||||||
| OrthoDB | EOG4VT5WB. | ||||||||||||
| PhylomeDB | Q14999. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| Reactome | REACT_116125. Disease. REACT_6900. Immune System. | ||||||||||||
| UniPathway | UPA00143. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q14999. | ||||||||||||
| Bgee | Q14999. | ||||||||||||
| CleanEx | HS_CUL7. | ||||||||||||
| Genevestigator | Q14999. | ||||||||||||
| GermOnline | ENSG00000044090. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| Gene3D | 2.30.30.30. 1 hit. | ||||||||||||
| InterPro | IPR004939. APC_su10/DOC_dom. IPR021097. CPH_domain. IPR016158. Cullin_homology. IPR001373. Cullin_N. IPR008979. Galactose-bd-like. IPR014722. Rib_L2_dom2. [Graphical view] | ||||||||||||
| Pfam | PF03256. APC10. 1 hit. PF11515. Cul7. 1 hit. PF00888. Cullin. 1 hit. [Graphical view] | ||||||||||||
| SUPFAM | SSF75632. Cullin_homology. 1 hit. SSF49785. Gal_bind_like. 1 hit. | ||||||||||||
| PROSITE | PS01256. CULLIN_1. False negative. PS50069. CULLIN_2. 1 hit. PS51284. DOC. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other | |||||||||||||
| EvolutionaryTrace | Q14999. | ||||||||||||
| GenomeRNAi | 9820. | ||||||||||||
| NextBio | 36986. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | CUL7_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q14999 Secondary accession number(s): B4DYZ0, F5H0L1, Q5T654 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
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 |
| SIMILARITY comments Index of protein domains and families |

Clusters with
