InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CUL7

Summary

InnateDB Protein

IDBP-87632.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CUL7

Protein Name

cullin 7

Synonyms

3M1; dJ20C7.5; KIAA0076;

Species

Homo sapiens

Ensembl Protein

ENSP00000265348

InnateDB Gene

IDBG-87630 (CUL7)

Protein Structure

UniProt Annotation

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 (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:0000269PubMed:16547496, ECO:0000269PubMed:17332328, ECO:0000269PubMed:18498745, ECO:0000269PubMed:20139075, ECO:0000269PubMed:21572988, ECO:0000269PubMed:24362026, ECO:0000269PubMed:24793695, ECO:0000269PubMed:24793696}.

Subcellular Localization

Cytoplasm. 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:0000269PubMed:24793695}.

Disease Associations

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. {ECO:0000269PubMed:16142236, ECO:0000269PubMed:17675530, ECO:0000269PubMed:23018678}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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. {ECO:0000269PubMed:16142236}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 38 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	38 [view]
Protein-Protein	37 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005488	binding
GO:0005515	protein binding
GO:0031625	ubiquitin protein ligase binding

Biological Process

GO:0000226	microtubule cytoskeleton organization
GO:0000281	mitotic cytokinesis
GO:0001570	vasculogenesis
GO:0001837	epithelial to mesenchymal transition
GO:0001890	placenta development
GO:0006508	proteolysis
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0006987	activation of signaling protein activity involved in unfolded protein response
GO:0007030	Golgi organization
GO:0007088	regulation of mitosis
GO:0016032	viral process
GO:0016567	protein ubiquitination
GO:0030968	endoplasmic reticulum unfolded protein response
GO:0044267	cellular protein metabolic process
GO:0050775	positive regulation of dendrite morphogenesis

Cellular Component

GO:0005634	nucleus
GO:0005680	anaphase-promoting complex
GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005813	centrosome
GO:0005829	cytosol
GO:0031461	cullin-RING ubiquitin ligase complex
GO:0031467	Cul7-RING ubiquitin ligase complex
GO:0048471	perinuclear region of cytoplasm
GO:1990393	3M complex

Protein Structure and Domains

PDB ID

InterPro

IPR001373 Cullin, N-terminal
IPR004939 Anaphase-promoting complex, subunit 10/DOC domain
IPR008979 Galactose-binding domain-like
IPR016024 Armadillo-type fold
IPR016158 Cullin homology
IPR019559 Cullin protein, neddylation domain
IPR021097 CPH domain

PFAM

PF00888
PF03256
PF10557
PF11515

PRINTS

PIRSF

SMART

SM00182
SM00884

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q14999