InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CYLD

Summary

InnateDB Protein

IDBP-752445.3

Last Modified

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

Gene Symbol

CYLD

Protein Name

Synonyms

BRSS; CDMT; CYLD1; CYLDI; EAC; MFT; MFT1; SBS; TEM; USPL2;

Species

Homo sapiens

Ensembl Protein

ENSP00000457576

InnateDB Gene

IDBG-30697 (CYLD)

Protein Structure

UniProt Annotation

Function

Protease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Has endodeubiquitinase activity. Plays an important role in the regulation of pathways leading to NF-kappa-B activation. Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation. Negative regulator of Wnt signaling. Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules. Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis. Required for normal cell cycle progress and normal cytokinesis. Inhibits nuclear translocation of NF-kappa-B. Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation. Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells. Negatively regulates TNFRSF11A signaling and osteoclastogenesis (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm. Cytoplasm, perinuclear region. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Detected at the microtubule cytoskeleton during interphase. Detected at the midbody during telophase.

Disease Associations

Cylindromatosis, familial (FCYL) [MIM:132700]: A disorder characterized by multiple skin tumors that develop from skin appendages, such as hair follicles and sweat glands. Affected individuals typically develop large numbers of tumors called cylindromas that arise predominantly in hairy parts of the body with approximately 90% on the head and neck. In severely affected individuals, cylindromas may combine into a confluent mass which may ulcerate or become infected (turban tumor syndrome). Individuals with familial cylindromatosis occasionally develop other types of tumors including spiradenomas that begin in sweat glands, and trichoepitheliomas arising from hair follicles. {ECO:0000269PubMed:12190880, ECO:0000269PubMed:16922728}. Note=The disease is caused by mutations affecting the gene represented in this entry.Multiple familial trichoepithelioma 1 (MFT1) [MIM:601606]: Autosomal dominant dermatosis characterized by the presence of many skin tumors predominantly on the face. Since histologic examination shows dermal aggregates of basaloid cells with connection to or differentiation toward hair follicles, this disorder has been thought to represent a benign hamartoma of the pilosebaceous apparatus. Trichoepitheliomas can degenerate into basal cell carcinoma. {ECO:0000269PubMed:14632188, ECO:0000269PubMed:16307661, ECO:0000269PubMed:16922728}. Note=The disease is caused by mutations affecting the gene represented in this entry.Brooke-Spiegler syndrome (BRSS) [MIM:605041]: An autosomal dominant disorder characterized by the appearance of multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These tumors are typically located in the head and neck region, appear in early adulthood, and gradually increase in size and number throughout life. {ECO:0000269PubMed:12190880, ECO:0000269PubMed:12950348, ECO:0000269PubMed:14632188, ECO:0000269PubMed:15854031}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Detected in fetal brain, testis, and skeletal muscle, and at a lower level in adult brain, leukocytes, liver, heart, kidney, spleen, ovary and lung. Isoform 2 is found in all tissues except kidney. {ECO:0000269PubMed:10835629}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 76 experimentally validated interaction(s) in this database.
They are also associated with 14 interaction(s) predicted by orthology.

Experimentally validated
Total	76 [view]
Protein-Protein	70 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	14 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004843	ubiquitin-specific protease activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0019901	protein kinase binding
GO:0036459	ubiquitinyl hydrolase activity
GO:0061578	Lys63-specific deubiquitinase activity
GO:0070064	proline-rich region binding

Biological Process

GO:0006511	ubiquitin-dependent protein catabolic process
GO:0007049	cell cycle
GO:0007346	regulation of mitotic cell cycle
GO:0016055	Wnt signaling pathway
GO:0032088	negative regulation of NF-kappaB transcription factor activity
GO:0032480	negative regulation of type I interferon production
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0042347	negative regulation of NF-kappaB import into nucleus
GO:0045087	innate immune response (InnateDB)
GO:0070266	necroptotic process
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway
GO:0070507	regulation of microtubule cytoskeleton organization
GO:0070536	protein K63-linked deubiquitination
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:2001238	positive regulation of extrinsic apoptotic signaling pathway
GO:2001242	regulation of intrinsic apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005813	centrosome
GO:0005829	cytosol
GO:0005881	cytoplasmic microtubule
GO:0030496	midbody
GO:0031234	extrinsic component of cytoplasmic side of plasma membrane
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000938 CAP Gly-rich domain
IPR001394 Peptidase C19, ubiquitin carboxyl-terminal hydrolase
IPR028889 Ubiquitin carboxyl-terminal hydrolase-like domain

PFAM

PF01302
PF00443

PRINTS

PIRSF

SMART

SM01052

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9NQC7