InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SHARPIN

Summary

InnateDB Protein

IDBP-232393.6

Last Modified

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

Gene Symbol

SHARPIN

Protein Name

SHANK-associated RH domain interactor

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000381698

InnateDB Gene

IDBG-40065 (SHARPIN)

Protein Structure

UniProt Annotation

Function

Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. {ECO:0000269PubMed:21455173, ECO:0000269PubMed:21455180, ECO:0000269PubMed:21455181}.

Subcellular Localization

Cytoplasm, cytosol {ECO:0000269PubMed:20179993}. Cell junction, synapse {ECO:0000250}. Note=Enriched at synaptic sites in mature neurons where it colocalizes with SHANK1. {ECO:0000250}.

Disease Associations

Tissue Specificity

Highly expressed in skeletal muscle and placenta and at lower levels in brain, heart, colon without mucosa, thymus, spleen, kidney, liver, small intestine, lung and peripheral blood leukocytes. Up-regulated in various tumor tissues such as kidney, liver, ovary and pancreas tumors. {ECO:0000269PubMed:20179993}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 44 experimentally validated interaction(s) in this database.
They are also associated with 23 interaction(s) predicted by orthology.

Experimentally validated
Total	44 [view]
Protein-Protein	44 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	23 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0031593	polyubiquitin binding
GO:0032403	protein complex binding
GO:0042802	identical protein binding

Biological Process

GO:0007005	mitochondrion organization
GO:0007420	brain development
GO:0008544	epidermis development
GO:0010803	regulation of tumor necrosis factor-mediated signaling pathway
GO:0030262	apoptotic nuclear changes
GO:0031424	keratinization
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0050728	negative regulation of inflammatory response
GO:0051260	protein homooligomerization
GO:0097039	protein linear polyubiquitination
GO:2000348	regulation of CD40 signaling pathway