InnateDB Protein
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IDBP-40067.7
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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SHARPIN
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Protein Name
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SHANK-associated RH domain interactor
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Synonyms
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000352551
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InnateDB Gene
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IDBG-40065 (SHARPIN)
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Protein Structure
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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}.
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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}.
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Disease Associations |
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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}.
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Comments |
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Number of Interactions
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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]
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Protein-Protein |
44
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
23 [view]
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Molecular Function |
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Biological Process |
GO:0010803
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regulation of tumor necrosis factor-mediated signaling pathway
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GO:0043123
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positive regulation of I-kappaB kinase/NF-kappaB signaling
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GO:0045087
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innate immune response (InnateDB)
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GO:0050728
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negative regulation of inflammatory response
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GO:0097039
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protein linear polyubiquitination
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GO:2000348
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regulation of CD40 signaling pathway
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Cellular Component |
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PDB ID |
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InterPro |
IPR029071
Ubiquitin-related domain
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PFAM |
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PRINTS |
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
Q9H0F6
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PhosphoSite |
PhosphoSite-Q9H0F6
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TrEMBL |
Q6PJD5
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UniProt Splice Variant |
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Entrez Gene |
81858
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UniGene |
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RefSeq |
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HUGO |
HGNC:25321
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OMIM |
611885
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CCDS |
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HPRD |
15463
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IMGT |
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EMBL |
AB052764
AB052765
AC104592
AK075518
AL136816
BC002688
BC017230
BC025244
BC034028
CH471162
FJ655995
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GenPept |
AAH02688
AAH17230
AAH25244
AAH34028
ACN38058
BAC11666
BAC53797
BAC53798
CAB66750
EAW82150
EAW82151
EAW82152
EAW82153
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