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SHARPIN (human)

Overview SHARPIN 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. Self-associates. Interacts with SHANK1, EYA1 and EYA2. Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31. LUBAC has a MW of approximative 600 kDa suggesting a heteromultimeric assembly of its subunits. Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation- dependent manner. 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. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB. Protein type: Apoptosis Cellular Component: postsynaptic density; cytosol Molecular Function: identical protein binding; protein binding; zinc ion binding; polyubiquitin binding Biological Process: mitochondrion organization and biogenesis; positive regulation of I-kappaB kinase/NF-kappaB cascade; apoptotic nuclear changes; negative regulation of inflammatory response; keratinization; brain development; protein homooligomerization Reference #:  Q9H0F6 (UniProtKB) Alt. Names/Synonyms: DKFZp434N1923; hSIPL1; SHANK-associated RH domain interactor; Shank-associated RH domain-interacting protein; Shank-interacting protein-like 1; SHARPIN; SHRPN; SIPL1 Gene Symbols: SHARPIN Molecular weight: 39,949 Da Basal Isoelectric point: 5.53  Predict pI for various phosphorylation states Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below SHARPIN 4EMO - A/D/C/B=1-127 (human)

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	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human ► Hide Isoforms
0	1		R29-m1	LAVHAAVrPLGAGPD
0	6		S165-p	PEADLPRsPGNLTER
0	25		K189-u	AIAGGDEkGAAQVAA
0	2		T224-p	GPIRLQVtLEDAASA
0	1		S312-p	EAPATGPsPQHPQkM
0	3		K318-u	PsPQHPQkMDGELGR
0	1		A383	PCTWDPLAAAST___

	SHARPIN iso3
R29	LAVHAAVRPLGAGPD
S165	PEADLPRSPGNLTER
K189	AIAGGDEKGAAQVAA
T224	GPIRLQVTLEDAASA
S312	EAPATGPSPQHPQKM
K318	PSPQHPQKMDGELGR
S406-p	PSLTSPTsPGPH___

	mouse
R28	LAVHAAVRPLGAGQD
S163	PEVDLPQSSGNFKKE
K186-u	AIAGGDEkAAAQVAA
T221	GPIRLQVTVEDATSV
S307	PREVSGQSLQNSkMD
K312-u	GQSLQNSkMDRKLGL
A376	PCAWDPLAAAST___

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