Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage Cell Signaling Technology
PhosphoSitePlus
HomeAbout PhosphoSiteUsing PhosphoSiteCuration ProcessContact
logos LINCs Logo Mt Sinai Logo NIH Logo NCI Logo
Protein Page:
SHARPIN (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

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
Chromosomal Location of Human Ortholog: 8q24.3
Cellular Component: cell junction; cytoplasm; cytosol; dendrite; nucleus; postsynaptic density
Molecular Function: identical protein binding; polyubiquitin binding; protein binding; protein complex binding; zinc ion binding
Biological Process: apoptotic nuclear changes; brain development; I-kappaB kinase/NF-kappaB cascade; keratinization; mitochondrion organization and biogenesis; negative regulation of inflammatory response; positive regulation of I-kappaB kinase/NF-kappaB cascade; 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® Total Proteins
Select Structure to View Below

SHARPIN

Protein Structure Not Found.
Download PyMol Script
Download ChimeraX Script


STRING  |  cBioPortal  |  Wikipedia  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Scansite  |  Pfam  |  RCSB PDB  |  Phospho.ELM  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene


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
 

Show Multiple Sequence Alignment


 LTP 

LTP: 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.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 R29‑m1 LAVHAAVrPLGAGPD
1 0 R43 DAEAQLRRLQLSADP
0 2 S146‑p ACPVSLPsPPEAStL
0 1 T152‑p PsPPEAStLKGPPPE
0 14 S165‑p PEADLPRsPGNLtER
0 1 T170‑p PRsPGNLtEREELAG
1 0 T170 PRsPGNLTEREELAG
1 0 R172 sPGNLtEREELAGSL
0 26 K189‑ub AIAGGDEkGAAQVAA
0 2 T224‑p GPIRLQVtLEDAASA
0 5 S312‑p EAPATGPsPQHPQkM
1 4 K318‑ub PsPQHPQkMDGELGR
  mouse

 
R28 LAVHAAVRPLGAGQD
K42‑ub DAEAQPRkLQLIADP
C144 MCPISPPCSSMAQIP
I150 PCSSMAQIPKATQPE
S163 PEVDLPQSSGNFkkE
K168 PQSSGNFKkEELATR
K168‑ub PQSSGNFkkEELATR
K169‑ub QSSGNFkkEELATRL
K186‑ub AIAGGDEkAAAQVAA
T221 GPIRLQVTVEDATSV
S307 PREVSGQSLQNSkMD
K312‑ub GQSLQNSkMDRKLGL
Home  |  Curator Login With enhanced literature mining using Linguamatics I2E I2E Logo Produced by 3rd Millennium  |  Design by Digizyme
©2003-2013 Cell Signaling Technology, Inc.