UniProt Accession

 SHRPN_HUMAN; Q9H0F6; A6NEG3; C0L3L2; D3DWL3; Q8IXF5; Q8IXF6; Q8N2E7; Q8TB25; Q9BUE4 

Genbank Protein ID

 AB052764; AB052765; FJ655995; AL136816; AK075518; AC104592; CH471162; CH471162; CH471162; CH471162; BC002688; BC025244; BC034028 

Genbank Nucleotide ID

 BAC53797.1; BAC53798.1; ACN38058.1; CAB66750.1; BAC11666.1; EAW82152.1; EAW82153.1; EAW82150.1; EAW82151.1; AAH02688.2; AAH25244.1; AAH34028.1 

Protein Name

 Sharpin 

Protein Synonyms/Alias

 Shank-associated RH domain-interacting protein; Shank-interacting protein-like 1; hSIPL1 

Gene Name

 SHARPIN 

Gene Synonyms/Alias

 SIPL1; PSEC0216 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
189	AIAGGDEKGAAQVAA	ubiquitination	[1]

Reference

 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 219 288 Ubiquitin-like.
 ZN_FING 348 377 RanBP2-type.
 REGION 1 180 Self-association (By similarity).
 REGION 175 310 Interaction with SHANK1 (By similarity).
 MOD_RES 165 165 Phosphoserine.
 MOD_RES 312 312 Phosphoserine.  

Keyword

 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Metal-binding; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 387 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0071797; C:LUBAC complex; IDA:UniProtKB.
 GO:0014069; C:postsynaptic density; IEA:Compara.
 GO:0031593; F:polyubiquitin binding; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0030262; P:apoptotic nuclear changes; IEA:Compara.
 GO:0007420; P:brain development; IEA:Compara.
 GO:0031424; P:keratinization; IEA:Compara.
 GO:0007005; P:mitochondrion organization; IEA:Compara.
 GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
 GO:0051260; P:protein homooligomerization; IEA:Compara.
 GO:0097039; P:protein linear polyubiquitination; IDA:UniProtKB.
 GO:2000348; P:regulation of CD40 signaling pathway; IDA:UniProtKB.
 GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB. 

Interpro

 IPR026168; SHARPIN.
 IPR001876; Znf_RanBP2. 

Pfam

 PF00641; zf-RanBP 

SMART

 SM00547; ZnF_RBZ 

PROSITE

 PS50053; UBIQUITIN_2
 PS01358; ZF_RANBP2_1
 PS50199; ZF_RANBP2_2 

PRINTS