SHARPIN (SHANK associated RH domain interactor)

Gene

• Entrez ID: 81858
• Gene name: SHANK associated RH domain interactor
• Gene symbol: SHARPIN
• Synonyms (NCBI Gene): AIFID, SIPL1
• Chromosome: 8
• Chromosome location: 8q24.3

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2622312	hsa-miR-1254	CLIP-seq
MIRT2622313	hsa-miR-1270	CLIP-seq
MIRT2622314	hsa-miR-199a-3p	CLIP-seq
MIRT2622315	hsa-miR-199b-3p	CLIP-seq
MIRT2622316	hsa-miR-2861	CLIP-seq
MIRT2622317	hsa-miR-3116	CLIP-seq
MIRT2622318	hsa-miR-3129-5p	CLIP-seq
MIRT2622319	hsa-miR-4254	CLIP-seq
MIRT2622320	hsa-miR-4274	CLIP-seq
MIRT2622321	hsa-miR-4276	CLIP-seq
MIRT2622322	hsa-miR-4447	CLIP-seq
MIRT2622323	hsa-miR-4472	CLIP-seq
MIRT2622324	hsa-miR-4488	CLIP-seq
MIRT2622325	hsa-miR-4683	CLIP-seq
MIRT2622326	hsa-miR-4697-5p	CLIP-seq
MIRT2622327	hsa-miR-4707-5p	CLIP-seq
MIRT2622328	hsa-miR-620	CLIP-seq
MIRT2622329	hsa-miR-936	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004842	Function	Ubiquitin-protein transferase activity	IBA
GO:0005515	Function	Protein binding	IPI	21455173, 21455180, 21455181, 21709223, 21947080, 22158122, 23032186, 23104095, 24141947, 27070702, 28514442, 30561431, 32296183, 33961781, 36179048
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA	20179993
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0007005	Process	Mitochondrion organization	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0008544	Process	Epidermis development	IEA
GO:0010803	Process	Regulation of tumor necrosis factor-mediated signaling pathway	IDA	21455173
GO:0010803	Process	Regulation of tumor necrosis factor-mediated signaling pathway	IEA
GO:0016567	Process	Protein ubiquitination	IEA
GO:0030262	Process	Apoptotic nuclear changes	IEA
GO:0030674	Function	Protein-macromolecule adaptor activity	IEA
GO:0031424	Process	Keratinization	IEA
GO:0031593	Function	Polyubiquitin modification-dependent protein binding	IDA	21455173, 21455181
GO:0042742	Process	Defense response to bacterium	IDA	28481331
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	IBA
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	IDA	21455173
GO:0043123	Process	Positive regulation of canonical NF-kappaB signal transduction	IEA
GO:0043130	Function	Ubiquitin binding	IBA
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IBA
GO:0045202	Component	Synapse	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0050728	Process	Negative regulation of inflammatory response	IEA
GO:0050728	Process	Negative regulation of inflammatory response	ISS
GO:0071797	Component	LUBAC complex	IBA
GO:0071797	Component	LUBAC complex	IDA	21455173, 21455180, 21455181, 24726323, 27523608, 28481331
GO:0071797	Component	LUBAC complex	IEA
GO:0071797	Component	LUBAC complex	IPI	21455180
GO:0097039	Process	Protein linear polyubiquitination	IBA
GO:0097039	Process	Protein linear polyubiquitination	IDA	21455173, 21455180, 21455181
GO:2000348	Process	Regulation of CD40 signaling pathway	IDA	21455173

Other IDs

• MIM: 611885
• HGNC: 25321
• e!Ensembl: ENSG00000179526

Protein

• UniProt ID: Q9H0F6
• Protein name: Sharpin (Shank-associated RH domain-interacting protein) (Shank-interacting protein-like 1) (hSIPL1)
• Protein 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 (PubMed:21455173, PubMed:21455180, PubMed:21455181).
• PDB: 4EMO, 5X0W, 8K6P
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16764	Sharpin_PH	15 → 127	Sharpin PH domain	Domain

• Tissue specificity: 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 suc
• Sequence:

  MAPPAGGAAAAASDLGSAAVLLAVHAAVRPLGAGPDAEAQLRRLQLSADPERPGRFRLEL
  LGAGPGAVNLEWPLESVSYTIRGPTQHELQPPPGGPGTLSLHFLNPQEAQRWAVLVRGAT
  VEGQNGSKSNSPPALGPEACPVSLPSPPEASTLKGPPPEADLPRSPGNLTEREELAGSLA
  RAIAGGDEKGAAQVAAVLAQHRVALSVQLQEACFPPGPIRLQVTLEDAASAASAASSAHV
  ALQVHPHCTVAALQEQVFSELGFPPAVQRWVIGRCLCVPERSLASYGVRQDGDPAFLYLL
  SAPREAPATGPSPQHPQKMDGELGRLFPPSLGLPPGPQPAASSLPSPLQPSWSCPSCTFI
  NAPDRPGCEMCSTQRPCTWDPLAAAST

• Sequence length: 387

Pathways

KEGG:

Necroptosis
NOD-like receptor signaling pathway
Shigellosis

Reactome:

Regulation of TNFR1 signaling
TNFR1-induced NFkappaB signaling pathway

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Autoinflammation with episodic fever and immune dysregulation	Pathogenic	rs1432748871, rs1564313667	RCV004525821 RCV004525822

Associations from Text Mining
Disease Name	Relationship Type	References
Alzheimer Disease	Associate	29684019, 31216982, 32558014, 34099642, 34737388, 34785643
Brain Damage Chronic	Associate	34785643
Branchio Oto Renal Syndrome	Associate	23851940
Breast Neoplasms	Stimulate	25992689
Breast Neoplasms	Associate	28063307, 29763465
Carcinogenesis	Associate	20458142, 25992689
Carcinogenesis	Inhibit	24925528
Carcinoma Basal Cell	Associate	32319607
Carcinoma Renal Cell	Associate	37908350
Cholangiocarcinoma	Associate	35968603
Esophageal Squamous Cell Carcinoma	Inhibit	31884247
Fatty Liver Alcoholic	Associate	39350187
Inflammation	Associate	29227283, 31216982, 32122970, 34737388
Malaria Cerebral	Associate	33942992
Melanoma	Associate	29227283
Neoplasms	Associate	20458142, 32319607, 35968603
Neoplasms	Stimulate	29763465
Neoplasms Basal Cell	Associate	32319607
Photosensitivity Disorders	Associate	32122970
Precancerous Conditions	Inhibit	32319607
Prostatic Neoplasms	Associate	24925528
Prostatitis	Associate	20458142
Uterine Cervical Neoplasms	Associate	20458142