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Aliases for SHARPIN Gene

Aliases for SHARPIN Gene

  • SHANK Associated RH Domain Interactor 2 3 5
  • Shank-Associated RH Domain-Interacting Protein 3 4
  • Shank-Interacting Protein-Like 1 3 4
  • HSIPL1 3 4
  • SIPL1 3 4
  • Sharpin 3

External Ids for SHARPIN Gene

Previous GeneCards Identifiers for SHARPIN Gene

  • GC08M145226
  • GC08M145153
  • GC08M140429

Summaries for SHARPIN Gene

GeneCards Summary for SHARPIN Gene

SHARPIN (SHANK Associated RH Domain Interactor) is a Protein Coding gene. Diseases associated with SHARPIN include Branchiootic Syndrome. Among its related pathways are Protein-protein interactions at synapses and Toll-Like receptor Signaling Pathways. GO annotations related to this gene include identical protein binding and polyubiquitin binding. An important paralog of this gene is RBCK1.

UniProtKB/Swiss-Prot for SHARPIN Gene

  • 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.

No data available for Entrez Gene Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SHARPIN Gene

Genomics for SHARPIN Gene

Regulatory Elements for SHARPIN Gene

Enhancers for SHARPIN Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH08F144073 1.6 FANTOM5 Ensembl ENCODE 12.2 +33.6 33624 2.2 TBP HDAC1 PKNOX1 ATF1 ARNT NFRKB ELK1 CREM KLF13 ZBTB2 WDR97 ENSG00000255224 SPATC1 CYC1 MAF1 SHARPIN PARP10 ZNF250 GRINA GSDMD
GH08F144062 1.3 FANTOM5 Ensembl ENCODE 12.2 +44.6 44623 2.3 ELF3 CTCF TFAP4 ZNF792 SAP130 ARID4B REST NR3C1 RAD21 HIC1 WDR97 ENSG00000255224 SPATC1 CYC1 MAF1 SHARPIN PARP10 PLEC OPLAH MIR6846
GH08F143968 1.4 Ensembl ENCODE 11.2 +133.9 133885 11.0 HDGF PKNOX1 CREB3L1 ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 PLEC GPAA1 MAF1 WDR97 C8orf82 ZNF251 LRRC14 ZNF623 ZNF250 MIR661
GH08F144077 1.1 ENCODE 11.8 +29.4 29357 3.4 HDGF PKNOX1 ARNT CREB3L1 WRNIP1 ARID4B SIN3A DMAP1 YY1 ZNF143 WDR97 MAF1 ENSG00000255224 C8orf82 SHARPIN PARP10 SPATC1 ZNF250 MIR6847
GH08F144002 1.1 Ensembl ENCODE 11.3 +103.6 103621 3.5 HDAC1 PKNOX1 SAP130 MAX CEBPG THRB RAD21 YY1 GATA3 SCRT2 PLEC WDR97 EXOSC4 ENSG00000255224 MIR6847 MIR661 GPAA1 CYC1 MAF1 SHARPIN
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SHARPIN on UCSC Golden Path with GeneCards custom track

Genomic Location for SHARPIN Gene

Chromosome:
8
Start:
144,098,633 bp from pter
End:
144,108,124 bp from pter
Size:
9,492 bases
Orientation:
Minus strand

Genomic View for SHARPIN Gene

Genes around SHARPIN on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SHARPIN Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SHARPIN Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SHARPIN Gene

Proteins for SHARPIN Gene

  • Protein details for SHARPIN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H0F6-SHRPN_HUMAN
    Recommended name:
    Sharpin
    Protein Accession:
    Q9H0F6
    Secondary Accessions:
    • A6NEG3
    • C0L3L2
    • D3DWL3
    • Q8IXF5
    • Q8IXF6
    • Q8N2E7
    • Q8TB25
    • Q9BUE4

    Protein attributes for SHARPIN Gene

    Size:
    387 amino acids
    Molecular mass:
    39949 Da
    Quaternary structure:
    • Monomer and homodimer. 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. Interacts with EYA1, EYA2, SHANK1 and SHANK3 (via ANK repeats).
    SequenceCaution:
    • Sequence=BAC11666.1; Type=Frameshift; Positions=334; Evidence={ECO:0000305}; Sequence=BAC53797.1; Type=Frameshift; Positions=218; Evidence={ECO:0000305}; Sequence=BAC53798.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SHARPIN Gene

    Alternative splice isoforms for SHARPIN Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SHARPIN Gene

Post-translational modifications for SHARPIN Gene

  • Ubiquitination at Lys 189 and Lys 318
  • Modification sites at PhosphoSitePlus

Other Protein References for SHARPIN Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for SHARPIN (SHARPIN)

No data available for DME Specific Peptides for SHARPIN Gene

Domains & Families for SHARPIN Gene

Gene Families for SHARPIN Gene

Protein Domains for SHARPIN Gene

Suggested Antigen Peptide Sequences for SHARPIN Gene

Graphical View of Domain Structure for InterPro Entry

Q9H0F6

UniProtKB/Swiss-Prot:

SHRPN_HUMAN :
  • The Ubiquitin-like domain is required for the interaction with RNF31.
  • Contains 1 RanBP2-type zinc finger.
Domain:
  • The Ubiquitin-like domain is required for the interaction with RNF31.
  • The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin. Binds preferentially linear polyubiquitin chains and Lys-63-linked polyubiquitin chains over Lys-48-linked polyubiquitin chains. Also binds monoubiquitin.
  • Contains 1 ubiquitin-like domain.
Similarity:
  • Contains 1 RanBP2-type zinc finger.
genes like me logo Genes that share domains with SHARPIN: view

Function for SHARPIN Gene

Molecular function for SHARPIN Gene

UniProtKB/Swiss-Prot 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.

Gene Ontology (GO) - Molecular Function for SHARPIN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IBA --
GO:0005515 protein binding IPI 21455173
GO:0008270 zinc ion binding IEA --
GO:0031593 polyubiquitin binding IDA 21455173
GO:0032403 protein complex binding IEA --
genes like me logo Genes that share ontologies with SHARPIN: view
genes like me logo Genes that share phenotypes with SHARPIN: view

Animal Model Products

miRNA for SHARPIN Gene

miRTarBase miRNAs that target SHARPIN

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for SHARPIN Gene

Localization for SHARPIN Gene

Subcellular locations from UniProtKB/Swiss-Prot for SHARPIN Gene

Cytoplasm, cytosol. Cell junction, synapse. Note=Enriched at synaptic sites in mature neurons where it colocalizes with SHANK1. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SHARPIN gene
Compartment Confidence
cytosol 5
nucleus 3
extracellular 2
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for SHARPIN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
GO:0014069 postsynaptic density IEA --
GO:0030054 cell junction IEA --
genes like me logo Genes that share ontologies with SHARPIN: view

Pathways & Interactions for SHARPIN Gene

genes like me logo Genes that share pathways with SHARPIN: view

Pathways by source for SHARPIN Gene

Gene Ontology (GO) - Biological Process for SHARPIN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007005 mitochondrion organization IEA --
GO:0007249 I-kappaB kinase/NF-kappaB signaling TAS --
GO:0007420 brain development IEA --
GO:0008544 epidermis development IEA --
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway TAS --
genes like me logo Genes that share ontologies with SHARPIN: view

No data available for SIGNOR curated interactions for SHARPIN Gene

Transcripts for SHARPIN Gene

Unigene Clusters for SHARPIN Gene

SHANK-associated RH domain interactor:
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SHARPIN Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12
SP1: -
SP2: - -
SP3: - - -
SP4: - - -
SP5: - -
SP6: -
SP7:
SP8: - - - - - - -
SP9:

Relevant External Links for SHARPIN Gene

GeneLoc Exon Structure for
SHARPIN
ECgene alternative splicing isoforms for
SHARPIN

Expression for SHARPIN Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SHARPIN Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SHARPIN Gene

This gene is overexpressed in Platelet (21.5), Peripheral blood mononuclear cells (21.2), and Skin (14.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SHARPIN Gene



Protein tissue co-expression partners for SHARPIN Gene

NURSA nuclear receptor signaling pathways regulating expression of SHARPIN Gene:

SHARPIN

SOURCE GeneReport for Unigene cluster for SHARPIN Gene:

Hs.529755

mRNA Expression by UniProt/SwissProt for SHARPIN Gene:

Q9H0F6-SHRPN_HUMAN
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.
genes like me logo Genes that share expression patterns with SHARPIN: view

Primer Products

No data available for mRNA differential expression in normal tissues for SHARPIN Gene

Orthologs for SHARPIN Gene

This gene was present in the common ancestor of chordates.

Orthologs for SHARPIN Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SHARPIN 34 35
  • 99 (n)
cow
(Bos Taurus)
Mammalia SHARPIN 34 35
  • 83.55 (n)
dog
(Canis familiaris)
Mammalia SHARPIN 34 35
  • 82.06 (n)
mouse
(Mus musculus)
Mammalia Sharpin 34 16 35
  • 76.3 (n)
rat
(Rattus norvegicus)
Mammalia Sharpin 34
  • 76.27 (n)
oppossum
(Monodelphis domestica)
Mammalia SHARPIN 35
  • 49 (a)
OneToOne
chicken
(Gallus gallus)
Aves SHARPIN 35
  • 22 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SHARPIN 35
  • 19 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii LOC793673 34
  • 51.21 (n)
sharpin 35
  • 31 (a)
OneToMany
shrprbck1r 35
  • 18 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 3 (a)
OneToMany
Species where no ortholog for SHARPIN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SHARPIN Gene

ENSEMBL:
Gene Tree for SHARPIN (if available)
TreeFam:
Gene Tree for SHARPIN (if available)

Paralogs for SHARPIN Gene

Paralogs for SHARPIN Gene

(1) SIMAP similar genes for SHARPIN Gene using alignment to 3 proteins:

Pseudogenes.org Pseudogenes for SHARPIN Gene

genes like me logo Genes that share paralogs with SHARPIN: view

Variants for SHARPIN Gene

Sequence variations from dbSNP and Humsavar for SHARPIN Gene

SNP ID Clin Chr 08 pos Sequence Context AA Info Type
rs111322040 -- 144,100,578(+) TGGGG(A/G)GGTCC intron-variant
rs11136254 -- 144,103,600(-) CTGAG(A/C)GGCCT nc-transcript-variant, upstream-variant-2KB, reference, synonymous-codon
rs11136255 -- 144,104,196(+) GGGCT(A/G)CCACC nc-transcript-variant, upstream-variant-2KB, utr-variant-5-prime
rs11136256 -- 144,105,743(+) GAGAC(C/T)GGAGA upstream-variant-2KB, reference, synonymous-codon
rs112028217 -- 144,098,481(+) ATGCC(A/G)TGCTT downstream-variant-500B

Structural Variations from Database of Genomic Variants (DGV) for SHARPIN Gene

Variant ID Type Subtype PubMed ID
nsv950015 CNV deletion 24416366
nsv6448 CNV insertion 18451855
nsv612915 CNV loss 21841781
nsv612914 CNV loss 21841781
nsv515809 CNV gain+loss 19592680
nsv470249 CNV loss 18288195
nsv466014 CNV loss 19166990
nsv428208 CNV gain 18775914
nsv1025071 CNV gain 25217958
esv29971 CNV loss 17803354
esv2759651 CNV gain 17122850
dgv906n27 CNV loss 19166990
dgv12433n54 CNV gain 21841781
dgv12431n54 CNV loss 21841781

Variation tolerance for SHARPIN Gene

Residual Variation Intolerance Score: 87.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.87; 67.39% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SHARPIN Gene

Human Gene Mutation Database (HGMD)
SHARPIN
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SHARPIN

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SHARPIN Gene

Disorders for SHARPIN Gene

MalaCards: The human disease database

(1) MalaCards diseases for SHARPIN Gene - From: DISEASES

Disorder Aliases PubMed IDs
branchiootic syndrome
  • branchiootic syndrome 1
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for SHARPIN

Genetic Association Database (GAD)
SHARPIN
Human Genome Epidemiology (HuGE) Navigator
SHARPIN
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SHARPIN
genes like me logo Genes that share disorders with SHARPIN: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SHARPIN Gene

Publications for SHARPIN Gene

  1. Novel human and mouse genes encoding a shank-interacting protein and its upregulation in gastric fundus of W/WV mouse. (PMID: 12753155) Daigo Y. … Fujino M.A. (J. Gastroenterol. Hepatol. 2003) 2 3 4 22 64
  2. Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins. (PMID: 11178875) Lim S. … Kim E. (Mol. Cell. Neurosci. 2001) 2 3 22 64
  3. Structural analysis of SHARPIN, a subunit of a large multi-protein E3 ubiquitin ligase, reveals a novel dimerization function for the pleckstrin homology superfold. (PMID: 22549881) Stieglitz B. … Rittinger K. (J. Biol. Chem. 2012) 3 4 64
  4. Linear ubiquitination prevents inflammation and regulates immune signalling. (PMID: 21455173) Gerlach B. … Walczak H. (Nature 2011) 3 4 64
  5. SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain assembly complex. (PMID: 21455180) Tokunaga F. … Iwai K. (Nature 2011) 3 4 64

Products for SHARPIN Gene

Sources for SHARPIN Gene

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