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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. Among its related pathways are Transmission across Chemical Synapses and Protein-protein interactions at synapses. Gene Ontology (GO) annotations related to this gene include identical protein binding and polyubiquitin modification-dependent protein 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.

Additional gene information for SHARPIN Gene

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

Genomics for SHARPIN Gene

GeneHancer (GH) Regulatory Elements for SHARPIN Gene

Promoters and enhancers for SHARPIN Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH08I144101 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 568 +4.2 4213 4 DMAP1 IRF4 YY1 ZNF213 E2F8 ZNF416 ZNF143 ZNF548 SP3 NFYC SHARPIN MAF1 ZNF623 ZNF7 ZNF16 ZNF696 ZNF517 ZNF251 ZNF250 CPSF1
GH08I144107 Enhancer 0.9 Ensembl ENCODE 550.8 -0.9 -923 3.7 CTCF PKNOX1 MAX BACH1 SIN3A BMI1 ZKSCAN1 E2F1 CTBP1 POLR2B WDR97 SHARPIN MAF1 GC08P144119
GH08I143289 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 34.2 +817.4 817439 3.4 PKNOX1 CLOCK SMAD1 MLX ARID4B SIN3A DMAP1 ZNF2 SLC30A9 POLR2B ENSG00000272172 ZNF696 SHARPIN MINCR BREA2 TOP1MT ZNF623 ZFP41 PARP10 GPAA1
GH08I144899 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE 25.8 -793.5 -793467 3.6 HDGF PKNOX1 FOXA2 MLX ARID4B SIN3A DMAP1 ZNF2 ZBTB7B IRF4 ZNF250 ZNF7 CPSF1 VPS28 RPL8 ZNF16 ZNF251 SHARPIN GPAA1 PARP10
GH08I144461 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 25.8 -356.7 -356719 7 PKNOX1 MLX ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 SLC30A9 CBX5 CYHR1 ENSG00000254578 KIFC2 CPSF1 PPP1R16A ZNF707 ZNF7 SHARPIN ZNF16 VPS28
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SHARPIN on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SHARPIN gene promoter:

Genomic Locations for SHARPIN Gene

Genomic Locations for SHARPIN Gene
chr8:144,098,633-144,108,124
(GRCh38/hg38)
Size:
9,492 bases
Orientation:
Minus strand
chr8:145,153,536-145,163,027
(GRCh37/hg19)

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 approximately 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 isoforms=2189 and posLast=318318
  • Modification sites at PhosphoSitePlus

Other Protein References for SHARPIN Gene

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.
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.
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.

Phenotypes From GWAS Catalog for SHARPIN Gene

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:0031593 polyubiquitin modification-dependent protein binding IDA 21455173
GO:0032403 protein complex binding IEA --
GO:0042802 identical protein 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

Clone 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

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleus (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SHARPIN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0014069 postsynaptic density IEA --
GO:0030054 cell junction IEA --
GO:0030425 dendrite 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,IDA --
genes like me logo Genes that share ontologies with SHARPIN: view

No data available for SIGNOR curated interactions for SHARPIN Gene

Drugs & Compounds for SHARPIN Gene

No Compound Related Data Available

Transcripts for SHARPIN Gene

Unigene Clusters for SHARPIN Gene

SHANK-associated RH domain interactor:
Representative Sequences:

Clone 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 CGAP 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.

Evidence on tissue expression from TISSUES for SHARPIN Gene

  • Pancreas(4.2)
  • Nervous system(3.5)
  • Muscle(2.3)
genes like me logo Genes that share expression patterns with SHARPIN: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer 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 33 34
  • 99 (n)
cow
(Bos Taurus)
Mammalia SHARPIN 33 34
  • 83.55 (n)
dog
(Canis familiaris)
Mammalia SHARPIN 33 34
  • 82.06 (n)
mouse
(Mus musculus)
Mammalia Sharpin 33 16 34
  • 76.3 (n)
rat
(Rattus norvegicus)
Mammalia Sharpin 33
  • 76.27 (n)
oppossum
(Monodelphis domestica)
Mammalia SHARPIN 34
  • 49 (a)
OneToOne
chicken
(Gallus gallus)
Aves SHARPIN 34
  • 22 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SHARPIN 34
  • 19 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii LOC793673 33
  • 51.21 (n)
sharpin 34
  • 31 (a)
OneToMany
shrprbck1r 34
  • 18 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 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 Variation AA Info Type
rs11136254 benign, not specified 144,103,600(-) G/T coding_sequence_variant, non_coding_transcript_variant, synonymous_variant
rs11136256 benign, not specified 144,105,743(-) T/A/C upstream_transcript_variant
rs12549149 benign, not specified 144,103,543(-) C/A/G/T intron_variant
rs34674752 benign, not specified 144,099,319(-) G/A coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs1000048438 -- 144,104,070(-) G/A/T 5_prime_UTR_variant, non_coding_transcript_variant

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

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

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)

Additional Variant Information 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

Additional Disease Information for SHARPIN

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for SHARPIN Gene.

No data available for MalaCards , 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 MA (Journal of gastroenterology and hepatology 2003) 2 3 4 22 58
  2. Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins. (PMID: 11178875) Lim S … Kim E (Molecular and cellular neurosciences 2001) 2 3 22 58
  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 (The Journal of biological chemistry 2012) 3 4 58
  4. Linear ubiquitination prevents inflammation and regulates immune signalling. (PMID: 21455173) Gerlach B … Walczak H (Nature 2011) 3 4 58
  5. SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex. (PMID: 21455180) Tokunaga F … Iwai K (Nature 2011) 3 4 58

Products for SHARPIN Gene

Sources for SHARPIN Gene

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