Sharpin SHANK-associated RH domain interacting protein [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Sharpinprovided by MGI
Official Full Name: SHANK-associated RH domain interacting proteinprovided by MGI
Primary source: MGI:MGI:1913331
See related: Ensembl:ENSMUSG00000022552 AllianceGenome:MGI:1913331
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: cpdm; SIPL1; RBCKL1; 0610041B22Rik
Summary: Predicted to enable several functions, including identical protein binding activity; ubiquitin binding activity; and ubiquitin-protein transferase activity. Involved in negative regulation of inflammatory response; positive regulation of I-kappaB kinase/NF-kappaB signaling; and regulation of tumor necrosis factor-mediated signaling pathway. Acts upstream of or within apoptotic nuclear changes; keratinization; and mitochondrion organization. Predicted to be located in cytosol; dendrite; and postsynaptic density. Predicted to be part of LUBAC complex. Is expressed in genitourinary system. Used to study atopic dermatitis. Orthologous to human SHARPIN (SHANK associated RH domain interactor). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in spleen adult (RPKM 39.1), thymus adult (RPKM 38.9) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 15 D3; 15 35.75 cM

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	15	NC_000081.7 (76231240..76235310, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	15	NC_000081.6 (76347040..76351110, complement)

Chromosome 15 - NC_000081.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mechanistic insights into the homo-dimerization of HOIL-1L and SHARPIN.
Title: Mechanistic insights into the homo-dimerization of HOIL-1L and SHARPIN.
Immune dysregulation in SHARPIN-deficient mice is dependent on CYLD-mediated cell death.
Title: Immune dysregulation in SHARPIN-deficient mice is dependent on CYLD-mediated cell death.
A novel role for SHARPIN in amyloid-beta phagocytosis and inflammation by peripheral blood-derived macrophages in Alzheimer's disease.
Title: A novel role for SHARPIN in amyloid-β phagocytosis and inflammation by peripheral blood-derived macrophages in Alzheimer's disease.
Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice.
Title: Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice.
The sharpin may complex with both kindlin-1 and the integrin beta1 CT to restrict the talin head domain binding, thus inhibiting beta1-integrin activation.
Title: Sharpin suppresses β1-integrin activation by complexing with the β1 tail and kindlin-1.
Fibroblasts derived from Sharpin(cpdm)Myd88(--) mice failed to provide protection against TNF-induced cell death. Sharpin(cpdm)Myd88(--) mice had reduced TNF production in their skin.
Title: Innate immune adaptor MyD88 deficiency prevents skin inflammation in SHARPIN-deficient mice.
SHARPIN, a protein previously associated with increased cancer growth and metastasis, may also have important regulatory roles in controlling the tumor microenvironment
Title: (68)Ga-DOTA-E[c(RGDfK)](2) PET Imaging of SHARPIN-Regulated Integrin Activity in Mice.
LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain.
Title: Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC Stabilization.
Data show that keratinocyte-specific deletion of ubiquitin-protein ligases HOIP, HOIL-1 (E-KO) and shank-interacting protein-like 1 protein (SHARPIN) results in severe dermatitis causing postnatal lethality.
Title: LUBAC prevents lethal dermatitis by inhibiting cell death induced by TNF, TRAIL and CD95L.
Both Sharpin/Fas and Sharpin/Fasl compound mutant mice developed an auto-inflammatory phenotype similar to that seen in Sharpin null mice, indicating that initiation of apoptosis by FAS signalling is likely not involved in the pathogenesis of this disease.
Title: Loss of FAS/FASL signalling does not reduce apoptosis in Sharpin null mice.

Submit: New GeneRIF Correction See all GeneRIFs (40)

Phenotypes

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Associated conditions

Description	Tests
chronic proliferative dermatitis GeneReviews: Not available

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Spontaneous (2) 1 citation
Targeted (2) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables polyubiquitin modification-dependent protein binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables protein-macromolecule adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ubiquitin binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin-protein transferase activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within apoptotic nuclear changes	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to bacterium	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within epidermis development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within keratinization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mitochondrion organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein linear polyubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein linear polyubiquitination	ISO Inferred from Sequence Orthology more info
involved_in regulation of CD40 signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in regulation of tumor necrosis factor-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of tumor necrosis factor-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in tumor necrosis factor-mediated signaling pathway	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of LUBAC complex	IBA Inferred from Biological aspect of Ancestor more info
part_of LUBAC complex	IDA Inferred from Direct Assay more info	PubMed
part_of LUBAC complex	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: sharpin

Names: mSIPL1; protein kinase C-interacting protein RBCC like 1; shank-associated RH domain-interacting protein; shank-interacting protein-like 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_025340.2 → NP_079616.2 sharpin

See identical proteins and their annotated locations for NP_079616.2

Status: VALIDATED

Source sequence(s)

BC016203, BI729629

Consensus CDS

CCDS37121.1

UniProtKB/Swiss-Prot

Q7TNT3, Q8CHL3, Q91WA6

Related

ENSMUSP00000023211.10, ENSMUST00000023211.16

Conserved Domains (4) summary

sd00029
Location:345 → 364

zf-RanBP2; RanBP2-type Zn finger [structural motif]

cd01799
Location:215 → 299

Ubl_HOIL1; ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins

pfam00641
Location:345 → 369

zf-RanBP; Zn-finger in Ran binding protein and others

pfam16764
Location:16 → 126

Sharpin_PH; Sharpin PH domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000081.7 Reference GRCm39 C57BL/6J

Range

76231240..76235310 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006520263.3 → XP_006520326.1 sharpin isoform X2

Related

ENSMUST00000144816.9

Conserved Domains (3) summary

smart00547
Location:209 → 230

ZnF_RBZ; Zinc finger domain

sd00029
Location:209 → 228

zf-RanBP2; RanBP2-type Zn finger [structural motif]

cd01799
Location:79 → 163

Ubl_HOIL1; ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins
XM_011245398.3 → XP_011243700.1 sharpin isoform X1

Conserved Domains (4) summary

smart00547
Location:293 → 314

ZnF_RBZ; Zinc finger domain

sd00029
Location:293 → 312

zf-RanBP2; RanBP2-type Zn finger [structural motif]

cd01799
Location:163 → 247

Ubl_HOIL1; ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins

cl17171
Location:16 → 65

PH-like; Pleckstrin homology-like domain