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SKAP2 src kinase associated phosphoprotein 2 [ Homo sapiens (human) ]

Gene ID: 8935, updated on 2-Nov-2024

Summary

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Official Symbol
SKAP2provided by HGNC
Official Full Name
src kinase associated phosphoprotein 2provided by HGNC
Primary source
HGNC:HGNC:15687
See related
Ensembl:ENSG00000005020 MIM:605215; AllianceGenome:HGNC:15687
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PRAP; RA70; SAPS; SCAP2; SKAP55R; SKAP-HOM
Summary
The protein encoded by this gene shares homology with Src kinase-associated phosphoprotein 1, and is a substrate of Src family kinases. It is an adaptor protein that is thought to play an essential role in the Src signaling pathway, and in regulating proper activation of the immune system. This protein contains an amino terminal coiled-coil domain for self-dimerization, a plecskstrin homology (PH) domain required for interactions with lipids at the membrane, and a Src homology (SH3) domain at the carboxy terminus. Some reports indicate that this protein inhibits actin polymerization through interactions with actin assembly factors, and might negatively regulate the invasiveness of tumors by modulating actin assembly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]
Expression
Ubiquitous expression in spleen (RPKM 10.6), appendix (RPKM 9.8) and 24 other tissues See more
Orthologs
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Genomic context

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See SKAP2 in Genome Data Viewer
Location:
7p15.2
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (26654770..26864590, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (26790493..27000391, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (26706687..26904209, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101928077 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:26653756-26654272 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:26657384-26658583 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:26669689-26670190 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:26670191-26670690 Neighboring gene long intergenic non-protein coding RNA 2860 Neighboring gene VISTA enhancer hs296 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:26774177-26774499 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr7:26823633-26824297 Neighboring gene uncharacterized LOC124901606 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:26897041-26897642 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25791 Neighboring gene ribosomal protein L7a pseudogene 38 Neighboring gene high mobility group box 3 pseudogene 20

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. SKAP2 acts downstream of CD11b/CD18 and regulates neutrophil effector function. Bouti P, et al. Front Immunol, 2024. PMID 38487529, Free PMC Article
  2. RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a Src-independent manner. Park SY, et al. J Biol Chem, 2004 Aug 6. PMID 15166227
  3. Genome-wide DNA copy number analysis in pancreatic cancer using high-density single nucleotide polymorphism arrays. Harada T, et al. Oncogene, 2008 Mar 20. PMID 17952125, Free PMC Article
  4. Src kinase-associated phosphoprotein2 expression is associated with poor prognosis in non-small cell lung cancer. Kuranami S, et al. Anticancer Res, 2015 Apr. PMID 25862907
  5. SKAP2, a Candidate Gene for Type 1 Diabetes, Regulates β-Cell Apoptosis and Glycemic Control in Newly Diagnosed Patients. Fløyel T, et al. Diabetes, 2021 Feb. PMID 33203694, Free PMC Article

See all (50) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. SKAP2 acts downstream of CD11b/CD18 and regulates neutrophil effector function.
    Title: SKAP2 acts downstream of CD11b/CD18 and regulates neutrophil effector function.
  2. SKAP2 is downregulated in the villous tissues of patients with missed abortion and regulates growth and migration in trophoblasts through the WAVE2-ARP2/3 signaling pathway.
    Title: SKAP2 is downregulated in the villous tissues of patients with missed abortion and regulates growth and migration in trophoblasts through the WAVE2-ARP2/3 signaling pathway.
  3. The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events.
    Title: The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events.
  4. Diabetes With Multiple Autoimmune and Inflammatory Conditions Linked to an Activating SKAP2 Mutation.
    Title: Diabetes With Multiple Autoimmune and Inflammatory Conditions Linked to an Activating SKAP2 Mutation.
  5. SKAP2, a Candidate Gene for Type 1 Diabetes, Regulates beta-Cell Apoptosis and Glycemic Control in Newly Diagnosed Patients.
    Title: SKAP2, a Candidate Gene for Type 1 Diabetes, Regulates β-Cell Apoptosis and Glycemic Control in Newly Diagnosed Patients.
  6. Macrophages assemble the appropriate motile machinery to infiltrate tumors and promote disease progression, and implicate SKAP2 as an attractive candidate for therapeutically targeting TAMs.
    Title: SKAP2 Promotes Podosome Formation to Facilitate Tumor-Associated Macrophage Infiltration and Metastatic Progression.
  7. Skap2 is necessary for macrophage migration, chemotaxis, global actin reorganization and local actin reorganization upon integrin engagement.
    Title: Macrophages require Skap2 and Sirpα for integrin-stimulated cytoskeletal rearrangement.
  8. SKAP2 expression levels in NSCLC tissues could be a powerful biomarker of poor prognosis. Therefore, SKAP2 is a promising candidate molecular target for Non-small cell lung cancer treatment.
    Title: Src kinase-associated phosphoprotein2 expression is associated with poor prognosis in non-small cell lung cancer.
  9. results suggest that SKAP2 negatively regulates cell migration and tumor invasion in fibroblasts and glioblastoma cells by suppressing actin assembly induced by the WAVE2-cortactin complex
    Title: The Src substrate SKAP2 regulates actin assembly by interacting with WAVE2 and cortactin proteins.
  10. analysis of substrate specificity of lymphoid-specific tyrosine phosphatase (Lyp) and identification of Src kinase-associated protein of 55 kDa homolog (SKAP-HOM) as a Lyp substrate
    Title: Substrate specificity of lymphoid-specific tyrosine phosphatase (Lyp) and identification of Src kinase-associated protein of 55 kDa homolog (SKAP-HOM) as a Lyp substrate.
Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
EBI GWAS Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC10411, MGC33304

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in B cell activation IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of cell population proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
src kinase-associated phosphoprotein 2
Names
Fyn-associated phosphoprotein SKAP55 homologue
Pyk2/RAFTK-associated protein
SKAP-55HOM
SKAP55 homolog
retinoic acid-induced protein 70
src family-associated phosphoprotein 2
src kinase-associated phosphoprotein of 55-related protein
src-associated adapter protein with PH and SH3 domains

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)

  1. NM_001303468.2 → NP_001290397.1  src kinase-associated phosphoprotein 2 isoform 2

    See identical proteins and their annotated locations for NP_001290397.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate 5' terminal exon and uses a downstream start codon compared to variant 1. It encodes isoform 2 which has a shorter N-terminus compared to isoform 1.
    Source sequence(s)
    AK299317, BC002893, BC036044, BQ433993, DA714447, DA738803
    UniProtKB/TrEMBL
    B7Z5R3
    Conserved Domains (3) summary
    pfam00169
    Location:7 → 46
    PH; PH domain
    cl17036
    Location:129 → 181
    SH3; Src Homology 3 domain superfamily
    cl17171
    Location:1 → 49
    PH-like; Pleckstrin homology-like domain

  2. NM_003930.5 → NP_003921.2  src kinase-associated phosphoprotein 2 isoform 1

    See identical proteins and their annotated locations for NP_003921.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AK313209, BC002893, BC036044, BQ433993, HY044523
    Consensus CDS
    CCDS5400.1
    UniProtKB/Swiss-Prot
    A4D173, O75563, Q53GP6, Q75MK6, Q75MZ4, Q9UBZ3, Q9UED8
    UniProtKB/TrEMBL
    B7Z5N4
    Related
    ENSP00000005587.2, ENST00000345317.7
    Conserved Domains (3) summary
    cd12045
    Location:301 → 353
    SH3_SKAP2; Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2
    cd13381
    Location:117 → 221
    PH_Skap-hom_Skap2; Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain
    pfam00169
    Location:117 → 218
    PH; PH domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    26654770..26864590 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017012771.3 → XP_016868260.1  src kinase-associated phosphoprotein 2 isoform X1

    UniProtKB/Swiss-Prot
    A4D173, O75563, Q53GP6, Q75MK6, Q75MZ4, Q9UBZ3, Q9UED8
    UniProtKB/TrEMBL
    B7Z5N4
    Conserved Domains (3) summary
    cd12045
    Location:301 → 353
    SH3_SKAP2; Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2
    cd13381
    Location:117 → 221
    PH_Skap-hom_Skap2; Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain
    pfam00169
    Location:117 → 218
    PH; PH domain

  2. XM_047421010.1 → XP_047276966.1  src kinase-associated phosphoprotein 2 isoform X2

    UniProtKB/TrEMBL
    B7Z5R3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    26790493..27000391 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054359293.1 → XP_054215268.1  src kinase-associated phosphoprotein 2 isoform X1

    UniProtKB/Swiss-Prot
    A4D173, O75563, Q53GP6, Q75MK6, Q75MZ4, Q9UBZ3, Q9UED8

  2. XM_054359294.1 → XP_054215269.1  src kinase-associated phosphoprotein 2 isoform X2

    UniProtKB/TrEMBL
    B7Z5R3
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O75563.1 GenPept UniProtKB/Swiss-Prot:O75563

Gene LinkOut

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