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SH2D1A SH2 domain containing 1A [ Homo sapiens (human) ]

Gene ID: 4068, updated on 2-Nov-2024

Summary

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Official Symbol
SH2D1Aprovided by HGNC
Official Full Name
SH2 domain containing 1Aprovided by HGNC
Primary source
HGNC:HGNC:10820
See related
Ensembl:ENSG00000183918 MIM:300490; AllianceGenome:HGNC:10820
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
LYP; SAP; XLP; DSHP; EBVS; IMD5; XLPD; MTCP1; XLPD1; SAP/SH2D1A
Summary
This gene encodes a protein that plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to its docking site. This protein can also bind to other related surface molecules that are expressed on activated T, B and NK cells, thereby modifying signal transduction pathways in these cells. Mutations in this gene cause lymphoproliferative syndrome X-linked type 1 or Duncan disease, a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus, with symptoms including severe mononucleosis and malignant lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Biased expression in lymph node (RPKM 17.0), spleen (RPKM 6.1) and 7 other tissues See more
Orthologs
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Genomic context

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See SH2D1A in Genome Data Viewer
Location:
Xq25
Exon count:
4
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (124346563..124373160)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (122657134..122683529)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (123480413..123507010)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene nucleophosmin 1 pseudogene 34 Neighboring gene uncharacterized LOC105373331 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:123539864-123541063 Neighboring gene TEX13 family member D Neighboring gene teneurin transmembrane protein 1 Neighboring gene NANOG hESC enhancer GRCh37_chrX:123622217-123622915 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:123667881-123668476 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:123668477-123669070 Neighboring gene ribosomal protein S26 pseudogene 57

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. SLAM-associated protein deficiency causes imbalanced early signal transduction and blocks downstream activation in T cells from X-linked lymphoproliferative disease patients. Sanzone S, et al. J Biol Chem, 2003 Aug 8. PMID 12766168
  2. Up-Regulation of LAT1 during Antiandrogen Therapy Contributes to Progression in Prostate Cancer Cells. Xu M, et al. J Urol, 2016 May. PMID 26682754
  3. Cerebral Vasculitis in X-linked Lymphoproliferative Disease Cured by Matched Unrelated Cord Blood Transplant. Gray PE, et al. J Clin Immunol, 2015 Oct. PMID 26433589
  4. Study of SH2D1A gene mutation in paediatric patients with B-cell lymphoma. Koochakzadeh L, et al. Allergol Immunopathol (Madr), 2015 Nov-Dec. PMID 25982576
  5. Consequence of the SLAM-SAP signaling pathway in innate-like and conventional lymphocytes. Veillette A, et al. Immunity, 2007 Nov. PMID 18031694

See all (152) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis.
    Title: SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis.
  2. Overexpression of SH2D1A promotes cancer progression and is associated with immune cell infiltration in hepatocellular carcinoma via bioinformatics and in vitro study.
    Title: Overexpression of SH2D1A promotes cancer progression and is associated with immune cell infiltration in hepatocellular carcinoma via bioinformatics and in vitro study.
  3. Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Naive Boy Is Associated With a Novel SH2D1A Mutation.
    Title: Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-NaĂŻve Boy Is Associated With a Novel SH2D1A Mutation.
  4. Epstein-Barr Virus-Negative Granulomatous Disease Due to SAP Deficiency.
    Title: Epstein-Barr Virus-Negative Granulomatous Disease Due to SAP Deficiency.
  5. SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves' Disease.
    Title: SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves' Disease.
  6. SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.
    Title: SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.
  7. Diagnostic challenges for a novel SH2D1A mutation associated with X-linked lymphoproliferative disease.
    Title: Diagnostic challenges for a novel SH2D1A mutation associated with X-linked lymphoproliferative disease.
  8. A Novel Missense Mutation Affecting the N-terminal Domain of SAP Protein in X-linked Lymphoproliferative Disease.
    Title: A Novel Missense Mutation Affecting the N-terminal Domain of SAP Protein in X-linked Lymphoproliferative Disease.
  9. hese data indicate NK cell-mediated cytotoxicity is not equally affected in Acute lymphoblastic leukemia (ALL) patients, nevertheless a positive correlation between low SAP expression and decreased NK cell-mediated cytotoxicity was observed in ALL patients with a leukocyte count >/=50,000xmm3
    Title: Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia.
  10. A new SH2D1A mutation in a female adult XLP disease with hemophagocytic lymphohistiocytosis and NK-cell leukemia.
    Title: A new SH2D1A mutation in a female adult XLP disease with hemophagocytic lymphohistiocytosis and NK-cell leukemia.
Submit: New GeneRIF Correction See all GeneRIFs (89)

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

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2021-01-27)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2021-01-27)

ClinGen Genome Curation PagePubMed

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

  • FLJ18687, FLJ92177

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-macromolecule adaptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in adaptive immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in cell-cell signaling IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular defense response IEA
Inferred from Electronic Annotation
more info
  
involved_in humoral immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in natural killer cell activation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in natural killer cell mediated cytotoxicity IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of T cell receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of natural killer cell mediated cytotoxicity IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of immune response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm TAS
Traceable Author Statement
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
SH2 domain-containing protein 1A
Names
Duncan disease SH2-protein
SLAM associated protein/SH2 domain protein 1A
SLAM-associated protein
T cell signal transduction molecule SAP
signaling lymphocyte activation molecule-associated protein
signaling lymphocytic activation molecule-associated protein

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.

Genomic

  1. NG_007464.1 RefSeqGene

    Range
    4983..31861
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_106

mRNA and Protein(s)

  1. NM_001114937.3 → NP_001108409.1  SH2 domain-containing protein 1A isoform 2

    See identical proteins and their annotated locations for NP_001108409.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.
    Source sequence(s)
    AA190204, AF100541, AL023657, DA007747
    Consensus CDS
    CCDS48162.1
    UniProtKB/Swiss-Prot
    O60880
    Related
    ENSP00000353126.4, ENST00000360027.5
    Conserved Domains (1) summary
    cd10400
    Location:2 → 104
    SH2_SAP1a; Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a

  2. NM_002351.5 → NP_002342.1  SH2 domain-containing protein 1A isoform 1

    See identical proteins and their annotated locations for NP_002342.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AA190204, AL023657
    Consensus CDS
    CCDS14608.1
    UniProtKB/Swiss-Prot
    A8MSW0, O60880, O95383, O95384, O95385, O95386, Q6FGS6, Q9UNR0
    Related
    ENSP00000360181.5, ENST00000371139.9
    Conserved Domains (1) summary
    cd10400
    Location:2 → 104
    SH2_SAP1a; Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a

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_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    124346563..124373160
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    122657134..122683529
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O60880.1 GenPept UniProtKB/Swiss-Prot:O60880

Gene LinkOut

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