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    Sh2d1a SH2 domain containing 1A [ Mus musculus (house mouse) ]

    Gene ID: 20400, updated on 5-Mar-2024

    Summary

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    Official Symbol
    Sh2d1aprovided by MGI
    Official Full Name
    SH2 domain containing 1Aprovided by MGI
    Primary source
    MGI:MGI:1328352
    See related
    Ensembl:ENSMUSG00000005696 AllianceGenome:MGI:1328352
    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
    SAP; Gm686
    Summary
    Acts upstream of or within humoral immune response and positive regulation of natural killer cell mediated cytotoxicity. Predicted to be located in cytoplasm. Is expressed in retina. Used to study X-linked lymphoproliferative syndrome 1. Human ortholog(s) of this gene implicated in X-linked lymphoproliferative syndrome 1. Orthologous to human SH2D1A (SH2 domain containing 1A). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Restricted expression toward thymus adult (RPKM 26.6) See more
    Orthologs
    human all
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    Genomic context

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    Location:
    X A4; X 23.2 cM
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) X NC_000086.8 (41591442..41610974)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) X NC_000086.7 (42502565..42522097)

    Chromosome X - NC_000086.8Genomic Context describing neighboring genes Neighboring gene RIKEN cDNA B230118I11 gene Neighboring gene STARR-seq mESC enhancer starr_47064 Neighboring gene STARR-seq mESC enhancer starr_47066 Neighboring gene STARR-seq mESC enhancer starr_47067 Neighboring gene STARR-seq mESC enhancer starr_47068 Neighboring gene TEX13 family member D Neighboring gene teneurin transmembrane protein 1 Neighboring gene predicted gene, 23705 Neighboring gene predicted gene, 46667

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. Allosteric inhibition of SHP2 rescues functional T-cell abnormalities in SAP deficiency. Panchal N, et al. J Allergy Clin Immunol, 2022 Dec. PMID 35839843
    2. Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor. Peled M, et al. Proc Natl Acad Sci U S A, 2018 Jan 16. PMID 29282323, Free PMC Article
    3. Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity. Chen S, et al. J Exp Med, 2017 Feb. PMID 28049627, Free PMC Article
    4. Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1. Ruffo E, et al. Sci Transl Med, 2016 Jan 13. PMID 26764158, Free PMC Article
    5. The adaptor protein SAP regulates type II NKT-cell development, cytokine production, and cytotoxicity against lymphoma. Weng X, et al. Eur J Immunol, 2014 Dec. PMID 25236978, Free PMC Article

    See all (140) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. T-B Lymphocyte Interactions Promote Type 1 Diabetes Independently of SLAM-Associated Protein.
      Title: T-B Lymphocyte Interactions Promote Type 1 Diabetes Independently of SLAM-Associated Protein.
    2. Critical Role for SLAM/SAP Signaling in the Thymic Developmental Programming of IL-17- and IFN-gamma-Producing gammadelta T Cells.
      Title: Critical Role for SLAM/SAP Signaling in the Thymic Developmental Programming of IL-17- and IFN-γ-Producing γδ T Cells.
    3. naive T cells regulate B cell survival in a SAP-dependent manner
      Title: T Cells Regulate Peripheral Naive Mature B Cell Survival by Cell-Cell Contact Mediated through SLAMF6 and SAP.
    4. SAP-dependent activating SFR signaling is essential for NKT cell selection.
      Title: Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity.
    5. SAP differentially regulates the late-stage lineage decisions of iNKT cell subsets. These results also provide evidence that iNKT1, iNKT2, and iNKT17 cells are differentially regulated by SAP. SAP-dependent signals are essential for the fate decisions that drive the differentiation of iNKT2 but not iNKT1 and NKT17 cells.
      Title: SLAM-associated protein favors the development of iNKT2 over iNKT17 cells.
    6. SAP is an essential molecule for autoimmune antibody production.
      Title: The Role of Follicular Helper T Cell Molecules and Environmental Influences in Autoantibody Production and Progression to Inflammatory Arthritis in Mice.
    7. In addition to their role in NK cell activation by hematopoietic cells, the SLAM-SAP-SHP1 pathways influence responsiveness toward nonhematopoietic targets by a process akin to NK cell 'education'.
      Title: A hematopoietic cell-driven mechanism involving SLAMF6 receptor, SAP adaptors and SHP-1 phosphatase regulates NK cell education.
    8. SLAM-SAP signaling promotes differentiation of IL-17-producing T cells and progression of experimental autoimmune encephalomyelitis.
      Title: SLAM-SAP signaling promotes differentiation of IL-17-producing T cells and progression of experimental autoimmune encephalomyelitis.
    9. these data suggest that SAP is critical for regulating type II NKT cell responses.
      Title: The adaptor protein SAP regulates type II NKT-cell development, cytokine production, and cytotoxicity against lymphoma.
    10. functional analysis in vitro indicates that SAP-2 is a non-functional isoform due to decreased protein stability
      Title: Identification of a new isoform of the murine Sh2d1a gene and its functional implications.
    Submit: New GeneRIF Correction See all GeneRIFs (54)

    Variation

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    Alleles

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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    acts_upstream_of_or_within 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
    		  
    acts_upstream_of_or_within humoral immune response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within immune system process IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of natural killer cell mediated cytotoxicity IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of natural killer cell mediated cytotoxicity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of T cell receptor signaling pathway ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within positive regulation of natural killer cell mediated cytotoxicity IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of natural killer cell mediated cytotoxicity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of immune response ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    SH2 domain-containing protein 1A
    Names
    Duncan disease homolog
    SH2 domain protein 1A
    T-cell signal transduction molecule SAP
    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.

    mRNA and Protein(s)

    1. NM_001313688.1 → NP_001300617.1  SH2 domain-containing protein 1A isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AF097632, AL831716, KF811030
      UniProtKB/TrEMBL
      Q6P0X5, W0BZ77
      Conserved Domains (1) summary
      cl15255
      Location:2 → 122
      SH2; Src homology 2 (SH2) domain

    2. NM_001313689.1 → NP_001300618.1  SH2 domain-containing protein 1A isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice junction at the 3' end of the first exon and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AF097632, AL831716
      Consensus CDS
      CCDS85770.1
      UniProtKB/TrEMBL
      Q6P0X5
      Related
      ENSMUSP00000110722.2, ENSMUST00000115070.8
      Conserved Domains (1) summary
      cl15255
      Location:2 → 101
      SH2; Src homology 2 (SH2) domain

    3. NM_001313691.1 → NP_001300620.1  SH2 domain-containing protein 1A isoform 4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) contains an alternate first exon and lacks an internal exon compared to variant 1. The resulting isoform (4) has a shorter and distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AF097632, BF019627
      UniProtKB/TrEMBL
      B2RWI0
      Conserved Domains (1) summary
      cl15255
      Location:1 → 59
      SH2; Src homology 2 (SH2) domain

    4. NM_011364.4 → NP_035494.1  SH2 domain-containing protein 1A isoform 2

      See identical proteins and their annotated locations for NP_035494.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AF097632, AK040076, AL831716
      Consensus CDS
      CCDS30099.1
      UniProtKB/Swiss-Prot
      A2ANL8, O88890, Q9QWV6
      UniProtKB/TrEMBL
      Q544F1, Q6P0X5
      Related
      ENSMUSP00000005839.5, ENSMUST00000005839.11
      Conserved Domains (1) summary
      cd10400
      Location:2 → 104
      SH2_SAP1a; Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a

    RNA

    1. NR_132588.1 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) lacks two alternate exons compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AF097632, AK040076, AL831716, BF721340

    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

    1. NC_000086.8 Reference GRCm39 C57BL/6J

      Range
      41591442..41610974
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017318440.1 → XP_017173929.1  SH2 domain-containing protein 1A isoform X1

      UniProtKB/TrEMBL
      B2RWI0
      Conserved Domains (1) summary
      cl15255
      Location:1 → 59
      SH2; Src homology 2 (SH2) domain
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O88890.1 GenPept UniProtKB/Swiss-Prot:O88890

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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