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    HSH2D hematopoietic SH2 domain containing [ Homo sapiens (human) ]

    Gene ID: 84941, updated on 27-Nov-2024

    Summary

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    Official Symbol
    HSH2Dprovided by HGNC
    Official Full Name
    hematopoietic SH2 domain containingprovided by HGNC
    Primary source
    HGNC:HGNC:24920
    See related
    Ensembl:ENSG00000196684 MIM:608349; AllianceGenome:HGNC:24920
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ALX; HSH2
    Summary
    T-cell activation requires 2 signals: recognition of antigen by the T-cell receptor (see TCR; MIM 186880) and a costimulatory signal provided primarily by CD28 (MIM 186760) in naive T cells. HSH2 is a target of both of these signaling pathways (Greene et al., 2003 [PubMed 12960172]).[supplied by OMIM, Mar 2008]
    Expression
    Biased expression in bone marrow (RPKM 13.9), spleen (RPKM 9.5) and 11 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HSH2D in Genome Data Viewer
    Location:
    19p13.11
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (16134028..16158575)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (16268094..16292640)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (16244838..16269386)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 14445 Neighboring gene Sharpr-MPRA regulatory region 6392 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14197 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10288 Neighboring gene long intergenic non-protein coding RNA 1855 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:16182106-16182670 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:16186189-16186918 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancers GRCh37_chr19:16186919-16187646 and GRCh37_chr19:16187647-16188376 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14198 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14199 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14200 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14201 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:16191291-16192018 Neighboring gene tropomyosin 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14202 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:16204789-16205662 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:16207997-16208194 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10290 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14203 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14204 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14205 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14206 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14207 Neighboring gene RAB8A, member RAS oncogene family Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14208 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14209 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:16253936-16254630 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14212 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14213 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10291 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14214 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14215 Neighboring gene Sharpr-MPRA regulatory region 5225 Neighboring gene calcium and integrin binding family member 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14216 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:16293505-16294004 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:16295228-16295863 Neighboring gene family with sequence similarity 32 member A

    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
    • 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. HSH2D contributes to methotrexate resistance in human T‑cell acute lymphoblastic leukaemia. Wang J, et al. Oncol Rep, 2020 Nov. PMID 33000278, Free PMC Article
    2. Phosphorylation at serine 318 is not required for inhibition of T cell activation by ALX. Shapiro MJ, et al. Biochem Biophys Res Commun, 2010 Jun 11. PMID 20471366, Free PMC Article
    3. The ALX Src homology 2 domain is both necessary and sufficient to inhibit T cell receptor/CD28-mediated up-regulation of RE/AP. Shapiro MJ, et al. J Biol Chem, 2004 Sep 24. PMID 15284240
    4. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Krishnamoorthy S, et al. Proc Natl Acad Sci U S A, 2010 Jan 26. PMID 20080636, Free PMC Article
    5. Lipoxin A₄ modulates adaptive immunity by decreasing memory B-cell responses via an ALX/FPR2-dependent mechanism. Ramon S, et al. Eur J Immunol, 2014 Feb. PMID 24166736, Free PMC Article

    See all (25) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. HSH2D contributes to methotrexate resistance in human Tcell acute lymphoblastic leukaemia.
      Title: HSH2D contributes to methotrexate resistance in human T‑cell acute lymphoblastic leukaemia.
    2. Both ALX and ChemR23 were present in human synovium and medial tibial plateau bone obtained following total knee replacement surgery for osteoarthritis.
      Title: Targeting the D Series Resolvin Receptor System for the Treatment of Osteoarthritis Pain.
    3. pro-inflammatory stimuli lead to FPR2/ALX expression while LXA4 induces an anti-inflammatory response
      Title: Differential regulation of monocytic expression of leukotriene and lipoxin receptors.
    4. LXA decreased IgM and IgG production on activated human B cells through ALX/FPR2-dependent signaling.
      Title: Lipoxin A₄ modulates adaptive immunity by decreasing memory B-cell responses via an ALX/FPR2-dependent mechanism.
    5. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    6. although ALX is inducibly phosphorylated upon TCR/CD28 stimulation, this phosphorylation is not required for ALX to inhibit T cell activation.
      Title: Phosphorylation at serine 318 is not required for inhibition of T cell activation by ALX.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: New genetic associations detected in a host response study to hepatitis B vaccine.
    8. results indicate that RvD1 specifically interacts with both ALX and GPR32 on phagocytes.
      Title: Resolvin D1 binds human phagocytes with evidence for proresolving receptors.
    9. ALX is an adaptor involved in T cell activation and interleukin-2 (IL-2) promoter activation
      Title: Cloning and characterization of ALX, an adaptor downstream of CD28.
    10. involved in tyrosine kinase signaling in hematopoietic cells
      Title: HSH2: a novel SH2 domain-containing adapter protein involved in tyrosine kinase signaling in hematopoietic cells.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ14886

    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 IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in T cell activation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of B cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of mitochondrial depolarization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    hematopoietic SH2 domain-containing protein
    Names
    adaptor in lymphocytes of unknown function X

    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_001352265.2 → NP_001339194.1  hematopoietic SH2 domain-containing protein isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC020911, AY319652, BC025237, BF242893, DA674933
      Conserved Domains (1) summary
      cd09946
      Location:26 → 127
      SH2_HSH2_like; Src homology 2 domain found in hematopoietic SH2 (HSH2) protein

    2. NM_001352266.2 → NP_001339195.1  hematopoietic SH2 domain-containing protein isoform 4

      Status: VALIDATED

      Source sequence(s)
      AY319652, BC025237, BF242893, DA372906
      Conserved Domains (1) summary
      cl15255
      Location:26 → 127
      SH2; Src homology 2 (SH2) domain

    3. NM_001369808.1 → NP_001356737.1  hematopoietic SH2 domain-containing protein isoform 5

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911, DA672492, KF495722
      Conserved Domains (1) summary
      cl15255
      Location:18 → 102
      SH2; Src homology 2 (SH2) domain

    4. NM_001369809.1 → NP_001356738.1  hematopoietic SH2 domain-containing protein isoform 6

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911
      Conserved Domains (1) summary
      cd09946
      Location:26 → 127
      SH2_HSH2_like; Src homology 2 domain found in hematopoietic SH2 (HSH2) protein

    5. NM_001382417.1 → NP_001369346.1  hematopoietic SH2 domain-containing protein isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911, KF495722
      Consensus CDS
      CCDS74304.1
      UniProtKB/Swiss-Prot
      B5ME72, Q6ZNG7, Q96JZ2
      Related
      ENSP00000483354.1, ENST00000613986.4
      Conserved Domains (1) summary
      cd09946
      Location:26 → 127
      SH2_HSH2_like; Src homology 2 domain found in hematopoietic SH2 (HSH2) protein

    6. NM_032855.4 → NP_116244.1  hematopoietic SH2 domain-containing protein isoform 1

      See identical proteins and their annotated locations for NP_116244.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AC008894, AY319652, BC025237
      Consensus CDS
      CCDS74304.1
      UniProtKB/Swiss-Prot
      B5ME72, Q6ZNG7, Q96JZ2
      Related
      ENSP00000482604.1, ENST00000616645.4
      Conserved Domains (1) summary
      cd09946
      Location:26 → 127
      SH2_HSH2_like; Src homology 2 domain found in hematopoietic SH2 (HSH2) protein

    RNA

    1. NR_111903.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC008894, AK307563, AY319652, BC025237

    2. NR_111904.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) includes an alternate internal exon structure, and the 3'-terminal exon extends past a splice site that is used in variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      AC008894, AK298682, AY319652, BF511682

    3. NR_163150.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911, KF495722

    4. NR_163151.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911, KF495722

    5. NR_163152.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911, KF495722

    6. NR_163153.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911, KF495722

    7. NR_163154.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911, KF495722

    8. NR_163155.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911, KF495722

    9. NR_163156.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC008894, AC020911, KF495722
      Related
      ENST00000616070.4

    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_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      16134028..16158575
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      16268094..16292640
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96JZ2.1 GenPept UniProtKB/Swiss-Prot:Q96JZ2

    Gene LinkOut

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

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