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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

HSH2D Gene

protein-coding   GIFtS: 46
GCID: GC19P016244

hematopoietic SH2 domain containing

 Explore 4 diseases affiliated with
HSH2D via our new
 Human Malady Compendium 
Biological research products
for HSH2D
    

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
Hematopoietic SH2 Domain Containing1 2     Hematopoietic SH2 Protein2 3
ALX1 2 3     FLJ148861
HSH21 2     Hematopoietic SH2 Domain-Containing Protein2
Adaptor In Lymphocytes Of Unknown Function X2 3     

External Ids:    HGNC: 249201   Entrez Gene: 849412   Ensembl: ENSG000001966847   OMIM: 6083495   UniProtKB: Q96JZ23   

Export aliases for HSH2D gene to outside databases

Previous GC identifers: GC19P016106 GC19P016107 GC19P015938 GC19P015815


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for HSH2D:
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)

UniProtKB/Swiss-Prot: HSH2D_HUMAN, Q96JZ2
Function: May be a modulator of the apoptotic response through its ability to affect mitochondrial stability (By
similarity). Adapter protein involved in tyrosine kinase and CD28 signaling. Seems to affect CD28-mediated activation
of the RE/AP element of the interleukin-2 promoter




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000019.9  NC_018930.1  NT_011295.11  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the HSH2D gene promoter:
         Sp1   AP-1   Brachyury   ATF-2   NF-kappaB   COMP1   c-Jun   NF-kappaB1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidHSH2D promoter sequence
   Search SABiosciences Chromatin IP Primers for HSH2D

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat HSH2D


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.12   Ensembl cytogenetic band:  19p13.12   HGNC cytogenetic band: 19p13.12

HSH2D Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HSH2D gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19P016244:  view genomic region     (about GC identifiers)

Start:
16,244,838 bp from pter      End:
16,269,386 bp from pter
Size:
24,549 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: HSH2D_HUMAN, Q96JZ2 (See protein sequence)
Recommended Name: Hematopoietic SH2 domain-containing protein  
Size: 352 amino acids; 39002 Da
Subunit: Interacts with FES and TNK2
Subcellular location: Cytoplasm. Nucleus
1 PDB 3D structure from and Proteopedia for HSH2D:
2CS0 (3D)    
Secondary accessions: B5ME72 Q6ZNG7
Alternative splicing: 2 isoforms:  Q96JZ2-1   Q96JZ2-2   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for HSH2D: NX_Q96JZ2

Post-translational modifications:

  • May be phosphorylated by FES and ACK11
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q96JZ2

  • HSH2D Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_116244.1  
    ENSEMBL proteins: 
     ENSP00000468495   ENSP00000468268   ENSP00000467576   ENSP00000442140   ENSP00000465636  
     ENSP00000467189   ENSP00000468142   ENSP00000380528   ENSP00000253680  

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    Uscn Proteins for HSH2D

    Gene Ontology (GO): 4 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--
    GO:0005737cytoplasm IEA--
    GO:0005739mitochondrion ----
    GO:0005829cytosol ----


    HSH2D for ontologies           About GeneDecksing



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    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    HSH2D for domains           About GeneDecksing

    1 InterPro domain/family:
     IPR000980 SH2

    Graphical View of Domain Structure for InterPro Entry Q96JZ2

    ProtoNet protein and cluster: Q96JZ2

    1 Blocks protein family: IPB000980 SH2 domain signature

    UniProtKB/Swiss-Prot: HSH2D_HUMAN, Q96JZ2
    Similarity: Contains 1 SH2 domain


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Function Summary:

         UniProtKB/Swiss-Prot: HSH2D_HUMAN, Q96JZ2
    Function: May be a modulator of the apoptotic response through its ability to affect mitochondrial stability (By
    similarity). Adapter protein involved in tyrosine kinase and CD28 signaling. Seems to affect CD28-mediated activation
    of the RE/AP element of the interleukin-2 promoter

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    Gene Ontology (GO): 1 molecular function term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005070SH3/SH2 adaptor activity ----


    HSH2D for ontologies           About GeneDecksing


    Animal Models:
         Mouse knock-out Hsh2dtm1Viss for HSH2D
         3 MGI mutant phenotypes (inferred from 1 allele(MGI details for Hsh2d):
     cellular  hematopoietic system  immune system 

    HSH2D for phenotypes           About GeneDecksing


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
    About This Section



    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for HSH2D

    STRING Interaction Network Preview (showing 3 interactants - click image to see more details)

    3 Interacting proteins for HSH2D (Q96JZ23 ENSP000002536804) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    FESP073323, ENSP000003315044I2D: score=2 STRING: ENSP00000331504
    TNK2Q079123, ENSP000003713414I2D: score=2 STRING: ENSP00000371341
    MPP3ENSP000003814254STRING: ENSP00000381425
    About this table

    Gene Ontology (GO): 3 biological process terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002903negative regulation of B cell apoptotic process ----
    GO:0042110T cell activation ----
    GO:0051902negative regulation of mitochondrial depolarization ----


    HSH2D for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for HSH2D
    Search CenterWatch for drugs/clinical trials and news about HSH2D 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
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    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for HSH2D gene: 
    NM_032855.2  

    Unigene Cluster for HSH2D:

    Hematopoietic SH2 domain containing
    Hs.631617  [show with all ESTs]
    Unigene Representative Sequence: AK131222
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000586872 ENST00000588246 ENST00000589463 ENST00000535834 ENST00000587963
    ENST00000593031 ENST00000591154 ENST00000397372 ENST00000253680(uc002ndp.4 uc002ndr.3 uc010ead.3)


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    Additional cDNA sequence: 

    AK027792.1 AK131222.1 AK298682.1 AK300027.1 AK307563.1 AY319652.1 BC016826.1 BC025237.2 

    9 DOTS entries:

    DT.206653  DT.40120606  DT.100756604  DT.75134736  DT.86852573  DT.121496134  DT.436661  DT.121496119 
    DT.75172695 

    24/536 AceView cDNA sequences (see all 536):

    BM978303 NM_005370 AA280958 H51041 BX492976 BM015854 AA654013 X56741 
    AU103188 BQ674769 CR597154 BQ892283 BC025237 CR542274 BP365166 CB132939 
    AA328139 BM811628 BG758569 BQ887312 AA322829 BM846890 BM475359 BE301626 

    GeneLoc Exon Structure

    5/6 Alternative Splicing Database (ASD) splice patterns (SP) for HSH2D (see all 6)    About this scheme

    ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c ^ 5a · 5b ^ 6 ^ 7a · 7b
    SP1:                                                                              
    SP2:                          -           -     -     -                           
    SP3:                          -           -     -                                 
    SP4:                          -           -     -     -                           
    SP5:                          -                                                   


    ECgene alternative splicing isoforms for HSH2D

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    HSH2D expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: --

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image
    See HSH2D Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for HSH2D

    SOURCE GeneReport for Unigene cluster: Hs.631617

    UniProtKB/Swiss-Prot: HSH2D_HUMAN, Q96JZ2
    Tissue specificity: Predominantly expressed in spleen and hematopoietic cells such as peripheral blood leukocytes and
    weakly expressed in prostate, thymus, heart, small intestine and placenta

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of chordates.

    Orthologs for HSH2D gene from 2/5 species (see all 5)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Hsh2d1 , 5 hematopoietic SH2 domain containing1, 5 67.79(n)1
    58.72(a)1
      8 (34.87 cM)5
    2094881  NM_197944.11  NP_922935.11 
     721896685 
    zebrafish
    (Danio rerio)
    Actinopterygii hsh2d1 hematopoietic SH2 domain containing 39.9(n)
    31.94(a)
      548337  NM_001017541.2  NP_001017541.2 


    ENSEMBL Gene Tree for HSH2D (if available)
    TreeFam Gene Tree for HSH2D (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for HSH2D gene
    SH2D4A2  SH2D2A2  SH2D4B2  
    5 SIMAP similar genes for HSH2D using alignment to 11 protein entries:     HSH2D_HUMAN (see all proteins):
    SS18    GRAP2    CSK    NARF    ZNF506

    HSH2D for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    9 NCBI SNPs in HSH2D are shown     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs350442421,2
    C,F,--16245421(+) TTGAA-/TGTCTC 1 -- int13Minor allele frequency- T:0.33NA CSA 6
    rs104110881,2
    C,F,A,--16248196(+) ACTTTG/CGGAGG 1 -- int13Minor allele frequency- C:0.50NA WA CSA 6
    rs1471338071,2
    --16248210(+) ACGTGC/GGTGGA 1 -- int10--------
    rs1891429091,2
    --16248236(+) AGTTCG/TAGACC 1 -- int10--------
    rs621179141,2
    --16248244(+) ACCAGC/TCTGGC 1 -- int11Minor allele frequency- T:0.50NA 2
    rs104189231,2
    C,F,--16248311(+) GAACCG/AGGGAG 1 -- int19Minor allele frequency- A:0.44NA WA CSA EA 134
    rs1920165611,2
    --16248356(+) CACTCC/TAGCCT 1 -- int10--------
    rs1496702421,2
    --16248422(+) GGTCTC/TGCTCT 1 -- int10--------
    rs789770601,2
    ----16248387(+) AAAAA-/AAGAAAA 1 -- int10--------

    HapMap Linkage Disequilibrium report for HSH2D (16244838 - 16269386 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for HSH2D: --

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

    HSH2D for disorders           About GeneDecksing

    OMIM gene information: 608349    OMIM disorders: --

    4 diseases for HSH2D:    About MalaCards
    alexander disease    hepatitis b    hepatitis    prostatitis

    Human Genome Epidemiology (HuGE) Navigator: HSH2D (4 documents)

    Export disorders for HSH2D gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for HSH2D gene, integrated from 9 sources (see all 13):
    (articles sorted by number of sources associating them with HSH2D)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. HSH2: a novel SH2 domain-containing adapter protein involved in tyrosine kinase signaling in hematopoietic cells. (PubMed id 11700021)1, 2, 3, 9 Oda T.... Yamashita T. (2001)
    2. Cloning and characterization of ALX, an adaptor downstream of CD28. (PubMed id 12960172)1, 2, 9 Greene T.A.... Shapiro V.S. (2003)
    3. The ALX Src homology 2 domain is both necessary and sufficient to inhibit T cell receptor/CD28-mediated up-regulation of RE/AP. (PubMed id 15284240)1, 2, 9 Shapiro M.J.... Shapiro V.S. (2004)
    4. The carboxyl-terminal segment of the adaptor protein ALX directs its nuclear export during T cell activation. (PubMed id 16169852)1, 2 Shapiro M.J.... Shapiro V.S. (2005)
    5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
    6. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (2004)
    7. New genetic associations detected in a host response study to hepatitis B vaccine. (PubMed id 20237496)1 Davila S....Seielstad M. (2010)
    8. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. (PubMed id 20080636)1 Krishnamoorthy S....Serhan C.N. (2010)
    9. Phosphorylation at serine 318 is not required for inh ibition of T cell activation by ALX. (PubMed id 20471366)1 Shapiro M.J....Shapiro V.S. (2010)
    10. Variation at the NFATC2 locus increases the risk of t hiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipr il and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1 Bailey S.D....Anand S. (2010)

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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 84941 HGNC: 24920 AceView: RAB8AandHSH2D Ensembl:ENSG00000196684 euGenes: HUgn84941
    ECgene: HSH2D H-InvDB: HSH2D

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for HSH2D Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for HSH2D gene:
    Search GeneIP for patents involving HSH2D

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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