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] See more...

Aliases for HSH2D Gene

Aliases for HSH2D Gene

  • Hematopoietic SH2 Domain Containing 2 3 5
  • Adaptor In Lymphocytes Of Unknown Function X 3 4
  • Hematopoietic SH2 Domain-Containing Protein 3 4
  • ALX 3 4
  • Hematopoietic SH2 Protein 4
  • HSH2 3

External Ids for HSH2D Gene

Previous GeneCards Identifiers for HSH2D Gene

  • GC19P016106
  • GC19P016107
  • GC19P015938
  • GC19P016244
  • GC19P015815
  • GC19P016499
  • GC19P016799
  • GC19P020434
  • GC19P020571
  • GC19P020687
  • GC19P017577
  • GC19P018243
  • GC19P018637
  • GC19P018953
  • GC19P019277
  • GC19P019603
  • GC19P019966
  • GC19P020288

Summaries for HSH2D Gene

Entrez Gene Summary for HSH2D Gene

  • 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]

GeneCards Summary for HSH2D Gene

HSH2D (Hematopoietic SH2 Domain Containing) is a Protein Coding gene. Diseases associated with HSH2D include Parietal Foramina. Gene Ontology (GO) annotations related to this gene include SH3/SH2 adaptor activity. An important paralog of this gene is SH2D7.

UniProtKB/Swiss-Prot Summary for HSH2D Gene

  • 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.

Additional gene information for HSH2D Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HSH2D Gene

Genomics for HSH2D Gene

GeneHancer (GH) Regulatory Elements for HSH2D Gene

Promoters and enhancers for HSH2D Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J016139 Promoter/Enhancer 2 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 500.4 +9.6 9632 9 ZNF217 POLR2G SP1 EP300 POLR2A CTCF RELA MEF2C CUX1 MYC HSH2D RAB8A EPS15L1 ENSG00000269243 lnc-EPS15L1-5
GH19J016133 Enhancer 0.7 dbSUPER 500.7 +0.4 396 1.6 SP1 EP300 MEF2C BCL11A TCF12 CBFB MEF2B NBN IRF4 POU2F2 HSH2D RAB8A ENSG00000269243
GH19J015639 Promoter/Enhancer 1.8 EPDnew FANTOM5 Ensembl ENCODE 15.4 -493.0 -493025 3 FOXK2 NCOR1 KDM6A FOXA1 REST ZBTB25 MYC TGIF2 EP300 CTBP1 CYP4F3 CYP4F12 HSH2D CYP4F10P OR10H5 RAB8A CLEC4O BRD4 AKAP8 lnc-CYP4F12-1
GH19J016091 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 18.2 -38.8 -38770 7.6 ZNF217 TCF12 NCOR1 TCF7 KLF4 CUX1 TGIF2 SKI TEAD1 TBX3 HSH2D CIB3 FAM32A EPS15L1 RAB8A ENSG00000267373 ENSG00000279198 TPM4
GH19J016084 Enhancer 1.3 Ensembl ENCODE dbSUPER 11.7 -46.4 -46446 6.8 CTCF TCF12 POLR2G PHB2 TCF7 MYC CTBP1 SKI TEAD1 TAF9B HSH2D RASAL3 ENSG00000279198 ENSG00000267373 TPM4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HSH2D on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HSH2D

Top Transcription factor binding sites by QIAGEN in the HSH2D gene promoter:
  • AP-1
  • ATF-2
  • Brachyury
  • c-Jun
  • COMP1
  • NF-kappaB
  • NF-kappaB1
  • Sp1

Genomic Locations for HSH2D Gene

Genomic Locations for HSH2D Gene
chr19:16,134,028-16,158,575
(GRCh38/hg38)
Size:
24,548 bases
Orientation:
Plus strand
chr19:16,244,838-16,269,386
(GRCh37/hg19)
Size:
24,549 bases
Orientation:
Plus strand

Genomic View for HSH2D Gene

Genes around HSH2D on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HSH2D Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HSH2D Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HSH2D Gene

Proteins for HSH2D Gene

  • Protein details for HSH2D Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96JZ2-HSH2D_HUMAN
    Recommended name:
    Hematopoietic SH2 domain-containing protein
    Protein Accession:
    Q96JZ2
    Secondary Accessions:
    • B5ME72
    • Q6ZNG7

    Protein attributes for HSH2D Gene

    Size:
    352 amino acids
    Molecular mass:
    39002 Da
    Quaternary structure:
    • Interacts with FES and TNK2.

    Three dimensional structures from OCA and Proteopedia for HSH2D Gene

    Alternative splice isoforms for HSH2D Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HSH2D Gene

Post-translational modifications for HSH2D Gene

No data available for DME Specific Peptides for HSH2D Gene

Domains & Families for HSH2D Gene

Gene Families for HSH2D Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for HSH2D Gene

Blocks:
  • SH2 domain signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for HSH2D Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ59974 (B4DT26_HUMAN)
  • Adaptor in lymphocytes of unknown function X (HSH2D_HUMAN)
  • HSH2D protein (Q96AS3_HUMAN)
genes like me logo Genes that share domains with HSH2D: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for HSH2D Gene

Function for HSH2D Gene

Molecular function for HSH2D Gene

UniProtKB/Swiss-Prot 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.

Phenotypes From GWAS Catalog for HSH2D Gene

Gene Ontology (GO) - Molecular Function for HSH2D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005070 SH3/SH2 adaptor activity IEA --
GO:0005515 protein binding IPI 24728074
genes like me logo Genes that share ontologies with HSH2D: view
genes like me logo Genes that share phenotypes with HSH2D: view

Animal Models for HSH2D Gene

MGI Knock Outs for HSH2D:

Animal Model Products

CRISPR Products

miRNA for HSH2D Gene

miRTarBase miRNAs that target HSH2D

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HSH2D

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HSH2D Gene

Localization for HSH2D Gene

Subcellular locations from UniProtKB/Swiss-Prot for HSH2D Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HSH2D gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 3
mitochondrion 3
extracellular 2
cytoskeleton 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Focal adhesion sites (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HSH2D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IBA 21873635
GO:0005739 mitochondrion IEA --
GO:0005829 cytosol IEA --
genes like me logo Genes that share ontologies with HSH2D: view

Pathways & Interactions for HSH2D Gene

PathCards logo

SuperPathways for HSH2D Gene

No Data Available

Gene Ontology (GO) - Biological Process for HSH2D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002903 negative regulation of B cell apoptotic process IEA --
GO:0007165 signal transduction IEA --
GO:0009967 positive regulation of signal transduction IEA --
GO:0042110 T cell activation IEA --
GO:0051902 negative regulation of mitochondrial depolarization IEA --
genes like me logo Genes that share ontologies with HSH2D: view

No data available for Pathways by source and SIGNOR curated interactions for HSH2D Gene

Drugs & Compounds for HSH2D Gene

No Compound Related Data Available

Transcripts for HSH2D Gene

mRNA/cDNA for HSH2D Gene

5 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HSH2D

Alternative Splicing Database (ASD) splice patterns (SP) for HSH2D Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c ^ 5a · 5b ^ 6 ^ 7a · 7b
SP1:
SP2: - - - -
SP3: - - -
SP4: - - - -
SP5: -
SP6: - -

Relevant External Links for HSH2D Gene

GeneLoc Exon Structure for
HSH2D

Expression for HSH2D Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HSH2D Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HSH2D Gene

This gene is overexpressed in Whole Blood (x17.8) and Spleen (x6.4).

Protein differential expression in normal tissues from HIPED for HSH2D Gene

This gene is overexpressed in NK cells (30.2), Blymphocyte (30.1), and CD8 Tcells (6.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HSH2D Gene



Protein tissue co-expression partners for HSH2D Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HSH2D

SOURCE GeneReport for Unigene cluster for HSH2D Gene:

Hs.631617

mRNA Expression by UniProt/SwissProt for HSH2D Gene:

Q96JZ2-HSH2D_HUMAN
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.

Evidence on tissue expression from TISSUES for HSH2D Gene

  • Spleen(4.3)
genes like me logo Genes that share expression patterns with HSH2D: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for HSH2D Gene

Orthologs for HSH2D Gene

This gene was present in the common ancestor of mammals.

Orthologs for HSH2D Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HSH2D 30
  • 99.53 (n)
dog
(Canis familiaris)
Mammalia HSH2D 30
  • 74.37 (n)
cow
(Bos Taurus)
Mammalia HSH2D 30
  • 74.09 (n)
mouse
(Mus musculus)
Mammalia Hsh2d 17 30
  • 69.87 (n)
rat
(Rattus norvegicus)
Mammalia Hsh2d 30
  • 66.77 (n)
Species where no ortholog for HSH2D was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for HSH2D Gene

ENSEMBL:
Gene Tree for HSH2D (if available)
TreeFam:
Gene Tree for HSH2D (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HSH2D: view image

Paralogs for HSH2D Gene

Paralogs for HSH2D Gene

(2) SIMAP similar genes for HSH2D Gene using alignment to 10 proteins:

  • HSH2D_HUMAN
  • B4DT26_HUMAN
  • H7BYQ7_HUMAN
  • K7EKI5_HUMAN
  • K7EP18_HUMAN
  • K7EPX4_HUMAN
  • K7ER77_HUMAN
  • K7ERI2_HUMAN
  • K7ES08_HUMAN
  • Q96AS3_HUMAN
genes like me logo Genes that share paralogs with HSH2D: view

Variants for HSH2D Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HSH2D Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
775578 Benign: not provided 16,157,232(+) G/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
777451 Benign: not provided 16,153,136(+) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for HSH2D Gene

Structural Variations from Database of Genomic Variants (DGV) for HSH2D Gene

Variant ID Type Subtype PubMed ID
esv2672837 CNV deletion 23128226
esv2718260 CNV deletion 23290073
esv2718261 CNV deletion 23290073
esv3643789 CNV loss 21293372
esv3643790 CNV gain 21293372
esv3643791 CNV loss 21293372
nsv1071917 CNV deletion 25765185
nsv1130729 CNV deletion 24896259
nsv1134759 CNV deletion 24896259
nsv833767 CNV loss 17160897

Variation tolerance for HSH2D Gene

Gene Damage Index Score: 1.16; 23.51% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HSH2D Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
HSH2D

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HSH2D Gene

Disorders for HSH2D Gene

MalaCards: The human disease database

(1) MalaCards diseases for HSH2D Gene - From: DISEASES

Disorder Aliases PubMed IDs
parietal foramina
  • pfm
- elite association - COSMIC cancer census association via MalaCards
Search HSH2D in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HSH2D

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with HSH2D: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HSH2D Gene

Publications for HSH2D Gene

  1. HSH2: a novel SH2 domain-containing adapter protein involved in tyrosine kinase signaling in hematopoietic cells. (PMID: 11700021) Oda T … Yamashita T (Biochemical and biophysical research communications 2001) 2 3 4 23 54
  2. The ALX Src homology 2 domain is both necessary and sufficient to inhibit T cell receptor/CD28-mediated up-regulation of RE/AP. (PMID: 15284240) Shapiro MJ … Shapiro VS (The Journal of biological chemistry 2004) 3 4 23 54
  3. Cloning and characterization of ALX, an adaptor downstream of CD28. (PMID: 12960172) Greene TA … Shapiro VS (The Journal of biological chemistry 2003) 3 4 23 54
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41 54
  5. The carboxyl-terminal segment of the adaptor protein ALX directs its nuclear export during T cell activation. (PMID: 16169852) Shapiro MJ … Shapiro VS (The Journal of biological chemistry 2005) 3 4 54

Products for HSH2D Gene

Sources for HSH2D Gene