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    SH2B2 SH2B adaptor protein 2 [ Homo sapiens (human) ]

    Gene ID: 10603, updated on 5-Mar-2024

    Summary

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    Official Symbol
    SH2B2provided by HGNC
    Official Full Name
    SH2B adaptor protein 2provided by HGNC
    Primary source
    HGNC:HGNC:17381
    See related
    Ensembl:ENSG00000160999 MIM:605300; AllianceGenome:HGNC:17381
    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
    APS
    Summary
    The protein encoded by this gene is expressed in B lymphocytes and contains pleckstrin homology and src homology 2 (SH2) domains. In Burkitt's lymphoma cell lines, it is tyrosine-phosphorylated in response to B cell receptor stimulation. Because it binds Shc independent of stimulation and Grb2 after stimulation, it appears to play a role in signal transduction from the receptor to the Shc/Grb2 pathway. [provided by RefSeq, Jun 2009]
    Expression
    Broad expression in lymph node (RPKM 2.3), spleen (RPKM 2.2) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    7q22.1
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (102285141..102321711)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (103602545..103639107)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (101928432..101962178)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene cut like homeobox 1 Neighboring gene small nucleolar RNA SNORA48 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:101841732-101842931 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26420 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18498 Neighboring gene uncharacterized LOC124901711 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:101911196-101911353 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:101917405-101918238 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:101922504-101923122 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:101923123-101923741 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:101927516-101927700 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18499 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18500 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26421 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26422 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18501 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26423 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:101937369-101938122 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:101949043-101949828 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26425 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:101951399-101952183 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:101957283-101957934 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:101957935-101958585 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:101959159-101959659 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:101960288-101961000 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:101962426-101963137 Neighboring gene uncharacterized LOC107986717 Neighboring gene microRNA 4285 Neighboring gene PMS1 homolog 2, mismatch repair system component pseudogene 12

    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. Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins. Hu J, et al. J Biol Chem, 2005 May 13. PMID 15737992
    2. Association studies of serum prostate-specific antigen levels and the genetic polymorphisms at the androgen receptor and prostate-specific antigen genes. Xu J, et al. Cancer Epidemiol Biomarkers Prev, 2002 Jul. PMID 12101115
    3. Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity. Yabana N, et al. Oncogene, 2002 Oct 31. PMID 12400014
    4. SH2-B family members differentially regulate JAK family tyrosine kinases. O'Brien KB, et al. J Biol Chem, 2002 Mar 8. PMID 11751854
    5. Cross-talk between the two divergent insulin signaling pathways is revealed by the protein kinase B (Akt)-mediated phosphorylation of adapter protein APS on serine 588. Katsanakis KD, et al. J Biol Chem, 2005 Nov 11. PMID 16141217

    See all (37) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Studies indicate that insulin receptor (IR) and IGF Type 1 Receptor (IGFR) have been identified as important partners of Grb10/14 and SH2B1/B2 adaptors.
      Title: Regulation of insulin and type 1 insulin-like growth factor signaling and action by the Grb10/14 and SH2B1/B2 adaptor proteins.
    2. Observational study of gene-disease association. (HuGE Navigator)
      Title: New genetic associations detected in a host response study to hepatitis B vaccine.
    3. N-terminal residues distal to the phosphotyrosine directly contact residues of the four-helix bundle of the TKB domain of the adapter protein APS
      Title: Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins.
    4. We present here a novel stimulatory mechanism of Vav3 in which APS directly relieves the autoinhibitory CH domain and furthermore enhances its tyrosine phosphorylation by Lck.
      Title: Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity.
    Submit: New GeneRIF Correction

    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)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 downregulates the expression of SH2B adaptor protein 2 (SH2B2) in human B cells PubMed
    Nef nef Genome-wide shRNA screening identifies SH2B2, which is required for HIV-1 Nef-induced downregulation of CD4 in HeLa CD4+ cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables SH2 domain binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling adaptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transmembrane receptor protein tyrosine kinase adaptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in B cell receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in B-1 B cell homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in actin cytoskeleton organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in antigen receptor-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in brown fat cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cytokine-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in insulin receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in nervous system development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of Ras protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in actin filament IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in ruffle IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in stress fiber IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    SH2B adapter protein 2
    Names
    SH2 and PH domain-containing adapter protein APS
    adapter protein with pleckstrin homology and Src homology 2 domains

    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_033220.1 RefSeqGene

      Range
      5028..41598
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001359228.2 → NP_001346157.1  SH2B adapter protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AB000520, AC091390, BI261466, CB053166, HY020205
      Consensus CDS
      CCDS78264.2
      UniProtKB/Swiss-Prot
      A0A0A0MTI2, A6ND74, O14492
      Related
      ENSP00000401883.3, ENST00000444095.3
      Conserved Domains (3) summary
      cd10411
      Location:409 → 504
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    2. NM_001359229.2 → NP_001346158.1  SH2B adapter protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AB000520, AC091390, BI261466, CB053166
      Consensus CDS
      CCDS78264.2
      UniProtKB/Swiss-Prot
      A0A0A0MTI2, A6ND74, O14492
      Conserved Domains (3) summary
      cd10411
      Location:409 → 504
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    3. NM_001359230.2 → NP_001346159.1  SH2B adapter protein 2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AA292710, AB000520, AC091390, BI261466, CB053166, HY020205
      Conserved Domains (3) summary
      cd10411
      Location:408 → 503
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    4. NM_001359231.2 → NP_001346160.1  SH2B adapter protein 2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AA292710, AB000520, AC091390, BI261466, CB053166
      Conserved Domains (3) summary
      cd10411
      Location:408 → 503
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    5. NM_001393990.3 → NP_001380919.2  SH2B adapter protein 2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC091390
      Conserved Domains (3) summary
      cd10411
      Location:408 → 503
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    6. NM_001393991.3 → NP_001380920.2  SH2B adapter protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC091390
      Consensus CDS
      CCDS78264.2
      UniProtKB/Swiss-Prot
      A0A0A0MTI2, A6ND74, O14492
      Conserved Domains (3) summary
      cd10411
      Location:409 → 504
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    7. NM_001393992.3 → NP_001380921.2  SH2B adapter protein 2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC091390
      Conserved Domains (3) summary
      cd10411
      Location:408 → 503
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    8. NM_001393993.1 → NP_001380922.1  SH2B adapter protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC091390
      Consensus CDS
      CCDS78264.2
      UniProtKB/Swiss-Prot
      A0A0A0MTI2, A6ND74, O14492
      Conserved Domains (3) summary
      cd10411
      Location:409 → 504
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    9. NM_001393994.1 → NP_001380923.1  SH2B adapter protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC091390
      Consensus CDS
      CCDS78264.2
      UniProtKB/Swiss-Prot
      A0A0A0MTI2, A6ND74, O14492
      Conserved Domains (3) summary
      cd10411
      Location:409 → 504
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    10. NM_001393995.1 → NP_001380924.1  SH2B adapter protein 2 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC091390
      Conserved Domains (2) summary
      cd10411
      Location:191 → 286
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cl17171
      Location:26 → 90
      PH-like; Pleckstrin homology-like domain

    11. NM_001394426.1 → NP_001381355.1  SH2B adapter protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC091390
      Consensus CDS
      CCDS78264.2
      UniProtKB/Swiss-Prot
      A0A0A0MTI2, A6ND74, O14492
      Related
      ENSP00000440273.4, ENST00000536178.3
      Conserved Domains (3) summary
      cd10411
      Location:409 → 504
      SH2_SH2B2; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:193 → 308
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:22 → 78
      Phe_ZIP; Phenylalanine zipper

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      102285141..102321711
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047419780.1 → XP_047275736.1  SH2B adapter protein 2 isoform X2

    2. XM_047419779.1 → XP_047275735.1  SH2B adapter protein 2 isoform X1

    3. XM_047419781.1 → XP_047275737.1  SH2B adapter protein 2 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      103602545..103639107
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054357095.1 → XP_054213070.1  SH2B adapter protein 2 isoform X2

    2. XM_054357094.1 → XP_054213069.1  SH2B adapter protein 2 isoform X1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_020979.5: Suppressed sequence

      Description
      NM_020979.5: This RefSeq was removed because currently there is support for the transcript but not for the N-terminus of the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O14492.2 GenPept UniProtKB/Swiss-Prot:O14492

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