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    SH2B3 SH2B adaptor protein 3 [ Homo sapiens (human) ]

    Gene ID: 10019, updated on 2-Nov-2024

    Summary

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    Official Symbol
    SH2B3provided by HGNC
    Official Full Name
    SH2B adaptor protein 3provided by HGNC
    Primary source
    HGNC:HGNC:29605
    See related
    Ensembl:ENSG00000111252 MIM:605093; AllianceGenome:HGNC:29605
    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
    LNK; IDDM20
    Summary
    This gene encodes a member of the SH2B adaptor family of proteins, which are involved in a range of signaling activities by growth factor and cytokine receptors. The encoded protein is a key negative regulator of cytokine signaling and plays a critical role in hematopoiesis. Mutations in this gene have been associated with susceptibility to celiac disease type 13 and susceptibility to insulin-dependent diabetes mellitus. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]
    Expression
    Ubiquitous expression in bone marrow (RPKM 12.8), spleen (RPKM 12.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SH2B3 in Genome Data Viewer
    Location:
    12q24.12
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (111404730..111451623)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (111385588..111432181)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (111843727..111889427)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:111799560-111800216 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4865 Neighboring gene long intergenic non-protein coding RNA 2356 Neighboring gene PH domain containing endocytic trafficking adaptor 1 Neighboring gene heat shock protein family A (Hsp70) member 8 pseudogene 14 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7031 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4866 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4867 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4868 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:111851003-111851850 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111855471-111856170 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111863315-111863890 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7032 Neighboring gene uncharacterized LOC124903019 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7033 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7034 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111873559-111874138 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111874139-111874718 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:111876422-111876935 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111877948-111878492 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:111880447-111880633 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7035 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7036 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7037 Neighboring gene ataxin 2 Neighboring gene U7 small nuclear RNA Neighboring gene ReSE screen-validated silencer GRCh37_chr12:112008371-112008568 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4869 Neighboring gene IFITM3 pseudogene 5

    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 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. LNK mutations in JAK2 mutation-negative erythrocytosis. Lasho TL, et al. N Engl J Med, 2010 Sep 16. PMID 20843259
    2. Role of SH2B3 R262W gene polymorphism and risk of coronary heart disease: A PRISMA-compliant meta-analysis. Hong L, et al. Medicine (Baltimore), 2018 Nov. PMID 30508957, Free PMC Article
    3. The carriage of the type 1 diabetes-associated R262W variant of human LNK correlates with increased proliferation of peripheral blood monocytes in diabetic patients. Lavrikova EY, et al. Pediatr Diabetes, 2011 Mar. PMID 20546165
    4. Clinical significance of novel SH2B3 mutations in adult Chinese acute lymphoblastic leukemia patients. Gu Y, et al. Leuk Res, 2018 Sep. PMID 30103202
    5. SH2B3 aberrations enriched in iAMP21 B lymphoblastic leukemia. Baughn LB, et al. Cancer Genet, 2018 Oct. PMID 30005852

    See all (123) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia.
      Title: LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia.
    2. Germline bi-allelic SH2B3/LNK alteration predisposes to a neonatal juvenile myelomonocytic leukemia-like disorder.
      Title: Germline bi-allelic SH2B3/LNK alteration predisposes to a neonatal juvenile myelomonocytic leukemia-like disorder.
    3. LNK/SH2B3 loss of function increases susceptibility to murine and human atrial fibrillation.
      Title: LNK/SH2B3 loss of function increases susceptibility to murine and human atrial fibrillation.
    4. Negative regulation of SH2B3 by SMYD5 controls epithelial-mesenchymal transition in lung cancer.
      Title: Negative regulation of SH2B3 by SMYD5 controls epithelial-mesenchymal transition in lung cancer.
    5. Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity.
      Title: Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity.
    6. Acquired uniparental isodisomies involving chromosome 12 in paediatric B-cell precursor acute lymphoblastic leukaemia: Associations with chromosome 21 gains and SH2B3 mutations.
      Title: Acquired uniparental isodisomies involving chromosome 12 in paediatric B-cell precursor acute lymphoblastic leukaemia: Associations with chromosome 21 gains and SH2B3 mutations.
    7. CTLA4, SH2B3, and CLEC16A diversely affect the progression of early islet autoimmunity in relatives of Type 1 diabetes patients.
      Title: CTLA4, SH2B3, and CLEC16A diversely affect the progression of early islet autoimmunity in relatives of Type 1 diabetes patients.
    8. The Autoimmune Risk R262W Variant of the Adaptor SH2B3 Improves Survival in Sepsis.
      Title: The Autoimmune Risk R262W Variant of the Adaptor SH2B3 Improves Survival in Sepsis.
    9. LNK promotes granulosa cell apoptosis in PCOS via negatively regulating insulin-stimulated AKT-FOXO3 pathway.
      Title: LNK promotes granulosa cell apoptosis in PCOS via negatively regulating insulin-stimulated AKT-FOXO3 pathway.
    10. The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects.
      Title: The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects.
    Submit: New GeneRIF Correction See all GeneRIFs (73)

    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

    Associated conditions

    Description Tests
    Primary familial polycythemia due to EPO receptor mutation
    MedGen: C4551637 OMIM: 133100 GeneReviews: Primary Familial and Congenital Polycythemia
    		Compare labs
    Primary myelofibrosis
    MedGen: C0001815 OMIM: 254450 GeneReviews: Not available
    		Compare labs
    Thrombocythemia 1
    MedGen: C3277671 OMIM: 187950 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects.
    EBI GWAS Catalog
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
    EBI GWAS Catalog
    Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
    EBI GWAS Catalog
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    EBI GWAS Catalog
    Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.
    EBI GWAS Catalog
    Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
    EBI GWAS Catalog
    Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
    EBI GWAS Catalog
    Genome-wide association study identified the human leukocyte antigen region as a novel locus for plasma beta-2 microglobulin.
    EBI GWAS Catalog
    Genome-wide association study identifies eight loci associated with blood pressure.
    EBI GWAS Catalog
    Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.
    EBI GWAS Catalog
    Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
    EBI GWAS Catalog
    Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
    EBI GWAS Catalog
    Genome-wide association study of blood pressure and hypertension.
    EBI GWAS Catalog
    Genome-wide association study of hematological and biochemical traits in a Japanese population.
    EBI GWAS Catalog
    Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.
    EBI GWAS Catalog
    Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.
    EBI GWAS Catalog
    Multiple common variants for celiac disease influencing immune gene expression.
    EBI GWAS Catalog
    Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
    EBI GWAS Catalog
    New gene functions in megakaryopoiesis and platelet formation.
    EBI GWAS Catalog
    Newly identified genetic risk variants for celiac disease related to the immune response.
    EBI GWAS Catalog
    Novel associations for hypothyroidism include known autoimmune risk loci.
    EBI GWAS Catalog
    Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction.
    EBI GWAS Catalog
    Seventy-five genetic loci influencing the human red blood cell.
    EBI GWAS Catalog
    Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
    EBI GWAS Catalog
    The ATXN2-SH2B3 locus is associated with peripheral arterial disease: an electronic medical record-based genome-wide association study.
    EBI GWAS Catalog

    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

    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 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein tyrosine kinase binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables signaling receptor complex adaptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables stem cell factor receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables transmembrane receptor protein tyrosine kinase adaptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in cell surface receptor protein tyrosine kinase signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within_negative_effect cellular response to chemokine ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cellular response to interleukin-3 ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    acts_upstream_of_negative_effect embryonic hemopoiesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in erythrocyte development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in hematopoietic stem cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in megakaryocyte development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in monocyte homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in negative regulation of Kit signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of MAPK cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of cell population proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of chemokine-mediated signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of platelet aggregation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in negative regulation of receptor signaling pathway via JAK-STAT IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of receptor signaling pathway via STAT ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of response to cytokine stimulus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in neutrophil homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    acts_upstream_of_or_within_negative_effect thrombopoietin-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in thrombopoietin-mediated signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    acts_upstream_of_or_within_negative_effect thrombopoietin-mediated signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    SH2B adapter protein 3
    Names
    lymphocyte-specific adapter protein Lnk
    signal transduction protein Lnk

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_021216.1 RefSeqGene

      Range
      5001..50676
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_621

    mRNA and Protein(s)

    1. NM_001291424.1 → NP_001278353.1  SH2B adapter protein 3 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two alternate exons in the 5' region, including a portion of the 5' coding region, and initiates translation at an alternate start codon in an alternate exon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AB208911, AK302173, BC015786, BC136451
      Consensus CDS
      CCDS76602.1
      UniProtKB/TrEMBL
      B7Z7K6, F5GYM4
      Related
      ENSP00000440597.1, ENST00000538307.1
      Conserved Domains (2) summary
      cd10412
      Location:153 → 249
      SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cl17171
      Location:1 → 107
      PH-like; Pleckstrin homology-like domain

    2. NM_005475.3 → NP_005466.1  SH2B adapter protein 3 isoform 1

      See identical proteins and their annotated locations for NP_005466.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AB208911, AC005805, AF055581
      Consensus CDS
      CCDS9153.1
      UniProtKB/Swiss-Prot
      B9EGG5, O95184, Q9UQQ2
      Related
      ENSP00000345492.2, ENST00000341259.7
      Conserved Domains (3) summary
      cd10412
      Location:355 → 451
      SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:194 → 309
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:25 → 80
      Phe_ZIP; Phenylalanine zipper

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      111404730..111451623
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011537720.4 → XP_011536022.1  SH2B adapter protein 3 isoform X1

      See identical proteins and their annotated locations for XP_011536022.1

      Conserved Domains (3) summary
      cd10412
      Location:396 → 492
      SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:194 → 349
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:25 → 80
      Phe_ZIP; Phenylalanine zipper

    2. XM_047428025.1 → XP_047283981.1  SH2B adapter protein 3 isoform X2

    3. XM_047428026.1 → XP_047283982.1  SH2B adapter protein 3 isoform X4

      UniProtKB/Swiss-Prot
      B9EGG5, O95184, Q9UQQ2

    4. XM_011537719.3 → XP_011536021.1  SH2B adapter protein 3 isoform X1

      See identical proteins and their annotated locations for XP_011536021.1

      Conserved Domains (3) summary
      cd10412
      Location:396 → 492
      SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:194 → 349
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:25 → 80
      Phe_ZIP; Phenylalanine zipper

    5. XM_005253818.5 → XP_005253875.1  SH2B adapter protein 3 isoform X2

      Conserved Domains (3) summary
      cd10412
      Location:395 → 491
      SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:194 → 349
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:25 → 80
      Phe_ZIP; Phenylalanine zipper

    6. XM_005253819.5 → XP_005253876.1  SH2B adapter protein 3 isoform X3

      Conserved Domains (3) summary
      cd10412
      Location:356 → 452
      SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cd01231
      Location:194 → 309
      PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
      pfam08916
      Location:25 → 80
      Phe_ZIP; Phenylalanine zipper

    7. XM_047428027.1 → XP_047283983.1  SH2B adapter protein 3 isoform X5

    8. XM_047428028.1 → XP_047283984.1  SH2B adapter protein 3 isoform X7

    9. XM_006719180.5 → XP_006719243.1  SH2B adapter protein 3 isoform X6

      UniProtKB/TrEMBL
      B7Z7K6
      Conserved Domains (2) summary
      cd10412
      Location:89 → 185
      SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
      cl17171
      Location:1 → 42
      PH-like; Pleckstrin homology-like domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      111385588..111432181
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054370694.1 → XP_054226669.1  SH2B adapter protein 3 isoform X4

    2. XM_054370690.1 → XP_054226665.1  SH2B adapter protein 3 isoform X1

    3. XM_054370692.1 → XP_054226667.1  SH2B adapter protein 3 isoform X2

    4. XM_054370689.1 → XP_054226664.1  SH2B adapter protein 3 isoform X1

    5. XM_054370691.1 → XP_054226666.1  SH2B adapter protein 3 isoform X2

    6. XM_054370693.1 → XP_054226668.1  SH2B adapter protein 3 isoform X3

    7. XM_054370695.1 → XP_054226670.1  SH2B adapter protein 3 isoform X5

    8. XM_054370697.1 → XP_054226672.1  SH2B adapter protein 3 isoform X7

    9. XM_054370696.1 → XP_054226671.1  SH2B adapter protein 3 isoform X6

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UQQ2.2 GenPept UniProtKB/Swiss-Prot:Q9UQQ2

    Gene LinkOut

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

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