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Sh2b3 SH2B adaptor protein 3 [ Mus musculus (house mouse) ]

Gene ID: 16923, updated on 5-Mar-2024

Summary

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Official Symbol
Sh2b3provided by MGI
Official Full Name
SH2B adaptor protein 3provided by MGI
Primary source
MGI:MGI:893598
See related
Ensembl:ENSMUSG00000042594 AllianceGenome:MGI:893598
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
Lnk
Summary
This gene encodes a member of the SH2B family of adapter proteins that play an important role in T cell receptor signaling. This gene is preferentially expressed in hematopoietic stem cells, hematopoietic progenitors, pre and immature B cells, as well as megakaryocytes and mastocytes. In hematopoietic stem cells, the encoded protein is a key regulator of self-renewal, proliferation and apoptosis. Mice lacking the encoded protein exhibit pre and immature B cell expansion in spleen and the bone marrow. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
Expression
Ubiquitous expression in spleen adult (RPKM 35.7), testis adult (RPKM 30.2) and 28 other tissues See more
Orthologs
human all
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Genomic context

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Location:
5 F; 5 61.99 cM
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 5 NC_000071.7 (121953544..121975706, complement)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 5 NC_000071.6 (121815481..121837645, complement)

Chromosome 5 - NC_000071.7Genomic Context describing neighboring genes Neighboring gene STARR-seq mESC enhancer starr_14261 Neighboring gene acyl-Coenzyme A dehydrogenase family, member 12 Neighboring gene acyl-Coenzyme A dehydrogenase family, member 10 Neighboring gene BRCA1 associated protein Neighboring gene ataxin 2 Neighboring gene STARR-seq mESC enhancer starr_14264 Neighboring gene microRNA 7031 Neighboring gene STARR-positive B cell enhancer mm9_chr5:122298757-122299058 Neighboring gene predicted gene, 32422 Neighboring gene PH domain containing endocytic trafficking adaptor 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency. Dou H, et al. Circulation, 2021 Dec 14. PMID 34846914, Free PMC Article
  2. LNK deficiency aggravates palmitate-induced preadipocyte apoptosis. Du JY, et al. Biochem Biophys Res Commun, 2017 Aug 19. PMID 28526415
  3. Specific disruption of Lnk in murine endothelial progenitor cells promotes dermal wound healing via enhanced vasculogenesis, activation of myofibroblasts, and suppression of inflammatory cell recruitment. Lee JH, et al. Stem Cell Res Ther, 2016 Oct 28. PMID 27793180, Free PMC Article
  4. Integrative network analysis reveals molecular mechanisms of blood pressure regulation. Huan T, et al. Mol Syst Biol, 2015 Apr 16. PMID 25882670, Free PMC Article
  5. Lnk/Sh2b3 controls the production and function of dendritic cells and regulates the induction of IFN-γ-producing T cells. Mori T, et al. J Immunol, 2014 Aug 15. PMID 25024389

See all (76) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency.
    Title: Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency.
  3. Nf1 and Sh2b3 mutations cooperate in vivo in a mouse model of juvenile myelomonocytic leukemia.
    Title: Nf1 and Sh2b3 mutations cooperate in vivo in a mouse model of juvenile myelomonocytic leukemia.
  4. 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.
  5. The requirement of PI3K-Akt activation for the cardioprotective effect of Lnk was confirmed.
    Title: The lymphocyte adapter protein: A negative regulator of myocardial ischemia/reperfusion injury.
  6. Study identified a role for LNK (SH2B3) in the pathology of aortic dissection in experimental animals and humans and described a new model that can be used to inform both inherited and acquired forms of this disease.
    Title: LNK deficiency promotes acute aortic dissection and rupture.
  7. Lnk regulates adipose inflammation and glucose tolerance through group 1 innate lymphoid cells.
    Title: Lnk/Sh2b3 Regulates Adipose Inflammation and Glucose Tolerance through Group 1 ILCs.
  8. Study found that LNK is significantly elevated in cutaneous melanoma; this elevation is correlated with hyperactive signaling of the RAS-RAF-MEK pathway. Elevated LNK enhances cell growth and survival in adverse conditions. Forced expression of LNK inhibits signaling by interferon-STAT1 and suppresses interferon induced cell cycle arrest and cell apoptosis.
    Title: LNK suppresses interferon signaling in melanoma.
  9. Data indicate that linker of T-cell receptor pathways protein(Lnk) deficiency restores phenotypic hematopoietic stem cells (HSCs) in Fanconi anemia, complementation group D2 protein knockout (Fancd2-/-) mice.
    Title: Lnk/Sh2b3 deficiency restores hematopoietic stem cell function and genome integrity in Fancd2 deficient Fanconi anemia.
  10. Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype
    Title: Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype.
Submit: New GeneRIF Correction See all GeneRIFs (46)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Targeted (2)  1 citation
  • Endonuclease-mediated (4) 

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 MGI

Function Evidence Code Pubs
enables phosphate ion binding ISO
Inferred from Sequence Orthology
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein tyrosine kinase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-containing complex binding ISO
Inferred from Sequence Orthology
more info
  
enables signaling adaptor activity IEA
Inferred from Electronic Annotation
more info
  
enables signaling receptor complex adaptor activity IPI
Inferred from Physical Interaction
more info
 PubMed 
enables stem cell factor receptor binding 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
acts_upstream_of_or_within_negative_effect cellular response to chemokine IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to interleukin-3 IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within embryonic hemopoiesis IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within embryonic hemopoiesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in erythrocyte development ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within hematopoietic stem cell differentiation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within hemopoiesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within intracellular signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in megakaryocyte development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in monocyte homeostasis IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in negative regulation of Kit signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of MAPK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of cell population proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of chemokine-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of platelet aggregation IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in negative regulation of receptor signaling pathway via JAK-STAT ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of receptor signaling pathway via STAT IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of response to cytokine stimulus ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of sprouting angiogenesis ISO
Inferred from Sequence Orthology
more info
  
involved_in neutrophil homeostasis IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in regulation of regulatory T cell differentiation ISO
Inferred from Sequence Orthology
more info
  
involved_in signal transduction IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_negative_effect thrombopoietin-mediated signaling pathway IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in thrombopoietin-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within_negative_effect thrombopoietin-mediated signaling pathway ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
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
linker of T-cell receptor pathways
lymphocyte-specific adapter protein Lnk
signal transduction protein Lnk

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_001306126.2 → NP_001293055.1  SH2B adapter protein 3 isoform 1

    See identical proteins and their annotated locations for NP_001293055.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein (isoform 1).
    Source sequence(s)
    AC113302
    Consensus CDS
    CCDS19641.1
    UniProtKB/Swiss-Prot
    O09039
    Related
    ENSMUSP00000113926.2, ENSMUST00000122426.8
    Conserved Domains (3) summary
    cd10412
    Location:327 → 423
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:168 → 281
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:23 → 76
    Phe_ZIP; Phenylalanine zipper

  2. NM_001306127.2 → NP_001293056.1  SH2B adapter protein 3 isoform 1

    See identical proteins and their annotated locations for NP_001293056.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein (isoform 1).
    Source sequence(s)
    AC113302
    Consensus CDS
    CCDS19641.1
    UniProtKB/Swiss-Prot
    O09039
    Related
    ENSMUSP00000083490.2, ENSMUST00000086310.8
    Conserved Domains (3) summary
    cd10412
    Location:327 → 423
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:168 → 281
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:23 → 76
    Phe_ZIP; Phenylalanine zipper

  3. NM_001306128.2 → NP_001293057.1  SH2B adapter protein 3 isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
    Source sequence(s)
    AC113302
    Consensus CDS
    CCDS84952.1
    UniProtKB/TrEMBL
    D3Z3Y5
    Related
    ENSMUSP00000113808.2, ENSMUST00000118580.6
    Conserved Domains (3) summary
    cd10412
    Location:317 → 413
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:168 → 281
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:23 → 76
    Phe_ZIP; Phenylalanine zipper

  4. NM_008507.5 → NP_032533.1  SH2B adapter protein 3 isoform 1

    See identical proteins and their annotated locations for NP_032533.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1). Variants 1, 2 and 3 encode the same protein (isoform 1).
    Source sequence(s)
    AC113302
    Consensus CDS
    CCDS19641.1
    UniProtKB/Swiss-Prot
    O09039
    Related
    ENSMUSP00000041611.8, ENSMUST00000040308.14
    Conserved Domains (3) summary
    cd10412
    Location:327 → 423
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:168 → 281
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:23 → 76
    Phe_ZIP; Phenylalanine zipper

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000071.7 Reference GRCm39 C57BL/6J

    Range
    121953544..121975706 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006530171.5 → XP_006530234.1  SH2B adapter protein 3 isoform X1

    See identical proteins and their annotated locations for XP_006530234.1

    UniProtKB/Swiss-Prot
    O09039
    Conserved Domains (3) summary
    cd10412
    Location:327 → 423
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:168 → 281
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:23 → 76
    Phe_ZIP; Phenylalanine zipper

  2. XM_036164833.1 → XP_036020726.1  SH2B adapter protein 3 isoform X1

    UniProtKB/Swiss-Prot
    O09039
    Conserved Domains (3) summary
    cd10412
    Location:327 → 423
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:168 → 281
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:23 → 76
    Phe_ZIP; Phenylalanine zipper

  3. XM_006530173.5 → XP_006530236.1  SH2B adapter protein 3 isoform X1

    See identical proteins and their annotated locations for XP_006530236.1

    UniProtKB/Swiss-Prot
    O09039
    Conserved Domains (3) summary
    cd10412
    Location:327 → 423
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:168 → 281
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:23 → 76
    Phe_ZIP; Phenylalanine zipper

  4. XM_006530172.1 → XP_006530235.1  SH2B adapter protein 3 isoform X1

    See identical proteins and their annotated locations for XP_006530235.1

    UniProtKB/Swiss-Prot
    O09039
    Conserved Domains (3) summary
    cd10412
    Location:327 → 423
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:168 → 281
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:23 → 76
    Phe_ZIP; Phenylalanine zipper

  5. XM_006530170.5 → XP_006530233.1  SH2B adapter protein 3 isoform X1

    See identical proteins and their annotated locations for XP_006530233.1

    UniProtKB/Swiss-Prot
    O09039
    Conserved Domains (3) summary
    cd10412
    Location:327 → 423
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:168 → 281
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:23 → 76
    Phe_ZIP; Phenylalanine zipper
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O09039.2 GenPept UniProtKB/Swiss-Prot:O09039

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