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

Summary

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: all
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Genomic context

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_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hematopoietic and eosinophil-specific LNK(SH2B3) deficiency promotes eosinophilia and arterial thrombosis.
Title: Hematopoietic and eosinophil-specific LNK(SH2B3) deficiency promotes eosinophilia and arterial thrombosis.
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.
Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency.
Title: Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency.
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.
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.
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.
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.
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.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (47)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (7) 1 citation
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:235300

Lnk (e-PCR), detects polymorphism
- UniSTS:279421

AI429800 (e-PCR)
- UniSTS:159438

AW476061 (e-PCR)
- UniSTS:207870

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 cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
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	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_negative_effect embryonic hemopoiesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within embryonic hemopoiesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in erythrocyte development	IEA Inferred from Electronic Annotation more info
involved_in erythrocyte development	ISO Inferred from Sequence Orthology more info
involved_in hemopoiesis	IBA Inferred from Biological aspect of Ancestor more info
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 myeloid cell development	IEA Inferred from Electronic Annotation more info
involved_in myeloid cell homeostasis	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation 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	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of response to cytokine stimulus	IEA Inferred from Electronic Annotation more info
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
involved_in thrombopoietin-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in thrombopoietin-mediated signaling pathway	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)

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
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
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
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

NC_000071.7 Reference GRCm39 C57BL/6J

Range

121953544..121975706 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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