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

Summary

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

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_000012.12 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: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia.
Title: LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia.
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.
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.
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.
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.
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.
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.
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.
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 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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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	not available
Primary myelofibrosis MedGen: C0001815 OMIM: 254450 GeneReviews: Not available	not available
Thrombocythemia 1 MedGen: C3277671 OMIM: 187950 GeneReviews: Not available	not available

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC35065 (e-PCR)
- UniSTS:78409

RH15682 (e-PCR)
- UniSTS:5457

D12S2142 (e-PCR)
- UniSTS:82296

RH44606 (e-PCR)
- UniSTS:40398

LNK_1461 (e-PCR)
- UniSTS:277456

LNK_v487 (e-PCR)
- UniSTS:277456

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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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

NG_021216.1 RefSeqGene

Range

5001..50676

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_621

mRNA and Protein(s)

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
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

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

111404730..111451623

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
XM_047428025.1 → XP_047283981.1 SH2B adapter protein 3 isoform X2
XM_047428026.1 → XP_047283982.1 SH2B adapter protein 3 isoform X4

UniProtKB/Swiss-Prot

B9EGG5, O95184, Q9UQQ2
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
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
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
XM_047428027.1 → XP_047283983.1 SH2B adapter protein 3 isoform X5
XM_047428028.1 → XP_047283984.1 SH2B adapter protein 3 isoform X7
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