SH2B2

Protein-coding gene in the species Homo sapiens

SH2B2

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
1Q2H

Identifiers

Aliases

SH2B2, APS, SH2B adaptor protein 2

External IDs

OMIM: 605300; MGI: 1345171; HomoloGene: 10309; GeneCards: SH2B2; OMA:SH2B2 - orthologs

Gene location (Human)

Chr.	Chromosome 7 (human)^[1]

Band	7q22.1	Start	102,285,091 bp^[1]
Band	7q22.1	End	102,321,711 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 5 (mouse)^[2]

Band	5\|5 G2	Start	136,247,001 bp^[2]
Band	5\|5 G2	End	136,275,410 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

triceps brachii muscle

Skeletal muscle tissue of biceps brachii

muscle of thigh

vastus lateralis muscle

renal medulla

muscle of trunk

Skeletal muscle tissue of rectus abdominis

thoracic diaphragm

tibialis anterior muscle

body of tongue

Top expressed in

brown adipose tissue

granulocyte

white adipose tissue

tunica adventitia of aorta

spermatocyte

ganglionic eminence

internal carotid artery

gastrula

tail of embryo

placenta

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	JAK pathway signal transduction adaptor activity protein binding signaling adaptor activity transmembrane receptor protein tyrosine kinase adaptor activity identical protein binding
Cellular component	cytoplasm cytosol plasma membrane membrane stress fiber ruffle actin filament
Biological process	insulin receptor signaling pathway blood coagulation signal transduction regulation of receptor signaling pathway via JAK-STAT positive regulation of signal transduction intracellular signal transduction B-1 B cell homeostasis nervous system development cytokine-mediated signaling pathway regulation of metabolic process actin cytoskeleton organization regulation of Ras protein signal transduction regulation of immune response antigen receptor-mediated signaling pathway brown fat cell differentiation
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


10603


23921

Ensembl


ENSG00000160999


ENSMUSG00000005057

UniProt


O14492


Q9JID9

RefSeq (mRNA)


NM_020979 NM_001359228 NM_001359229 NM_001359230 NM_001359231


NM_018825 NM_001302938 NM_001302939

RefSeq (protein)


NP_066189 NP_001346157 NP_001346158 NP_001346159 NP_001346160


NP_001289867 NP_001289868 NP_061295

Location (UCSC)

Chr 7: 102.29 – 102.32 Mb

Chr 5: 136.25 – 136.28 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

SH2B adapter protein 2 is a protein that in humans is encoded by the SH2B2 gene.^[5]^[6]

Function

The protein encoded by this gene is expressed in B lymphocytes and contains pleckstrin homology and src homology 2 (SH2) domains. In Burkitt 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 Shc/Grb2.^[6]

Interactions

SH2B2 has been shown to interact with TrkA^[7] and Cbl gene.^[8]^[9]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000160999 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000005057 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Yokouchi M, Suzuki R, Masuhara M, Komiya S, Inoue A, Yoshimura A (Aug 1997). "Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation". Oncogene. 15 (1): 7–15. doi:10.1038/sj.onc.1201163. PMID 9233773.
^ ^a ^b "Entrez Gene: SH2B2 SH2B adaptor protein 2".
^ Qian X, Riccio A, Zhang Y, Ginty DD (Nov 1998). "Identification and characterization of novel substrates of Trk receptors in developing neurons". Neuron. 21 (5): 1017–29. doi:10.1016/S0896-6273(00)80620-0. PMID 9856458. S2CID 12354383.
^ Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A (May 1999). "APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl". Leukemia. 13 (5): 760–7. doi:10.1038/sj/leu/2401397. PMID 10374881.
^ Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J (Mar 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". EMBO J. 27 (5): 804–16. doi:10.1038/emboj.2008.18. PMC 2265755. PMID 18273061.

Glöckner G, Scherer S, Schattevoy R, Boright A, Weber J, Tsui LC, Rosenthal A (1998). "Large-Scale Sequencing of Two Regions in Human Chromosome 7q22: Analysis of 650 kb of Genomic Sequence around the EPO and CUTL1 Loci Reveals 17 Genes". Genome Res. 8 (10): 1060–73. doi:10.1101/gr.8.10.1060. PMC 310788. PMID 9799793.
Qian X, Riccio A, Zhang Y, Ginty DD (1999). "Identification and characterization of novel substrates of Trk receptors in developing neurons". Neuron. 21 (5): 1017–29. doi:10.1016/S0896-6273(00)80620-0. PMID 9856458. S2CID 12354383.
Yokouchi M, Wakioka T, Sakamoto H, Yasukawa H, Ohtsuka S, Sasaki A, Ohtsubo M, Valius M, Inoue A, Komiya S, Yoshimura A (1999). "APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis". Oncogene. 18 (3): 759–67. doi:10.1038/sj.onc.1202326. PMID 9989826.
Moodie SA, Alleman-Sposeto J, Gustafson TA (1999). "Identification of the APS protein as a novel insulin receptor substrate". J. Biol. Chem. 274 (16): 11186–93. doi:10.1074/jbc.274.16.11186. PMID 10196204.
Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A (1999). "APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl". Leukemia. 13 (5): 760–7. doi:10.1038/sj/leu/2401397. PMID 10374881.
Iseki M, Takaki S, Takatsu K (2000). "Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins". Biochem. Biophys. Res. Commun. 272 (1): 45–54. doi:10.1006/bbrc.2000.2736. PMID 10872802.
O'Brien KB, O'Shea JJ, Carter-Su C (2002). "SH2-B family members differentially regulate JAK family tyrosine kinases". J. Biol. Chem. 277 (10): 8673–81. doi:10.1074/jbc.M109165200. PMID 11751854.
Liu J, Kimura A, Baumann CA, Saltiel AR (2002). "APS Facilitates c-Cbl Tyrosine Phosphorylation and GLUT4 Translocation in Response to Insulin in 3T3-L1 Adipocytes". Mol. Cell. Biol. 22 (11): 3599–609. doi:10.1128/MCB.22.11.3599-3609.2002. PMC 133825. PMID 11997497.
Yabana N, Shibuya M (2002). "Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity". Oncogene. 21 (50): 7720–9. doi:10.1038/sj.onc.1205927. PMID 12400014.
Ahn MY, Katsanakis KD, Bheda F, Pillay TS (2004). "Primary and essential role of the adaptor protein APS for recruitment of both c-Cbl and its associated protein CAP in insulin signaling". J. Biol. Chem. 279 (20): 21526–32. doi:10.1074/jbc.M307740200. PMID 15031295.
Wilcox A, Katsanakis KD, Bheda F, Pillay TS (2004). "Asb6, an adipocyte-specific ankyrin and SOCS box protein, interacts with APS to enable recruitment of elongins B and C to the insulin receptor signaling complex". J. Biol. Chem. 279 (37): 38881–8. doi:10.1074/jbc.M406101200. PMID 15231829.
Hu J, Hubbard SR (2005). "Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins". J. Biol. Chem. 280 (19): 18943–9. doi:10.1074/jbc.M414157200. PMID 15737992.
Iseki M, Kubo-Akashi C, Kwon SM, Yamaguchi A, Takatsu K, Takaki S (2005). "APS, an adaptor molecule containing PH and SH2 domains, has a negative regulatory role in B cell proliferation". Biochem. Biophys. Res. Commun. 330 (3): 1005–13. doi:10.1016/j.bbrc.2005.03.073. PMID 15809095.
Katsanakis KD, Pillay TS (2006). "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". J. Biol. Chem. 280 (45): 37827–32. doi:10.1074/jbc.M505959200. PMID 16141217.
Li M, Li Z, Morris DL, Rui L (2007). "Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling". Endocrinology. 148 (4): 1615–21. doi:10.1210/en.2006-1010. PMC 4710543. PMID 17204555.

PDB gallery

1q2h: Phenylalanine Zipper Mediates APS Dimerization
1rpy: CRYSTAL STRUCTURE OF THE DIMERIC SH2 DOMAIN OF APS
1rqq: Crystal Structure of the Insulin Receptor Kinase in Complex with the SH2 Domain of APS
1v5m: Solution Structure of the Pleckstrin Homology Domain of Mouse APS