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O14492 (SH2B2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
SH2B adapter protein 2
Alternative name(s):
Adapter protein with pleckstrin homology and Src homology 2 domains
SH2 and PH domain-containing adapter protein APS
Gene names
Name:SH2B2
Synonyms:APS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length632 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. May be involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis. May induce cytoskeletal reorganization via interaction with VAV3. Ref.3 Ref.4 Ref.5 Ref.7

Subunit structure

Homodimer. Interacts with KIT/c-KIT, SHC1, EPOR, PDGFR, VAV1 and VAV3. Interacts (via N-terminal region) with SHC1. Interacts (via the phosphorylated C-terminus) with GRB2. Interacts (via its SH2 domain) with EPOR, INSR and KIT. Interacts with GRB2 after B-cell antigen receptor stimulation. Interacts (via PH domain) with VAV3. Interacts with NTRK1, NTRK2 and NTRK3 (phosphorylated); after stimulation of the receptor by its extracellular ligand and subsequent autophosphorylation of the receptor. Binds INSR, GRB2, ASB6 and CAP. Insulin stimulation leads to dissociation of CAP. Binds CBS only when SH2B2/APS has become phosphorylated. INSR binding does not depend on the phosphorylation of SH2B2/APS By similarity. Ref.1 Ref.3 Ref.4 Ref.5 Ref.7

Subcellular location

Cytoplasm. Cell membrane. Note: Cytoplasmic before PDGF stimulation. After PDGF stimulation, localized at the cell membrane and peripheral region. Ref.4

Tissue specificity

Expressed in spleen, prostate, testis, uterus, small intestine and skeletal muscle. Among hematopoietic cell lines, expressed exclusively in B-cells. Not expressed in most tumor cell lines. Ref.1 Ref.4

Post-translational modification

Tyrosine phosphorylated by JAK2, KIT and other kinases activated by B-cell receptor in response to stimulation with cytokines, IL3, IL5, PDGF, IGF1, IGF2, CSF2/GM-CSF and cross-linking of the B-cell receptor complex. Ref.1 Ref.3 Ref.4 UniProtKB Q9JID9

Sequence similarities

Belongs to the SH2B adapter family.

Contains 1 PH domain.

Contains 1 SH2 domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CBLP226817EBI-7507432,EBI-518228

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 632632SH2B adapter protein 2
PRO_0000064647

Regions

Domain193 – 306114PH
Domain417 – 51599SH2

Amino acid modifications

Modified residue6291Phosphotyrosine Ref.1 Ref.3

Experimental info

Sequence conflict1111P → S in BAA22514. Ref.1

Secondary structure

....... 632
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O14492 [UniParc].

Last modified September 23, 2008. Version 2.
Checksum: 823DF1699D404227

FASTA63267,738
        10         20         30         40         50         60 
MNGAGPGPAA AAPVPVPVPV PDWRQFCELH AQAAAVDFAH KFCRFLRDNP AYDTPDAGAS 

        70         80         90        100        110        120 
FSRHFAANFL DVFGEEVRRV LVAGPTTRGA AVSAEAMEPE LADTSALKAA PYGHSRSSED 

       130        140        150        160        170        180 
VSTHAATKAR VRKGFSLRNM SLCVVDGVRD MWHRRASPEP DAAAAPRTAE PRDKWTRRLR 

       190        200        210        220        230        240 
LSRTLAAKVE LVDIQREGAL RFMVADDAAA GSGGSAQWQK CRLLLRRAVA EERFRLEFFV 

       250        260        270        280        290        300 
PPKASRPKVS IPLSAIIEVR TTMPLEMPEK DNTFVLKVEN GAEYILETID SLQKHSWVAD 

       310        320        330        340        350        360 
IQGCVDPGDS EEDTELSCTR GGCLASRVAS CSCELLTDAV DLPRPPETTA VGAVVTAPHS 

       370        380        390        400        410        420 
RGRDAVRESL IHVPLETFLQ TLESPGGSGS DSNNTGEQGA ETDPEAEPEL ELSDYPWFHG 

       430        440        450        460        470        480 
TLSRVKAAQL VLAGGPRNHG LFVIRQSETR PGEYVLTFNF QGKAKHLRLS LNGHGQCHVQ 

       490        500        510        520        530        540 
HLWFQSVLDM LRHFHTHPIP LESGGSADIT LRSYVRAQDP PPEPGPTPPA APASPACWSD 

       550        560        570        580        590        600 
SPGQHYFSSL AAAACPPASP SDAAGASSSS ASSSSAASGP APPRPVEGQL SARSRSNSAE 

       610        620        630 
RLLEAVAATA AEEPPEAAPG RARAVENQYS FY 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation."
Yokouchi M., Suzuki R., Masuhara M., Komiya S., Inoue A., Yoshimura A.
Oncogene 15:7-15(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH GRB2; KIT AND SHC1, PHOSPHORYLATION AT TYR-629.
Tissue: B-cell.
[2]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"APS, an adaptor protein containing pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl."
Wakioka T., Sasaki A., Mitsui K., Yokouchi M., Inoue A., Komiya S., Yoshimura A.
Leukemia 13:760-767(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH CBL AND EPOR.
[4]"APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis."
Yokouchi M., Wakioka T., Sakamoto H., Yasukawa H., Ohtsuka S., Sasaki A., Ohtsubo M., Valius M., Inoue A., Komiya S., Yoshimura A.
Oncogene 18:759-767(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH CBL AND PDGFR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]"Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity."
Yabana N., Shibuya M.
Oncogene 21:7720-7729(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH VAV1 AND VAV3.
[6]"Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor."
Roskoski R. Jr.
Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[7]"A phenylalanine zipper mediates APS dimerization."
Dhe-Paganon S., Werner E.D., Nishi M., Hansen L., Chi Y.-I., Shoelson S.E.
Nat. Struct. Mol. Biol. 11:968-974(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 21-85, FUNCTION, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB000520 mRNA. Translation: BAA22514.1.
AC005088 Genomic DNA. No translation available.
RefSeqNP_066189.3. NM_020979.4.
XP_005277034.1. XM_005276977.2.
XP_005277036.1. XM_005276979.1.
UniGeneHs.489448.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Q2HX-ray1.70A/B/C21-85[»]
ProteinModelPortalO14492.
SMRO14492. Positions 21-83, 182-310, 410-494.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115850. 13 interactions.
IntActO14492. 5 interactions.
MINTMINT-1498797.
STRING9606.ENSP00000304701.

PTM databases

PhosphoSiteO14492.

Proteomic databases

MaxQBO14492.
PaxDbO14492.
PRIDEO14492.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000306803; ENSP00000304701; ENSG00000160999.
ENST00000563740; ENSP00000455175; ENSG00000259885.
GeneID10603.
KEGGhsa:10603.
UCSCuc011kko.2. human.

Organism-specific databases

CTD10603.
GeneCardsGC07P101928.
HGNCHGNC:17381. SH2B2.
HPAHPA051131.
MIM605300. gene.
neXtProtNX_O14492.
PharmGKBPA145148106.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG77816.
HOGENOMHOG000047355.
HOVERGENHBG006707.
KOK07193.
OMACVGSSQW.
PhylomeDBO14492.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.
SignaLinkO14492.

Gene expression databases

ArrayExpressO14492.
BgeeO14492.
CleanExHS_SH2B2.
GenevestigatorO14492.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProIPR011993. PH_like_dom.
IPR015012. Phe_ZIP.
IPR001849. Pleckstrin_homology.
IPR000980. SH2.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF08916. Phe_ZIP. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF109805. SSF109805. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO14492.
GeneWikiSH2B2.
GenomeRNAi10603.
NextBio40266.
PROO14492.
SOURCESearch...

Entry information

Entry nameSH2B2_HUMAN
AccessionPrimary (citable) accession number: O14492
Secondary accession number(s): A6ND74
Entry history
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: September 23, 2008
Last modified: June 11, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM