O14492 (SH2B2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	632 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome insulin receptor signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL intracellular signal transduction Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	JAK pathway signal transduction adaptor activity Inferred from direct assay Ref.3. Source: UniProtKB SH3/SH2 adaptor activity Inferred from direct assay Ref.1. Source: UniProtKB phospholipid binding Inferred from electronic annotation. Source: InterPro signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 632

632

SH2B adapter protein 2

PRO_0000064647

Regions

Domain

193 – 306

114

PH

Domain

417 – 515

99

SH2

Amino acid modifications

Modified residue

629

1

Phosphotyrosine Ref.1 Ref.3

Experimental info

Sequence conflict

111

1

P → S in BAA22514. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

632

Helix Strand Turn

Details...

Helix

23 – 48

26

Helix

50 – 52

3

Helix

57 – 82

26

Sequences

	Sequence		Length	Mass (Da)
	O14492 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: 823DF1699D404227	FASTA	632	67,738
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00155706.

RefSeq

NP_066189.3. NM_020979.3.

UniGene

Hs.489448.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q2H	X-ray	1.70	A/B/C	21-85	[»]

ProteinModelPortal

O14492.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1498797.

STRING

9606.ENSP00000304701.

PTM databases

PhosphoSite

O14492.

Proteomic databases

PaxDb

O14492.

PRIDE

O14492.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000306803; ENSP00000304701; ENSG00000160999.
ENST00000563740; ENSP00000455175; ENSG00000259885.

GeneID

10603.

KEGG

hsa:10603.

UCSC

uc011kko.2. human.

Organism-specific databases

CTD

10603.

GeneCards

GC07P101928.

HGNC

HGNC:17381. SH2B2.

HPA

HPA051131.

MIM

605300. gene.

neXtProt

NX_O14492.

PharmGKB

PA145148106.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG77816.

HOGENOM

HOG000047355.

HOVERGEN

HBG006707.

KO

K07193.

OrthoDB

EOG43FGWQ.

Enzyme and pathway databases

Pathway_Interaction_DB

insulin_pathway. Insulin Pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

SignaLink

O14492.

Gene expression databases

ArrayExpress

O14492.

Bgee

O14492.

CleanEx

HS_SH2B2.

Genevestigator

O14492.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.
3.30.505.10. 1 hit.

InterPro

IPR011993. PH_like_dom.
IPR015012. Phe_ZIP.
IPR001849. Pleckstrin_homology.
IPR000980. SH2.
[Graphical view]

Pfam

PF00169. PH. 1 hit.
PF08916. Phe_ZIP. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.

SMART

SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]

SUPFAM

SSF109805. Phe_ZIP. 1 hit.

PROSITE

PS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O14492.

GenomeRNAi

10603.

NextBio

40266.

SOURCE

Search...

Entry information

Entry name

SH2B2_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.