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Protein

SH2B adapter protein 2

Gene

SH2B2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 VAV3.4 Publications

GO - Molecular functioni

  • JAK pathway signal transduction adaptor activity Source: UniProtKB
  • SH3/SH2 adaptor activity Source: UniProtKB
  • signal transducer activity Source: InterPro

GO - Biological processi

  • blood coagulation Source: Reactome
  • insulin receptor signaling pathway Source: BHF-UCL
  • intracellular signal transduction Source: UniProtKB
  • positive regulation of signal transduction Source: GOC
  • regulation of JAK-STAT cascade Source: GOC
  • signal transduction Source: ProtInc
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_111225. Regulation of KIT signaling.
REACT_24970. Factors involved in megakaryocyte development and platelet production.
SignaLinkiO14492.

Names & Taxonomyi

Protein namesi
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 namesi
Name:SH2B2
Synonyms:APS
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:17381. SH2B2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA145148106.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 632632SH2B adapter protein 2PRO_0000064647Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei629 – 6291Phosphotyrosine1 Publication

Post-translational modificationi

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.By similarity3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO14492.
PaxDbiO14492.
PRIDEiO14492.

PTM databases

PhosphoSiteiO14492.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiO14492.
CleanExiHS_SH2B2.
GenevestigatoriO14492.

Organism-specific databases

HPAiHPA051131.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CBLP226817EBI-7507432,EBI-518228

Protein-protein interaction databases

BioGridi115850. 14 interactions.
IntActiO14492. 5 interactions.
MINTiMINT-1498797.
STRINGi9606.ENSP00000304701.

Structurei

Secondary structure

1
632
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi23 – 4826Combined sources
Helixi50 – 523Combined sources
Helixi57 – 8226Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1Q2HX-ray1.70A/B/C21-85[»]
ProteinModelPortaliO14492.
SMRiO14492. Positions 21-83, 182-310, 410-494.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14492.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini193 – 306114PHPROSITE-ProRule annotationCuratedAdd
BLAST
Domaini417 – 51599SH2PROSITE-ProRule annotationCuratedAdd
BLAST

Sequence similaritiesi

Belongs to the SH2B adapter family.Curated
Contains 1 PH domain.PROSITE-ProRule annotationCurated
Contains 1 SH2 domain.PROSITE-ProRule annotationCurated

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG77816.
HOGENOMiHOG000047355.
HOVERGENiHBG006707.
InParanoidiO14492.
KOiK07193.
OMAiCTRGGCL.
PhylomeDBiO14492.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR015012. Phe_ZIP.
IPR000980. SH2.
IPR030523. SH2B.
IPR030520. SH2B2.
[Graphical view]
PANTHERiPTHR10872. PTHR10872. 1 hit.
PTHR10872:SF4. PTHR10872:SF4. 1 hit.
PfamiPF00169. PH. 1 hit.
PF08916. Phe_ZIP. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF109805. SSF109805. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O14492-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNGAGPGPAA AAPVPVPVPV PDWRQFCELH AQAAAVDFAH KFCRFLRDNP
60 70 80 90 100
AYDTPDAGAS FSRHFAANFL DVFGEEVRRV LVAGPTTRGA AVSAEAMEPE
110 120 130 140 150
LADTSALKAA PYGHSRSSED VSTHAATKAR VRKGFSLRNM SLCVVDGVRD
160 170 180 190 200
MWHRRASPEP DAAAAPRTAE PRDKWTRRLR LSRTLAAKVE LVDIQREGAL
210 220 230 240 250
RFMVADDAAA GSGGSAQWQK CRLLLRRAVA EERFRLEFFV PPKASRPKVS
260 270 280 290 300
IPLSAIIEVR TTMPLEMPEK DNTFVLKVEN GAEYILETID SLQKHSWVAD
310 320 330 340 350
IQGCVDPGDS EEDTELSCTR GGCLASRVAS CSCELLTDAV DLPRPPETTA
360 370 380 390 400
VGAVVTAPHS RGRDAVRESL IHVPLETFLQ TLESPGGSGS DSNNTGEQGA
410 420 430 440 450
ETDPEAEPEL ELSDYPWFHG TLSRVKAAQL VLAGGPRNHG LFVIRQSETR
460 470 480 490 500
PGEYVLTFNF QGKAKHLRLS LNGHGQCHVQ HLWFQSVLDM LRHFHTHPIP
510 520 530 540 550
LESGGSADIT LRSYVRAQDP PPEPGPTPPA APASPACWSD SPGQHYFSSL
560 570 580 590 600
AAAACPPASP SDAAGASSSS ASSSSAASGP APPRPVEGQL SARSRSNSAE
610 620 630
RLLEAVAATA AEEPPEAAPG RARAVENQYS FY
Length:632
Mass (Da):67,738
Last modified:September 23, 2008 - v2
Checksum:i823DF1699D404227
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti111 – 1111P → S in BAA22514 (PubMed:9233773).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000520 mRNA. Translation: BAA22514.1.
AC005088 Genomic DNA. No translation available.
RefSeqiNP_066189.3. NM_020979.4.
XP_005277034.1. XM_005276977.3.
XP_005277036.1. XM_005276979.2.
UniGeneiHs.489448.

Genome annotation databases

GeneIDi10603.
KEGGihsa:10603.
UCSCiuc011kko.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000520 mRNA. Translation: BAA22514.1.
AC005088 Genomic DNA. No translation available.
RefSeqiNP_066189.3. NM_020979.4.
XP_005277034.1. XM_005276977.3.
XP_005277036.1. XM_005276979.2.
UniGeneiHs.489448.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1Q2HX-ray1.70A/B/C21-85[»]
ProteinModelPortaliO14492.
SMRiO14492. Positions 21-83, 182-310, 410-494.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115850. 14 interactions.
IntActiO14492. 5 interactions.
MINTiMINT-1498797.
STRINGi9606.ENSP00000304701.

PTM databases

PhosphoSiteiO14492.

Proteomic databases

MaxQBiO14492.
PaxDbiO14492.
PRIDEiO14492.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi10603.
KEGGihsa:10603.
UCSCiuc011kko.2. human.

Organism-specific databases

CTDi10603.
GeneCardsiGC07P101928.
HGNCiHGNC:17381. SH2B2.
HPAiHPA051131.
MIMi605300. gene.
neXtProtiNX_O14492.
PharmGKBiPA145148106.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG77816.
HOGENOMiHOG000047355.
HOVERGENiHBG006707.
InParanoidiO14492.
KOiK07193.
OMAiCTRGGCL.
PhylomeDBiO14492.

Enzyme and pathway databases

ReactomeiREACT_111225. Regulation of KIT signaling.
REACT_24970. Factors involved in megakaryocyte development and platelet production.
SignaLinkiO14492.

Miscellaneous databases

EvolutionaryTraceiO14492.
GeneWikiiSH2B2.
GenomeRNAii10603.
NextBioi40266.
PROiO14492.
SOURCEiSearch...

Gene expression databases

BgeeiO14492.
CleanExiHS_SH2B2.
GenevestigatoriO14492.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR015012. Phe_ZIP.
IPR000980. SH2.
IPR030523. SH2B.
IPR030520. SH2B2.
[Graphical view]
PANTHERiPTHR10872. PTHR10872. 1 hit.
PTHR10872:SF4. PTHR10872:SF4. 1 hit.
PfamiPF00169. PH. 1 hit.
PF08916. Phe_ZIP. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF109805. SSF109805. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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-cell1 Publication.
  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. Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 21-85, FUNCTION, SUBUNIT.

Entry informationi

Entry nameiSH2B2_HUMAN
AccessioniPrimary (citable) accession number: O14492
Secondary accession number(s): A6ND74
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: September 23, 2008
Last modified: May 27, 2015
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.