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Protein

SH2B adapter protein 2

Gene

Sh2b2

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

GO - Molecular functioni

  • JAK pathway signal transduction adaptor activity Source: MGI
  • SH3/SH2 adaptor activity Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: MGI

GO - Biological processi

  • actin cytoskeleton organization Source: MGI
  • antigen receptor-mediated signaling pathway Source: MGI
  • B-1 B cell homeostasis Source: MGI
  • brown fat cell differentiation Source: MGI
  • cytokine-mediated signaling pathway Source: MGI
  • glucose homeostasis Source: MGI
  • insulin receptor signaling pathway Source: MGI
  • intracellular signal transduction Source: UniProtKB
  • negative regulation of glucose import Source: MGI
  • nervous system development Source: Ensembl
  • positive regulation of signal transduction Source: MGI
  • regulation of immune response Source: MGI
  • regulation of JAK-STAT cascade Source: MGI
  • regulation of metabolic process Source: MGI
  • regulation of Ras protein signal transduction Source: Ensembl
Complete GO annotation...

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
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1345171. Sh2b2.

Subcellular locationi

  • Cytoplasm By similarity
  • Cell membrane By similarity

  • Note: Cytoplasmic before PDGF stimulation. After PDGF stimulation, localized at the cell membrane and peripheral region (By similarity).By similarity

GO - Cellular componenti

  • actin filament Source: MGI
  • cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • ruffle Source: MGI
  • stress fiber Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 621621SH2B adapter protein 2PRO_0000064648Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei130 – 1301PhosphoserineCombined sources
Modified residuei303 – 3031PhosphoserineCombined sources
Modified residuei589 – 5891PhosphothreonineBy similarity
Modified residuei597 – 5971PhosphoserineCombined sources
Modified residuei618 – 6181Phosphotyrosine1 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.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9JID9.
MaxQBiQ9JID9.
PaxDbiQ9JID9.
PRIDEiQ9JID9.

PTM databases

iPTMnetiQ9JID9.
PhosphoSiteiQ9JID9.

Expressioni

Tissue specificityi

Strongly expressed in brain; also expressed in spleen, kidney and skeletal muscle, and at low levels in small intestine and bone marrow. Strongly expressed in B-cell lines, but not T-cell lines. Also expressed in myeloid and fibroblast cell lines.1 Publication

Gene expression databases

BgeeiQ9JID9.
CleanExiMM_SH2B2.
ExpressionAtlasiQ9JID9. baseline and differential.
GenevisibleiQ9JID9. MM.

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
Fgfr3Q618513EBI-8100899,EBI-6287052

GO - Molecular functioni

  • JAK pathway signal transduction adaptor activity Source: MGI
  • SH3/SH2 adaptor activity Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: MGI

Protein-protein interaction databases

BioGridi204795. 9 interactions.
IntActiQ9JID9. 1 interaction.
STRINGi10090.ENSMUSP00000005188.

Structurei

Secondary structure

1
621
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi189 – 1979Combined sources
Beta strandi203 – 2053Combined sources
Beta strandi212 – 2209Combined sources
Beta strandi222 – 2243Combined sources
Beta strandi227 – 2348Combined sources
Beta strandi237 – 2393Combined sources
Turni246 – 2483Combined sources
Beta strandi258 – 2603Combined sources
Beta strandi276 – 2805Combined sources
Helixi284 – 29916Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1V5MNMR-A177-299[»]
ProteinModelPortaliQ9JID9.
SMRiQ9JID9. Positions 16-76, 178-303, 402-486.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9JID9.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini186 – 299114PHPROSITE-ProRule annotationCuratedAdd
BLAST
Domaini409 – 50799SH2PROSITE-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

eggNOGiENOG410IMWK. Eukaryota.
ENOG41102PH. LUCA.
GeneTreeiENSGT00530000063355.
HOGENOMiHOG000047355.
HOVERGENiHBG006707.
InParanoidiQ9JID9.
KOiK07193.
OMAiFDMLRHF.
OrthoDBiEOG7034GG.
TreeFamiTF323184.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
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]
SMARTiSM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF109805. SSF109805. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9JID9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNGATPSSAA APAPVPDWRQ FCELHAQVAA VDFAHKFCRF LRDNPTYDTP
60 70 80 90 100
DAGTSFSRHF AANFLAVFSE EVRRVLGSAA DTMEPEPAVT SVTSALKTAT
110 120 130 140 150
YGHSRSSEDV SAHAATKARV RKGFSLRNMS LCVVDGVRDL WHRRSSPEPD
160 170 180 190 200
GGATPKAAEP ASEPRDKWTR RLRLARTLAA KVELVDIQRE GALRFMVADD
210 220 230 240 250
AASGPGGTAQ WQKCRLLLRR AVAGERFRLE FFVPPKASRP KVSIPLSAII
260 270 280 290 300
EVRTTMPLEM PEKDNTFVLK VENGAEYILE TIDSLQKHSW VADIQGCVDP
310 320 330 340 350
GDSEEDTGLS CARGGCLASR VASCSCELLT DADMPRPPET TTAVGAVVTA
360 370 380 390 400
PHGRARDTVG ESLAHVPLET FLQTLESSGG VSENNNPGDE GAELDTDAEA
410 420 430 440 450
ELELSDYPWF HGTLSRVKAA QLVLAGGPRS HGLFVIRQSE TRPGECVLTF
460 470 480 490 500
NFQGKAKHLR LSLNGHGQCH VQHLWFQSVF DMLRHFHTHP IPLESGGSAD
510 520 530 540 550
ITLRSYVRAQ GPPPDPGPAP NTAAPVPACW TEPAGQHYFS SLATATCPPA
560 570 580 590 600
SPSNGAGASS SSGSSSSATS LPPRPAEGPL SAHSRSNSTE HLLDAASGAT
610 620
EEPTEATLGR ARAVENQYSF Y
Length:621
Mass (Da):66,557
Last modified:July 27, 2011 - v2
Checksum:iDB20BD352F96D69E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti125 – 1251S → W in AAF37891 (PubMed:10872802).Curated
Sequence conflicti442 – 4421R → K in AAC36336 (Ref. 4) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF234838 mRNA. Translation: AAF37891.1.
AK140319 mRNA. Translation: BAE24331.1.
AK140325 mRNA. Translation: BAE24336.1.
AF086810 mRNA. Translation: AAC36336.1.
BC057334 mRNA. Translation: AAH57334.1.
CCDSiCCDS39327.1.
PIRiJC7278.
RefSeqiNP_001289867.1. NM_001302938.1.
NP_001289868.1. NM_001302939.1.
NP_061295.2. NM_018825.4.
XP_006504483.2. XM_006504420.2.
XP_006504485.1. XM_006504422.2.
UniGeneiMm.425294.

Genome annotation databases

EnsembliENSMUST00000005188; ENSMUSP00000005188; ENSMUSG00000005057.
ENSMUST00000196397; ENSMUSP00000142398; ENSMUSG00000005057.
GeneIDi23921.
KEGGimmu:23921.
UCSCiuc009aag.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF234838 mRNA. Translation: AAF37891.1.
AK140319 mRNA. Translation: BAE24331.1.
AK140325 mRNA. Translation: BAE24336.1.
AF086810 mRNA. Translation: AAC36336.1.
BC057334 mRNA. Translation: AAH57334.1.
CCDSiCCDS39327.1.
PIRiJC7278.
RefSeqiNP_001289867.1. NM_001302938.1.
NP_001289868.1. NM_001302939.1.
NP_061295.2. NM_018825.4.
XP_006504483.2. XM_006504420.2.
XP_006504485.1. XM_006504422.2.
UniGeneiMm.425294.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1V5MNMR-A177-299[»]
ProteinModelPortaliQ9JID9.
SMRiQ9JID9. Positions 16-76, 178-303, 402-486.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204795. 9 interactions.
IntActiQ9JID9. 1 interaction.
STRINGi10090.ENSMUSP00000005188.

PTM databases

iPTMnetiQ9JID9.
PhosphoSiteiQ9JID9.

Proteomic databases

EPDiQ9JID9.
MaxQBiQ9JID9.
PaxDbiQ9JID9.
PRIDEiQ9JID9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000005188; ENSMUSP00000005188; ENSMUSG00000005057.
ENSMUST00000196397; ENSMUSP00000142398; ENSMUSG00000005057.
GeneIDi23921.
KEGGimmu:23921.
UCSCiuc009aag.2. mouse.

Organism-specific databases

CTDi10603.
MGIiMGI:1345171. Sh2b2.

Phylogenomic databases

eggNOGiENOG410IMWK. Eukaryota.
ENOG41102PH. LUCA.
GeneTreeiENSGT00530000063355.
HOGENOMiHOG000047355.
HOVERGENiHBG006707.
InParanoidiQ9JID9.
KOiK07193.
OMAiFDMLRHF.
OrthoDBiEOG7034GG.
TreeFamiTF323184.

Miscellaneous databases

EvolutionaryTraceiQ9JID9.
PROiQ9JID9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JID9.
CleanExiMM_SH2B2.
ExpressionAtlasiQ9JID9. baseline and differential.
GenevisibleiQ9JID9. MM.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
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]
SMARTiSM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF109805. SSF109805. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins."
    Iseki M., Takaki S., Takatsu K.
    Biochem. Biophys. Res. Commun. 272:45-54(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, PHOSPHORYLATION.
    Tissue: SplenocyteImported.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Adipose tissue.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain.
  4. "Insulin receptor cytoplasmic domain contains five functional SH2 motifs: mapping SH2 motifs for p85alpha, c-Src, c-Abl, Grb-10, ras-Gap, and mouse APS."
    Belhadri A., Goren H.J.
    Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 370-525.
  5. "The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit."
    Wollberg P., Lennartsson J., Gottfridsson E., Yoshimura A., Ronnstrand L.
    Biochem. J. 370:1033-1038(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EPOR AND KIT.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  7. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-597, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130 AND SER-303, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Kidney and Testis.
  9. "Solution structure of the pleckstrin homology domain of mouse APS."
    RIKEN structural genomics initiative (RSGI)
    Submitted (MAY-2004) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 178-299.

Entry informationi

Entry nameiSH2B2_MOUSE
AccessioniPrimary (citable) accession number: Q9JID9
Secondary accession number(s): O88936, Q6PG00
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: July 27, 2011
Last modified: June 8, 2016
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.