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Protein

SH2 domain-containing adapter protein B

Gene

Shb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter protein which regulates several signal transduction cascades by linking activated receptors to downstream signaling components. May play a role in angiogenesis by regulating FGFR1, VEGFR2 and PDGFR signaling. May also play a role in T-cell antigen receptor/TCR signaling, interleukin-2 signaling, apoptosis and neuronal cells differentiation by mediating basic-FGF and NGF-induced signaling cascades. May also regulate IRS1 and IRS2 signaling in insulin-producing cells (By similarity).By similarity

GO - Molecular functioni

  • glycoprotein binding Source: MGI
  • SH3/SH2 adaptor activity Source: MGI

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • apoptotic process Source: UniProtKB-KW
  • B cell proliferation Source: MGI
  • blood vessel development Source: MGI
  • blood vessel morphogenesis Source: MGI
  • cell differentiation Source: UniProtKB-KW
  • hematopoietic stem cell proliferation Source: MGI
  • hemopoiesis Source: MGI
  • negative regulation of oocyte maturation Source: MGI
  • negative regulation of protein kinase activity Source: MGI
  • positive regulation of mitotic cell cycle Source: MGI
  • positive regulation of T-helper cell differentiation Source: MGI
  • T cell receptor signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Angiogenesis, Apoptosis, Differentiation

Enzyme and pathway databases

ReactomeiR-MMU-3928663. EPHA-mediated growth cone collapse.
R-MMU-4420097. VEGFA-VEGFR2 Pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
SH2 domain-containing adapter protein B
Gene namesi
Name:Shb
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:98294. Shb.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 503503SH2 domain-containing adapter protein BPRO_0000246325Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei101 – 1011PhosphoserineBy similarity
Modified residuei301 – 3011PhosphoserineBy similarity
Modified residuei311 – 3111PhosphoserineBy similarity
Modified residuei382 – 3821PhosphoserineCombined sources

Post-translational modificationi

Phosphorylated upon PDGFRA, PDGFRB, TCR, IL2 receptor, FGFR1 or VEGFR2 activation.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ6PD21.
PaxDbiQ6PD21.
PRIDEiQ6PD21.

PTM databases

iPTMnetiQ6PD21.
PhosphoSiteiQ6PD21.

Expressioni

Tissue specificityi

Expressed in heart, liver, brain and kidney (at protein level).1 Publication

Inductioni

Up-regulated by okadaic acid and genistein.1 Publication

Gene expression databases

BgeeiQ6PD21.
ExpressionAtlasiQ6PD21. baseline and differential.
GenevisibleiQ6PD21. MM.

Interactioni

Subunit structurei

Interacts with phosphorylated 'Tyr-720' of the ligand-activated receptor PDGFRA via its SH2 domain. Interacts with the ligand-activated receptors PDGFRB, FGFR1, KDR/VEGFR2, IL2RB and IL2RG. Interacts with EPS8 and V-SRC. Interacts with GRB2 and GRAP. Interacts with CD3Z. Interacts with tyrosine-phosphorylated LAT upon T-cell antigen receptor activation. Interacts with PLCG1. Interacts with ZAP70, LCP2/SLP-76, VAV1 and GRAP2. Interacts with JAK1 and JAK3. Interacts with PTK2/FAK1. Interacts with CRK/CrKII. Interacts with IRS2 (By similarity). Interacts with PTPN11.By similarity1 Publication

GO - Molecular functioni

  • glycoprotein binding Source: MGI
  • SH3/SH2 adaptor activity Source: MGI

Protein-protein interaction databases

BioGridi230937. 1 interaction.
IntActiQ6PD21. 2 interactions.
MINTiMINT-8013521.
STRINGi10090.ENSMUSP00000060433.

Structurei

3D structure databases

ProteinModelPortaliQ6PD21.
SMRiQ6PD21. Positions 399-481.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini404 – 49895SH2PROSITE-ProRule annotationAdd
BLAST

Domaini

The SH2 domain preferentially binds phosphopeptides with the consensus sequence Y-[TVI]-X-L and mediates interaction with PDGFRA, PDGFRB, FGRFR1, IL2RB, IL2RG, CD3Z and CRK/CrKII.By similarity

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IGWI. Eukaryota.
ENOG410XQJ2. LUCA.
GeneTreeiENSGT00390000015203.
HOGENOMiHOG000038038.
HOVERGENiHBG066172.
InParanoidiQ6PD21.
OMAiRPDYREQ.
OrthoDBiEOG793B9C.
PhylomeDBiQ6PD21.
TreeFamiTF325799.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6PD21-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAKWLNKYFS LGNSKTKSPP QPPRPDYREQ RRRGERREQP PQAVPQACSA
60 70 80 90 100
SSASCGSAAA CFSASSGSLP DDSGSTSDLI RAYRAQKERD FEDPYNGPGS
110 120 130 140 150
SLRKLRAMCR LDYCGGGGGG DPGGGQRAFT AAAGAAGCCC AAAGAGAAAS
160 170 180 190 200
SSSSSGSPHL YRSSSERRPT TPAEVRYISP KHRLIKVESA SAAGDPPGGV
210 220 230 240 250
CSGGRTWSPT TCGGKKLLNK CSAEETGAGQ KDKVTIADDY SDPFDAKSDL
260 270 280 290 300
KSKAGKGESA GYMEPYEAQR IMTEFQRQES VRSQHKGIQL YDTPYEPEGQ
310 320 330 340 350
SVDSDSESTV SLRLRESKLP QDDDRPADEY DQPWEWNRVT IPALAAQFNG
360 370 380 390 400
NEKRQSSPSP SRDRRRQLRA PGGGFKPIKH GSPEFCGILG ERVDPTIPLE
410 420 430 440 450
KQIWYHGAIS RSDAENLLRL CKECSYLVRN SQTSKHDYSL SLKSNQGFMH
460 470 480 490 500
MKLAKTKEKY VLGQNSPPFD SVPEVIHYYT TRKLPIKGAE HLSLLYPVAV

RTL
Length:503
Mass (Da):54,708
Last modified:July 25, 2006 - v2
Checksum:i9A668DFC429F41E3
GO
Isoform 2 (identifier: Q6PD21-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-262: Missing.
     443-479: KSNQGFMHMKLAKTKEKYVLGQNSPPFDSVPEVIHYY → NYADPEAVCAMPILPRTARPSVRPSVHPSVRKICARR
     480-503: Missing.

Note: No experimental confirmation available.
Show »
Length:217
Mass (Da):24,821
Checksum:i987B28E09A5E16D3
GO

Sequence cautioni

The sequence AAH58986.1 differs from that shown. Reason: Erroneous initiation. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 262262Missing in isoform 2. 1 PublicationVSP_019848Add
BLAST
Alternative sequencei443 – 47937KSNQG…VIHYY → NYADPEAVCAMPILPRTARP SVRPSVHPSVRKICARR in isoform 2. 1 PublicationVSP_019849Add
BLAST
Alternative sequencei480 – 50324Missing in isoform 2. 1 PublicationVSP_019850Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK145414 mRNA. Translation: BAE26425.1.
AL772376 Genomic DNA. Translation: CAM20448.1.
BC058986 mRNA. Translation: AAH58986.1. Different initiation.
CCDSiCCDS51173.1. [Q6PD21-1]
RefSeqiNP_001028478.1. NM_001033306.1. [Q6PD21-1]
UniGeneiMm.251716.

Genome annotation databases

EnsembliENSMUST00000061986; ENSMUSP00000060433; ENSMUSG00000044813. [Q6PD21-1]
GeneIDi230126.
KEGGimmu:230126.
UCSCiuc008sst.2. mouse. [Q6PD21-1]
uc008ssu.1. mouse. [Q6PD21-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK145414 mRNA. Translation: BAE26425.1.
AL772376 Genomic DNA. Translation: CAM20448.1.
BC058986 mRNA. Translation: AAH58986.1. Different initiation.
CCDSiCCDS51173.1. [Q6PD21-1]
RefSeqiNP_001028478.1. NM_001033306.1. [Q6PD21-1]
UniGeneiMm.251716.

3D structure databases

ProteinModelPortaliQ6PD21.
SMRiQ6PD21. Positions 399-481.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230937. 1 interaction.
IntActiQ6PD21. 2 interactions.
MINTiMINT-8013521.
STRINGi10090.ENSMUSP00000060433.

PTM databases

iPTMnetiQ6PD21.
PhosphoSiteiQ6PD21.

Proteomic databases

MaxQBiQ6PD21.
PaxDbiQ6PD21.
PRIDEiQ6PD21.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000061986; ENSMUSP00000060433; ENSMUSG00000044813. [Q6PD21-1]
GeneIDi230126.
KEGGimmu:230126.
UCSCiuc008sst.2. mouse. [Q6PD21-1]
uc008ssu.1. mouse. [Q6PD21-2]

Organism-specific databases

CTDi6461.
MGIiMGI:98294. Shb.

Phylogenomic databases

eggNOGiENOG410IGWI. Eukaryota.
ENOG410XQJ2. LUCA.
GeneTreeiENSGT00390000015203.
HOGENOMiHOG000038038.
HOVERGENiHBG066172.
InParanoidiQ6PD21.
OMAiRPDYREQ.
OrthoDBiEOG793B9C.
PhylomeDBiQ6PD21.
TreeFamiTF325799.

Enzyme and pathway databases

ReactomeiR-MMU-3928663. EPHA-mediated growth cone collapse.
R-MMU-4420097. VEGFA-VEGFR2 Pathway.

Miscellaneous databases

ChiTaRSiShb. mouse.
PROiQ6PD21.
SOURCEiSearch...

Gene expression databases

BgeeiQ6PD21.
ExpressionAtlasiQ6PD21. baseline and differential.
GenevisibleiQ6PD21. MM.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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] (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Embryo.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  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] (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Fetal brain.
  4. "Shb is a ubiquitously expressed Src homology 2 protein."
    Welsh M., Mares J., Karlsson T., Lavergne C., Breant B., Claesson-Welsh L.
    Oncogene 9:19-27(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. "Control of SHB gene expression by protein phosphorylation."
    Lavergne C., Mares J., Karlsson T., Breant B., Welsh M.
    Cell. Signal. 8:55-58(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY OKADAIC ACID AND GENISTEIN.
  6. "The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates the Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells."
    Cross M.J., Lu L., Magnusson P., Nyqvist D., Holmqvist K., Welsh M., Claesson-Welsh L.
    Mol. Biol. Cell 13:2881-2893(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTPN11.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  8. "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-382, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Heart, Kidney, Lung and Pancreas.

Entry informationi

Entry nameiSHB_MOUSE
AccessioniPrimary (citable) accession number: Q6PD21
Secondary accession number(s): A2AKW3, Q3ULM3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: July 25, 2006
Last modified: July 6, 2016
This is version 90 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

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.