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Q15464 (SHB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
SH2 domain-containing adapter protein B
Gene names
Name:SHB
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length509 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19

Subunit structure

Interacts with PTPN11 By similarity. 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. Ref.1 Ref.5 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note: Associates with membrane lipid rafts upon TCR stimulation. Ref.1 Ref.14

Tissue specificity

Widely expressed. Ref.8

Domain

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.

Post-translational modification

Phosphorylated upon PDGFRA, PDGFRB, TCR, IL2 receptor, FGFR1 or VEGFR2 activation. Ref.9

Sequence similarities

Contains 1 SH2 domain.

Sequence caution

The sequence AAH94765.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAA53091.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q15464-1)

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.
Isoform 2 (identifier: Q15464-2)

The sequence of this isoform differs from the canonical sequence as follows:
     280-297: EFQRQESVRSQHKGIQLY → GLQEAWRHSPSGCFPVGP
     298-509: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 509509SH2 domain-containing adapter protein B
PRO_0000246324

Regions

Domain410 – 50495SH2
Region1 – 410410Mediates interaction with LAT, PTK2/FAK1, JAK1 and JAK3

Amino acid modifications

Modified residue3171Phosphoserine Ref.21
Modified residue3881Phosphoserine Ref.20

Natural variations

Alternative sequence280 – 29718EFQRQ…GIQLY → GLQEAWRHSPSGCFPVGP in isoform 2.
VSP_019846
Alternative sequence298 – 509212Missing in isoform 2.
VSP_019847

Experimental info

Mutagenesis4351R → K: Loss of interaction with CD3Z. Alters LAT, PLCG1, VAV1 and LCP2 phosphorylation, MAP kinase signaling, Rac1 and JNK activation, intracellular calcium increase, activation of the nuclear factor for activation of T-cells and subsequent interleukin-2 expression which normally occur upon T-cells stimulation. Ref.8
Sequence conflict91 – 933DFE → HFQ in CAA53091. Ref.1
Sequence conflict3471I → S in CAA53091. Ref.1
Sequence conflict4451S → P in CAA53091. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 25, 2006. Version 2.
Checksum: 15C392A6EEB761D6

FASTA50955,042
        10         20         30         40         50         60 
MAKWLNKYFS LGNSKTKSPP QPPRPDYREQ RRRGERPSQP PQAVPQASSA ASASCGPATA 

        70         80         90        100        110        120 
SCFSASSGSL PDDSGSTSDL IRAYRAQKER DFEDPYNGPG SSLRKLRAMC RLDYCGGSGE 

       130        140        150        160        170        180 
PGGVQRAFSA SSASGAAGCC CASSGAGAAA SSSSSSGSPH LYRSSSERRP ATPAEVRYIS 

       190        200        210        220        230        240 
PKHRLIKVES AAGGGAGDPL GGACAGGRTW SPTACGGKKL LNKCAASAAE ESGAGKKDKV 

       250        260        270        280        290        300 
TIADDYSDPF DAKNDLKSKA GKGESAGYME PYEAQRIMTE FQRQESVRSQ HKGIQLYDTP 

       310        320        330        340        350        360 
YEPEGQSVDS DSESTVSPRL RESKLPQDDD RPADEYDQPW EWNRVTIPAL AAQFNGNEKR 

       370        380        390        400        410        420 
QSSPSPSRDR RRQLRAPGGG FKPIKHGSPE FCGILGERVD PAVPLEKQIW YHGAISRGDA 

       430        440        450        460        470        480 
ENLLRLCKEC SYLVRNSQTS KHDYSLSLRS NQGFMHMKLA KTKEKYVLGQ NSPPFDSVPE 

       490        500 
VIHYYTTRKL PIKGAEHLSL LYPVAVRTL 

« Hide

Isoform 2 [UniParc].

Checksum: 81ECB44A67B0D8AD
Show »

FASTA29730,703

References

« Hide 'large scale' references
[1]"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION WITH PDGFRB.
Tissue: Fetal brain.
[2]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORMS 1 AND 2).
Tissue: Placenta and Testis.
[5]"Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins."
Karlsson T., Songyang Z., Landgren E., Lavergne C., Di Fiore P.P., Anafi M., Pawson T., Cantley L.C., Claesson-Welsh L., Welsh M.
Oncogene 10:1475-1483(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PDGFRB; FGFR1; EPS8 AND V-SRC.
[6]"Apoptosis of NIH3T3 cells overexpressing the Src homology 2 domain protein Shb."
Karlsson T., Welsh M.
Oncogene 13:955-961(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"The Src homology 2 domain protein Shb transmits basic fibroblast growth factor- and nerve growth factor-dependent differentiation signals in PC12 cells."
Karlsson T., Kullander K., Welsh M.
Cell Growth Differ. 9:757-766(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Stimulation through the T cell receptor leads to interactions between SHB and several signaling proteins."
Welsh M., Songyang Z., Frantz J.D., Trueb T., Reedquist K.A., Karlsson T., Miyazaki M., Cantley L.C., Band H., Shoelson S.E.
Oncogene 16:891-901(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH GRB2; GRAP AND CD3Z, MUTAGENESIS OF ARG-435.
[9]"Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells."
Lindholm C.K., Gylfe E., Zhang W., Samelson L.E., Welsh M.
J. Biol. Chem. 274:28050-28057(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH LAT AND PLCG1.
[10]"Endostatin-induced tyrosine kinase signaling through the Shb adaptor protein regulates endothelial cell apoptosis."
Dixelius J., Larsson H., Sasaki T., Holmqvist K., Lu L., Engstroem A., Timpl R., Welsh M., Claesson-Welsh L.
Blood 95:3403-3411(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Platelet-derived growth factor-mediated signaling through the Shb adaptor protein: effects on cytoskeletal organization."
Hooshmand-Rad R., Lu L., Heldin C.-H., Claesson-Welsh L., Welsh M.
Exp. Cell Res. 257:245-254(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PDGFRA.
[12]"NGF-dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway."
Lu L., Anneren C., Reedquist K.A., Bos J.L., Welsh M.
Exp. Cell Res. 259:370-377(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CRK.
[13]"IL-2 receptor signaling through the Shb adapter protein in T and NK cells."
Lindholm C.K.
Biochem. Biophys. Res. Commun. 296:929-936(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IL2RB; IL2RG; JAK1 AND JAK3.
[14]"Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells."
Lindholm C.K., Henriksson M.L., Hallberg B., Welsh M.
Eur. J. Biochem. 269:3279-3288(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ZAP70; LCP2; VAV1 AND GRAP2, SUBCELLULAR LOCATION.
[15]"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 FGFR1.
[16]"Overexpression of the Shb SH2 domain-protein in insulin-producing cells leads to altered signaling through the IRS-1 and IRS-2 proteins."
Welsh N., Makeeva N., Welsh M.
Mol. Med. 8:695-704(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IRS2.
[17]"The Shb adaptor protein causes Src-dependent cell spreading and activation of focal adhesion kinase in murine brain endothelial cells."
Holmqvist K., Cross M.J., Riley D., Welsh M.
Cell. Signal. 15:171-179(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PTK2/FAK1.
[18]"The adaptor protein shb binds to tyrosine 1175 in vascular endothelial growth factor (VEGF) receptor-2 and regulates VEGF-dependent cellular migration."
Holmqvist K., Cross M.J., Rolny C., Haegerkvist R., Rahimi N., Matsumoto T., Claesson-Welsh L., Welsh M.
J. Biol. Chem. 279:22267-22275(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH KDR.
[19]"Shb promotes blood vessel formation in embryoid bodies by augmenting vascular endothelial growth factor receptor-2 and platelet-derived growth factor receptor-beta signaling."
Rolny C., Lu L., Aagren N., Nilsson I., Roe C., Webb G.C., Welsh M.
Exp. Cell Res. 308:381-393(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-388, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-317, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X75342 mRNA. Translation: CAA53091.1. Different initiation.
AL583849, AL138752, AL161448 Genomic DNA. Translation: CAH73120.1.
AL161448, AL138752, AL583849 Genomic DNA. Translation: CAH73192.1.
AL138752, AL161448, AL583849 Genomic DNA. Translation: CAI13876.1.
CH471071 Genomic DNA. Translation: EAW58254.1.
CH471071 Genomic DNA. Translation: EAW58255.1.
BC094765 mRNA. Translation: AAH94765.1. Different initiation.
BC136581 mRNA. Translation: AAI36582.1.
BC136582 mRNA. Translation: AAI36583.1.
CCDSCCDS43806.1. [Q15464-1]
PIRI38228.
RefSeqNP_003019.2. NM_003028.2. [Q15464-1]
UniGeneHs.521482.

3D structure databases

ProteinModelPortalQ15464.
SMRQ15464. Positions 405-487.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112358. 16 interactions.
IntActQ15464. 8 interactions.
MINTMINT-7046528.
STRING9606.ENSP00000366936.

PTM databases

PhosphoSiteQ15464.

Polymorphism databases

DMDM110816415.

Proteomic databases

MaxQBQ15464.
PaxDbQ15464.
PRIDEQ15464.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377700; ENSP00000366929; ENSG00000107338. [Q15464-2]
ENST00000377707; ENSP00000366936; ENSG00000107338. [Q15464-1]
GeneID6461.
KEGGhsa:6461.
UCSCuc004aax.3. human. [Q15464-1]

Organism-specific databases

CTD6461.
GeneCardsGC09M037953.
H-InvDBHIX0008049.
HIX0079163.
HIX0189186.
HGNCHGNC:10838. SHB.
HPACAB010161.
HPA049911.
MIM600314. gene.
neXtProtNX_Q15464.
PharmGKBPA35744.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG80632.
HOGENOMHOG000038038.
HOVERGENHBG066172.
InParanoidQ15464.
OMARPDYREQ.
OrthoDBEOG793B9C.
PhylomeDBQ15464.
TreeFamTF325799.

Enzyme and pathway databases

SignaLinkQ15464.

Gene expression databases

BgeeQ15464.
CleanExHS_SHB.
GenevestigatorQ15464.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
[Graphical view]
PfamPF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSHB. human.
GeneWikiSHB_(gene).
GenomeRNAi6461.
NextBio25105.
PROQ15464.
SOURCESearch...

Entry information

Entry nameSHB_HUMAN
AccessionPrimary (citable) accession number: Q15464
Secondary accession number(s): B9EGM0 expand/collapse secondary AC list , D3DRQ5, Q504U5, Q5VUM8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: July 25, 2006
Last modified: July 9, 2014
This is version 106 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

MIM cross-references

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

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM