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UniProtKB - Q15464 (SHB_HUMAN)

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Protein

SH2 domain-containing adapter protein B

Gene

SHB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.10 Publications

GO - Molecular functioni

  • phosphotyrosine residue binding Source: CAFA
  • SH3/SH2 adaptor activity Source: ProtInc
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein
Biological processAngiogenesis, Apoptosis, Differentiation

Enzyme and pathway databases

ReactomeiR-HSA-4420097 VEGFA-VEGFR2 Pathway
SignaLinkiQ15464

Names & Taxonomyi

Protein namesi
Recommended name:
SH2 domain-containing adapter protein B
Gene namesi
Name:SHB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000107338.9
HGNCiHGNC:10838 SHB
MIMi600314 gene
neXtProtiNX_Q15464

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi435R → 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. 1 Publication1

Organism-specific databases

DisGeNETi6461
OpenTargetsiENSG00000107338
PharmGKBiPA35744

Polymorphism and mutation databases

BioMutaiSHB
DMDMi110816415

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002463241 – 509SH2 domain-containing adapter protein BAdd BLAST509

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei102PhosphoserineCombined sources1
Cross-linki187Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei307PhosphoserineCombined sources1
Modified residuei317PhosphoserineCombined sources1
Modified residuei388PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated upon PDGFRA, PDGFRB, TCR, IL2 receptor, FGFR1 or VEGFR2 activation.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ15464
MaxQBiQ15464
PaxDbiQ15464
PeptideAtlasiQ15464
PRIDEiQ15464
ProteomicsDBi60600
60601 [Q15464-2]

PTM databases

iPTMnetiQ15464
PhosphoSitePlusiQ15464

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000107338
CleanExiHS_SHB
GenevisibleiQ15464 HS

Organism-specific databases

HPAiCAB010161
HPA049911
HPA052108

Interactioni

Subunit structurei

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.By similarity12 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • phosphotyrosine residue binding Source: CAFA
  • SH3/SH2 adaptor activity Source: ProtInc
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112358, 23 interactors
IntActiQ15464, 9 interactors
MINTiQ15464
STRINGi9606.ENSP00000366936

Chemistry databases

BindingDBiQ15464

Structurei

3D structure databases

ProteinModelPortaliQ15464
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini410 – 504SH2PROSITE-ProRule annotationAdd BLAST95

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 410Mediates interaction with LAT, PTK2/FAK1, JAK1 and JAK32 PublicationsAdd BLAST410

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.

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IGWI Eukaryota
ENOG410XQJ2 LUCA
GeneTreeiENSGT00390000015203
HOGENOMiHOG000038038
HOVERGENiHBG066172
InParanoidiQ15464
OMAiRPDYREQ
OrthoDBiEOG091G0I06
PhylomeDBiQ15464
TreeFamiTF325799

Family and domain databases

CDDicd10389 SH2_SHB, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR035040 SHB
IPR035045 SHB_SH2
PANTHERiPTHR15127:SF31 PTHR15127:SF31, 1 hit
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SUPFAMiSSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q15464-1) [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 RRRGERPSQP PQAVPQASSA 
        60         70         80         90        100
ASASCGPATA SCFSASSGSL PDDSGSTSDL IRAYRAQKER DFEDPYNGPG 
       110        120        130        140        150
SSLRKLRAMC RLDYCGGSGE PGGVQRAFSA SSASGAAGCC CASSGAGAAA 
       160        170        180        190        200
SSSSSSGSPH LYRSSSERRP ATPAEVRYIS PKHRLIKVES AAGGGAGDPL 
       210        220        230        240        250
GGACAGGRTW SPTACGGKKL LNKCAASAAE ESGAGKKDKV TIADDYSDPF 
       260        270        280        290        300
DAKNDLKSKA GKGESAGYME PYEAQRIMTE FQRQESVRSQ HKGIQLYDTP 
       310        320        330        340        350
YEPEGQSVDS DSESTVSPRL RESKLPQDDD RPADEYDQPW EWNRVTIPAL 
       360        370        380        390        400
AAQFNGNEKR QSSPSPSRDR RRQLRAPGGG FKPIKHGSPE FCGILGERVD 
       410        420        430        440        450
PAVPLEKQIW YHGAISRGDA ENLLRLCKEC SYLVRNSQTS KHDYSLSLRS 
       460        470        480        490        500
NQGFMHMKLA KTKEKYVLGQ NSPPFDSVPE VIHYYTTRKL PIKGAEHLSL 

LYPVAVRTL
Length:509
Mass (Da):55,042
Last modified:July 25, 2006 - v2
Checksum:i15C392A6EEB761D6
GO
Isoform 2 (identifier: Q15464-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     280-297: EFQRQESVRSQHKGIQLY → GLQEAWRHSPSGCFPVGP
     298-509: Missing.

Note: No experimental confirmation available.
Show »
Length:297
Mass (Da):30,703
Checksum:i81ECB44A67B0D8AD
GO

Sequence cautioni

The sequence AAH94765 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA53091 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti91 – 93DFE → HFQ in CAA53091 (PubMed:8302579).Curated3
Sequence conflicti347I → S in CAA53091 (PubMed:8302579).Curated1
Sequence conflicti445S → P in CAA53091 (PubMed:8302579).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_019846280 – 297EFQRQ…GIQLY → GLQEAWRHSPSGCFPVGP in isoform 2. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_019847298 – 509Missing in isoform 2. 1 PublicationAdd BLAST212

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X75342 mRNA Translation: CAA53091.1 Different initiation.
AL138752 Genomic DNA No translation available.
AL161448 Genomic DNA No translation available.
AL583849 Genomic DNA No translation available.
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
CCDSiCCDS43806.1 [Q15464-1]
PIRiI38228
RefSeqiNP_003019.2, NM_003028.2 [Q15464-1]
UniGeneiHs.521482

Genome annotation databases

EnsembliENST00000377707; ENSP00000366936; ENSG00000107338 [Q15464-1]
GeneIDi6461
KEGGihsa:6461
UCSCiuc004aax.4 human [Q15464-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSHB_HUMAN
AccessioniPrimary (citable) accession number: Q15464
Secondary accession number(s): B9EGM0
, D3DRQ5, Q504U5, Q5VUM8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: July 25, 2006
Last modified: July 18, 2018
This is version 144 of the entry and version 2 of the sequence. See 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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