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Q9UQQ2 (SH2B3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
SH2B adapter protein 3
Alternative name(s):
Lymphocyte adapter protein
Lymphocyte-specific adapter protein Lnk
Signal transduction protein Lnk
Gene names
Name:SH2B3
Synonyms:LNK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length575 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase By similarity.

Subunit structure

Binds to the tyrosine-phosphorylated TCR zeta chain via its SH2 domain.

Tissue specificity

Preferentially expressed by lymphoid cell lines.

Post-translational modification

Tyrosine phosphorylated by LCK.

Involvement in disease

Celiac disease 13 (CELIAC13) [MIM:612011]: A multifactorial, chronic disorder of the small intestine caused by intolerance to gluten. It is characterized by immune-mediated enteropathy associated with failed intestinal absorption, and malnutrition. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.6

Diabetes mellitus, insulin-dependent (IDDM) [MIM:222100]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the SH2B adapter family.

Contains 1 PH domain.

Contains 1 SH2 domain.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 575575SH2B adapter protein 3
PRO_0000084454

Regions

Domain194 – 307114PH
Domain364 – 46299SH2

Amino acid modifications

Modified residue1501Phosphoserine Ref.7

Natural variations

Natural variant1821F → L.
Corresponds to variant rs7972796 [ dbSNP | Ensembl ].
VAR_046210
Natural variant2621W → R Associated with susceptibility to CELIAC13 and IDDM. Ref.5 Ref.6
Corresponds to variant rs3184504 [ dbSNP | Ensembl ].
VAR_024168

Experimental info

Sequence conflict3091G → GR in CAB42642. Ref.2
Sequence conflict4911H → P in CAB42642. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9UQQ2 [UniParc].

Last modified April 27, 2001. Version 2.
Checksum: EE30B9E21E0009E5

FASTA57563,225
        10         20         30         40         50         60 
MNGPALQPSS PSSAPSASPA AAPRGWSEFC ELHAVAAARE LARQYWLFAR EHPQHAPLRA 

        70         80         90        100        110        120 
ELVSLQFTDL FQRYFCREVR DGRAPGRDYR DTGRGPPAKA EASPEPGPGP AAPGLPKARS 

       130        140        150        160        170        180 
SEELAPPRPP GPCSFQHFRR SLRHIFRRRS AGELPAAHTA AAPGTPGEAA ETPARPGLAK 

       190        200        210        220        230        240 
KFLPWSLARE PPPEALKEAV LRYSLADEAS MDSGARWQRG RLALRRAPGP DGPDRVLELF 

       250        260        270        280        290        300 
DPPKSSRPKL QAACSSIQEV RWCTRLEMPD NLYTFVLKVK DRTDIIFEVG DEQQLNSWMA 

       310        320        330        340        350        360 
ELSECTGRGL ESTEAEMHIP SALEPSTSSS PRGSTDSLNQ GASPGGLLDP ACQKTDHFLS 

       370        380        390        400        410        420 
CYPWFHGPIS RVKAAQLVQL QGPDAHGVFL VRQSETRRGE YVLTFNFQGI AKHLRLSLTE 

       430        440        450        460        470        480 
RGQCRVQHLH FPSVVDMLHH FQRSPIPLEC GAACDVRLSS YVVVVSQPPG SCNTVLFPFS 

       490        500        510        520        530        540 
LPHWDSESLP HWGSELGLPH LSSSGCPRGL SPEGLPGRSS PPEQIFHLVP SPEELANSLQ 

       550        560        570 
HLEHEPVNRA RDSDYEMDSS SRSHLRAIDN QYTPL 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of human Lnk, an adaptor protein with pleckstrin homology and Src homology 2 domains that can inhibit T cell activation."
Li Y., He X., Schembri-King J., Jakes S., Hayashi J.
J. Immunol. 164:5199-5206(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Characterisation of human Lnk a lymphocyte adaptor protein with a multiple domain structure."
Bartholomew M.A., Morse M.A., Vivier R.G., Blanchard A.D., Boyhan A., Tite J.P., Fuller K.J., Lewis A.P., Sims M.J.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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 (JUL-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].
Tissue: Brain.
[5]"Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes."
Genetics of type 1 diabetes in Finland, The Wellcome Trust case control consortium
Todd J.A., Walker N.M., Cooper J.D., Smyth D.J., Downes K., Plagnol V., Bailey R., Nejentsev S., Field S.F., Payne F., Lowe C.E., Szeszko J.S., Hafler J.P., Zeitels L., Yang J.H.M., Vella A., Nutland S., Stevens H.E. expand/collapse author list , Schuilenburg H., Coleman G., Maisuria M., Meadows W., Smink L.J., Healy B., Burren O.S., Lam A.A.C., Ovington N.R., Allen J., Adlem E., Leung H.-T., Wallace C., Howson J.M.M., Guja C., Ionescu-Tirgoviste C., Simmonds M.J., Heward J.M., Gough S.C.L., Dunger D.B., Wicker L.S., Clayton D.G.
Nat. Genet. 39:857-864(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO IDDM, VARIANT ARG-262.
[6]"Newly identified genetic risk variants for celiac disease related to the immune response."
Hunt K.A., Zhernakova A., Turner G., Heap G.A.R., Franke L., Bruinenberg M., Romanos J., Dinesen L.C., Ryan A.W., Panesar D., Gwilliam R., Takeuchi F., McLaren W.M., Holmes G.K.T., Howdle P.D., Walters J.R.F., Sanders D.S., Playford R.J. expand/collapse author list , Trynka G., Mulder C.J., Mearin M.L., Verbeek W.H.M., Trimble V., Stevens F.M., O'Morain C., Kennedy N.P., Kelleher D., Pennington D.J., Strachan D.P., McArdle W.L., Mein C.A., Wapenaar M.C., Deloukas P., McGinnis R., McManus R., Wijmenga C., van Heel D.A.
Nat. Genet. 40:395-402(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO CELIAC13, VARIANT ARG-262.
[7]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF055581 mRNA. Translation: AAC71695.1.
AJ012793 mRNA. Translation: CAB42642.1.
CH471054 Genomic DNA. Translation: EAW97955.1.
BC136451 mRNA. Translation: AAI36452.1.
RefSeqNP_005466.1. NM_005475.2.
UniGeneHs.506784.

3D structure databases

ProteinModelPortalQ9UQQ2.
SMRQ9UQQ2. Positions 24-84, 197-312, 359-441.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115336. 8 interactions.
IntActQ9UQQ2. 3 interactions.
MINTMINT-1494618.
STRING9606.ENSP00000345492.

PTM databases

PhosphoSiteQ9UQQ2.

Polymorphism databases

DMDM13628527.

Proteomic databases

PaxDbQ9UQQ2.
PRIDEQ9UQQ2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000341259; ENSP00000345492; ENSG00000111252.
GeneID10019.
KEGGhsa:10019.
UCSCuc001tse.3. human.

Organism-specific databases

CTD10019.
GeneCardsGC12P111843.
HGNCHGNC:29605. SH2B3.
HPAHPA005483.
MIM222100. phenotype.
605093. gene.
612011. phenotype.
neXtProtNX_Q9UQQ2.
PharmGKBPA145148124.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG77816.
HOGENOMHOG000047355.
HOVERGENHBG093951.
InParanoidQ9UQQ2.
KOK12459.
OMAPWSLARE.
OrthoDBEOG70CR6F.
PhylomeDBQ9UQQ2.
TreeFamTF323184.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.
SignaLinkQ9UQQ2.

Gene expression databases

ArrayExpressQ9UQQ2.
BgeeQ9UQQ2.
CleanExHS_SH2B3.
GenevestigatorQ9UQQ2.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR015012. Phe_ZIP.
IPR001849. Pleckstrin_homology.
IPR000980. SH2.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF08916. Phe_ZIP. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF109805. SSF109805. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSH2B3. human.
GeneWikiSH2B3.
GenomeRNAi10019.
NextBio37857.
PROQ9UQQ2.
SOURCESearch...

Entry information

Entry nameSH2B3_HUMAN
AccessionPrimary (citable) accession number: Q9UQQ2
Secondary accession number(s): B9EGG5, O95184
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 27, 2001
Last modified: April 16, 2014
This is version 104 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM