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Protein

SH2 domain-containing protein 2A

Gene

Sh2d2a

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

Functioni

Could be a T-cell-specific adapter protein involved in the control of T-cell activation. May play a role in p56-LCK-mediated T-cell signaling. Could be involved in the regulation of responses to T-cell activation stimuli, specifically proliferation and lymphokine production. Interactions with ITK and TXK may provide important biochemical links of these two important kinases with other components in the T-cell activation machinery.1 Publication

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: MGI

GO - Biological processi

  • cell proliferation Source: MGI
  • positive regulation of signal transduction Source: GOC
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-MMU-4420097. VEGFA-VEGFR2 Pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
SH2 domain-containing protein 2A
Alternative name(s):
Lck-associated adapter protein
Short name:
Lad
Rlk/Itk-binding protein
Short name:
Ribp
Gene namesi
Name:Sh2d2a
Synonyms:Lad, Ribp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1351596. Sh2d2a.

Subcellular locationi

  • Cytoplasm
  • Cell membrane

  • Note: Redistributed from cytoplasm to the plasma membrane in a T-cell activation-dependent manner.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 374374SH2 domain-containing protein 2APRO_0000097727Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei237 – 2371PhosphoserineBy similarity
Modified residuei316 – 3161PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated on tyrosine residues upon TCR-stimulation.

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9QXK9.
PaxDbiQ9QXK9.
PRIDEiQ9QXK9.

PTM databases

iPTMnetiQ9QXK9.
PhosphoSiteiQ9QXK9.

Expressioni

Tissue specificityi

Expression limited to tissues of the immune system and, in particular, activated T-cells and natural killer cells. Expressed in the thymus, lymph node, and to a lesser extent, in the spleen and bone marrow. According to PubMed:10553045, also expressed in the lung.

Inductioni

Up-regulated substantially after T-cell activation.

Gene expression databases

BgeeiQ9QXK9.
CleanExiMM_SH2D2A.
ExpressionAtlasiQ9QXK9. baseline and differential.
GenevisibleiQ9QXK9. MM.

Interactioni

Subunit structurei

Interacts with KDR (By similarity). Interacts with p56-LCK, TXK and ITK.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
LckP062403EBI-1644,EBI-1401

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: MGI

Protein-protein interaction databases

IntActiQ9QXK9. 1 interaction.
STRINGi10090.ENSMUSP00000103207.

Structurei

3D structure databases

ProteinModelPortaliQ9QXK9.
SMRiQ9QXK9. Positions 114-215.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini116 – 20792SH2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi267 – 2737SH3-bindingSequence analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi267 – 30842Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3-binding

Phylogenomic databases

eggNOGiENOG410IVEH. Eukaryota.
ENOG4111Y35. LUCA.
GeneTreeiENSGT00570000079047.
HOGENOMiHOG000008700.
HOVERGENiHBG055180.
InParanoidiQ9QXK9.
KOiK08273.
OMAiFPLAQIC.
OrthoDBiEOG7H793D.
PhylomeDBiQ9QXK9.
TreeFamiTF336893.

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: Q9QXK9-1) [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
MEFCLAQPCP QGNHEATSST FNTFQPMNLT QGRCQNLSCG SRPSMQVMKE
60 70 80 90 100
QGVQLSPRTN HTVVSASAPG TAWVLGNADR AEEVPGKGDL SLQAETRAWV
110 120 130 140 150
QKTQAHWLLL KTAPLWFHGF ITRREAERLL QPQPLGCYLV RFSESAVTFV
160 170 180 190 200
LSYRSQTCCR HFLLAQLGDG RHVVLGEDSA HAQLQDLLEH YTECPLSPYG
210 220 230 240 250
EILTQPLARQ TAEPAGLSLR ADSDSGSKRQ DPDTQLSLLL QQGQAQASGH
260 270 280 290 300
TEKVWASQQK ATSQASRPRP PIPAKPQLPP EVYTSPASRL HQAPPINPIY
310 320 330 340 350
QEPDEPIAFY AMGRGSPGDA PSNIYAEVEG PSGTAPIGHP ILRKCWSRPI
360 370
SRGQVREVQG KISSRSRAER GSPS
Length:374
Mass (Da):40,953
Last modified:May 1, 2000 - v1
Checksum:i6215FF96CE764359
GO
Isoform 2 (identifier: Q9QXK9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     254-261: Missing.

Show »
Length:366
Mass (Da):40,054
Checksum:i536EF3BBF6FDCAAA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti14 – 141H → R in AAB58422 (PubMed:10553045).Curated
Sequence conflicti70 – 701G → E in AAB58422 (PubMed:10553045).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei254 – 2618Missing in isoform 2. 2 PublicationsVSP_003967

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U69490 mRNA. Translation: AAB58422.1.
AF203343 mRNA. Translation: AAF19396.1.
CCDSiCCDS17455.1. [Q9QXK9-2]
CCDS38476.1. [Q9QXK9-1]
RefSeqiNP_067284.1. NM_021309.3. [Q9QXK9-1]
UniGeneiMm.86361.

Genome annotation databases

EnsembliENSMUST00000029709; ENSMUSP00000029709; ENSMUSG00000028071. [Q9QXK9-2]
ENSMUST00000107581; ENSMUSP00000103207; ENSMUSG00000028071. [Q9QXK9-1]
GeneIDi27371.
KEGGimmu:27371.
UCSCiuc008pta.1. mouse. [Q9QXK9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U69490 mRNA. Translation: AAB58422.1.
AF203343 mRNA. Translation: AAF19396.1.
CCDSiCCDS17455.1. [Q9QXK9-2]
CCDS38476.1. [Q9QXK9-1]
RefSeqiNP_067284.1. NM_021309.3. [Q9QXK9-1]
UniGeneiMm.86361.

3D structure databases

ProteinModelPortaliQ9QXK9.
SMRiQ9QXK9. Positions 114-215.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9QXK9. 1 interaction.
STRINGi10090.ENSMUSP00000103207.

PTM databases

iPTMnetiQ9QXK9.
PhosphoSiteiQ9QXK9.

Proteomic databases

EPDiQ9QXK9.
PaxDbiQ9QXK9.
PRIDEiQ9QXK9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029709; ENSMUSP00000029709; ENSMUSG00000028071. [Q9QXK9-2]
ENSMUST00000107581; ENSMUSP00000103207; ENSMUSG00000028071. [Q9QXK9-1]
GeneIDi27371.
KEGGimmu:27371.
UCSCiuc008pta.1. mouse. [Q9QXK9-1]

Organism-specific databases

CTDi9047.
MGIiMGI:1351596. Sh2d2a.

Phylogenomic databases

eggNOGiENOG410IVEH. Eukaryota.
ENOG4111Y35. LUCA.
GeneTreeiENSGT00570000079047.
HOGENOMiHOG000008700.
HOVERGENiHBG055180.
InParanoidiQ9QXK9.
KOiK08273.
OMAiFPLAQIC.
OrthoDBiEOG7H793D.
PhylomeDBiQ9QXK9.
TreeFamiTF336893.

Enzyme and pathway databases

ReactomeiR-MMU-4420097. VEGFA-VEGFR2 Pathway.

Miscellaneous databases

PROiQ9QXK9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QXK9.
CleanExiMM_SH2D2A.
ExpressionAtlasiQ9QXK9. baseline and differential.
GenevisibleiQ9QXK9. 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

  1. "Lad, an adapter protein interacting with the SH2 domain of p56lck, is required for T cell activation."
    Choi Y.B., Kim C.K., Yun Y.
    J. Immunol. 163:5242-5249(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Strain: C57BL/Kaplan.
    Tissue: Lung and Spleen.
  2. "RIBP, a novel Rlk/Txk- and Itk-binding adaptor protein that regulates T cell activation."
    Rajagopal K., Sommers C.L., Decker D.C., Mitchell E.O., Korthauer U., Sperling A.I., Kozak C.A., Love P.E., Bluestone J.A.
    J. Exp. Med. 190:1657-1668(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH TXK AND ITK.
    Strain: C57BL/Kaplan.
    Tissue: Fetal thymus and T-cell lymphoma.

Entry informationi

Entry nameiSH22A_MOUSE
AccessioniPrimary (citable) accession number: Q9QXK9
Secondary accession number(s): Q9JHP6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Proliferation of SH2D2A-deficient T-cells in response to T-cell receptor (TCR)-mediated activation is significantly impaired. These activated T-cells are defective in the production of interleukin (IL)-2 and interferon gamma, but not IL-4.

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.