SH22A_MOUSE
ID SH22A_MOUSE Reviewed; 374 AA.
AC Q9QXK9; Q9JHP6;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=SH2 domain-containing protein 2A;
DE AltName: Full=Lck-associated adapter protein;
DE Short=Lad;
DE AltName: Full=Rlk/Itk-binding protein;
DE Short=Ribp;
GN Name=Sh2d2a; Synonyms=Lad, Ribp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/Kaplan; TISSUE=Lung, and Spleen;
RX PubMed=10553045;
RA Choi Y.B., Kim C.K., Yun Y.;
RT "Lad, an adapter protein interacting with the SH2 domain of p56lck, is
RT required for T cell activation.";
RL J. Immunol. 163:5242-5249(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND INTERACTION
RP WITH TXK AND ITK.
RC STRAIN=C57BL/Kaplan; TISSUE=Fetal thymus, and T-cell lymphoma;
RX PubMed=10587356; DOI=10.1084/jem.190.11.1657;
RA Rajagopal K., Sommers C.L., Decker D.C., Mitchell E.O., Korthauer U.,
RA Sperling A.I., Kozak C.A., Love P.E., Bluestone J.A.;
RT "RIBP, a novel Rlk/Txk- and Itk-binding adaptor protein that regulates T
RT cell activation.";
RL J. Exp. Med. 190:1657-1668(1999).
CC -!- FUNCTION: Could be a T-cell-specific adapter protein involved in the
CC control of T-cell activation. May play a role in p56-LCK-mediated T-
CC cell signaling. Could be involved in the regulation of responses to T-
CC cell activation stimuli, specifically proliferation and lymphokine
CC production. Interactions with ITK and TXK may provide important
CC biochemical links of these two important kinases with other components
CC in the T-cell activation machinery. {ECO:0000269|PubMed:10587356}.
CC -!- SUBUNIT: Interacts with KDR (By similarity). Interacts with p56-LCK,
CC TXK and ITK. {ECO:0000250, ECO:0000269|PubMed:10587356}.
CC -!- INTERACTION:
CC Q9QXK9; P06240: Lck; NbExp=3; IntAct=EBI-1644, EBI-1401;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Redistributed from
CC cytoplasm to the plasma membrane in a T-cell activation-dependent
CC manner.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9QXK9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9QXK9-2; Sequence=VSP_003967;
CC -!- TISSUE SPECIFICITY: Expression limited to tissues of the immune system
CC and, in particular, activated T-cells and natural killer cells.
CC Expressed in the thymus, lymph node, and to a lesser extent, in the
CC spleen and bone marrow. According to PubMed:10553045, also expressed in
CC the lung.
CC -!- INDUCTION: Up-regulated substantially after T-cell activation.
CC -!- PTM: Phosphorylated on tyrosine residues upon TCR-stimulation.
CC -!- MISCELLANEOUS: Proliferation of SH2D2A-deficient T-cells in response to
CC T-cell receptor (TCR)-mediated activation is significantly impaired.
CC These activated T-cells are defective in the production of interleukin
CC (IL)-2 and interferon gamma, but not IL-4.
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DR EMBL; U69490; AAB58422.1; -; mRNA.
DR EMBL; AF203343; AAF19396.1; -; mRNA.
DR CCDS; CCDS17455.1; -. [Q9QXK9-2]
DR CCDS; CCDS38476.1; -. [Q9QXK9-1]
DR RefSeq; NP_067284.1; NM_021309.3. [Q9QXK9-1]
DR AlphaFoldDB; Q9QXK9; -.
DR SMR; Q9QXK9; -.
DR IntAct; Q9QXK9; 1.
DR STRING; 10090.ENSMUSP00000103207; -.
DR iPTMnet; Q9QXK9; -.
DR PhosphoSitePlus; Q9QXK9; -.
DR EPD; Q9QXK9; -.
DR jPOST; Q9QXK9; -.
DR PaxDb; Q9QXK9; -.
DR PRIDE; Q9QXK9; -.
DR ProteomicsDB; 256995; -. [Q9QXK9-1]
DR ProteomicsDB; 256996; -. [Q9QXK9-2]
DR Antibodypedia; 20445; 332 antibodies from 29 providers.
DR DNASU; 27371; -.
DR Ensembl; ENSMUST00000029709; ENSMUSP00000029709; ENSMUSG00000028071. [Q9QXK9-2]
DR Ensembl; ENSMUST00000107581; ENSMUSP00000103207; ENSMUSG00000028071. [Q9QXK9-1]
DR GeneID; 27371; -.
DR KEGG; mmu:27371; -.
DR UCSC; uc008pta.1; mouse. [Q9QXK9-1]
DR CTD; 9047; -.
DR MGI; MGI:1351596; Sh2d2a.
DR VEuPathDB; HostDB:ENSMUSG00000028071; -.
DR eggNOG; ENOG502RE0K; Eukaryota.
DR GeneTree; ENSGT00940000161903; -.
DR HOGENOM; CLU_709723_0_0_1; -.
DR InParanoid; Q9QXK9; -.
DR OMA; TVPMQKE; -.
DR OrthoDB; 593999at2759; -.
DR PhylomeDB; Q9QXK9; -.
DR TreeFam; TF336893; -.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR BioGRID-ORCS; 27371; 0 hits in 73 CRISPR screens.
DR PRO; PR:Q9QXK9; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9QXK9; protein.
DR Bgee; ENSMUSG00000028071; Expressed in thymus and 31 other tissues.
DR ExpressionAtlas; Q9QXK9; baseline and differential.
DR Genevisible; Q9QXK9; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
DR CDD; cd10416; SH2_SH2D2A; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR035884; SH2D2A_SH2.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome; SH2 domain; SH3-binding.
FT CHAIN 1..374
FT /note="SH2 domain-containing protein 2A"
FT /id="PRO_0000097727"
FT DOMAIN 116..207
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 213..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 321..340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 353..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 267..273
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 241..266
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 357..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NP31"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NP31"
FT VAR_SEQ 254..261
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10553045,
FT ECO:0000303|PubMed:10587356"
FT /id="VSP_003967"
FT CONFLICT 14
FT /note="H -> R (in Ref. 1; AAB58422)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="G -> E (in Ref. 1; AAB58422)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 374 AA; 40953 MW; 6215FF96CE764359 CRC64;
MEFCLAQPCP QGNHEATSST FNTFQPMNLT QGRCQNLSCG SRPSMQVMKE QGVQLSPRTN
HTVVSASAPG TAWVLGNADR AEEVPGKGDL SLQAETRAWV QKTQAHWLLL KTAPLWFHGF
ITRREAERLL QPQPLGCYLV RFSESAVTFV LSYRSQTCCR HFLLAQLGDG RHVVLGEDSA
HAQLQDLLEH YTECPLSPYG EILTQPLARQ TAEPAGLSLR ADSDSGSKRQ DPDTQLSLLL
QQGQAQASGH TEKVWASQQK ATSQASRPRP PIPAKPQLPP EVYTSPASRL HQAPPINPIY
QEPDEPIAFY AMGRGSPGDA PSNIYAEVEG PSGTAPIGHP ILRKCWSRPI SRGQVREVQG
KISSRSRAER GSPS
