LCP2_MOUSE
ID LCP2_MOUSE Reviewed; 533 AA.
AC Q60787; Q922M0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Lymphocyte cytosolic protein 2;
DE AltName: Full=SH2 domain-containing leukocyte protein of 76 kDa;
DE AltName: Full=SLP-76 tyrosine phosphoprotein;
DE Short=SLP76;
GN Name=Lcp2;
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], AND INTERACTION WITH GRB2.
RC TISSUE=T-cell lymphoma;
RX PubMed=7706237; DOI=10.1074/jbc.270.13.7029;
RA Jackman J.K., Motto D.G., Sun Q., Tanemoto M., Turck C.W., Peltz G.A.,
RA Koretzky G.A., Findell P.R.;
RT "Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated
RT with Grb2 in T cells.";
RL J. Biol. Chem. 270:7029-7032(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND PHOSPHORYLATION BY TXK.
RX PubMed=10660534; DOI=10.1074/jbc.275.6.3835;
RA Schneider H., Guerette B., Guntermann C., Rudd C.E.;
RT "Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the
RT cooperative activation of interleukin-2 transcription in T-cells.";
RL J. Biol. Chem. 275:3835-3840(2000).
RN [6]
RP INTERACTION WITH SLA.
RX PubMed=10662792; DOI=10.1084/jem.191.3.463;
RA Sosinowski T., Pandey A., Dixit V.M., Weiss A.;
RT "Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor
RT signaling.";
RL J. Exp. Med. 191:463-474(2000).
RN [7]
RP INTERACTION WITH CBLB.
RX PubMed=10646608; DOI=10.1038/35003228;
RA Bachmaier K., Krawczyk C., Kozieradzki I., Kong Y.-Y., Sasaki T.,
RA Oliveira-dos-Santos A., Mariathasan S., Bouchard D., Wakeham A., Itie A.,
RA Le J., Ohashi P.S., Sarosi I., Nishina H., Lipkowitz S., Penninger J.M.;
RT "Negative regulation of lymphocyte activation and autoimmunity by the
RT molecular adaptor Cbl-b.";
RL Nature 403:211-216(2000).
RN [8]
RP INTERACTION WITH CD6.
RX PubMed=16914752; DOI=10.1128/mcb.00688-06;
RA Hassan N.J., Simmonds S.J., Clarkson N.G., Hanrahan S., Puklavec M.J.,
RA Bomb M., Barclay A.N., Brown M.H.;
RT "CD6 regulates T-cell responses through activation-dependent recruitment of
RT the positive regulator SLP-76.";
RL Mol. Cell. Biol. 26:6727-6738(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-23, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP INTERACTION WITH CD6.
RX PubMed=24584089; DOI=10.1038/ni.2843;
RA Roncagalli R., Hauri S., Fiore F., Liang Y., Chen Z., Sansoni A.,
RA Kanduri K., Joly R., Malzac A., Laehdesmaeki H., Lahesmaa R., Yamasaki S.,
RA Saito T., Malissen M., Aebersold R., Gstaiger M., Malissen B.;
RT "Quantitative proteomics analysis of signalosome dynamics in primary T
RT cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR
RT signaling hub.";
RL Nat. Immunol. 15:384-392(2014).
CC -!- FUNCTION: Involved in T-cell antigen receptor mediated signaling.
CC {ECO:0000269|PubMed:10660534}.
CC -!- SUBUNIT: Interacts with SHB. Interacts with PRAM1 (By similarity).
CC Interacts with SLA (PubMed:10662792). Interacts with GRB2
CC (PubMed:7706237). Interacts with CBLB (PubMed:10646608). Interacts (via
CC SH2 domain) with CD6 (via tyrosine phosphorylated C-terminus)
CC (PubMed:16914752, PubMed:24584089). Interacts with FYB1 and the
CC phosphorylated form of FYB2 (By similarity).
CC {ECO:0000250|UniProtKB:Q13094, ECO:0000269|PubMed:10646608,
CC ECO:0000269|PubMed:10662792, ECO:0000269|PubMed:16914752,
CC ECO:0000269|PubMed:24584089, ECO:0000269|PubMed:7706237}.
CC -!- INTERACTION:
CC Q60787; Q61003: Cd6; NbExp=9; IntAct=EBI-5324248, EBI-12601992;
CC Q60787; O35601: Fyb1; NbExp=7; IntAct=EBI-5324248, EBI-7353747;
CC Q60787; O89100: Grap2; NbExp=7; IntAct=EBI-5324248, EBI-642151;
CC Q60787; O54957: Lat; NbExp=8; IntAct=EBI-5324248, EBI-6390034;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in spleen, thymus, and peripheral
CC blood leukocytes.
CC -!- DOMAIN: The SH2 domain mediates interaction with SHB. {ECO:0000250}.
CC -!- PTM: Phosphorylated after T-cell receptor activation by ZAP70, ITK and
CC TXK, which leads to the up-regulation of Th1 preferred cytokine IL-2.
CC SYK-dependent phosphorylation is required for recruitment of PI3K
CC signaling components (By similarity). {ECO:0000250}.
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DR EMBL; U20159; AAC52189.1; -; mRNA.
DR EMBL; AK036727; BAC29553.1; -; mRNA.
DR EMBL; AK170491; BAE41833.1; -; mRNA.
DR EMBL; CH466604; EDL23730.1; -; Genomic_DNA.
DR EMBL; BC006948; AAH06948.1; -; mRNA.
DR CCDS; CCDS48768.1; -.
DR PIR; B56110; B56110.
DR RefSeq; NP_034826.2; NM_010696.3.
DR PDB; 1OEB; X-ray; 1.76 A; C/D=231-243.
DR PDB; 2ETZ; NMR; -; B=143-148.
DR PDB; 2EU0; NMR; -; B=143-148.
DR PDBsum; 1OEB; -.
DR PDBsum; 2ETZ; -.
DR PDBsum; 2EU0; -.
DR AlphaFoldDB; Q60787; -.
DR SMR; Q60787; -.
DR BioGRID; 201124; 3.
DR CORUM; Q60787; -.
DR ELM; Q60787; -.
DR IntAct; Q60787; 28.
DR MINT; Q60787; -.
DR STRING; 10090.ENSMUSP00000056621; -.
DR iPTMnet; Q60787; -.
DR PhosphoSitePlus; Q60787; -.
DR EPD; Q60787; -.
DR jPOST; Q60787; -.
DR MaxQB; Q60787; -.
DR PaxDb; Q60787; -.
DR PRIDE; Q60787; -.
DR ProteomicsDB; 286182; -.
DR Antibodypedia; 3884; 723 antibodies from 45 providers.
DR DNASU; 16822; -.
DR Ensembl; ENSMUST00000052413; ENSMUSP00000056621; ENSMUSG00000002699.
DR GeneID; 16822; -.
DR KEGG; mmu:16822; -.
DR UCSC; uc007ikv.1; mouse.
DR CTD; 3937; -.
DR MGI; MGI:1321402; Lcp2.
DR VEuPathDB; HostDB:ENSMUSG00000002699; -.
DR eggNOG; ENOG502QV3T; Eukaryota.
DR GeneTree; ENSGT00940000156835; -.
DR InParanoid; Q60787; -.
DR OMA; AHHNVIF; -.
DR OrthoDB; 744111at2759; -.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization.
DR BioGRID-ORCS; 16822; 1 hit in 70 CRISPR screens.
DR EvolutionaryTrace; Q60787; -.
DR PRO; PR:Q60787; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q60787; protein.
DR Bgee; ENSMUSG00000002699; Expressed in granulocyte and 121 other tissues.
DR ExpressionAtlas; Q60787; baseline and differential.
DR Genevisible; Q60787; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR GO; GO:0036398; C:TCR signalosome; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0045576; P:mast cell activation; IMP:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR IDEAL; IID50090; -.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR Pfam; PF07647; SAM_2; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..533
FT /note="Lymphocyte cytosolic protein 2"
FT /id="PRO_0000084369"
FT DOMAIN 12..78
FT /note="SAM"
FT DOMAIN 422..530
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 78..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 374..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..97
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..141
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 151..178
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 182..215
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 285..299
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..327
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..355
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 23
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 207
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13094"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13094"
FT CONFLICT 306
FT /note="P -> S (in Ref. 1; AAC52189)"
FT /evidence="ECO:0000305"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:1OEB"
SQ SEQUENCE 533 AA; 60238 MW; 50AEA025EF0DAD01 CRC64;
MALKNVPFRS EVLAWNSDNL ADYFRKLNYR DCEKAVKKYH IDGARFLNLT ENDIQKFPKL
RMPLLSKLSQ DINKNEERRS IFTRKPQIPR FLEETESHEE DDGGWSSFED DYESPNDDDP
DGEDDGDYES PNEEEQALVD DAADYEPPPS NNEEALQSSI LPPNSFHNTN SMYIDRPPTG
KVSQQPPVPP LRPKPALPPL PTGRNHSPLS PPHPNHEEPS RSGNNKTAKL PAPSIDRSTK
PPLDRSLAPL DREPFILGKK PPFSDKPSAP LGREHLPKIQ KPPLPPAMDR HERNERLGPV
TTRKPPVPRH GRGPDRREND EDDVHQRPLP QPSLPSMSSN TFPSRSVQPS SKNTFPLAHM
PGAFSESNIG FQQSASLPPY FSQGPGNRPP LRSEGRNLPL PVPNRPQPPS PGEEETPLDE
EWYVSYITRP EAEAALRKIN QDGTFLVRDS SKKTANNPYV LMVLYKDKVY NIQIRYQEES
QVYLLGTGLR GKEDFLSVSD IIDYFRKMPL LLIDGKNRGS RYQCTLTHAA GCL
