ID   LIME1_MOUSE             Reviewed;         269 AA.
AC   Q9EQR5;
DT   20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   24-JAN-2024, entry version 131.
DE   RecName: Full=Lck-interacting transmembrane adapter 1;
DE   AltName: Full=Lck-interacting molecule;
GN   Name=Lime1; Synonyms=Lime;
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], INTERACTION WITH LCK; PTPN11; GRB2; PIK3R1 AND
RP   GRAP2, TISSUE SPECIFICITY, INDUCTION, MUTAGENESIS OF CYS-28; CYS-31;
RP   TYR-242 AND TYR-261, PALMITOYLATION AT CYS-28 AND CYS-31, PHOSPHORYLATION
RP   AT TYR-242 AND TYR-261, SUBCELLULAR LOCATION, AND FUNCTION.
RC   TISSUE=Lung;
RX   PubMed=14610044; DOI=10.1084/jem.20030232;
RA   Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.;
RT   "LIME, a novel transmembrane adaptor protein, associates with p56lck and
RT   mediates T cell activation.";
RL   J. Exp. Med. 198:1463-1473(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
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   [3]
RP   TISSUE SPECIFICITY, PHOSPHORYLATION AT TYR-137, INTERACTION WITH PIK3R1;
RP   LYN; PLCG2 AND GRB2, MUTAGENESIS OF TYR-137; TYR-242 AND TYR-261, AND
RP   FUNCTION.
RX   PubMed=16249387; DOI=10.1182/blood-2005-05-1859;
RA   Ahn E., Lee H., Yun Y.;
RT   "LIME acts as a transmembrane adapter mediating BCR-dependent B-cell
RT   activation.";
RL   Blood 107:1521-1527(2006).
CC   -!- FUNCTION: Involved in BCR (B-cell antigen receptor)-mediated signaling
CC       in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling
CC       in T-cells. In absence of TCR signaling, may be involved in CD4-
CC       mediated inhibition of T-cell activation. Couples activation of these
CC       receptors and their associated kinases with distal intracellular events
CC       such as calcium mobilization or MAPK activation through the recruitment
CC       of PLCG2, GRB2, GRAP2, and other signaling molecules.
CC       {ECO:0000269|PubMed:14610044, ECO:0000269|PubMed:16249387}.
CC   -!- SUBUNIT: When phosphorylated in response to TCR stimulation and/or CD4
CC       costimulation, interacts with LCK, CSK, FYN, PTPN11/SHP2, GRB2, PIK3R1
CC       and GRAP2 (By similarity). When phosphorylated in response to BCR
CC       activation, interacts with LYN, PIK3R1, PLCG2 and GRB2. {ECO:0000250,
CC       ECO:0000269|PubMed:14610044, ECO:0000269|PubMed:16249387}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14610044};
CC       Single-pass type III membrane protein {ECO:0000269|PubMed:14610044}.
CC       Note=Present in lipid rafts. Recruited to the immunological synapse
CC       upon conjugation of T-cell with antigen-presenting cell.
CC   -!- TISSUE SPECIFICITY: Expressed in spleen and lung. Present in primary B-
CC       cells and peripheral T-cells (at protein level).
CC       {ECO:0000269|PubMed:14610044, ECO:0000269|PubMed:16249387}.
CC   -!- INDUCTION: Up-regulated in T-cells following TCR engagement.
CC       {ECO:0000269|PubMed:14610044}.
CC   -!- PTM: Palmitoylation of Cys-28 and Cys-31 is required for raft
CC       targeting. {ECO:0000269|PubMed:14610044}.
CC   -!- PTM: Phosphorylated on tyrosines upon TCR activation and/or CD4
CC       coreceptor stimulation, or upon BCR stimulation; which leads to the
CC       recruitment of SH2-containing proteins. {ECO:0000269|PubMed:14610044,
CC       ECO:0000269|PubMed:16249387}.
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DR   EMBL; AF115339; AAG35210.1; -; mRNA.
DR   EMBL; BC023065; AAH23065.1; -; mRNA.
DR   CCDS; CCDS17211.1; -.
DR   RefSeq; NP_076173.1; NM_023684.2.
DR   AlphaFoldDB; Q9EQR5; -.
DR   SMR; Q9EQR5; -.
DR   STRING; 10090.ENSMUSP00000045010; -.
DR   iPTMnet; Q9EQR5; -.
DR   PhosphoSitePlus; Q9EQR5; -.
DR   SwissPalm; Q9EQR5; -.
DR   EPD; Q9EQR5; -.
DR   jPOST; Q9EQR5; -.
DR   PaxDb; 10090-ENSMUSP00000045010; -.
DR   ProteomicsDB; 292258; -.
DR   DNASU; 72699; -.
DR   Ensembl; ENSMUST00000048077.12; ENSMUSP00000045010.6; ENSMUSG00000090077.10.
DR   GeneID; 72699; -.
DR   KEGG; mmu:72699; -.
DR   UCSC; uc008omd.1; mouse.
DR   AGR; MGI:1919949; -.
DR   CTD; 54923; -.
DR   MGI; MGI:1919949; Lime1.
DR   VEuPathDB; HostDB:ENSMUSG00000090077; -.
DR   eggNOG; ENOG502RGRF; Eukaryota.
DR   GeneTree; ENSGT00510000050080; -.
DR   HOGENOM; CLU_094813_0_0_1; -.
DR   InParanoid; Q9EQR5; -.
DR   OMA; YESIREM; -.
DR   OrthoDB; 4640555at2759; -.
DR   PhylomeDB; Q9EQR5; -.
DR   TreeFam; TF337416; -.
DR   BioGRID-ORCS; 72699; 2 hits in 78 CRISPR screens.
DR   ChiTaRS; Lime1; mouse.
DR   PRO; PR:Q9EQR5; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q9EQR5; Protein.
DR   Bgee; ENSMUSG00000090077; Expressed in granulocyte and 70 other cell types or tissues.
DR   ExpressionAtlas; Q9EQR5; baseline and differential.
DR   GO; GO:0019815; C:B cell receptor complex; IDA:MGI.
DR   GO; GO:0019901; F:protein kinase binding; IPI:MGI.
DR   GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR   GO; GO:0050853; P:B cell receptor signaling pathway; IDA:MGI.
DR   GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IMP:MGI.
DR   GO; GO:1901222; P:regulation of non-canonical NF-kappaB signal transduction; IMP:MGI.
DR   GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:MGI.
DR   GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IMP:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; IEA:InterPro.
DR   InterPro; IPR026072; Lime1.
DR   PANTHER; PTHR47740:SF1; LCK-INTERACTING TRANSMEMBRANE ADAPTER 1; 1.
DR   PANTHER; PTHR47740; LCK-INTERACTING TRANSMEMBRANE ADAPTER 1, LIME1; 1.
DR   Pfam; PF15332; LIME1; 1.
DR   Genevisible; Q9EQR5; MM.
PE   1: Evidence at protein level;
KW   Adaptive immunity; Cell membrane; Immunity; Lipoprotein; Membrane;
KW   Palmitate; Phosphoprotein; Reference proteome; Signal-anchor;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..269
FT                   /note="Lck-interacting transmembrane adapter 1"
FT                   /id="PRO_0000083333"
FT   TOPO_DOM        1..7
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        8..28
FT                   /note="Helical; Signal-anchor for type III membrane
FT                   protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        29..269
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          102..134
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          137..140
FT                   /note="Interaction with GRB2"
FT   REGION          175..178
FT                   /note="Interaction with CSK"
FT                   /evidence="ECO:0000250"
FT   REGION          207..210
FT                   /note="Interaction with CSK"
FT                   /evidence="ECO:0000250"
FT   REGION          242..245
FT                   /note="Interaction with LCK and PIK3R1"
FT                   /evidence="ECO:0000269|PubMed:14610044"
FT   REGION          261..264
FT                   /note="Interaction with LCK, PLCG2 and PIK3R1"
FT                   /evidence="ECO:0000269|PubMed:14610044,
FT                   ECO:0000269|PubMed:16249387"
FT   MOD_RES         137
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000305|PubMed:16249387"
FT   MOD_RES         175
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H400"
FT   MOD_RES         207
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H400"
FT   MOD_RES         242
FT                   /note="Phosphotyrosine; by LYN or LCK"
FT                   /evidence="ECO:0000305|PubMed:14610044"
FT   MOD_RES         261
FT                   /note="Phosphotyrosine; by LYN or LCK"
FT                   /evidence="ECO:0000305|PubMed:14610044"
FT   MOD_RES         263
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H400"
FT   LIPID           28
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000305|PubMed:14610044"
FT   LIPID           31
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000305|PubMed:14610044"
FT   MUTAGEN         28
FT                   /note="C->S: Abolishes palmitoylation and lipid raft
FT                   localization; when associated with S-31."
FT                   /evidence="ECO:0000269|PubMed:14610044"
FT   MUTAGEN         31
FT                   /note="C->S: Abolishes palmitoylation and lipid raft
FT                   localization; when associated with S-28."
FT                   /evidence="ECO:0000269|PubMed:14610044"
FT   MUTAGEN         137
FT                   /note="Y->F: Reduces GRB2 binding."
FT                   /evidence="ECO:0000269|PubMed:16249387"
FT   MUTAGEN         242
FT                   /note="Y->F: Abolishes LCK, PIK3R1 and LYN binding; when
FT                   associated with F-261."
FT                   /evidence="ECO:0000269|PubMed:14610044,
FT                   ECO:0000269|PubMed:16249387"
FT   MUTAGEN         261
FT                   /note="Y->F: Strongly reduces PLCG2 binding. Abolishes LCK,
FT                   PIK3R1 and LYN binding; when associated with F-242."
FT                   /evidence="ECO:0000269|PubMed:14610044,
FT                   ECO:0000269|PubMed:16249387"
SQ   SEQUENCE   269 AA;  29551 MW;  B37A1059EB723FBF CRC64;
     MRPPVPSAPL ALWVLGCFSL LLWLWALCTA CHRKRAQRQQ TGLQDSLVPV EMPLLRQTHL
     CSLSKSDTRL HELHRGPRSS IAPRPASMDL LHPRWLEMSR GSTRSQVPNS AFPPRQLPRA
     PPAAPATAPS TSSEATYSNV GLAAIPRASL AASPVVWAGT QLTISCARLG PGAEYACIQK
     HKGTEQGCQE LQQKAKVIPA TQMDVLYSRV CKPKRRDPRP VTDQLNLQDG RTSLPLGSDV
     EYEAINLRGQ DMKQGPLENV YESIKEMGL
//