TRML4_MOUSE
ID TRML4_MOUSE Reviewed; 263 AA.
AC Q3LRV9; A6XA78; E9Q825; Q3LRW0;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Trem-like transcript 4 protein;
DE Short=TLT-4;
DE AltName: Full=Triggering receptor expressed on myeloid cells-like protein 3;
DE AltName: Full=Triggering receptor expressed on myeloid cells-like protein 4;
DE Flags: Precursor;
GN Name=Treml4; Synonyms=TLT4, Treml3;
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 1), AND NUCLEOTIDE SEQUENCE [MRNA] OF
RP 1-223 (ISOFORM 3).
RC STRAIN=C57BL/6J;
RA Melchior B., Carson M.J.;
RT "Trem-like transcripts expression in microglia and peripheral myeloid cells
RT display a common pattern.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RA van der Holst R., Helander I., Karre K., Sundback J.;
RT "Cloning and characterization of a novel activating TREM family molecule
RT expressed on antigen presenting cells, TRAPC.";
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis, and Thymus;
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 [6]
RP FUNCTION, INTERACTION WITH TYROBP, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=19155473; DOI=10.4049/jimmunol.182.3.1278;
RA Hemmi H., Idoyaga J., Suda K., Suda N., Kennedy K., Noda M., Aderem A.,
RA Steinman R.M.;
RT "A new triggering receptor expressed on myeloid cells (Trem) family member,
RT Trem-like 4, binds to dead cells and is a DNAX activation protein 12-linked
RT marker for subsets of mouse macrophages and dendritic cells.";
RL J. Immunol. 182:1278-1286(2009).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=22210914; DOI=10.4049/jimmunol.1102541;
RA Hemmi H., Zaidi N., Wang B., Matos I., Fiorese C., Lubkin A., Zbytnuik L.,
RA Suda K., Zhang K., Noda M., Kaisho T., Steinman R.M., Idoyaga J.;
RT "Treml4, an Ig superfamily member, mediates presentation of several
RT antigens to T cells in vivo, including protective immunity to HER2
RT protein.";
RL J. Immunol. 188:1147-1155(2012).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, DOMAIN, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF LYS-209.
RX PubMed=25848864; DOI=10.1038/ni.3143;
RA Ramirez-Ortiz Z.G., Prasad A., Griffith J.W., Pendergraft W.F. III,
RA Cowley G.S., Root D.E., Tai M., Luster A.D., El Khoury J., Hacohen N.,
RA Means T.K.;
RT "The receptor TREML4 amplifies TLR7-mediated signaling during antiviral
RT responses and autoimmunity.";
RL Nat. Immunol. 16:495-504(2015).
CC -!- FUNCTION: Positively regulates Toll-like receptor signaling via TLR7,
CC TLR9 and TLR13 in neutrophils and splenic macrophages
CC (PubMed:25848864). Regulates TLR7 signaling by controlling ligand-
CC induced recruitment of TLR7 from the endoplasmic reticulum to endosomes
CC and lysosomes (PubMed:25848864). Positively regulates Toll-like
CC receptor TLR9-induced production of inflammatory cytokines but is
CC dispensable for IFNB1 production (PubMed:25848864). Involved in the
CC anti-viral response to several viruses including influenza virus,
CC vesicular stomatitis virus and cytomegalovirus (PubMed:25848864). Binds
CC to late apoptotic, and necrotic cells, but not living or early
CC apoptotic cells, but is not essential for uptake of dying cells by
CC dendritic cells (DCs) (PubMed:22210914, PubMed:19155473,
CC PubMed:25848864). Does not bind nucleic acids (PubMed:25848864). May
CC participate in antigen presentation (PubMed:22210914).
CC {ECO:0000269|PubMed:19155473, ECO:0000269|PubMed:22210914,
CC ECO:0000269|PubMed:25848864}.
CC -!- SUBUNIT: Interacts with TYROBP/DAP12. {ECO:0000269|PubMed:19155473}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:19155473,
CC ECO:0000305|PubMed:22210914}; Single-pass type I membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3LRV9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3LRV9-2; Sequence=VSP_044083;
CC Name=3;
CC IsoId=Q3LRV9-3; Sequence=VSP_044084;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in spleen, with highest
CC levels on selected populations of macrophages, including red pulp
CC macrophages, and on subsets of dendritic cells (DC), mostly on
CC CD8alpha(+) DC (at protein level) (PubMed:19155473, PubMed:22210914,
CC PubMed:25848864). Also expressed on blood and spleen Ly6C(low)
CC monocytes (at protein level) (PubMed:22210914). Not expressed on
CC lymphocytes or granulocytes (at protein level) (PubMed:19155473,
CC PubMed:22210914). {ECO:0000269|PubMed:19155473,
CC ECO:0000269|PubMed:22210914, ECO:0000269|PubMed:25848864}.
CC -!- INDUCTION: Induced by synthetic TLR7 ligand gardiquimod (GRD) in
CC cultured splenic macrophages. {ECO:0000269|PubMed:25848864}.
CC -!- DOMAIN: The cytoplasmic tail appears to be dispensable for TLR7-
CC mediated signaling. {ECO:0000269|PubMed:25848864}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:22210914). Mutant
CC mice are born at the expected Mendelian frequency and are fertile and
CC healthy (PubMed:22210914). In response to gardiquimod (GRD) or
CC Resiquimod (R-848), 2 synthetic TLR7 ligands, levels of TNF, IL12B,
CC IFNB1 and CXCL10 in splenic macrophages and in serum are severely
CC reduced (PubMed:25848864). In response to CpG DNA, a TLR9 ligand,
CC levels of TNF and IL12B but not IFNB1 and CXCL10 are severely reduced
CC (PubMed:25848864). In response to infection with influenza virus
CC (strain A/PuertoRico/8/34 (PR8)) the production of TNF, IL12B, IFNB1
CC and CXCL10 is severely impaired, the viral load is higher in the lungs,
CC recovery after weight loss and survival are also impaired
CC (PubMed:25848864). No defects in response to lipopolysaccharide (LPS)
CC (PubMed:25848864). Reduced symptom severity in a mouse model for the
CC autoimmune disease systemic lupus erythematosus (SLE)
CC (PubMed:25848864). {ECO:0000269|PubMed:22210914,
CC ECO:0000269|PubMed:25848864}.
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DR EMBL; DQ087185; ABA38681.1; -; mRNA.
DR EMBL; DQ087186; ABA38682.1; -; mRNA.
DR EMBL; DQ186654; ABA29758.1; -; mRNA.
DR EMBL; DQ186655; ABA29759.1; -; mRNA.
DR EMBL; AC166164; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466559; EDL23604.1; -; Genomic_DNA.
DR EMBL; BC117091; AAI17092.1; -; mRNA.
DR EMBL; BC137666; AAI37667.1; -; mRNA.
DR CCDS; CCDS28862.1; -. [Q3LRV9-1]
DR CCDS; CCDS50141.1; -. [Q3LRV9-2]
DR RefSeq; NP_001029094.1; NM_001033922.2. [Q3LRV9-2]
DR RefSeq; NP_766211.2; NM_172623.2. [Q3LRV9-1]
DR RefSeq; XP_006524212.1; XM_006524149.3. [Q3LRV9-3]
DR AlphaFoldDB; Q3LRV9; -.
DR SMR; Q3LRV9; -.
DR STRING; 10090.ENSMUSP00000118772; -.
DR GlyGen; Q3LRV9; 1 site.
DR iPTMnet; Q3LRV9; -.
DR PhosphoSitePlus; Q3LRV9; -.
DR MaxQB; Q3LRV9; -.
DR PaxDb; Q3LRV9; -.
DR PRIDE; Q3LRV9; -.
DR ProteomicsDB; 298237; -. [Q3LRV9-1]
DR ProteomicsDB; 298238; -. [Q3LRV9-2]
DR ProteomicsDB; 298239; -. [Q3LRV9-3]
DR ABCD; Q3LRV9; 1 sequenced antibody.
DR Antibodypedia; 70761; 41 antibodies from 14 providers.
DR DNASU; 224840; -.
DR Ensembl; ENSMUST00000059873; ENSMUSP00000054121; ENSMUSG00000051682. [Q3LRV9-1]
DR Ensembl; ENSMUST00000125426; ENSMUSP00000119177; ENSMUSG00000051682. [Q3LRV9-2]
DR GeneID; 224840; -.
DR KEGG; mmu:224840; -.
DR UCSC; uc008cwz.1; mouse. [Q3LRV9-2]
DR UCSC; uc008cxa.1; mouse. [Q3LRV9-1]
DR UCSC; uc012avb.1; mouse. [Q3LRV9-3]
DR CTD; 285852; -.
DR MGI; MGI:1923239; Treml4.
DR VEuPathDB; HostDB:ENSMUSG00000051682; -.
DR eggNOG; ENOG502TG0M; Eukaryota.
DR GeneTree; ENSGT00940000153835; -.
DR InParanoid; Q3LRV9; -.
DR PhylomeDB; Q3LRV9; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR BioGRID-ORCS; 224840; 2 hits in 71 CRISPR screens.
DR PRO; PR:Q3LRV9; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q3LRV9; protein.
DR Bgee; ENSMUSG00000051682; Expressed in granulocyte and 32 other tissues.
DR ExpressionAtlas; Q3LRV9; baseline and differential.
DR Genevisible; Q3LRV9; MM.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006911; P:phagocytosis, engulfment; IDA:MGI.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB.
DR GO; GO:0034181; P:positive regulation of toll-like receptor 13 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034157; P:positive regulation of toll-like receptor 7 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; IMP:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR GO; GO:0002457; P:T cell antigen processing and presentation; IMP:MGI.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiviral defense; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Innate immunity; Membrane;
KW Receptor; Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..263
FT /note="Trem-like transcript 4 protein"
FT /id="PRO_0000418835"
FT TOPO_DOM 29..200
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..263
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 29..132
FT /note="Ig-like V-type"
FT REGION 168..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 47..116
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 21..24
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_044083"
FT VAR_SEQ 184..263
FT /note="NQSSSSPGWTSPGLLVSVQYGLLLLKALMLSVFCVLLCWRSGQGREYMAETM
FT ELSKLPHISKSLDTVSHISGYEKKANWY -> DESTWQRRWSFQNYLTSPSPWTRLATS
FT QGMRRRLTGTKAEQAKLPLYRSHQASPRETTARPASQIARAN (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_044084"
FT MUTAGEN 209
FT /note="K->L: Loss of TLR7 signaling."
FT /evidence="ECO:0000269|PubMed:25848864"
SQ SEQUENCE 263 AA; 29355 MW; 0759F18001396EB8 CRC64;
MAWRYSQLLL VPVQLVFLAS VCCPGVWGST VSEELHRMVG QSLSVQCQYK PKEESYVLKT
WCRQTAPSKC TRVVTTSEPR KAARELQHTI WDDPEAGFFN ITMTQLTEDD SAFYWCGPYY
PSLREVTVLR NISLVVSPAP STLPSQTIAP LPESTATIFM PFPVLTTSPE ETTDSSINGT
GHRNQSSSSP GWTSPGLLVS VQYGLLLLKA LMLSVFCVLL CWRSGQGREY MAETMELSKL
PHISKSLDTV SHISGYEKKA NWY
