TRML1_HUMAN
ID TRML1_HUMAN Reviewed; 311 AA.
AC Q86YW5; Q496B3; Q8IWY1; Q8IWY2;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Trem-like transcript 1 protein;
DE Short=TLT-1;
DE AltName: Full=Triggering receptor expressed on myeloid cells-like protein 1;
DE Flags: Precursor;
GN Name=TREML1; Synonyms=TLT1; ORFNames=UNQ1825/PRO3438;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12393607; DOI=10.1182/blood-2002-02-0523;
RA Washington A.V., Quigley L., McVicar D.W.;
RT "Initial characterization of TREM-like transcript (TLT)-1: a putative
RT inhibitory receptor within the TREM cluster.";
RL Blood 100:3822-3824(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=12645956; DOI=10.1002/immu.200310033;
RA Allcock R.J.N., Barrow A.D., Forbes S., Beck S., Trowsdale J.;
RT "The human TREM gene cluster at 6p21.1 encodes both activating and
RT inhibitory single IgV domain receptors and includes NKp44.";
RL Eur. J. Immunol. 33:567-577(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
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 SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15100151; DOI=10.1182/blood-2004-01-0315;
RA Washington A.V., Schubert R.L., Quigley L., Disipio T., Feltz R., Cho E.H.,
RA McVicar D.W.;
RT "A TREM family member, TLT-1, is found exclusively in the alpha-granules of
RT megakaryocytes and platelets.";
RL Blood 104:1042-1047(2004).
RN [7]
RP FUNCTION, PHOSPHORYLATION, INTERACTION WITH PTPN11, ALTERNATIVE SPLICING,
RP AND TISSUE SPECIFICITY.
RX PubMed=15128762; DOI=10.4049/jimmunol.172.10.5838;
RA Barrow A.D., Astoul E., Floto A., Brooke G., Relou I.A.M., Jennings N.S.,
RA Smith K.G.C., Ouwehand W., Farndale R.W., Alexander D.R., Trowsdale J.;
RT "TREM-like transcript-1, a platelet immunoreceptor tyrosine-based
RT inhibition motif encoding costimulatory immunoreceptor that enhances,
RT rather than inhibits, calcium signaling via SHP-2.";
RL J. Immunol. 172:5838-5842(2004).
RN [8]
RP PALMITOYLATION AT CYS-196.
RC TISSUE=Platelet;
RX PubMed=21813449; DOI=10.1182/blood-2011-05-353078;
RA Dowal L., Yang W., Freeman M.R., Steen H., Flaumenhaft R.;
RT "Proteomic analysis of palmitoylated platelet proteins.";
RL Blood 118:E62-E73(2011).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.19 ANGSTROMS) OF 20-125, DISULFIDE BONDS, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=16505478; DOI=10.1074/jbc.m600489200;
RA Gattis J.L., Washington A.V., Chisholm M.M., Quigley L., Szyk A.,
RA McVicar D.W., Lubkowski J.;
RT "The structure of the extracellular domain of triggering receptor expressed
RT on myeloid cells like transcript-1 and evidence for a naturally occurring
RT soluble fragment.";
RL J. Biol. Chem. 281:13396-13403(2006).
RN [10]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-6.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Cell surface receptor that may play a role in the innate and
CC adaptive immune response. {ECO:0000269|PubMed:15128762}.
CC -!- SUBUNIT: When phosphorylated, interacts with PTPN6 (By similarity).
CC When phosphorylated, interacts with PTPN11. {ECO:0000250,
CC ECO:0000269|PubMed:15128762}.
CC -!- INTERACTION:
CC Q86YW5; P55061: TMBIM6; NbExp=3; IntAct=EBI-17245072, EBI-1045825;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15100151};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:15100151}.
CC Cytoplasm {ECO:0000269|PubMed:15100151}. Note=Sequestered in
CC cytoplasmic vesicles in resting platelets (PubMed:15100151).
CC Transported to the cell surface after stimulation by thrombin
CC (PubMed:15100151). Soluble fragments can be released into the serum by
CC proteolysis (PubMed:16505478).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q86YW5-1; Sequence=Displayed;
CC Name=2; Synonyms=TLT1sv;
CC IsoId=Q86YW5-2; Sequence=VSP_021125, VSP_021126;
CC Name=3;
CC IsoId=Q86YW5-3; Sequence=VSP_021124;
CC -!- TISSUE SPECIFICITY: Detected in platelets, monocytic leukemia and in T-
CC cell leukemia. {ECO:0000269|PubMed:12645956,
CC ECO:0000269|PubMed:15100151, ECO:0000269|PubMed:15128762,
CC ECO:0000269|PubMed:16505478}.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000269|PubMed:15128762}.
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DR EMBL; AF508193; AAO37827.1; ALT_TERM; mRNA.
DR EMBL; AF534822; AAO15020.1; -; mRNA.
DR EMBL; AF534823; AAO15021.1; -; mRNA.
DR EMBL; AY358357; AAQ88723.1; -; mRNA.
DR EMBL; AL133404; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC100944; AAI00945.1; -; mRNA.
DR EMBL; BC100945; AAI00946.1; -; mRNA.
DR EMBL; BC100946; AAI00947.1; -; mRNA.
DR CCDS; CCDS4851.1; -. [Q86YW5-1]
DR CCDS; CCDS64420.1; -. [Q86YW5-3]
DR CCDS; CCDS64421.1; -. [Q86YW5-2]
DR RefSeq; NP_001258736.1; NM_001271807.1. [Q86YW5-2]
DR RefSeq; NP_001258737.1; NM_001271808.1. [Q86YW5-3]
DR RefSeq; NP_835468.1; NM_178174.3. [Q86YW5-1]
DR RefSeq; XP_016866312.1; XM_017010823.1. [Q86YW5-1]
DR RefSeq; XP_016866313.1; XM_017010824.1. [Q86YW5-1]
DR PDB; 2FRG; X-ray; 1.19 A; P=20-125.
DR PDBsum; 2FRG; -.
DR AlphaFoldDB; Q86YW5; -.
DR SMR; Q86YW5; -.
DR BioGRID; 131013; 9.
DR ELM; Q86YW5; -.
DR IntAct; Q86YW5; 2.
DR STRING; 9606.ENSP00000402855; -.
DR GlyGen; Q86YW5; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86YW5; -.
DR PhosphoSitePlus; Q86YW5; -.
DR SwissPalm; Q86YW5; -.
DR BioMuta; TREML1; -.
DR DMDM; 116256098; -.
DR MassIVE; Q86YW5; -.
DR PaxDb; Q86YW5; -.
DR PeptideAtlas; Q86YW5; -.
DR PRIDE; Q86YW5; -.
DR ProteomicsDB; 70482; -. [Q86YW5-1]
DR ProteomicsDB; 70483; -. [Q86YW5-2]
DR ProteomicsDB; 70484; -. [Q86YW5-3]
DR ABCD; Q86YW5; 6 sequenced antibodies.
DR Antibodypedia; 2655; 289 antibodies from 31 providers.
DR DNASU; 340205; -.
DR Ensembl; ENST00000373127.8; ENSP00000362219.4; ENSG00000161911.12. [Q86YW5-2]
DR Ensembl; ENST00000426005.7; ENSP00000402855.2; ENSG00000161911.12. [Q86YW5-1]
DR Ensembl; ENST00000437044.2; ENSP00000400405.1; ENSG00000161911.12. [Q86YW5-3]
DR GeneID; 340205; -.
DR KEGG; hsa:340205; -.
DR MANE-Select; ENST00000426005.7; ENSP00000402855.2; NM_178174.4; NP_835468.1.
DR UCSC; uc003opx.5; human. [Q86YW5-1]
DR CTD; 340205; -.
DR DisGeNET; 340205; -.
DR GeneCards; TREML1; -.
DR HGNC; HGNC:20434; TREML1.
DR HPA; ENSG00000161911; Tissue enhanced (bone marrow, brain, lymphoid tissue).
DR MIM; 609714; gene.
DR neXtProt; NX_Q86YW5; -.
DR OpenTargets; ENSG00000161911; -.
DR PharmGKB; PA134878709; -.
DR VEuPathDB; HostDB:ENSG00000161911; -.
DR eggNOG; ENOG502SRZV; Eukaryota.
DR GeneTree; ENSGT00470000042300; -.
DR HOGENOM; CLU_077694_1_0_1; -.
DR InParanoid; Q86YW5; -.
DR OMA; IQVQCHY; -.
DR OrthoDB; 1390184at2759; -.
DR PhylomeDB; Q86YW5; -.
DR TreeFam; TF337145; -.
DR PathwayCommons; Q86YW5; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; Q86YW5; -.
DR BioGRID-ORCS; 340205; 8 hits in 1058 CRISPR screens.
DR EvolutionaryTrace; Q86YW5; -.
DR GeneWiki; TREML1; -.
DR GenomeRNAi; 340205; -.
DR Pharos; Q86YW5; Tbio.
DR PRO; PR:Q86YW5; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q86YW5; protein.
DR Bgee; ENSG00000161911; Expressed in monocyte and 88 other tissues.
DR Genevisible; Q86YW5; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0031091; C:platelet alpha granule; IDA:UniProtKB.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0019722; P:calcium-mediated signaling; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; NAS:UniProtKB.
DR GO; GO:0030168; P:platelet activation; IEP:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR SUPFAM; SSF48726; SSF48726; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasm;
KW Disulfide bond; Immunoglobulin domain; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..311
FT /note="Trem-like transcript 1 protein"
FT /id="PRO_0000253855"
FT TOPO_DOM 16..162
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..311
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 16..121
FT /note="Ig-like V-type"
FT REGION 229..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..311
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 279..284
FT /note="ITIM"
FT COMPBIAS 237..253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..311
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 196
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:21813449"
FT DISULFID 38..104
FT /evidence="ECO:0000269|PubMed:16505478"
FT DISULFID 52..59
FT /evidence="ECO:0000269|PubMed:16505478"
FT VAR_SEQ 15..125
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021124"
FT VAR_SEQ 190..199
FT /note="GNRLGVCGRF -> ESLLSGPPRQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12645956,
FT ECO:0000303|PubMed:12975309"
FT /id="VSP_021125"
FT VAR_SEQ 200..311
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12645956,
FT ECO:0000303|PubMed:12975309"
FT /id="VSP_021126"
FT VARIANT 6
FT /note="L -> V (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035526"
FT VARIANT 231
FT /note="H -> P (in dbSNP:rs34254490)"
FT /id="VAR_049950"
FT STRAND 24..28
FT /evidence="ECO:0007829|PDB:2FRG"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:2FRG"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:2FRG"
FT STRAND 47..55
FT /evidence="ECO:0007829|PDB:2FRG"
FT STRAND 58..64
FT /evidence="ECO:0007829|PDB:2FRG"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:2FRG"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:2FRG"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:2FRG"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:2FRG"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:2FRG"
FT STRAND 100..108
FT /evidence="ECO:0007829|PDB:2FRG"
FT STRAND 111..122
FT /evidence="ECO:0007829|PDB:2FRG"
SQ SEQUENCE 311 AA; 32679 MW; 60A2B0BDC2B2D4C1 CRC64;
MGLTLLLLLL LGLEGQGIVG SLPEVLQAPV GSSILVQCHY RLQDVKAQKV WCRFLPEGCQ
PLVSSAVDRR APAGRRTFLT DLGGGLLQVE MVTLQEEDAG EYGCMVDGAR GPQILHRVSL
NILPPEEEEE THKIGSLAEN AFSDPAGSAN PLEPSQDEKS IPLIWGAVLL VGLLVAAVVL
FAVMAKRKQG NRLGVCGRFL SSRVSGMNPS SVVHHVSDSG PAAELPLDVP HIRLDSPPSF
DNTTYTSLPL DSPSGKPSLP APSSLPPLPP KVLVCSKPVT YATVIFPGGN KGGGTSCGPA
QNPPNNQTPS S
