##gff-version 3 Q9NZC2 UniProtKB Signal peptide 1 18 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255 Q9NZC2 UniProtKB Chain 19 230 . . . ID=PRO_0000014987;Note=Triggering receptor expressed on myeloid cells 2 Q9NZC2 UniProtKB Topological domain 19 174 . . . Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 Q9NZC2 UniProtKB Transmembrane 175 195 . . . Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 Q9NZC2 UniProtKB Topological domain 196 230 . . . Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 Q9NZC2 UniProtKB Domain 29 112 . . . Note=Ig-like V-type Q9NZC2 UniProtKB Binding site 67 67 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:29794134,ECO:0007744|PDB:6B8O;Dbxref=PMID:29794134 Q9NZC2 UniProtKB Binding site 68 68 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:29794134,ECO:0007744|PDB:6B8O;Dbxref=PMID:29794134 Q9NZC2 UniProtKB Binding site 77 77 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:29794134,ECO:0007744|PDB:6B8O;Dbxref=PMID:29794134 Q9NZC2 UniProtKB Binding site 88 88 . . . Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:29794134,ECO:0007744|PDB:6B8O;Dbxref=PMID:29794134 Q9NZC2 UniProtKB Site 157 158 . . . Note=Cleavage of ectodomain;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:28855300,ECO:0000269|PubMed:28855301;Dbxref=PMID:28855300,PMID:28855301 Q9NZC2 UniProtKB Glycosylation 20 20 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:29794134,ECO:0007744|PDB:6B8O;Dbxref=PMID:29794134 Q9NZC2 UniProtKB Glycosylation 79 79 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000269,ECO:0000269,ECO:0007744,ECO:0007744;evidence=ECO:0000269|PubMed:27995897,ECO:0000269|PubMed:29794134,ECO:0007744|PDB:5ELI,ECO:0007744|PDB:6B8O;Dbxref=PMID:27995897,PMID:29794134 Q9NZC2 UniProtKB Disulfide bond 36 110 . . . Ontology_term=ECO:0000269,ECO:0000269,ECO:0007744,ECO:0007744,ECO:0007744,ECO:0007744;evidence=ECO:0000269|PubMed:27995897,ECO:0000269|PubMed:29794134,ECO:0007744|PDB:5ELI,ECO:0007744|PDB:5UD7,ECO:0007744|PDB:5UD8,ECO:0007744|PDB:6B8O;Dbxref=PMID:27995897,PMID:29794134 Q9NZC2 UniProtKB Disulfide bond 51 60 . . . Ontology_term=ECO:0000269,ECO:0000269,ECO:0007744,ECO:0007744,ECO:0007744;evidence=ECO:0000269|PubMed:27995897,ECO:0000269|PubMed:29794134,ECO:0007744|PDB:5ELI,ECO:0007744|PDB:5UD8,ECO:0007744|PDB:6B8O;Dbxref=PMID:27995897,PMID:29794134 Q9NZC2 UniProtKB Alternative sequence 162 230 . . . ID=VSP_010792;Note=In isoform 2. SLLEGEIPFPPTSILLLLACIFLIKILAASALWAAAWHGQKPGTHPPSELDCGHDPGYQLQTLPGLRDT->AERHVKEDDGRKSPGEVPPGTSPACILATWPPGLLVLLWQETTLPEHCFSWTLEAGTG;Ontology_term=ECO:0000303;evidence=ECO:0000303|Ref.2 Q9NZC2 UniProtKB Alternative sequence 162 230 . . . ID=VSP_010793;Note=In isoform 3. SLLEGEIPFPPTSILLLLACIFLIKILAASALWAAAWHGQKPGTHPPSELDCGHDPGYQLQTLPGLRDT->PSQGSHLPSCLSKEPLGRRNPLPTHFHPSPPGLHLSHQDSSSQRPLGCSLAWTEARDTSTQ;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:15489334;Dbxref=PMID:15489334 Q9NZC2 UniProtKB Natural variant 14 230 . . . ID=VAR_081676;Note=In PLOSL2%3B results in decreased osteoclast differentiation%3B no TREM2 transcripts can be detected in patient cells homozygous for the variant. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12925681;Dbxref=PMID:12925681 Q9NZC2 UniProtKB Natural variant 27 27 . . . ID=VAR_081812;Note=Found in patients with late onset Alzheimer disease%3B uncertain significance%3B no effect on cell membrane localization. V->M;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=dbSNP:rs768745050,PMID:27589997 Q9NZC2 UniProtKB Natural variant 28 28 . . . ID=VAR_081813;Note=Found in patients with late onset Alzheimer disease%3B uncertain significance%3B increases cell membrane localization. A->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=dbSNP:rs2234252,PMID:27589997 Q9NZC2 UniProtKB Natural variant 31 31 . . . ID=VAR_081814;Note=Found in patients with late onset Alzheimer disease%3B uncertain significance%3B decreases cell membrane localization. S->F;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=dbSNP:rs746216516,PMID:27589997 Q9NZC2 UniProtKB Natural variant 33 230 . . . ID=VAR_081677;Note=In PLOSL2%3B no protein detected by Wester blot. Missing;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:12754369,ECO:0000269|PubMed:15883308,ECO:0000269|PubMed:23399524,ECO:0000269|PubMed:25615530,ECO:0000269|PubMed:29142083;Dbxref=PMID:12754369,PMID:15883308,PMID:23399524,PMID:25615530,PMID:29142083 Q9NZC2 UniProtKB Natural variant 38 38 . . . ID=VAR_081815;Note=Results in defective protein maturation and trafficking%3B loss of proteolytic cleavage by ADAM10 and ectodomain shedding%3B increases protein aggregation%3B decreases cell membrane localization%3B decreased phagocytosis%3B loss of LDL%2C CLU and APOE binding%3B greatly decreases LDL and CLU uptake into cells. Y->C;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:24990881,ECO:0000269|PubMed:25615530,ECO:0000269|PubMed:27477018,ECO:0000269|PubMed:27589997,ECO:0000269|PubMed:27995897,ECO:0000269|PubMed:28768830;Dbxref=dbSNP:rs797044603,PMID:24990881,PMID:25615530,PMID:27477018,PMID:27589997,PMID:27995897,PMID:28768830 Q9NZC2 UniProtKB Natural variant 44 230 . . . ID=VAR_081678;Note=In PLOSL2. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12080485;Dbxref=PMID:12080485 Q9NZC2 UniProtKB Natural variant 47 47 . . . ID=VAR_081816;Note=Found in patients with late onset Alzheimer disease%3B uncertain significance%3B decreases cell membrane localization. R->C;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=dbSNP:rs753325601,PMID:27589997 Q9NZC2 UniProtKB Natural variant 47 47 . . . ID=VAR_081817;Note=Found in patients with late onset Alzheimer disease%3B uncertain significance%3B no effect on cell membrane localization%3B no effect on autophagy in microglia%3B no effect on phagocystosis%2C including amyloid plaque clearance by microglia%3B reduces ectodomain shedding caused by proteolytic cleavage by ADAM10%2C while also reducing the oligomerization of the extracellular domain after shedding%3B decreases binding to and uptake of LDL and CLU into cells%3B decreases binding to APOE%2C phospholipids and oligomeric APP cleavage product beta-amyloid peptide 42. R->H;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:24990881,ECO:0000269|PubMed:25615530,ECO:0000269|PubMed:27477018,ECO:0000269|PubMed:27589997,ECO:0000269|PubMed:27995897,ECO:0000269|PubMed:28802038,ECO:0000269|PubMed:29518356,ECO:0000269|PubMed:29794134,ECO:0000269|PubMed:30442540;Dbxref=dbSNP:rs75932628,PMID:24990881,PMID:25615530,PMID:27477018,PMID:27589997,PMID:27995897,PMID:28802038,PMID:29518356,PMID:29794134,PMID:30442540 Q9NZC2 UniProtKB Natural variant 62 62 . . . ID=VAR_081818;Note=Does not affect protein structure%3B no effect on cell membrane localization%3B increases autophagy in microglia%3B decreases LDL%2C CLU and APOE binding%3B decreases LDL uptake into cells%3B no effect on CLU uptake into cells%3B decreases the uptake of APP-LDL complex in macrophages%3B decreases binding to oligomeric APP cleavage product beta-amyloid peptide 42. R->H;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:27477018,ECO:0000269|PubMed:27995897,ECO:0000269|PubMed:28802038,ECO:0000269|PubMed:29518356;Dbxref=dbSNP:rs143332484,PMID:27477018,PMID:27995897,PMID:28802038,PMID:29518356 Q9NZC2 UniProtKB Natural variant 66 66 . . . ID=VAR_081819;Note=Results in defective protein maturation and trafficking%3B loss of proteolytic cleavage by ADAM10 and ectodomain shedding%3B increases protein aggregation%3B decreases cell membrane localization%3B decreases phagocytosis%3B loss of LDL%2C CLU and APOE binding%3B greatly decreases LDL and CLU uptake into cells. T->M;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:24990881,ECO:0000269|PubMed:25615530,ECO:0000269|PubMed:27477018,ECO:0000269|PubMed:27995897,ECO:0000269|PubMed:28768830;Dbxref=dbSNP:rs201258663,PMID:24990881,PMID:25615530,PMID:27477018,PMID:27995897,PMID:28768830 Q9NZC2 UniProtKB Natural variant 78 230 . . . ID=VAR_081679;Note=In PLOSL2. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12080485;Dbxref=PMID:12080485 Q9NZC2 UniProtKB Natural variant 87 87 . . . ID=VAR_081820;Note=Decreases LDL%2C CLU and APOE binding%3B decreases LDL and CLU uptake into cells%3B no effect on cell membrane localization. D->N;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:27477018,ECO:0000269|PubMed:27589997,ECO:0000269|PubMed:27995897;Dbxref=dbSNP:rs142232675,PMID:27477018,PMID:27589997,PMID:27995897 Q9NZC2 UniProtKB Natural variant 96 96 . . . ID=VAR_061329;Note=Does not change protein structure%3B changes protein stability%3B increases binding to THP-1 cells. T->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27995897;Dbxref=dbSNP:rs2234253,PMID:27995897 Q9NZC2 UniProtKB Natural variant 96 96 . . . ID=VAR_061330;Note=T->R;Dbxref=dbSNP:rs2234253 Q9NZC2 UniProtKB Natural variant 126 126 . . . ID=VAR_081680;Note=In PLOSL2%3B results in defective protein maturation%3B increases protein aggregation%3B decreases cell membrane localization. V->G;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15883308,ECO:0000269|PubMed:27995897,ECO:0000269|PubMed:28768830;Dbxref=dbSNP:rs121908402,PMID:15883308,PMID:27995897,PMID:28768830 Q9NZC2 UniProtKB Natural variant 130 130 . . . ID=VAR_081821;Note=No effect on protein expression and maturation. A->S;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=PMID:27589997 Q9NZC2 UniProtKB Natural variant 134 134 . . . ID=VAR_019334;Note=In PLOSL2%3B uncertain significance%3B decreased protein level. D->G;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:12080485,ECO:0000269|PubMed:28768830;Dbxref=dbSNP:rs28939079,PMID:12080485,PMID:28768830 Q9NZC2 UniProtKB Natural variant 136 136 . . . ID=VAR_081822;Note=Found in patients with Alzheimer disease%3B uncertain significance%3B slightly decreases cell membrane localization. R->Q;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=dbSNP:rs149622783,PMID:27589997 Q9NZC2 UniProtKB Natural variant 136 136 . . . ID=VAR_081823;Note=Found in patients with Alzheimer disease%3B uncertain significance%3B decreases cell membrane localization. R->W;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=dbSNP:rs772641807,PMID:27589997 Q9NZC2 UniProtKB Natural variant 151 151 . . . ID=VAR_081824;Note=Found in patients with late onset Alzheimer disease%3B uncertain significance%3B decreases cell membrane localization. E->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=dbSNP:rs79011726,PMID:27589997 Q9NZC2 UniProtKB Natural variant 157 157 . . . ID=VAR_033625;Note=Probable risk factor for late-onset Alzheimer disease%3B accelerates ectodomain shedding but does not alter the cleavage site%3B decreases cell membrane localization%3B decreases phagocytosis. H->Y;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:27067662,ECO:0000269|PubMed:28855300,ECO:0000269|PubMed:28855301;Dbxref=dbSNP:rs2234255,PMID:27067662,PMID:28855300,PMID:28855301 Q9NZC2 UniProtKB Natural variant 162 162 . . . ID=VAR_081825;Note=No effect on protein expression and maturation. S->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=dbSNP:rs371702633,PMID:27589997 Q9NZC2 UniProtKB Natural variant 186 186 . . . ID=VAR_019335;Note=In PLOSL2%3B uncertain significance%3B increased localization at the cell membrane. K->N;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:12080485,ECO:0000269|PubMed:28768830;Dbxref=dbSNP:rs28937876,PMID:12080485,PMID:28768830 Q9NZC2 UniProtKB Natural variant 192 192 . . . ID=VAR_077696;Note=A->T;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27067662;Dbxref=dbSNP:rs150277350,PMID:27067662 Q9NZC2 UniProtKB Natural variant 211 211 . . . ID=VAR_033626;Note=L->P;Dbxref=dbSNP:rs2234256 Q9NZC2 UniProtKB Natural variant 223 223 . . . ID=VAR_081826;Note=Affects protein maturation. T->I;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27589997;Dbxref=dbSNP:rs138355759,PMID:27589997 Q9NZC2 UniProtKB Mutagenesis 20 20 . . . Note=Loss of glycosylation. N->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29794134;Dbxref=PMID:29794134 Q9NZC2 UniProtKB Mutagenesis 36 36 . . . Note=Loss of proteolytic cleavage by ADAM10 and ectodomain shedding. Decreases protein maturation and cell membrane localization. C->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24990881;Dbxref=PMID:24990881 Q9NZC2 UniProtKB Mutagenesis 48 48 . . . Note=Loss of LDL%2C CLU and APOE binding. K->M;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27477018;Dbxref=PMID:27477018 Q9NZC2 UniProtKB Mutagenesis 60 60 . . . Note=Loss of proteolytic cleavage by ADAM10 and ectodomain shedding. Decreases protein maturation and cell membrane localization. C->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24990881;Dbxref=PMID:24990881 Q9NZC2 UniProtKB Mutagenesis 68 68 . . . Note=No effect on cell membrane localization. N->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27995897;Dbxref=PMID:27995897 Q9NZC2 UniProtKB Mutagenesis 76 76 . . . Note=Decreases binding to THP-1 cells. R->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27995897;Dbxref=PMID:27995897 Q9NZC2 UniProtKB Mutagenesis 77 77 . . . Note=Decreases binding to THP-1 cells. R->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27995897;Dbxref=PMID:27995897 Q9NZC2 UniProtKB Beta strand 19 27 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Beta strand 32 37 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Turn 40 45 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Beta strand 48 53 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Turn 55 57 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Beta strand 60 65 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Helix 70 72 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6B8O Q9NZC2 UniProtKB Beta strand 74 77 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Beta strand 80 87 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Turn 88 91 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Beta strand 92 99 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Helix 102 104 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Beta strand 106 114 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Beta strand 117 129 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Helix 132 135 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6XDS Q9NZC2 UniProtKB Helix 163 165 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6Z0G Q9NZC2 UniProtKB Helix 172 189 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6Z0G Q9NZC2 UniProtKB Helix 191 198 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6Z0G Q9NZC2 UniProtKB Natural variant 183 183 . . . ID=VAR_082839;Note=S->C;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27067662;Dbxref=dbSNP:rs200820365,PMID:27067662 Q9NZC2 UniProtKB Natural variant 200 200 . . . ID=VAR_082840;Note=W->C;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:27067662;Dbxref=dbSNP:rs1391283629,PMID:27067662