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TRIL_HUMAN
ID   TRIL_HUMAN              Reviewed;         811 AA.
AC   Q7L0X0; A4D1A6; O75139;
DT   02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 2.
DT   03-AUG-2022, entry version 137.
DE   RecName: Full=TLR4 interactor with leucine rich repeats;
DE   AltName: Full=Leucine-rich repeat-containing protein KIAA0644;
DE   Flags: Precursor;
GN   Name=TRIL; Synonyms=KIAA0644;
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 [LARGE SCALE MRNA], AND VARIANT SER-240.
RC   TISSUE=Brain;
RX   PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA   Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA   Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. X. The
RT   complete sequences of 100 new cDNA clones from brain which can code for
RT   large proteins in vitro.";
RL   DNA Res. 5:169-176(1998).
RN   [2]
RP   SEQUENCE REVISION.
RA   Ohara O., Suyama M., Nagase T., Ishikawa K.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-240.
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-240.
RC   TISSUE=Brain;
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   [7]
RP   FUNCTION, TISSUE SPECIFICITY, INDUCTION BY LPS IN COMPLEX WITH TLR4,
RP   INTERACTION WITH LPS, AND GLYCOSYLATION.
RX   PubMed=19710467; DOI=10.4049/jimmunol.0901518;
RA   Carpenter S., Carlson T., Dellacasagrande J., Garcia A., Gibbons S.,
RA   Hertzog P., Lyons A., Lin L.L., Lynch M., Monie T., Murphy C., Seidl K.J.,
RA   Wells C., Dunne A., O'Neill L.A.;
RT   "TRIL, a functional component of the TLR4 signaling complex, highly
RT   expressed in brain.";
RL   J. Immunol. 183:3989-3995(2009).
RN   [8]
RP   VARIANT ARG-666.
RX   PubMed=26477546; DOI=10.1016/j.ajhg.2015.09.009;
RG   Care4Rare Canada Consortium;
RA   Srour M., Hamdan F.F., McKnight D., Davis E., Mandel H.,
RA   Schwartzentruber J., Martin B., Patry L., Nassif C., Dionne-Laporte A.,
RA   Ospina L.H., Lemyre E., Massicotte C., Laframboise R., Maranda B.,
RA   Labuda D., Decarie J.C., Rypens F., Goldsher D., Fallet-Bianco C.,
RA   Soucy J.F., Laberge A.M., Maftei C., Boycott K., Brais B., Boucher R.M.,
RA   Rouleau G.A., Katsanis N., Majewski J., Elpeleg O., Kukolich M.K.,
RA   Shalev S., Michaud J.L.;
RT   "Joubert Syndrome in French Canadians and Identification of Mutations in
RT   CEP104.";
RL   Am. J. Hum. Genet. 97:744-753(2015).
CC   -!- FUNCTION: Component of the TLR4 signaling complex. Mediates the innate
CC       immune response to bacterial lipopolysaccharide (LPS) leading to
CC       cytokine secretion. {ECO:0000269|PubMed:19710467}.
CC   -!- SUBUNIT: Belongs to the lipopolysaccharide (LPS) receptor, a multi-
CC       protein complex containing at least CD14, MD-2 and TLR4. Interacts with
CC       TLR4; this interaction is greatly enhanced by LPS stimulation.
CC       Interacts with LPS. {ECO:0000269|PubMed:19710467}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in the brain, ovary, small
CC       intestine and spleen. {ECO:0000269|PubMed:19710467}.
CC   -!- INDUCTION: By bacterial lipopolysaccharides (LPS).
CC       {ECO:0000269|PubMed:19710467}.
CC   -!- PTM: N-glycolysaled.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA31619.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=EAL24209.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AB014544; BAA31619.2; ALT_INIT; mRNA.
DR   EMBL; AC005013; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH236948; EAL24208.1; -; Genomic_DNA.
DR   EMBL; CH236948; EAL24209.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; CH471073; EAW93913.1; -; Genomic_DNA.
DR   EMBL; BC036337; AAH36337.1; -; mRNA.
DR   CCDS; CCDS75573.1; -.
DR   RefSeq; NP_055632.2; NM_014817.3.
DR   AlphaFoldDB; Q7L0X0; -.
DR   SMR; Q7L0X0; -.
DR   BioGRID; 115198; 1.
DR   IntAct; Q7L0X0; 1.
DR   STRING; 9606.ENSP00000479256; -.
DR   GlyGen; Q7L0X0; 8 sites, 2 O-linked glycans (5 sites).
DR   iPTMnet; Q7L0X0; -.
DR   PhosphoSitePlus; Q7L0X0; -.
DR   BioMuta; TRIL; -.
DR   DMDM; 311033514; -.
DR   jPOST; Q7L0X0; -.
DR   MassIVE; Q7L0X0; -.
DR   PeptideAtlas; Q7L0X0; -.
DR   PRIDE; Q7L0X0; -.
DR   ProteomicsDB; 68737; -.
DR   Antibodypedia; 73340; 20 antibodies from 9 providers.
DR   DNASU; 9865; -.
DR   Ensembl; ENST00000539664.3; ENSP00000479256.1; ENSG00000255690.3.
DR   GeneID; 9865; -.
DR   KEGG; hsa:9865; -.
DR   MANE-Select; ENST00000539664.3; ENSP00000479256.1; NM_014817.4; NP_055632.2.
DR   UCSC; uc032zip.2; human.
DR   CTD; 9865; -.
DR   GeneCards; TRIL; -.
DR   HGNC; HGNC:22200; TRIL.
DR   HPA; ENSG00000255690; Tissue enriched (brain).
DR   MIM; 613356; gene.
DR   neXtProt; NX_Q7L0X0; -.
DR   OpenTargets; ENSG00000255690; -.
DR   VEuPathDB; HostDB:ENSG00000255690; -.
DR   eggNOG; KOG0619; Eukaryota.
DR   GeneTree; ENSGT00940000161975; -.
DR   HOGENOM; CLU_357128_0_0_1; -.
DR   InParanoid; Q7L0X0; -.
DR   OMA; PHDVLTY; -.
DR   OrthoDB; 826997at2759; -.
DR   PhylomeDB; Q7L0X0; -.
DR   PathwayCommons; Q7L0X0; -.
DR   SignaLink; Q7L0X0; -.
DR   BioGRID-ORCS; 9865; 7 hits in 201 CRISPR screens.
DR   ChiTaRS; TRIL; human.
DR   GeneWiki; KIAA0644; -.
DR   GenomeRNAi; 9865; -.
DR   Pharos; Q7L0X0; Tbio.
DR   PRO; PR:Q7L0X0; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q7L0X0; protein.
DR   Bgee; ENSG00000255690; Expressed in medial globus pallidus and 160 other tissues.
DR   Genevisible; Q7L0X0; HS.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0046696; C:lipopolysaccharide receptor complex; IDA:UniProtKB.
DR   GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0002718; P:regulation of cytokine production involved in immune response; IDA:UniProtKB.
DR   GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR   CDD; cd00063; FN3; 1.
DR   Gene3D; 3.80.10.10; -; 2.
DR   InterPro; IPR000483; Cys-rich_flank_reg_C.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   Pfam; PF13855; LRR_8; 4.
DR   Pfam; PF01463; LRRCT; 1.
DR   SMART; SM00369; LRR_TYP; 11.
DR   SMART; SM00082; LRRCT; 1.
DR   PROSITE; PS51450; LRR; 13.
PE   1: Evidence at protein level;
KW   Glycoprotein; Immunity; Inflammatory response; Innate immunity;
KW   Leucine-rich repeat; Membrane; Phosphoprotein; Reference proteome; Repeat;
KW   Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..811
FT                   /note="TLR4 interactor with leucine rich repeats"
FT                   /id="PRO_0000349255"
FT   TOPO_DOM        26..696
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        697..717
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        718..811
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          26..57
FT                   /note="LRRNT"
FT   REPEAT          61..81
FT                   /note="LRR 1"
FT   REPEAT          84..105
FT                   /note="LRR 2"
FT   REPEAT          108..129
FT                   /note="LRR 3"
FT   REPEAT          132..153
FT                   /note="LRR 4"
FT   REPEAT          156..177
FT                   /note="LRR 5"
FT   REPEAT          180..201
FT                   /note="LRR 6"
FT   REPEAT          204..223
FT                   /note="LRR 7"
FT   REPEAT          230..251
FT                   /note="LRR 8"
FT   REPEAT          254..275
FT                   /note="LRR 9"
FT   REPEAT          278..299
FT                   /note="LRR 10"
FT   REPEAT          302..323
FT                   /note="LRR 11"
FT   REPEAT          326..347
FT                   /note="LRR 12"
FT   DOMAIN          359..416
FT                   /note="LRRCT"
FT   REGION          484..549
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         798
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q496Z2"
FT   CARBOHYD        73
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        209
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        589
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         240
FT                   /note="N -> S (in dbSNP:rs740250)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:9734811, ECO:0000269|Ref.5"
FT                   /id="VAR_046307"
FT   VARIANT         347
FT                   /note="A -> T (in dbSNP:rs3735561)"
FT                   /id="VAR_046308"
FT   VARIANT         369
FT                   /note="G -> D (in dbSNP:rs3735562)"
FT                   /id="VAR_046309"
FT   VARIANT         666
FT                   /note="G -> R"
FT                   /evidence="ECO:0000269|PubMed:26477546"
FT                   /id="VAR_075695"
SQ   SEQUENCE   811 AA;  88723 MW;  5272376356F1A686 CRC64;
     MEAARALRLL LVVCGCLALP PLAEPVCPER CDCQHPQHLL CTNRGLRVVP KTSSLPSPHD
     VLTYSLGGNF ITNITAFDFH RLGQLRRLDL QYNQIRSLHP KTFEKLSRLE ELYLGNNLLQ
     ALAPGTLAPL RKLRILYANG NEISRLSRGS FEGLESLVKL RLDGNALGAL PDAVFAPLGN
     LLYLHLESNR IRFLGKNAFA QLGKLRFLNL SANELQPSLR HAATFAPLRS LSSLILSANN
     LQHLGPRIFQ HLPRLGLLSL RGNQLTHLAP EAFWGLEALR ELRLEGNRLS QLPTALLEPL
     HSLEALDLSG NELSALHPAT FGHLGRLREL SLRNNALSAL SGDIFAASPA LYRLDLDGNG
     WTCDCRLRGL KRWMGDWHSQ GRLLTVFVQC RHPPALRGKY LDYLDDQQLQ NGSCADPSPS
     ASLTADRRRQ PLPTAAGEEM TPPAGLAEEL PPQPQLQQQG RFLAGVAWDG AARELVGNRS
     ALRLSRRGPG LQQPSPSVAA AAGPAPQSLD LHKKPQRGRP TRADPALAEP TPTASPGSAP
     SPAGDPWQRA TKHRLGTEHQ ERAAQSDGGA GLPPLVSDPC DFNKFILCNL TVEAVGADSA
     SVRWAVREHR SPRPLGGARF RLLFDRFGQQ PKFHRFVYLP ESSDSATLRE LRGDTPYLVC
     VEGVLGGRVC PVAPRDHCAG LVTLPEAGSR GGVDYQLLTL ALLTVNALLV LLALAAWASR
     WLRRKLRARR KGGAPVHVRH MYSTRRPLRS MGTGVSADFS GFQSHRPRTT VCALSEADLI
     EFPCDRFMDS AGGGAGGSLR REDRLLQRFA D
 
 
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