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
