ID LRC19_MOUSE Reviewed; 364 AA.
AC Q8BZT5; B1AWG3; Q6P8J1;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 24-JAN-2024, entry version 147.
DE RecName: Full=Leucine-rich repeat-containing protein 19 {ECO:0000305};
DE Flags: Precursor;
GN Name=Lrrc19 {ECO:0000312|MGI:MGI:2140219};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [4]
RP FUNCTION, TISSUE SPECIFICITY, AND ACTIVITY REGULATION.
RX PubMed=19679103; DOI=10.1016/j.bbrc.2009.08.043;
RA Chai L., Dai L., Che Y., Xu J., Liu G., Zhang Z., Yang R.;
RT "LRRC19, a novel member of the leucine-rich repeat protein family,
RT activates NF-kappaB and induces expression of proinflammatory cytokines.";
RL Biochem. Biophys. Res. Commun. 388:543-548(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=25026888; DOI=10.1038/ncomms5434;
RA Su X., Min S., Cao S., Yan H., Zhao Y., Li H., Chai L., Mei S., Yang J.,
RA Zhang Y., Zhang Z., Liu F., Sun W., Che Y., Yang R.;
RT "LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent
RT infection by uropathogenic bacteria.";
RL Nat. Commun. 5:4434-4434(2014).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=26776522; DOI=10.1016/j.celrep.2015.12.070;
RA Cao S., Su X., Zeng B., Yan H., Huang Y., Wang E., Yun H., Zhang Y.,
RA Liu F., Li W., Wei H., Che Y., Yang R.;
RT "The Gut Epithelial Receptor LRRC19 Promotes the Recruitment of Immune
RT Cells and Gut Inflammation.";
RL Cell Rep. 14:695-707(2016).
CC -!- FUNCTION: Pathogen-recognition receptor which mediates the activation
CC of TRAF2- and TRAF6 NF-kappa-B signaling pathways and induces the
CC expression of pro-inflammatory cytokines (PubMed:26776522,
CC PubMed:19679103, PubMed:25026888). In kidney, prevents infection by
CC uropathogenic bacteria by inducing the production of cytokines,
CC chemokines and antimicrobial substances (PubMed:25026888). In gut,
CC involved in host-microbiota interactions, plays a critical role in
CC promoting the recruitment of immune cells and intestinal inflammation
CC (PubMed:26776522). {ECO:0000269|PubMed:19679103,
CC ECO:0000269|PubMed:25026888, ECO:0000269|PubMed:26776522}.
CC -!- ACTIVITY REGULATION: Activated by TLR ligands such as LPS, bacterial
CC DNA and peptidoglycan. {ECO:0000269|PubMed:19679103}.
CC -!- SUBUNIT: Interacts with TRAF2 and TRAF6.
CC {ECO:0000250|UniProtKB:Q9H756}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in kidney, also expressed in
CC spleen, intestine and colon (PubMed:26776522, PubMed:19679103). Highly
CC expressed in epithelial cells (PubMed:26776522). In kidney, mainly
CC expressed in renal collecting duct epithelial cells (PubMed:25026888).
CC {ECO:0000269|PubMed:19679103, ECO:0000269|PubMed:25026888,
CC ECO:0000269|PubMed:26776522}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice display increased longevity
CC compared with the cohoused wild-type littermates. Almost all mutant
CC mice remain alive, whereas most of the wild-type mice (>80%) di after 2
CC years on standard chow. Mutant body weights are lower than those of
CC wild-type. Gut tissues of wild-type mice show slight inflammation
CC whereas mutant mouse gut tissues do not. The gut tissues of mutant mice
CC are more yellow and the colon tissues are thinner in mutant mice than
CC in WT mice and the ceca are enlarged significantly (PubMed:26776522).
CC They show lower expression of cytokines such as TNF, ILB, IL6, IFNG,
CC IL17 and IL12 in the gut tissues (PubMed:26776522). Mice are resistant
CC to dextran sodium sulfate (DSS)-induced colitis and colon cancer
CC (PubMed:26776522). They have fewer and smaller gut tissue-associated
CC lymph node Peyer plaques compared with cohoused wild-type mice with
CC fewer adaptive immune cells that have accumulated in their gut immune
CC systems (PubMed:26776522). Mutants show reduced expression of several
CC chemokines, including CCL6, CCL9, CXCL9, and CXCL10 (PubMed:26776522).
CC They also show an altered gut microbiota and reduced expression of REGs
CC (PubMed:26776522). Mutants are more susceptible to uropathogenic
CC Escherichia coli infections (PubMed:25026888).
CC {ECO:0000269|PubMed:25026888, ECO:0000269|PubMed:26776522}.
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DR EMBL; AK033594; BAC28378.1; -; mRNA.
DR EMBL; AL732597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC061228; AAH61228.1; -; mRNA.
DR CCDS; CCDS18360.1; -.
DR RefSeq; NP_780514.1; NM_175305.4.
DR RefSeq; XP_006502677.1; XM_006502614.3.
DR AlphaFoldDB; Q8BZT5; -.
DR SMR; Q8BZT5; -.
DR STRING; 10090.ENSMUSP00000102718; -.
DR GlyCosmos; Q8BZT5; 11 sites, No reported glycans.
DR GlyGen; Q8BZT5; 11 sites.
DR PhosphoSitePlus; Q8BZT5; -.
DR jPOST; Q8BZT5; -.
DR MaxQB; Q8BZT5; -.
DR PaxDb; 10090-ENSMUSP00000102718; -.
DR ProteomicsDB; 252667; -.
DR Antibodypedia; 2688; 161 antibodies from 24 providers.
DR Ensembl; ENSMUST00000053419.9; ENSMUSP00000056094.3; ENSMUSG00000049799.14.
DR Ensembl; ENSMUST00000107101.2; ENSMUSP00000102718.2; ENSMUSG00000049799.14.
DR GeneID; 100061; -.
DR KEGG; mmu:100061; -.
DR UCSC; uc008tsh.1; mouse.
DR AGR; MGI:2140219; -.
DR CTD; 64922; -.
DR MGI; MGI:2140219; Lrrc19.
DR VEuPathDB; HostDB:ENSMUSG00000049799; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000161278; -.
DR HOGENOM; CLU_063696_1_0_1; -.
DR InParanoid; Q8BZT5; -.
DR OMA; EVKCNFT; -.
DR OrthoDB; 5353250at2759; -.
DR PhylomeDB; Q8BZT5; -.
DR TreeFam; TF335466; -.
DR BioGRID-ORCS; 100061; 4 hits in 76 CRISPR screens.
DR PRO; PR:Q8BZT5; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8BZT5; Protein.
DR Bgee; ENSMUSG00000049799; Expressed in right kidney and 152 other cell types or tissues.
DR Genevisible; Q8BZT5; MM.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IDA:MGI.
DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; IMP:UniProtKB.
DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IDA:MGI.
DR GO; GO:0001817; P:regulation of cytokine production; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; IDA:MGI.
DR GO; GO:0038008; P:TRAF-mediated signal transduction; IMP:UniProtKB.
DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 2.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR PANTHER; PTHR31450:SF4; LEUCINE-RICH REPEAT-CONTAINING PROTEIN 19; 1.
DR PANTHER; PTHR31450; LEUCINE-RICH REPEAT-CONTAINING PROTEIN 19 LRRC19 FAMILY MEMBER; 1.
DR Pfam; PF15176; LRR19-TM; 1.
DR Pfam; PF13855; LRR_8; 1.
DR SMART; SM00369; LRR_TYP; 4.
DR SMART; SM00082; LRRCT; 1.
DR SUPFAM; SSF52058; L domain-like; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Leucine-rich repeat; Membrane; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..364
FT /note="Leucine-rich repeat-containing protein 19"
FT /id="PRO_0000021611"
FT TOPO_DOM 21..264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..364
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 44..69
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 70..93
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 94..117
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 118..141
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 143..163
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 164..190
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT DOMAIN 174..225
FT /note="LRRCT"
FT /evidence="ECO:0000255"
FT CARBOHYD 30
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 44
FT /note="S -> G (in Ref. 3; AAH61228)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="I -> T (in Ref. 3; AAH61228)"
FT /evidence="ECO:0000305"
FT CONFLICT 357
FT /note="I -> V (in Ref. 3; AAH61228)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 364 AA; 41573 MW; EFD5E3B188735C1A CRC64;
MKVTRFMFWL FSMLLPSVKS QASETEVPCN FSRRNYTLIP EGISTNVTIL DLSYNRITLN
AADSRVLQMY SLLTELYLME NNIIALYNSS FRNLLNLEIL NICGNSISVI QQGSFVGLNE
LKQLFLCQNK ILQLNPDTFV PLNNLKVLNL QGNLIRLFDA PQLPHLEILT LDGNPWNCTC
GLLELHNWLN TSNVTLENEN MTMCSYPDEL KHDSIKSAPF TTECHSTFIS TITEDFQSTR
NSSFNSSSHN LTWTSEHEPL GKSWAFLVGV VATVLLTSLL IFIAIKCPVW YNILLSYNHH
RLEEHEAETY ENGLTRNPSS LSQITDTNSE DTTVIFEQLH AFVVDDDGFI EDRYIDINEV
HEEK
//
