ILDR1_MOUSE
ID ILDR1_MOUSE Reviewed; 537 AA.
AC Q8CBR1; Q6PFB3; Q8CB39; Q91VS0;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Immunoglobulin-like domain-containing receptor 1 {ECO:0000305};
DE AltName: Full=Angulin-2 {ECO:0000303|PubMed:23239027, ECO:0000303|PubMed:28785060};
DE Flags: Precursor;
GN Name=Ildr1 {ECO:0000312|MGI:MGI:2146574};
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Urinary bladder, and Vagina;
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 MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=FVB/N; TISSUE=Mammary gland, and Salivary gland;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-490 AND SER-492, AND
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 [4]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=21255762; DOI=10.1016/j.ajhg.2010.12.011;
RA Borck G., Ur Rehman A., Lee K., Pogoda H.M., Kakar N., von Ameln S.,
RA Grillet N., Hildebrand M.S., Ahmed Z.M., Nurnberg G., Ansar M., Basit S.,
RA Javed Q., Morell R.J., Nasreen N., Shearer A.E., Ahmad A., Kahrizi K.,
RA Shaikh R.S., Ali R.A., Khan S.N., Goebel I., Meyer N.C., Kimberling W.J.,
RA Webster J.A., Stephan D.A., Schiller M.R., Bahlo M., Najmabadi H.,
RA Gillespie P.G., Nurnberg P., Wollnik B., Riazuddin S., Smith R.J.,
RA Ahmad W., Muller U., Hammerschmidt M., Friedman T.B., Riazuddin S.,
RA Leal S.M., Ahmad J., Kubisch C.;
RT "Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing
RT impairment DFNB42.";
RL Am. J. Hum. Genet. 88:127-137(2011).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=23863714; DOI=10.1172/jci68587;
RA Chandra R., Wang Y., Shahid R.A., Vigna S.R., Freedman N.J., Liddle R.A.;
RT "Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated
RT cholecystokinin secretion.";
RL J. Clin. Invest. 123:3343-3352(2013).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP MARVELD2 AND OCLN.
RX PubMed=23239027; DOI=10.1242/jcs.116442;
RA Higashi T., Tokuda S., Kitajiri S., Masuda S., Nakamura H., Oda Y.,
RA Furuse M.;
RT "Analysis of the 'angulin' proteins LSR, ILDR1 and ILDR2--tricellulin
RT recruitment, epithelial barrier function and implication in deafness
RT pathogenesis.";
RL J. Cell Sci. 126:966-977(2013).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=25217574; DOI=10.1093/hmg/ddu474;
RA Morozko E.L., Nishio A., Ingham N.J., Chandra R., Fitzgerald T.,
RA Martelletti E., Borck G., Wilson E., Riordan G.P., Wangemann P., Forge A.,
RA Steel K.P., Liddle R.A., Friedman T.B., Belyantseva I.A.;
RT "ILDR1 null mice, a model of human deafness DFNB42, show structural
RT aberrations of tricellular tight junctions and degeneration of auditory
RT hair cells.";
RL Hum. Mol. Genet. 24:609-624(2015).
RN [8]
RP FUNCTION, INTERACTION WITH TRA2A; TRA2B AND SRSF1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=28785060; DOI=10.1038/s41598-017-07530-z;
RA Liu Y., Nie H., Liu C., Zhai X., Sang Q., Wang Y., Shi D., Wang L., Xu Z.;
RT "Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing
RT through binding to splicing factors TRA2A, TRA2B, or SRSF1.";
RL Sci. Rep. 7:7466-7466(2017).
CC -!- FUNCTION: Maintains epithelial barrier function by recruiting
CC MARVELD2/tricellulin to tricellular tight junctions (tTJs)
CC (PubMed:23239027). Crucial for normal hearing by maintaining the
CC structural and functional integrity of tTJs, which are critical for the
CC survival of auditory neurosensory HCs (PubMed:25217574). Mediates fatty
CC acids and lipoproteins-stimulated CCK/cholecystokinin secretion in the
CC small intestine (PubMed:23863714). In the inner ear, may regulate
CC alternative pre-mRNA splicing via binding to TRA2A, TRA2B and SRSF1
CC (PubMed:28785060). {ECO:0000269|PubMed:23239027,
CC ECO:0000269|PubMed:23863714, ECO:0000269|PubMed:25217574,
CC ECO:0000269|PubMed:28785060}.
CC -!- SUBUNIT: Homooligomer (By similarity). Interacts with MARVELD2 and
CC OCLN; the interaction is required to recruit MARVELD2 to tricellular
CC contacts (PubMed:23239027). Interacts (via C-terminus) with TRA2A,
CC TRA2B and SRSF1 (PubMed:28785060). {ECO:0000250|UniProtKB:Q86SU0,
CC ECO:0000269|PubMed:23239027, ECO:0000269|PubMed:28785060}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23239027,
CC ECO:0000269|PubMed:25217574}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell junction, tight junction
CC {ECO:0000269|PubMed:23239027, ECO:0000269|PubMed:25217574}. Nucleus
CC {ECO:0000269|PubMed:28785060}. Note=Localizes to tricellular tight
CC junctions (tTJs) between epithelial cells.
CC {ECO:0000269|PubMed:23239027, ECO:0000269|PubMed:25217574}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha {ECO:0000303|PubMed:28785060};
CC IsoId=Q8CBR1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CBR1-2; Sequence=VSP_019689, VSP_019690;
CC Name=3;
CC IsoId=Q8CBR1-3; Sequence=VSP_019688;
CC -!- TISSUE SPECIFICITY: Expressed in the vestibule and in hair cells and
CC supporting cells of the cochlea. Expressed in epithelial tissues.
CC Highly expressed in colon but also detected in small intestine, bladder
CC and lung (PubMed:23239027). In colon, expressed in the upper portion of
CC the crypts (at protein level) (PubMed:23239027). Expressed in CCK
CC secretory cells of the proximal small intestine (at protein level)
CC (PubMed:23863714). Expressed in the organ of Corti, stria vascularis,
CC utricle and saccule of the inner ear (PubMed:23239027,
CC PubMed:25217574). {ECO:0000269|PubMed:21255762,
CC ECO:0000269|PubMed:23239027, ECO:0000269|PubMed:23863714,
CC ECO:0000269|PubMed:25217574}.
CC -!- DEVELOPMENTAL STAGE: Expressed early in development.
CC {ECO:0000269|PubMed:21255762}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice have early-onset severe deafness
CC associated with a rapid degeneration of cochlear hair cells but have a
CC normal endocochlear potential (PubMed:25217574). Mutants show no
CC increase in plasma CCK levels after orogastric gavage with fatty acids
CC (PubMed:23863714). {ECO:0000269|PubMed:23863714,
CC ECO:0000269|PubMed:25217574}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. LISCH7 family.
CC {ECO:0000305}.
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DR EMBL; AK035504; BAC29081.1; -; mRNA.
DR EMBL; AK036844; BAC29604.1; -; mRNA.
DR EMBL; BC010485; AAH10485.1; -; mRNA.
DR EMBL; BC057644; AAH57644.1; -; mRNA.
DR CCDS; CCDS49841.1; -. [Q8CBR1-2]
DR CCDS; CCDS70718.1; -. [Q8CBR1-1]
DR CCDS; CCDS70719.1; -. [Q8CBR1-3]
DR RefSeq; NP_001272717.1; NM_001285788.1. [Q8CBR1-1]
DR RefSeq; NP_001272720.1; NM_001285791.1. [Q8CBR1-3]
DR RefSeq; NP_598870.1; NM_134109.2. [Q8CBR1-2]
DR AlphaFoldDB; Q8CBR1; -.
DR STRING; 10090.ENSMUSP00000112539; -.
DR iPTMnet; Q8CBR1; -.
DR PhosphoSitePlus; Q8CBR1; -.
DR PaxDb; Q8CBR1; -.
DR PRIDE; Q8CBR1; -.
DR ProteomicsDB; 266971; -. [Q8CBR1-1]
DR ProteomicsDB; 266972; -. [Q8CBR1-2]
DR ProteomicsDB; 266973; -. [Q8CBR1-3]
DR ABCD; Q8CBR1; 20 sequenced antibodies.
DR Antibodypedia; 3021; 74 antibodies from 14 providers.
DR DNASU; 106347; -.
DR Ensembl; ENSMUST00000023617; ENSMUSP00000023617; ENSMUSG00000022900. [Q8CBR1-1]
DR Ensembl; ENSMUST00000089618; ENSMUSP00000087045; ENSMUSG00000022900. [Q8CBR1-3]
DR Ensembl; ENSMUST00000119464; ENSMUSP00000112539; ENSMUSG00000022900. [Q8CBR1-2]
DR GeneID; 106347; -.
DR KEGG; mmu:106347; -.
DR UCSC; uc007zcs.2; mouse. [Q8CBR1-2]
DR UCSC; uc007zct.2; mouse. [Q8CBR1-1]
DR UCSC; uc007zcu.2; mouse. [Q8CBR1-3]
DR CTD; 286676; -.
DR MGI; MGI:2146574; Ildr1.
DR VEuPathDB; HostDB:ENSMUSG00000022900; -.
DR eggNOG; ENOG502QS11; Eukaryota.
DR GeneTree; ENSGT00950000183058; -.
DR HOGENOM; CLU_037131_1_0_1; -.
DR InParanoid; Q8CBR1; -.
DR OMA; REYEHHA; -.
DR OrthoDB; 860055at2759; -.
DR PhylomeDB; Q8CBR1; -.
DR TreeFam; TF330877; -.
DR BioGRID-ORCS; 106347; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Ildr1; mouse.
DR PRO; PR:Q8CBR1; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q8CBR1; protein.
DR Bgee; ENSMUSG00000022900; Expressed in parotid gland and 78 other tissues.
DR Genevisible; Q8CBR1; MM.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0070160; C:tight junction; IDA:UniProtKB.
DR GO; GO:0061689; C:tricellular tight junction; IDA:CACAO.
DR GO; GO:0070506; F:high-density lipoprotein particle receptor activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0010669; P:epithelial structure maintenance; IDA:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR GO; GO:0030072; P:peptide hormone secretion; IDA:MGI.
DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; IDA:MGI.
DR GO; GO:0061833; P:protein localization to tricellular tight junction; IMP:UniProtKB.
DR GO; GO:0043484; P:regulation of RNA splicing; IMP:UniProtKB.
DR GO; GO:0070542; P:response to fatty acid; IMP:UniProtKB.
DR GO; GO:1904274; P:tricellular tight junction assembly; IMP:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR008664; LISCH7.
DR Pfam; PF05624; LSR; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Disulfide bond;
KW Immunoglobulin domain; Membrane; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Signal; Tight junction; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..537
FT /note="Immunoglobulin-like domain-containing receptor 1"
FT /id="PRO_0000245305"
FT TOPO_DOM 23..166
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..537
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 23..161
FT /note="Ig-like V-type"
FT REGION 333..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..358
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..379
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 395..409
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..426
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 510..530
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT DISULFID 44..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 215..258
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019688"
FT VAR_SEQ 512..516
FT /note="KNNRK -> ERELP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_019689"
FT VAR_SEQ 517..537
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_019690"
FT CONFLICT 25
FT /note="V -> L (in Ref. 1; BAC29604)"
FT /evidence="ECO:0000305"
FT CONFLICT 71
FT /note="D -> G (in Ref. 1; BAC29081)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 537 AA; 61277 MW; 7757BFBD6188A16A CRC64;
MGCGLLAAGL LLFTWLPAGC LSLLVTVQHT ERYVTLFASV TLKCDYTTSA QLQDVVVTWR
FKSFCKDPIF DYFSASYQAA LSLGQDPSND CSDNQREVRI VAQRRGQSEP VLGVDYRQRK
ITIQNRADLV INEVMWWDHG VYYCTIEAPG DTSGDPDKEV KLIVLHWLTV IFIILGALLL
LLLIGVCWCQ CCPQYCCCYI RCPCCPTRCC CPEEALARHR YMKQVQALGP QMMEKPLYWG
ADRSSQVSSY AMNPLLQRDL SLQSSLPQMP MTQMAAHPPV ANGVLEYLEK ELRNLNPAQP
LPADLRAKSG HPCSMLSSLG SAEVVERRVI HLPPLIRDPP SSRTSNPSHQ QRLNAVSSRH
CDLSERPRQR HHSDFLRELQ DQGMRPWAPG RGELDPHWSG RHHRSRPSES SMPWSDWDSL
SECPSSSEAP WPPRRPEPRE GAQRRERRRH RSYSPPLPSG PSSWSSEEEK ESLPRNWGAQ
RRHHHRRRRS QSPNWPEEKP PSYRSLDVTP GKNNRKKGNV ERRLERESSH SGRSVVI
