ILDR1_HUMAN
ID ILDR1_HUMAN Reviewed; 546 AA.
AC Q86SU0; Q6ZP61; Q7Z578;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Immunoglobulin-like domain-containing receptor 1 {ECO:0000305};
DE AltName: Full=Angulin-2 {ECO:0000303|PubMed:23239027};
DE Flags: Precursor;
GN Name=ILDR1 {ECO:0000312|HGNC:HGNC:28741};
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 [MRNA] (ISOFORMS 1; 5 AND 6), TOPOLOGY, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND SUBUNIT.
RC TISSUE=Lymphoma, and Prostate;
RX PubMed=15381095; DOI=10.1016/j.bbrc.2004.08.188;
RA Hauge H., Patzke S., Delabie J., Aasheim H.-C.;
RT "Characterization of a novel immunoglobulin-like domain containing
RT receptor.";
RL Biochem. Biophys. Res. Commun. 323:970-978(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Kidney;
RA Guo J.H., Yu L.;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [5]
RP VARIANTS DFNB42 GLN-97; 195-GLN--ILE-546 DEL; 379-GLU--ILE-546 DEL AND
RP GLN-453, AND VARIANT CYS-463.
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 [6]
RP CHARACTERIZATION OF VARIANTS DFNB42 GLN-97; 195-GLN--ILE-546 DEL;
RP 379-GLU--ILE-546 DEL AND GLN-453, FUNCTION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH 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 VARIANT VAL-357.
RX PubMed=28887846; DOI=10.1002/humu.23335;
RA Zhou X.L., He L.X., Yu L.J., Wang Y., Wang X.J., Wang E.D., Yang T.;
RT "Mutations in KARS cause early-onset hearing loss and leukoencephalopathy:
RT Potential pathogenic mechanism.";
RL Hum. Mutat. 38:1740-1750(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. Mediates fatty acids and
CC lipoproteins-stimulated CCK/cholecystokinin secretion in the small
CC intestine. In the inner ear, may regulate alternative pre-mRNA splicing
CC via binding to TRA2A, TRA2B and SRSF1 (By similarity).
CC {ECO:0000250|UniProtKB:Q8CBR1, ECO:0000269|PubMed:23239027}.
CC -!- SUBUNIT: Homooligomer (PubMed:15381095). 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 (By similarity). {ECO:0000250|UniProtKB:Q8CBR1,
CC ECO:0000269|PubMed:15381095, ECO:0000269|PubMed:23239027}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15381095};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:15381095}. Cell
CC junction, tight junction {ECO:0000269|PubMed:23239027}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm, cytosol
CC {ECO:0000269|PubMed:15381095}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q86SU0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86SU0-2; Sequence=VSP_019683;
CC Name=3;
CC IsoId=Q86SU0-3; Sequence=VSP_019684, VSP_019685;
CC Name=4;
CC IsoId=Q86SU0-4; Sequence=VSP_019680, VSP_019686, VSP_019687;
CC Name=5; Synonyms=Beta;
CC IsoId=Q86SU0-5; Sequence=VSP_019681, VSP_019682;
CC Name=6; Synonyms=Alpha';
CC IsoId=Q86SU0-6; Sequence=VSP_019679, VSP_019683;
CC -!- TISSUE SPECIFICITY: Mainly expressed in prostate and to a lower extent
CC in testis, pancreas, kidney, heart and liver.
CC {ECO:0000269|PubMed:15381095}.
CC -!- DISEASE: Deafness, autosomal recessive, 42 (DFNB42) [MIM:609646]: A
CC prelingual, non-progressive form of non-syndromic sensorineural hearing
CC loss. Sensorineural deafness results from damage to the neural
CC receptors of the inner ear, the nerve pathways to the brain, or the
CC area of the brain that receives sound information.
CC {ECO:0000269|PubMed:21255762, ECO:0000269|PubMed:23239027}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. LISCH7 family.
CC {ECO:0000305}.
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DR EMBL; AY672837; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY672838; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY672839; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY134857; AAN10256.1; -; mRNA.
DR EMBL; AK129974; BAC85264.1; -; mRNA.
DR EMBL; BC044240; AAH44240.1; -; mRNA.
DR CCDS; CCDS3008.1; -. [Q86SU0-2]
DR CCDS; CCDS56270.1; -. [Q86SU0-5]
DR CCDS; CCDS56271.1; -. [Q86SU0-1]
DR RefSeq; NP_001186728.1; NM_001199799.1. [Q86SU0-1]
DR RefSeq; NP_001186729.1; NM_001199800.1. [Q86SU0-5]
DR RefSeq; NP_787120.1; NM_175924.3. [Q86SU0-2]
DR RefSeq; XP_005247446.1; XM_005247389.4. [Q86SU0-6]
DR AlphaFoldDB; Q86SU0; -.
DR BioGRID; 130413; 10.
DR IntAct; Q86SU0; 5.
DR STRING; 9606.ENSP00000345667; -.
DR iPTMnet; Q86SU0; -.
DR PhosphoSitePlus; Q86SU0; -.
DR BioMuta; ILDR1; -.
DR DMDM; 110279019; -.
DR jPOST; Q86SU0; -.
DR MassIVE; Q86SU0; -.
DR PaxDb; Q86SU0; -.
DR PeptideAtlas; Q86SU0; -.
DR PRIDE; Q86SU0; -.
DR ProteomicsDB; 69633; -. [Q86SU0-1]
DR ProteomicsDB; 69634; -. [Q86SU0-2]
DR ProteomicsDB; 69635; -. [Q86SU0-3]
DR ProteomicsDB; 69636; -. [Q86SU0-4]
DR ProteomicsDB; 69637; -. [Q86SU0-5]
DR ProteomicsDB; 69638; -. [Q86SU0-6]
DR Antibodypedia; 3021; 74 antibodies from 14 providers.
DR DNASU; 286676; -.
DR Ensembl; ENST00000273691.7; ENSP00000273691.3; ENSG00000145103.15. [Q86SU0-2]
DR Ensembl; ENST00000344209.10; ENSP00000345667.5; ENSG00000145103.15. [Q86SU0-1]
DR Ensembl; ENST00000393631.5; ENSP00000377251.1; ENSG00000145103.15. [Q86SU0-5]
DR Ensembl; ENST00000642615.1; ENSP00000495499.1; ENSG00000145103.15. [Q86SU0-3]
DR GeneID; 286676; -.
DR KEGG; hsa:286676; -.
DR MANE-Select; ENST00000344209.10; ENSP00000345667.5; NM_001199799.2; NP_001186728.1.
DR UCSC; uc003eeq.4; human. [Q86SU0-1]
DR CTD; 286676; -.
DR DisGeNET; 286676; -.
DR GeneCards; ILDR1; -.
DR HGNC; HGNC:28741; ILDR1.
DR HPA; ENSG00000145103; Tissue enhanced (parathyroid).
DR MalaCards; ILDR1; -.
DR MIM; 609646; phenotype.
DR MIM; 609739; gene.
DR neXtProt; NX_Q86SU0; -.
DR OpenTargets; ENSG00000145103; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA134883110; -.
DR VEuPathDB; HostDB:ENSG00000145103; -.
DR eggNOG; ENOG502QS11; Eukaryota.
DR GeneTree; ENSGT00950000183058; -.
DR HOGENOM; CLU_037131_1_0_1; -.
DR InParanoid; Q86SU0; -.
DR OMA; REYEHHA; -.
DR OrthoDB; 860055at2759; -.
DR PhylomeDB; Q86SU0; -.
DR TreeFam; TF330877; -.
DR PathwayCommons; Q86SU0; -.
DR SignaLink; Q86SU0; -.
DR BioGRID-ORCS; 286676; 16 hits in 1064 CRISPR screens.
DR GenomeRNAi; 286676; -.
DR Pharos; Q86SU0; Tbio.
DR PRO; PR:Q86SU0; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q86SU0; protein.
DR Bgee; ENSG00000145103; Expressed in corpus epididymis and 102 other tissues.
DR Genevisible; Q86SU0; HS.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0070160; C:tight junction; IDA:UniProtKB.
DR GO; GO:0061689; C:tricellular tight junction; ISS:UniProtKB.
DR GO; GO:0070506; F:high-density lipoprotein particle receptor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0010669; P:epithelial structure maintenance; ISS:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0030072; P:peptide hormone secretion; IEA:Ensembl.
DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; ISS:UniProtKB.
DR GO; GO:0061833; P:protein localization to tricellular tight junction; ISS:UniProtKB.
DR GO; GO:0043484; P:regulation of RNA splicing; ISS:UniProtKB.
DR GO; GO:0070542; P:response to fatty acid; ISS:UniProtKB.
DR GO; GO:1904274; P:tricellular tight junction assembly; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
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.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Cytoplasm; Deafness;
KW Disease variant; Disulfide bond; Immunoglobulin domain; Membrane;
KW Non-syndromic deafness; Phosphoprotein; Receptor; Reference proteome;
KW Signal; Tight junction; Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..546
FT /note="Immunoglobulin-like domain-containing receptor 1"
FT /id="PRO_0000245304"
FT TOPO_DOM 24..167
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..546
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..162
FT /note="Ig-like V-type"
FT REGION 399..546
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..429
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 435..454
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..510
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 519..539
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBR1"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBR1"
FT DISULFID 45..145
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..19
FT /note="MAWPKLPAPWLLLCTWLPA -> MAGNIFCPFALFFLPMSRVGHLQHFLLLL
FT AL (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15381095"
FT /id="VSP_019679"
FT VAR_SEQ 92..209
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_019680"
FT VAR_SEQ 127
FT /note="R -> P (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15381095"
FT /id="VSP_019681"
FT VAR_SEQ 128..216
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15381095"
FT /id="VSP_019682"
FT VAR_SEQ 216..259
FT /note="Missing (in isoform 2 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15381095,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_019683"
FT VAR_SEQ 260..265
FT /note="DLSLPS -> ASRRCQ (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_019684"
FT VAR_SEQ 266..546
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_019685"
FT VAR_SEQ 324..329
FT /note="VVERRI -> NQIEEF (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_019686"
FT VAR_SEQ 330..546
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_019687"
FT VARIANT 97
FT /note="R -> Q (in DFNB42; no effect on interaction with
FT MARVELD2; loss of tight junction location;
FT dbSNP:rs771818841)"
FT /evidence="ECO:0000269|PubMed:21255762"
FT /id="VAR_065352"
FT VARIANT 195..546
FT /note="Missing (in DFNB42; loss of interaction with
FT MARVELD2; loss of tight junction location)"
FT /evidence="ECO:0000269|PubMed:21255762"
FT /id="VAR_085556"
FT VARIANT 357
FT /note="I -> V (in dbSNP:rs1448131970)"
FT /evidence="ECO:0000269|PubMed:28887846"
FT /id="VAR_079750"
FT VARIANT 379..546
FT /note="Missing (in DFNB42; no effect on interaction with
FT MARVELD2; loss of tight junction location)"
FT /evidence="ECO:0000269|PubMed:21255762"
FT /id="VAR_085557"
FT VARIANT 453
FT /note="R -> Q (in DFNB42; uncertain pathological
FT significance; no effect on interaction with MARVELD2; no
FT effect on tight junction location; dbSNP:rs372564314)"
FT /evidence="ECO:0000269|PubMed:21255762"
FT /id="VAR_065353"
FT VARIANT 463
FT /note="R -> C (in dbSNP:rs778163752)"
FT /evidence="ECO:0000269|PubMed:21255762"
FT /id="VAR_065354"
SQ SEQUENCE 546 AA; 62815 MW; E2FDF8AD9032B5D7 CRC64;
MAWPKLPAPW LLLCTWLPAG CLSLLVTVQH TERYVTLFAS IILKCDYTTS AQLQDVVVTW
RFKSFCKDPI FDYYSASYQA ALSLGQDPSN DCNDNQREVR IVAQRRGQNE PVLGVDYRQR
KITIQNRADL VINEVMWWDH GVYYCTIEAP GDTSGDPDKE VKLIVLHWLT VIFIILGALL
LLLLIGVCWC QCCPQYCCCY IRCPCCPAHC CCPEEALARH RYMKQAQALG PQMMGKPLYW
GADRSSQVSS YPMHPLLQRD LSLPSSLPQM PMTQTTNQPP IANGVLEYLE KELRNLNLAQ
PLPPDLKGRF GHPCSMLSSL GSEVVERRII HLPPLIRDLS SSRRTSDSLH QQWLTPIPSR
PWDLREGRSH HHYPDFHQEL QDRGPKSWAL ERRELDPSWS GRHRSSRLNG SPIHWSDRDS
LSDVPSSSEA RWRPSHPPFR SRCQERPRRP SPRESTQRHG RRRRHRSYSP PLPSGLSSWS
SEEDKERQPQ SWRAHRRGSH SPHWPEEKPP SYRSLDITPG KNSRKKGSVE RRSEKDSSHS
GRSVVI
