ILDR2_MOUSE
ID ILDR2_MOUSE Reviewed; 661 AA.
AC B5TVM2; B5TVM3; B5TVM4; B5TVM5; B5TVM6; B5TVM7; B5TVM8; B5TVM9; E9Q9U5;
DT 22-JAN-2014, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 2.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Immunoglobulin-like domain-containing receptor 2 {ECO:0000305};
DE AltName: Full=Angulin-3 {ECO:0000303|PubMed:23239027, ECO:0000303|PubMed:28785060};
DE AltName: Full=Lisch-like protein {ECO:0000303|PubMed:18654634};
DE Flags: Precursor;
GN Name=Ildr2 {ECO:0000312|MGI:MGI:1196370}; Synonyms=D1Ertd471e, Ll;
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 [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=18654634; DOI=10.1371/journal.pgen.1000137;
RA Dokmanovic-Chouinard M., Chung W.K., Chevre J.C., Watson E., Yonan J.,
RA Wiegand B., Bromberg Y., Wakae N., Wright C.V., Overton J., Ghosh S.,
RA Sathe G.M., Ammala C.E., Brown K.K., Ito R., LeDuc C., Solomon K.,
RA Fischer S.G., Leibel R.L.;
RT "Positional cloning of 'Lisch-Like', a candidate modifier of susceptibility
RT to type 2 diabetes in mice.";
RL PLoS Genet. 4:E1000137-E1000137(2008).
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487 AND SER-594, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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 FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=23826244; DOI=10.1371/journal.pone.0067234;
RA Watanabe K., Watson E., Cremona M.L., Millings E.J., Lefkowitch J.H.,
RA Fischer S.G., LeDuc C.A., Leibel R.L.;
RT "ILDR2: an endoplasmic reticulum resident molecule mediating hepatic lipid
RT homeostasis.";
RL PLoS ONE 8:E67234-E67234(2013).
RN [5]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-559, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING,
RP AND 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 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).
RN [8]
RP FUNCTION.
RX PubMed=29431694; DOI=10.4049/jimmunol.1700325;
RA Hecht I., Toporik A., Podojil J.R., Vaknin I., Cojocaru G., Oren A.,
RA Aizman E., Liang S.C., Leung L., Dicken Y., Novik A., Marbach-Bar N.,
RA Elmesmari A., Tange C., Gilmour A., McIntyre D., Kurowska-Stolarska M.,
RA McNamee K., Leitner J., Greenwald S., Dassa L., Levine Z., Steinberger P.,
RA Williams R.O., Miller S.D., McInnes I.B., Neria E., Rotman G.;
RT "ILDR2 Is a Novel B7-like Protein That Negatively Regulates T Cell
RT Responses.";
RL J. Immunol. 200:2025-2037(2018).
RN [9]
RP INTERACTION WITH P4HB AND HSPA5, AND FUNCTION.
RX PubMed=33863978; DOI=10.1038/s41598-021-87884-7;
RA Watanabe K., Nakayama K., Ohta S., Matsumoto A., Tsuda H., Iwamoto S.;
RT "ILDR2 stabilization is regulated by its interaction with GRP78.";
RL Sci. Rep. 11:8414-8414(2021).
CC -!- FUNCTION: May be involved in ER stress pathways with effects on lipid
CC homeostasis and insulin secretion (PubMed:33863978, PubMed:23826244).
CC With ILDR1 and LSR, involved in the maintain of the epithelial barrier
CC function through the recruitment of MARVELD2/tricellulin to tricellular
CC tight junctions (PubMed:23239027). Also functions as a B7-like protein
CC family member expressed on immune cells and inflamed tissue and with T-
CC cell inhibitory activity (PubMed:29431694). In the inner ear, may
CC regulate alternative pre-mRNA splicing via binding to TRA2A, TRA2B and
CC SRSF1 (PubMed:28785060). {ECO:0000269|PubMed:23239027,
CC ECO:0000269|PubMed:23826244, ECO:0000269|PubMed:28785060,
CC ECO:0000269|PubMed:29431694, ECO:0000269|PubMed:33863978}.
CC -!- SUBUNIT: Interacts with MARVELD2 and OCLN (PubMed:23239027). Interacts
CC with P4HB AND HSPA5; the interaction with HSPA5 stabilizes ILDR2
CC expression (PubMed:33863978). Interacts (via C-terminus) with TRA2A,
CC TRA2B and SRSF1 (PubMed:28785060). {ECO:0000269|PubMed:23239027,
CC ECO:0000269|PubMed:28785060, ECO:0000269|PubMed:33863978}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23826244}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:23826244}. Cell junction, tight junction
CC {ECO:0000269|PubMed:23239027}. Nucleus {ECO:0000269|PubMed:28785060}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=B5TVM2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=B5TVM2-2; Sequence=VSP_061358;
CC Name=3;
CC IsoId=B5TVM2-3; Sequence=VSP_061354;
CC Name=4;
CC IsoId=B5TVM2-4; Sequence=VSP_061355;
CC Name=5;
CC IsoId=B5TVM2-5; Sequence=VSP_061357;
CC Name=6;
CC IsoId=B5TVM2-6; Sequence=VSP_061359, VSP_061360;
CC Name=7;
CC IsoId=B5TVM2-7; Sequence=VSP_061356;
CC -!- TISSUE SPECIFICITY: Expressed in epithelial tissues, mainly in liver,
CC kidney and colon. {ECO:0000269|PubMed:23239027}.
CC -!- DISRUPTION PHENOTYPE: Steatotic liver with increased hepatic and
CC circulating triglycerides and total cholesterol. Shows reduced
CC expression of genes mediating synthesis and oxidation of hepatic
CC lipids. {ECO:0000269|PubMed:23826244}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. LISCH7 family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-16 is the initiator.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; FJ024494; ACH90402.1; -; mRNA.
DR EMBL; FJ024495; ACH90403.1; -; mRNA.
DR EMBL; FJ024496; ACH90404.1; -; mRNA.
DR EMBL; FJ024497; ACH90405.1; -; mRNA.
DR EMBL; FJ024498; ACH90406.1; -; mRNA.
DR EMBL; FJ024499; ACH90407.1; -; mRNA.
DR EMBL; FJ024500; ACH90408.1; -; mRNA.
DR EMBL; FJ024501; ACH90409.1; -; mRNA.
DR EMBL; AC034122; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS48431.1; -. [B5TVM2-1]
DR CCDS; CCDS87912.1; -. [B5TVM2-6]
DR CCDS; CCDS87913.1; -. [B5TVM2-2]
DR CCDS; CCDS87914.1; -. [B5TVM2-5]
DR CCDS; CCDS87915.1; -. [B5TVM2-4]
DR CCDS; CCDS87916.1; -. [B5TVM2-3]
DR RefSeq; NP_001158000.1; NM_001164528.1.
DR AlphaFoldDB; B5TVM2; -.
DR BioGRID; 783207; 13.
DR IntAct; B5TVM2; 1.
DR MINT; B5TVM2; -.
DR STRING; 10090.ENSMUSP00000107047; -.
DR iPTMnet; B5TVM2; -.
DR PhosphoSitePlus; B5TVM2; -.
DR PaxDb; B5TVM2; -.
DR PeptideAtlas; B5TVM2; -.
DR PRIDE; B5TVM2; -.
DR ProteomicsDB; 266974; -.
DR Antibodypedia; 2487; 30 antibodies from 9 providers.
DR Ensembl; ENSMUST00000111416; ENSMUSP00000107047; ENSMUSG00000040612. [B5TVM2-1]
DR Ensembl; ENSMUST00000192638; ENSMUSP00000142311; ENSMUSG00000040612. [B5TVM2-4]
DR Ensembl; ENSMUST00000192732; ENSMUSP00000141502; ENSMUSG00000040612. [B5TVM2-3]
DR Ensembl; ENSMUST00000193860; ENSMUSP00000141323; ENSMUSG00000040612. [B5TVM2-5]
DR Ensembl; ENSMUST00000194964; ENSMUSP00000142152; ENSMUSG00000040612. [B5TVM2-2]
DR GeneID; 100039795; -.
DR KEGG; mmu:100039795; -.
DR UCSC; uc011wvd.1; mouse. [B5TVM2-1]
DR CTD; 387597; -.
DR MGI; MGI:1196370; Ildr2.
DR VEuPathDB; HostDB:ENSMUSG00000040612; -.
DR eggNOG; ENOG502QSI2; Eukaryota.
DR GeneTree; ENSGT00950000183058; -.
DR HOGENOM; CLU_028969_0_0_1; -.
DR OMA; EMEVLEY; -.
DR OrthoDB; 457764at2759; -.
DR PhylomeDB; B5TVM2; -.
DR TreeFam; TF330877; -.
DR BioGRID-ORCS; 100039795; 4 hits in 72 CRISPR screens.
DR PRO; PR:B5TVM2; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; B5TVM2; protein.
DR Bgee; ENSMUSG00000040612; Expressed in median eminence of neurohypophysis and 192 other tissues.
DR ExpressionAtlas; B5TVM2; baseline and differential.
DR Genevisible; B5TVM2; MM.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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:0070160; C:tight junction; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IMP:MGI.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IMP:MGI.
DR GO; GO:0030073; P:insulin secretion; IMP:MGI.
DR GO; GO:0050868; P:negative regulation of T cell activation; IDA:UniProtKB.
DR GO; GO:0031016; P:pancreas development; IMP:MGI.
DR GO; GO:0043484; P:regulation of RNA splicing; IMP:UniProtKB.
DR GO; GO:0009749; P:response to glucose; IMP:MGI.
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; Disulfide bond; Endoplasmic reticulum;
KW Immunoglobulin domain; Membrane; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Signal; Tight junction; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..661
FT /note="Immunoglobulin-like domain-containing receptor 2"
FT /id="PRO_0000425154"
FT TOPO_DOM 36..201
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..661
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 36..177
FT /note="Ig-like V-type"
FT REGION 288..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..429
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 453..661
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..424
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..479
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..565
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 633..651
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 559
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 594
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT DISULFID 57..160
FT /evidence="ECO:0000250"
FT VAR_SEQ 182..308
FT /note="Missing (in isoform 3)"
FT /id="VSP_061354"
FT VAR_SEQ 182..200
FT /note="Missing (in isoform 4)"
FT /id="VSP_061355"
FT VAR_SEQ 183..661
FT /note="Missing (in isoform 7)"
FT /id="VSP_061356"
FT VAR_SEQ 201..308
FT /note="Missing (in isoform 5)"
FT /id="VSP_061357"
FT VAR_SEQ 250..309
FT /note="LYEAGKAAKAGYPPSVSGVPGPYSIPSVPLGGAPSSGMLMDKPHPPPLAPSD
FT STGGSHSV -> F (in isoform 2)"
FT /id="VSP_061358"
FT VAR_SEQ 418..427
FT /note="SQQRSKSEML -> RVTFQPGCPL (in isoform 6)"
FT /id="VSP_061359"
FT VAR_SEQ 428..661
FT /note="Missing (in isoform 6)"
FT /id="VSP_061360"
FT CONFLICT 587
FT /note="T -> A (in Ref. 1; ACH90403/ACH90404/ACH90405/
FT ACH90406/ACH90407)"
FT /evidence="ECO:0000305"
FT CONFLICT 647
FT /note="A -> V (in Ref. 1; ACH90403/ACH90404/ACH90405/
FT ACH90406/ACH90407)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 661 AA; 73235 MW; E80BEDD0D21D5DA2 CRC64;
MPAFPTLDLD GKLGKMDRVV LGWTAVFWLT AMVEGLQVTV PDKKKVAMLF QPTVLRCHFS
TSSHQPAVVQ WKFKSYCQDR MGESLGMSSP RAQALSKRNL EWDPYLDCLD SRRTVRVVAS
KQGSTVTLGD FYRGREITIV HDADLQIGKL MWGDSGLYYC IITTPDDLEG KNEDSVELLV
LGRTGLLADL LPSFAVEIMP EWVFVGLVIL GIFLFFVLVG ICWCQCCPHS CCCYVRCPCC
PDSCCCPQAL YEAGKAAKAG YPPSVSGVPG PYSIPSVPLG GAPSSGMLMD KPHPPPLAPS
DSTGGSHSVR KGYRIQADKE RDSMKVLYYV EKELAQFDPA RRMRGRYNNT ISELSSLHDD
DSNFRQSYHQ MRNKQFPMSG DLESNPDYWS GVMGGNSGTN RGPALEYNKE DRESFRHSQQ
RSKSEMLSRK NFATGVPAVS MDELAAFADS YGQRSRRANG NSHEARAGSR FERSESRAHG
AFYQDGSLDE YYGRGRSREP PGDGERGWTY SPAPARRRPP EDAPLPRLVS RTPGTAPKYD
HSYLSSVLER QARPESSSRG GSLETPSKLG AQLGPRSASY YAWSPPTTYK AGASEGEDED
DAADEDALPP YSELELSRGE LSRGPSYRGR DLSFHSNSEK RRKKEPAKKP GDFPTRMSLV
V
