LRIT3_HUMAN
ID LRIT3_HUMAN Reviewed; 679 AA.
AC Q3SXY7; C9J1C2; Q6ZTG1;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 3.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3;
DE Flags: Precursor;
GN Name=LRIT3;
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] (ISOFORM 2), AND VARIANT LEU-336.
RC TISSUE=Cerebellum;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-336.
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-83, IDENTIFICATION OF EXON 1, FUNCTION,
RP GLYCOSYLATION, VARIANTS THR-494 AND TYR-592, AND MUTAGENESIS OF THR-53.
RX PubMed=22673519; DOI=10.1016/j.febslet.2012.04.010;
RA Kim S.D., Liu J.L., Roscioli T., Buckley M.F., Yagnik G., Boyadjiev S.A.,
RA Kim J.;
RT "Leucine-rich repeat, immunoglobulin-like and transmembrane domain 3
RT (LRIT3) is a modulator of FGFR1.";
RL FEBS Lett. 586:1516-1521(2012).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 108-634 (ISOFORM 1), AND VARIANTS
RP ASN-175; THR-486 AND MET-503.
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 [6]
RP FUNCTION.
RX PubMed=28334377; DOI=10.1167/iovs.16-20745;
RA Neuille M., Cao Y., Caplette R., Guerrero-Given D., Thomas C., Kamasawa N.,
RA Sahel J.A., Hamel C.P., Audo I., Picaud S., Martemyanov K.A., Zeitz C.;
RT "LRIT3 Differentially Affects Connectivity and Synaptic Transmission of
RT Cones to ON- and OFF-Bipolar Cells.";
RL Invest. Ophthalmol. Vis. Sci. 58:1768-1778(2017).
RN [7]
RP VARIANT CSNB1F TYR-328, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23246293; DOI=10.1016/j.ajhg.2012.10.023;
RG Congenital Stationary Night Blindness Consortium;
RA Zeitz C., Jacobson S.G., Hamel C.P., Bujakowska K., Neuille M., Orhan E.,
RA Zanlonghi X., Lancelot M.E., Michiels C., Schwartz S.B., Bocquet B.,
RA Antonio A., Audier C., Letexier M., Saraiva J.P., Luu T.D., Sennlaub F.,
RA Nguyen H., Poch O., Dollfus H., Lecompte O., Kohl S., Sahel J.A.,
RA Bhattacharya S.S., Audo I.;
RT "Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-
RT recessive complete congenital stationary night blindness.";
RL Am. J. Hum. Genet. 92:67-75(2013).
RN [8]
RP VARIANT CSNB1F LEU-203.
RX PubMed=27428514; DOI=10.1080/13816810.2016.1193876;
RA Dan H., Song X., Li J., Xing Y., Li T.;
RT "Mutation screening of the LRIT3, CABP4, and GPR179 genes in Chinese
RT patients with Schubert-Bornschein congenital stationary night blindness.";
RL Ophthalmic Genet. 38:206-210(2017).
CC -!- FUNCTION: Plays a role in the synapse formation and synaptic
CC transmission between cone photoreceptor cells and retinal bipolar cells
CC (By similarity). Required for normal transmission of a light-evoked
CC stimulus from the cone photoreceptor cells to the ON-bipolar cells and
CC ON-ganglion cells in the inner retina (PubMed:28334377). Required in
CC retinal ON-bipolar cells for normal localization of the cation channel
CC TRPM1 at dendrite tips (By similarity). Seems to play a specific role
CC in synaptic contacts made by ON-bipolar cells with cone photoreceptor
CC pedicles (By similarity). May also have a role in cone synapse
CC formation (By similarity). Might facilitate FGFR1 exit from the
CC endoplasmic reticulum to the Golgi (PubMed:22673519). Could be a
CC regulator of the FGFRs (PubMed:22673519).
CC {ECO:0000250|UniProtKB:W8DXL4, ECO:0000269|PubMed:22673519,
CC ECO:0000269|PubMed:28334377}.
CC -!- SUBCELLULAR LOCATION: Cell projection, dendrite
CC {ECO:0000269|PubMed:23246293}. Perikaryon
CC {ECO:0000250|UniProtKB:W8DXL4}. Endoplasmic reticulum membrane
CC {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}.
CC Note=Punctate expression at dendrite tips.
CC {ECO:0000269|PubMed:23246293}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3SXY7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3SXY7-2; Sequence=VSP_029126, VSP_029127;
CC -!- TISSUE SPECIFICITY: Detected in the outer plexiform layer (OPL) of the
CC retina where it localizes to ON-bipolar cells (at protein level).
CC {ECO:0000269|PubMed:23246293}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:22673519}.
CC -!- DISEASE: Night blindness, congenital stationary, 1F (CSNB1F)
CC [MIM:615058]: An autosomal recessive form of congenital stationary
CC night blindness, a non-progressive retinal disorder characterized by
CC impaired night vision, often associated with nystagmus and myopia.
CC {ECO:0000269|PubMed:23246293, ECO:0000269|PubMed:27428514}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI04038.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK126648; BAC86628.1; -; mRNA.
DR EMBL; AC005509; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX06256.1; -; Genomic_DNA.
DR EMBL; JQ354981; AFH56665.1; -; mRNA.
DR EMBL; BC104037; AAI04038.1; ALT_INIT; mRNA.
DR CCDS; CCDS3688.3; -. [Q3SXY7-1]
DR RefSeq; NP_940908.3; NM_198506.4. [Q3SXY7-1]
DR AlphaFoldDB; Q3SXY7; -.
DR SMR; Q3SXY7; -.
DR BioGRID; 131342; 12.
DR IntAct; Q3SXY7; 1.
DR STRING; 9606.ENSP00000469759; -.
DR GlyGen; Q3SXY7; 1 site.
DR iPTMnet; Q3SXY7; -.
DR PhosphoSitePlus; Q3SXY7; -.
DR BioMuta; LRIT3; -.
DR DMDM; 476007838; -.
DR MassIVE; Q3SXY7; -.
DR PaxDb; Q3SXY7; -.
DR PeptideAtlas; Q3SXY7; -.
DR PRIDE; Q3SXY7; -.
DR ProteomicsDB; 61821; -. [Q3SXY7-1]
DR ProteomicsDB; 61822; -. [Q3SXY7-2]
DR Antibodypedia; 2679; 78 antibodies from 18 providers.
DR DNASU; 345193; -.
DR Ensembl; ENST00000594814.6; ENSP00000469759.1; ENSG00000183423.12. [Q3SXY7-1]
DR GeneID; 345193; -.
DR KEGG; hsa:345193; -.
DR MANE-Select; ENST00000594814.6; ENSP00000469759.1; NM_198506.5; NP_940908.3.
DR UCSC; uc031sgv.2; human. [Q3SXY7-1]
DR CTD; 345193; -.
DR DisGeNET; 345193; -.
DR GeneCards; LRIT3; -.
DR HGNC; HGNC:24783; LRIT3.
DR HPA; ENSG00000183423; Tissue enriched (retina).
DR MalaCards; LRIT3; -.
DR MIM; 615004; gene.
DR MIM; 615058; phenotype.
DR neXtProt; NX_Q3SXY7; -.
DR OpenTargets; ENSG00000183423; -.
DR Orphanet; 215; Congenital stationary night blindness.
DR PharmGKB; PA162394355; -.
DR VEuPathDB; HostDB:ENSG00000183423; -.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG3510; Eukaryota.
DR GeneTree; ENSGT00940000156627; -.
DR HOGENOM; CLU_019650_0_0_1; -.
DR InParanoid; Q3SXY7; -.
DR OMA; AELDNCV; -.
DR OrthoDB; 317712at2759; -.
DR PhylomeDB; Q3SXY7; -.
DR TreeFam; TF330861; -.
DR PathwayCommons; Q3SXY7; -.
DR BioGRID-ORCS; 345193; 6 hits in 1059 CRISPR screens.
DR GenomeRNAi; 345193; -.
DR Pharos; Q3SXY7; Tbio.
DR PRO; PR:Q3SXY7; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q3SXY7; protein.
DR Bgee; ENSG00000183423; Expressed in superior frontal gyrus and 80 other tissues.
DR ExpressionAtlas; Q3SXY7; baseline and differential.
DR GO; GO:0030425; C:dendrite; 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:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
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; IPR003598; Ig_sub2.
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; 2.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00369; LRR_TYP; 4.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51450; LRR; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection;
KW Congenital stationary night blindness; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Immunoglobulin domain;
KW Leucine-rich repeat; Membrane; Reference proteome; Repeat;
KW Sensory transduction; Signal; Transmembrane; Transmembrane helix; Vision.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..679
FT /note="Leucine-rich repeat, immunoglobulin-like domain and
FT transmembrane domain-containing protein 3"
FT /id="PRO_0000309284"
FT TOPO_DOM 20..582
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 583..603
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 604..679
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 56..79
FT /note="LRR 1"
FT REPEAT 80..103
FT /note="LRR 2"
FT REPEAT 104..128
FT /note="LRR 3"
FT REPEAT 129..151
FT /note="LRR 4"
FT REPEAT 152..175
FT /note="LRR 5"
FT DOMAIN 201..253
FT /note="LRRCT"
FT DOMAIN 254..344
FT /note="Ig-like"
FT DOMAIN 486..574
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 351..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 275..328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 46..183
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_029126"
FT VAR_SEQ 184..196
FT /note="SGVLDLSPSRIIL -> MVEPHQEPRHSKV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_029127"
FT VARIANT 175
FT /note="S -> N (in dbSNP:rs4698797)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_061317"
FT VARIANT 203
FT /note="W -> L (in CSNB1F)"
FT /evidence="ECO:0000269|PubMed:27428514"
FT /id="VAR_081904"
FT VARIANT 328
FT /note="C -> Y (in CSNB1F; dbSNP:rs376610215)"
FT /evidence="ECO:0000269|PubMed:23246293"
FT /id="VAR_069746"
FT VARIANT 336
FT /note="M -> L (in dbSNP:rs764205)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.3"
FT /id="VAR_036927"
FT VARIANT 486
FT /note="A -> T (in dbSNP:rs2347131)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_036928"
FT VARIANT 494
FT /note="S -> T (in one non-syndromic craniosynostosis
FT patient; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22673519"
FT /id="VAR_069133"
FT VARIANT 503
FT /note="T -> M (in dbSNP:rs2347132)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_036929"
FT VARIANT 592
FT /note="C -> Y (found in a patient with non-syndromic
FT craniosynostosis; unknown pathological significance;
FT dbSNP:rs766899767)"
FT /evidence="ECO:0000269|PubMed:22673519"
FT /id="VAR_069134"
FT MUTAGEN 53
FT /note="T->M: No effect on LRIT3 function."
FT /evidence="ECO:0000269|PubMed:22673519"
FT CONFLICT 169
FT /note="P -> T (in Ref. 5; AAI04038)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 679 AA; 74754 MW; 76CADAE7080021E5 CRC64;
MHLFACLCIV LSFLEGVGCL CPSQCTCDYH GRNDGSGSRL VLCNDMDMNE LPTNLPVDTV
KLRIEKTVIR RISAEAFYYL VELQYLWVTY NSVASIDPSS FYNLKQLHEL RLDGNSLAAF
PWASLLDMPL LRTLDLHNNK ITSVPNEALR YLKNLAYLDL SSNRLTTLPP DFLESWTHLV
STPSGVLDLS PSRIILGLQD NPWFCDCHIS KMIELSKVVD PAIVLLDPLM TCSEPERLTG
ILFQRAELEH CLKPSVMTSA TKIMSALGSN VLLRCDATGF PTPQITWTRS DSSPVNYTVI
QESPEEGVRW SIMSLTGISS KDAGDYKCKA KNLAGMSEAV VTVTVLGITT TPIPPDTSER
TGDHPEWDVQ PGSGRSTSVS SASSYLWSSS FSPTSSFSAS TLSPPSTASF SLSPFSSSTV
SSTTTLSTSI SASTTMANKR SFQLHQGGKR NLKVAKNGSK LPPASTSKKE ELALLDQTML
TETNAAIENL RVVSETKESV TLTWNMINTT HNSAVTVLYS KYGGKDLLLL NADSSKNQVT
IDGLEPGGQY MACVCPKGVP PQKDQCITFS TERVEGDDSQ WSLLLVVTST ACVVILPLIC
FLLYKVCKLQ CKSEPFWEDD LAKETYIQFE TLFPRSQSVG ELWTRSHRDD SEKLLLCSRS
SVESQVTFKS EGSRPEYYC
