LCTL_HUMAN
ID LCTL_HUMAN Reviewed; 567 AA.
AC Q6UWM7; B3KQY0;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Lactase-like protein;
DE AltName: Full=Klotho/lactase-phlorizin hydrolase-related protein;
DE Flags: Precursor;
GN Name=LCTL; Synonyms=KLPH; ORFNames=UNQ3022/PRO9820;
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 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP PROTEIN SEQUENCE OF 22-36.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
CC -!- FUNCTION: Plays a role in formation of the lens suture in the eye,
CC which is important for normal optical properties of the lens.
CC {ECO:0000250|UniProtKB:Q8K1F9}.
CC -!- SUBUNIT: May form dimers. {ECO:0000250|UniProtKB:Q8K1F9}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6UWM7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6UWM7-2; Sequence=VSP_054596;
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 1 family. Klotho
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: Although it belongs to the glycosyl hydrolase 1 family, Asp-
CC 201 is present instead of the conserved Glu which is an active site
CC residue. It is therefore expected that this protein lacks glycosidase
CC activity. {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; AY358729; AAQ89091.1; -; mRNA.
DR EMBL; AK090598; BAG52192.1; -; mRNA.
DR EMBL; AC116913; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS10220.1; -. [Q6UWM7-1]
DR CCDS; CCDS61678.1; -. [Q6UWM7-2]
DR RefSeq; NP_001265491.1; NM_001278562.1. [Q6UWM7-2]
DR RefSeq; NP_997221.2; NM_207338.3. [Q6UWM7-1]
DR AlphaFoldDB; Q6UWM7; -.
DR SMR; Q6UWM7; -.
DR BioGRID; 128236; 30.
DR STRING; 9606.ENSP00000343490; -.
DR DrugBank; DB03430; (S)-4-hydroxymandelonitrile.
DR DrugBank; DB02185; 2,4-Dihydroxy-7-(Methyloxy)-2h-1,4-Benzoxazin-3(4h)-One.
DR DrugBank; DB02379; Beta-D-Glucose.
DR DrugBank; DB02471; Nojirimycine Tetrazole.
DR DrugBank; DB08430; PARA-NITROPHENYL 1-THIO-BETA-D-GLUCOPYRANOSIDE.
DR CAZy; GH1; Glycoside Hydrolase Family 1.
DR GlyGen; Q6UWM7; 3 sites.
DR iPTMnet; Q6UWM7; -.
DR PhosphoSitePlus; Q6UWM7; -.
DR BioMuta; LCTL; -.
DR DMDM; 77416521; -.
DR MassIVE; Q6UWM7; -.
DR PaxDb; Q6UWM7; -.
DR PeptideAtlas; Q6UWM7; -.
DR PRIDE; Q6UWM7; -.
DR Antibodypedia; 26209; 45 antibodies from 17 providers.
DR DNASU; 197021; -.
DR Ensembl; ENST00000341509.9; ENSP00000343490.5; ENSG00000188501.11. [Q6UWM7-1]
DR Ensembl; ENST00000537670.5; ENSP00000445419.1; ENSG00000188501.11. [Q6UWM7-2]
DR GeneID; 197021; -.
DR KEGG; hsa:197021; -.
DR UCSC; uc002aqc.5; human. [Q6UWM7-1]
DR CTD; 197021; -.
DR DisGeNET; 197021; -.
DR GeneCards; LCTL; -.
DR HGNC; HGNC:15583; LCTL.
DR HPA; ENSG00000188501; Tissue enhanced (brain).
DR neXtProt; NX_Q6UWM7; -.
DR OpenTargets; ENSG00000188501; -.
DR PharmGKB; PA142671560; -.
DR VEuPathDB; HostDB:ENSG00000188501; -.
DR eggNOG; KOG0626; Eukaryota.
DR GeneTree; ENSGT00940000157369; -.
DR HOGENOM; CLU_001859_1_3_1; -.
DR InParanoid; Q6UWM7; -.
DR OMA; VEACDRK; -.
DR OrthoDB; 408001at2759; -.
DR PhylomeDB; Q6UWM7; -.
DR TreeFam; TF314803; -.
DR PathwayCommons; Q6UWM7; -.
DR BioGRID-ORCS; 197021; 11 hits in 1071 CRISPR screens.
DR GenomeRNAi; 197021; -.
DR Pharos; Q6UWM7; Tdark.
DR PRO; PR:Q6UWM7; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q6UWM7; protein.
DR Bgee; ENSG00000188501; Expressed in sural nerve and 92 other tissues.
DR ExpressionAtlas; Q6UWM7; baseline and differential.
DR Genevisible; Q6UWM7; HS.
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:0004553; F:hydrolase activity, hydrolyzing O-glycosyl compounds; IEA:InterPro.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR InterPro; IPR001360; Glyco_hydro_1.
DR InterPro; IPR018120; Glyco_hydro_1_AS.
DR InterPro; IPR033132; Glyco_hydro_1_N_CS.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR PANTHER; PTHR10353; PTHR10353; 1.
DR Pfam; PF00232; Glyco_hydro_1; 1.
DR PRINTS; PR00131; GLHYDRLASE1.
DR SUPFAM; SSF51445; SSF51445; 1.
DR PROSITE; PS00572; GLYCOSYL_HYDROL_F1_1; 1.
DR PROSITE; PS00653; GLYCOSYL_HYDROL_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Endoplasmic reticulum;
KW Glycoprotein; Membrane; Reference proteome; Sensory transduction; Signal;
KW Transmembrane; Transmembrane helix; Vision.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 22..567
FT /note="Lactase-like protein"
FT /id="PRO_0000042251"
FT TOPO_DOM 23..541
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 542..562
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 563..567
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..173
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054596"
FT VARIANT 212
FT /note="T -> M (in dbSNP:rs7179073)"
FT /id="VAR_049297"
FT VARIANT 240
FT /note="A -> T (in dbSNP:rs1030986)"
FT /id="VAR_023586"
SQ SEQUENCE 567 AA; 65088 MW; DA840A92E933C0AE CRC64;
MKPVWVATLL WMLLLVPRLG AARKGSPEEA SFYYGTFPLG FSWGVGSSAY QTEGAWDQDG
KGPSIWDVFT HSGKGKVLGN ETADVACDGY YKVQEDIILL RELHVNHYRF SLSWPRLLPT
GIRAEQVNKK GIEFYSDLID ALLSSNITPI VTLHHWDLPQ LLQVKYGGWQ NVSMANYFRD
YANLCFEAFG DRVKHWITFS DPRAMAEKGY ETGHHAPGLK LRGTGLYKAA HHIIKAHAKA
WHSYNTTWRS KQQGLVGISL NCDWGEPVDI SNPKDLEAAE RYLQFCLGWF ANPIYAGDYP
QVMKDYIGRK SAEQGLEMSR LPVFSLQEKS YIKGTSDFLG LGHFTTRYIT ERNYPSRQGP
SYQNDRDLIE LVDPNWPDLG SKWLYSVPWG FRRLLNFAQT QYGDPPIYVM ENGASQKFHC
TQLCDEWRIQ YLKGYINEML KAIKDGANIK GYTSWSLLDK FEWEKGYSDR YGFYYVEFND
RNKPRYPKAS VQYYKKIIIA NGFPNPREVE SWYLKALETC SINNQMLAAE PLLSHMQMVT
EIVVPTVCSL CVLITAVLLM LLLRRQS
