ID   CLD14_HUMAN             Reviewed;         239 AA.
AC   O95500;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   24-JAN-2024, entry version 187.
DE   RecName: Full=Claudin-14;
GN   Name=CLDN14; ORFNames=UNQ777/PRO1571;
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 [GENOMIC DNA].
RA   Keen T.J., Inglehearn C.F.;
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT DFNB29 ASP-85.
RC   TISSUE=Liver;
RX   PubMed=11163249; DOI=10.1016/s0092-8674(01)00200-8;
RA   Wilcox E.R., Burton Q.L., Naz S., Riazuddin S., Smith T.N., Ploplis B.,
RA   Belyantseva I., Ben-Yosef T., Liburd N.A., Morell R.J., Kachar B., Wu D.K.,
RA   Griffith A.J., Riazuddin S., Friedman T.B.;
RT   "Mutations in the gene encoding tight junction claudin-14 cause autosomal
RT   recessive deafness DFNB29.";
RL   Cell 104:165-172(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Placenta, and Testis;
RA   Wattenhofer M., Falciola V., Charollais A., Caille D., Borel C.,
RA   Estivill X., Petersen M.B., Antonarakis S.E., Meda P., Reymond A.;
RT   "Claudin 14 and deafness.";
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10830953; DOI=10.1038/35012518;
RA   Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA   Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA   Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA   Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA   Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA   Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA   Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA   Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA   Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA   Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA   Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT   "The DNA sequence of human chromosome 21.";
RL   Nature 405:311-319(2000).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skin;
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   [7]
RP   VARIANT MET-4.
RX   PubMed=12791041; DOI=10.1034/j.1399-0004.2003.00101.x;
RA   Uyguner O., Emiroglu M., Uzumcu A., Hafiz G., Ghanbari A., Baserer N.,
RA   Yuksel-Apak M., Wollnik B.;
RT   "Frequencies of gap- and tight-junction mutations in Turkish families with
RT   autosomal-recessive non-syndromic hearing loss.";
RL   Clin. Genet. 64:65-69(2003).
RN   [8]
RP   VARIANTS DFNB29 HIS-81; ASP-85 AND ARG-232.
RX   PubMed=22246673; DOI=10.1002/ajmg.a.34407;
RA   Lee K., Ansar M., Andrade P.B., Khan B., Santos-Cortez R.L., Ahmad W.,
RA   Leal S.M.;
RT   "Novel CLDN14 mutations in Pakistani families with autosomal recessive non-
RT   syndromic hearing loss.";
RL   Am. J. Med. Genet. A 158:315-321(2012).
RN   [9]
RP   VARIANT MET-4.
RX   PubMed=23590985; DOI=10.1016/j.gene.2013.03.123;
RA   Charif M., Bakhchane A., Abidi O., Boulouiz R., Eloualid A., Roky R.,
RA   Rouba H., Kandil M., Lenaers G., Barakat A.;
RT   "Analysis of CLDN14 gene in deaf Moroccan patients with non-syndromic
RT   hearing loss.";
RL   Gene 523:103-105(2013).
RN   [10]
RP   VARIANTS DFNB29 HIS-81; ASP-85; ILE-87 AND VAL-94, AND VARIANT VAL-86.
RX   PubMed=23235333; DOI=10.1038/jhg.2012.143;
RA   Bashir Z.E., Latief N., Belyantseva I.A., Iqbal F., Amer Riazuddin S.,
RA   Khan S.N., Friedman T.B., Riazuddin S., Riazuddin S.;
RT   "Phenotypic variability of CLDN14 mutations causing DFNB29 hearing loss in
RT   the Pakistani population.";
RL   J. Hum. Genet. 58:102-108(2013).
CC   -!- FUNCTION: Plays a major role in tight junction-specific obliteration of
CC       the intercellular space, through calcium-independent cell-adhesion
CC       activity. {ECO:0000250}.
CC   -!- INTERACTION:
CC       O95500; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-11742599, EBI-12019274;
CC       O95500; P21145: MAL; NbExp=3; IntAct=EBI-11742599, EBI-3932027;
CC       O95500; Q9Y342: PLLP; NbExp=3; IntAct=EBI-11742599, EBI-3919291;
CC   -!- SUBCELLULAR LOCATION: Cell junction, tight junction. Cell membrane;
CC       Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Liver, kidney. Also found in ear.
CC   -!- DISEASE: Deafness, autosomal recessive, 29 (DFNB29) [MIM:614035]: A
CC       form of non-syndromic sensorineural hearing loss. Sensorineural
CC       deafness results from damage to the neural receptors of the inner ear,
CC       the nerve pathways to the brain, or the area of the brain that receives
CC       sound information. {ECO:0000269|PubMed:11163249,
CC       ECO:0000269|PubMed:22246673, ECO:0000269|PubMed:23235333}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
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DR   EMBL; AJ132445; CAA10669.1; -; Genomic_DNA.
DR   EMBL; AF314090; AAG60052.1; -; mRNA.
DR   EMBL; AY355348; AAR05858.1; -; mRNA.
DR   EMBL; AY355349; AAR05859.1; -; mRNA.
DR   EMBL; AJ566765; CAD97762.1; -; mRNA.
DR   EMBL; AJ566766; CAD97763.1; -; mRNA.
DR   EMBL; AY358533; AAQ88897.1; -; mRNA.
DR   EMBL; AP001726; BAA95509.1; -; Genomic_DNA.
DR   EMBL; BC012126; AAH12126.1; -; mRNA.
DR   CCDS; CCDS13645.1; -.
DR   RefSeq; NP_001139549.1; NM_001146077.1.
DR   RefSeq; NP_001139550.1; NM_001146078.2.
DR   RefSeq; NP_001139551.1; NM_001146079.1.
DR   RefSeq; NP_036262.1; NM_012130.3.
DR   RefSeq; NP_652763.1; NM_144492.2.
DR   AlphaFoldDB; O95500; -.
DR   SMR; O95500; -.
DR   BioGRID; 117105; 17.
DR   IntAct; O95500; 4.
DR   STRING; 9606.ENSP00000382090; -.
DR   GlyGen; O95500; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O95500; -.
DR   PhosphoSitePlus; O95500; -.
DR   SwissPalm; O95500; -.
DR   BioMuta; CLDN14; -.
DR   MassIVE; O95500; -.
DR   PaxDb; 9606-ENSP00000382090; -.
DR   PeptideAtlas; O95500; -.
DR   Antibodypedia; 23104; 274 antibodies from 32 providers.
DR   DNASU; 23562; -.
DR   Ensembl; ENST00000342108.2; ENSP00000339292.2; ENSG00000159261.12.
DR   Ensembl; ENST00000399135.6; ENSP00000382087.1; ENSG00000159261.12.
DR   Ensembl; ENST00000399136.5; ENSP00000382088.1; ENSG00000159261.12.
DR   Ensembl; ENST00000399137.5; ENSP00000382090.1; ENSG00000159261.12.
DR   Ensembl; ENST00000399139.5; ENSP00000382092.1; ENSG00000159261.12.
DR   GeneID; 23562; -.
DR   KEGG; hsa:23562; -.
DR   MANE-Select; ENST00000399135.6; ENSP00000382087.1; NM_001146079.2; NP_001139551.1.
DR   UCSC; uc002yvk.3; human.
DR   AGR; HGNC:2035; -.
DR   CTD; 23562; -.
DR   DisGeNET; 23562; -.
DR   GeneCards; CLDN14; -.
DR   GeneReviews; CLDN14; -.
DR   HGNC; HGNC:2035; CLDN14.
DR   HPA; ENSG00000159261; Group enriched (kidney, liver).
DR   MalaCards; CLDN14; -.
DR   MIM; 605608; gene.
DR   MIM; 614035; phenotype.
DR   neXtProt; NX_O95500; -.
DR   OpenTargets; ENSG00000159261; -.
DR   Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR   PharmGKB; PA26561; -.
DR   VEuPathDB; HostDB:ENSG00000159261; -.
DR   eggNOG; ENOG502QR8Z; Eukaryota.
DR   GeneTree; ENSGT00940000161312; -.
DR   HOGENOM; CLU_076370_1_1_1; -.
DR   InParanoid; O95500; -.
DR   OMA; PTAYKDN; -.
DR   OrthoDB; 4040914at2759; -.
DR   PhylomeDB; O95500; -.
DR   TreeFam; TF331936; -.
DR   PathwayCommons; O95500; -.
DR   Reactome; R-HSA-420029; Tight junction interactions.
DR   SignaLink; O95500; -.
DR   BioGRID-ORCS; 23562; 12 hits in 1146 CRISPR screens.
DR   GeneWiki; CLDN14; -.
DR   GenomeRNAi; 23562; -.
DR   Pharos; O95500; Tbio.
DR   PRO; PR:O95500; -.
DR   Proteomes; UP000005640; Chromosome 21.
DR   RNAct; O95500; Protein.
DR   Bgee; ENSG00000159261; Expressed in right lobe of liver and 60 other cell types or tissues.
DR   GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; HDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR   GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0070830; P:bicellular tight junction assembly; IBA:GO_Central.
DR   GO; GO:0016338; P:calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules; ISS:UniProtKB.
DR   GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR   GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR   Gene3D; 1.20.140.150; -; 1.
DR   InterPro; IPR006187; Claudin.
DR   InterPro; IPR017974; Claudin_CS.
DR   InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR   PANTHER; PTHR12002; CLAUDIN; 1.
DR   PANTHER; PTHR12002:SF99; CLAUDIN-14; 1.
DR   Pfam; PF00822; PMP22_Claudin; 1.
DR   PRINTS; PR01077; CLAUDIN.
DR   PRINTS; PR01385; CLAUDIN14.
DR   PROSITE; PS01346; CLAUDIN; 1.
DR   Genevisible; O95500; HS.
PE   1: Evidence at protein level;
KW   Cell junction; Cell membrane; Deafness; Disease variant; Membrane;
KW   Non-syndromic deafness; Reference proteome; Tight junction; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..239
FT                   /note="Claudin-14"
FT                   /id="PRO_0000144769"
FT   TOPO_DOM        1..7
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        8..28
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        29..81
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        82..102
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        103..115
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        116..136
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        137..162
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        163..183
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        184..239
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          196..228
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         4
FT                   /note="T -> M (in dbSNP:rs113831133)"
FT                   /evidence="ECO:0000269|PubMed:12791041,
FT                   ECO:0000269|PubMed:23590985"
FT                   /id="VAR_017227"
FT   VARIANT         81
FT                   /note="R -> H (in DFNB29; dbSNP:rs368027306)"
FT                   /evidence="ECO:0000269|PubMed:22246673,
FT                   ECO:0000269|PubMed:23235333"
FT                   /id="VAR_069979"
FT   VARIANT         85
FT                   /note="V -> D (in DFNB29; dbSNP:rs74315437)"
FT                   /evidence="ECO:0000269|PubMed:11163249,
FT                   ECO:0000269|PubMed:22246673, ECO:0000269|PubMed:23235333"
FT                   /id="VAR_010738"
FT   VARIANT         86
FT                   /note="I -> V"
FT                   /evidence="ECO:0000269|PubMed:23235333"
FT                   /id="VAR_069980"
FT   VARIANT         87
FT                   /note="S -> I (in DFNB29)"
FT                   /evidence="ECO:0000269|PubMed:23235333"
FT                   /id="VAR_069981"
FT   VARIANT         94
FT                   /note="A -> V (in DFNB29)"
FT                   /evidence="ECO:0000269|PubMed:23235333"
FT                   /id="VAR_069982"
FT   VARIANT         232
FT                   /note="G -> R (in DFNB29; dbSNP:rs786204841)"
FT                   /evidence="ECO:0000269|PubMed:22246673"
FT                   /id="VAR_069983"
SQ   SEQUENCE   239 AA;  25699 MW;  DD41652F7FD0E09A CRC64;
     MASTAVQLLG FLLSFLGMVG TLITTILPHW RRTAHVGTNI LTAVSYLKGL WMECVWHSTG
     IYQCQIYRSL LALPQDLQAA RALMVISCLL SGIACACAVI GMKCTRCAKG TPAKTTFAIL
     GGTLFILAGL LCMVAVSWTT NDVVQNFYNP LLPSGMKFEI GQALYLGFIS SSLSLIGGTL
     LCLSCQDEAP YRPYQAPPRA TTTTANTAPA YQPPAAYKDN RAPSVTSATH SGYRLNDYV
//