CLD17_HUMAN
ID CLD17_HUMAN Reviewed; 224 AA.
AC P56750; Q3MJB5; Q6UY37;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Claudin-17;
GN Name=CLDN17; ORFNames=UNQ758/PRO1489;
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 (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 SUBCELLULAR LOCATION, AND INTERACTION WITH OCLN.
RX PubMed=20375010; DOI=10.1074/jbc.m110.104836;
RA Harris H.J., Davis C., Mullins J.G., Hu K., Goodall M., Farquhar M.J.,
RA Mee C.J., McCaffrey K., Young S., Drummer H., Balfe P., McKeating J.A.;
RT "Claudin association with CD81 defines hepatitis C virus entry.";
RL J. Biol. Chem. 285:21092-21102(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP LYS-65.
RX PubMed=22402829; DOI=10.1007/s00018-012-0949-x;
RA Krug S.M., Guenzel D., Conrad M.P., Rosenthal R., Fromm A., Amasheh S.,
RA Schulzke J.D., Fromm M.;
RT "Claudin-17 forms tight junction channels with distinct anion
RT selectivity.";
RL Cell. Mol. Life Sci. 69:2765-2778(2012).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF ARG-31; GLU-44; ARG-45; GLU-48; ARG-56;
RP ARG-59; ARG-61; LYS-65; SER-68; TYR-149 AND HIS-154.
RX PubMed=26194246; DOI=10.1007/s00018-015-1987-y;
RA Conrad M.P., Piontek J., Guenzel D., Fromm M., Krug S.M.;
RT "Molecular basis of claudin-17 anion selectivity.";
RL Cell. Mol. Life Sci. 73:185-200(2016).
CC -!- FUNCTION: Channel-forming tight junction protein with selectivity for
CC anions, including chloride and bicarbonate, and for solutes smaller
CC than 9 Angstrom in diameter. In the kidney proximal tubule, may be
CC involved in quantitative reabsorption of filtered anions. Does not
CC affect water permeability. {ECO:0000269|PubMed:22402829}.
CC -!- SUBUNIT: Interacts with OCLN (PubMed:20375010).
CC {ECO:0000269|PubMed:20375010}.
CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction
CC {ECO:0000269|PubMed:22402829}. Cell membrane
CC {ECO:0000269|PubMed:20375010}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: In the kidney, expressed in the proximal tubule and
CC in the Henle's loop. In the distal convoluted tubule, not expressed in
CC all tubules. Not detected in the collecting duct (at protein level).
CC {ECO:0000269|PubMed:22402829}.
CC -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ88461.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AJ250712; CAB60616.1; -; Genomic_DNA.
DR EMBL; AY358094; AAQ88461.1; ALT_FRAME; mRNA.
DR EMBL; AP001707; BAA95566.1; -; Genomic_DNA.
DR EMBL; BC101503; AAI01504.1; -; mRNA.
DR EMBL; BC101505; AAI01506.1; -; mRNA.
DR CCDS; CCDS13586.1; -.
DR RefSeq; NP_036263.1; NM_012131.2.
DR AlphaFoldDB; P56750; -.
DR SMR; P56750; -.
DR BioGRID; 117667; 9.
DR IntAct; P56750; 2.
DR STRING; 9606.ENSP00000286808; -.
DR TCDB; 1.H.1.1.13; the claudin tight junction (claudin1) family.
DR iPTMnet; P56750; -.
DR PhosphoSitePlus; P56750; -.
DR BioMuta; CLDN17; -.
DR DMDM; 6685309; -.
DR MassIVE; P56750; -.
DR PaxDb; P56750; -.
DR PeptideAtlas; P56750; -.
DR PRIDE; P56750; -.
DR Antibodypedia; 6585; 127 antibodies from 24 providers.
DR DNASU; 26285; -.
DR Ensembl; ENST00000286808.5; ENSP00000286808.3; ENSG00000156282.5.
DR GeneID; 26285; -.
DR KEGG; hsa:26285; -.
DR MANE-Select; ENST00000286808.5; ENSP00000286808.3; NM_012131.3; NP_036263.1.
DR UCSC; uc011acv.3; human.
DR CTD; 26285; -.
DR DisGeNET; 26285; -.
DR GeneCards; CLDN17; -.
DR HGNC; HGNC:2038; CLDN17.
DR HPA; ENSG00000156282; Group enriched (esophagus, salivary gland, vagina).
DR MIM; 617005; gene.
DR neXtProt; NX_P56750; -.
DR OpenTargets; ENSG00000156282; -.
DR PharmGKB; PA26564; -.
DR VEuPathDB; HostDB:ENSG00000156282; -.
DR eggNOG; ENOG502RTNJ; Eukaryota.
DR GeneTree; ENSGT00940000162550; -.
DR HOGENOM; CLU_076370_1_2_1; -.
DR InParanoid; P56750; -.
DR OMA; VCWTANI; -.
DR OrthoDB; 1314055at2759; -.
DR PhylomeDB; P56750; -.
DR TreeFam; TF331936; -.
DR PathwayCommons; P56750; -.
DR Reactome; R-HSA-420029; Tight junction interactions.
DR SignaLink; P56750; -.
DR BioGRID-ORCS; 26285; 10 hits in 1056 CRISPR screens.
DR GeneWiki; CLDN17; -.
DR GenomeRNAi; 26285; -.
DR Pharos; P56750; Tbio.
DR PRO; PR:P56750; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P56750; protein.
DR Bgee; ENSG00000156282; Expressed in lower esophagus mucosa and 41 other tissues.
DR Genevisible; P56750; HS.
DR GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; IEA:UniProtKB-KW.
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 InterPro; IPR006187; Claudin.
DR InterPro; IPR017974; Claudin_CS.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR PANTHER; PTHR12002; PTHR12002; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PROSITE; PS01346; CLAUDIN; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Chloride; Chloride channel; Ion channel;
KW Ion transport; Membrane; Reference proteome; Tight junction; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..224
FT /note="Claudin-17"
FT /id="PRO_0000144777"
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..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 146..164
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186..224
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VARIANT 82
FT /note="A -> T (in dbSNP:rs35531957)"
FT /id="VAR_033774"
FT MUTAGEN 31
FT /note="R->E: Decreased transepithelial resistance and anion
FT selectivity. Higher permeability to chloride, sodium and
FT also to larger anions, including pyruvate, nitrate, and
FT thiocyanate."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 44
FT /note="E->A: Decreased transepithelial resistance and anion
FT selectivity."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 45
FT /note="R->A: Decreased transepithelial resistance, no
FT effect on anion selectivity."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 48
FT /note="E->K,Q: Decreased transepithelial resistance and
FT anion selectivity. Higher permeability to chloride, sodium
FT and also to larger anions, including pyruvate, nitrate, and
FT thiocyanate."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 56
FT /note="R->A: No effect on transepithelial resistance, nor
FT on anion selectivity. Elevated permeabilities not only for
FT chloride, but also for sodium and the larger anions,
FT including pyruvate, nitrate and thiocyanate."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 56
FT /note="R->T: Decreased anion selectivity. Increased
FT permeabilities not only for chloride, but also for sodium
FT and thiocyanate. No effect on transepithelial resistance."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 59
FT /note="R->A: No effect on transepithelial resistance, nor
FT on anion selectivity. Increased permeability for
FT thiocyanate."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 61
FT /note="R->A: Decreased anion selectivity. No effect on
FT transepithelial resistance."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 65
FT /note="K->A: Reduced channel formation ability. Increased
FT transepithelial resistance. Loss of anion selectivity in
FT favor of cation selectivity."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 65
FT /note="K->E: No effect on channel formation ability. Loss
FT of anion selectivity in favor of cation selectivity. No
FT effect on transepithelial resistance."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 65
FT /note="K->R: Strongly reduced channel formation ability.
FT Increased transepithelial resistance. Loss of anion
FT selectivity in favor of cation selectivity."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 68
FT /note="S->E: Increased transepithelial resistance. Loss of
FT anion selectivity in favor of cation (sodium) selectivity."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 149
FT /note="Y->A: Increased transepithelial resistance. No
FT effect on localization to cell-cell junctions."
FT /evidence="ECO:0000269|PubMed:22402829"
FT MUTAGEN 154
FT /note="H->A: Loss of anion selectivity. Strongly increased
FT permeabilities not only for chloride, but also for sodium
FT and the larger anions, including pyruvate, nitrate and
FT thiocyanate. No effect on localization to cell-cell
FT junctions."
FT /evidence="ECO:0000269|PubMed:22402829"
SQ SEQUENCE 224 AA; 24603 MW; 1833ED3178B7F63A CRC64;
MAFYPLQIAG LVLGFLGMVG TLATTLLPQW RVSAFVGSNI IVFERLWEGL WMNCIRQARV
RLQCKFYSSL LALPPALETA RALMCVAVAL SLIALLIGIC GMKQVQCTGS NERAKAYLLG
TSGVLFILTG IFVLIPVSWT ANIIIRDFYN PAIHIGQKRE LGAALFLGWA SAAVLFIGGG
LLCGFCCCNR KKQGYRYPVP GYRVPHTDKR RNTTMLSKTS TSYV
