ID   CLD16_HUMAN             Reviewed;         235 AA.
AC   Q9Y5I7;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   23-FEB-2022, sequence version 2.
DT   24-JAN-2024, entry version 182.
DE   RecName: Full=Claudin-16;
DE   AltName: Full=Paracellin-1;
DE            Short=PCLN-1;
GN   Name=CLDN16; Synonyms=PCLN1;
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 [MRNA], AND VARIANTS HOMG3 PRO-97; ARG-121; ASP-128;
RP   CYS-162; ASP-163; PHE-165 AND ARG-169.
RX   PubMed=10390358; DOI=10.1126/science.285.5424.103;
RA   Simon D.B., Lu Y., Choate K.A., Velazquez H., Al-Sabban E., Praga M.,
RA   Casari G., Bettinelli A., Colussi G., Rodriguez-Soriano J., McCredie D.,
RA   Milford D., Sanjad S., Lifton R.P.;
RT   "Paracellin-1, a renal tight junction protein required for paracellular
RT   Mg2+ resorption.";
RL   Science 285:103-106(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [3]
RP   VARIANTS HOMG3 ASP-71; PRO-75; PHE-81; PRO-81; TRP-81; ASP-128 AND ARG-169.
RX   PubMed=10878661; DOI=10.1038/sj.ejhg.5200475;
RA   Weber S., Hoffmann K., Jeck N., Saar K., Boeswald M., Kuwertz-Broeking E.,
RA   Meij I.I., Knoers N.V., Cochat P., Sulakova T., Bonzel K.E., Soergel M.,
RA   Manz F., Schaerer K., Seyberth H.W., Reis A., Konrad M.;
RT   "Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to
RT   chromosome 3q27 and is associated with mutations in the PCLN-1 gene.";
RL   Eur. J. Hum. Genet. 8:414-422(2000).
RN   [4]
RP   VARIANTS HOMG3 ASP-71; PRO-75; LEU-79; PHE-81; TRP-81; ALA-128; THR-139;
RP   THR-146; PRO-165 AND ARG-169.
RX   PubMed=11518780; DOI=10.1681/asn.v1291872;
RA   Weber S., Schneider L., Peters M., Misselwitz J., Roennefarth G.,
RA   Boeswald M., Bonzel K.E., Seeman T., Sulakova T., Kuwertz-Broeking E.,
RA   Gregoric A., Palcoux J.-B., Tasic V., Manz F., Schaerer K., Seyberth H.W.,
RA   Konrad M.;
RT   "Novel paracellin-1 mutations in 25 families with familial hypomagnesemia
RT   with hypercalciuria and nephrocalcinosis.";
RL   J. Am. Soc. Nephrol. 12:1872-1881(2001).
CC   -!- FUNCTION: Plays a major role in tight junction-specific obliteration of
CC       the intercellular space, through calcium-independent cell-adhesion
CC       activity. Involved in paracellular magnesium reabsorption. Required for
CC       a selective paracellular conductance. May form, alone or in partnership
CC       with other constituents, an intercellular pore permitting paracellular
CC       passage of magnesium and calcium ions down their electrochemical
CC       gradients. Alternatively, it could be a sensor of magnesium
CC       concentration that could alter paracellular permeability mediated by
CC       other factors.
CC   -!- INTERACTION:
CC       Q9Y5I7; Q9Z0S3: Cldn14; Xeno; NbExp=3; IntAct=EBI-7774981, EBI-7774956;
CC   -!- SUBCELLULAR LOCATION: Cell junction, tight junction. Cell membrane;
CC       Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Kidney-specific, including the thick ascending limb
CC       of Henle (TAL).
CC   -!- DISEASE: Hypomagnesemia 3 (HOMG3) [MIM:248250]: A progressive renal
CC       disease characterized by primary renal magnesium wasting with
CC       hypomagnesemia, hypercalciuria and nephrocalcinosis. Recurrent urinary
CC       tract infections and kidney stones are often observed. In spite of
CC       hypercalciuria, patients do not show hypocalcemia.
CC       {ECO:0000269|PubMed:10390358, ECO:0000269|PubMed:10878661,
CC       ECO:0000269|PubMed:11518780}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
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DR   EMBL; AF152101; AAD43096.1; -; mRNA.
DR   EMBL; BC069662; AAH69662.1; -; mRNA.
DR   EMBL; BC069682; AAH69682.1; -; mRNA.
DR   EMBL; BC069759; AAH69759.1; -; mRNA.
DR   EMBL; BC069777; AAH69777.1; -; mRNA.
DR   CCDS; CCDS3296.2; -.
DR   RefSeq; NP_006571.1; NM_006580.3.
DR   AlphaFoldDB; Q9Y5I7; -.
DR   SMR; Q9Y5I7; -.
DR   BioGRID; 115925; 3.
DR   DIP; DIP-48951N; -.
DR   IntAct; Q9Y5I7; 3.
DR   MINT; Q9Y5I7; -.
DR   STRING; 9606.ENSP00000264734; -.
DR   DrugBank; DB14513; Magnesium.
DR   TCDB; 1.H.1.1.1; the claudin tight junction (claudin1) family.
DR   iPTMnet; Q9Y5I7; -.
DR   PhosphoSitePlus; Q9Y5I7; -.
DR   BioMuta; CLDN16; -.
DR   DMDM; 6685318; -.
DR   MassIVE; Q9Y5I7; -.
DR   PaxDb; 9606-ENSP00000264734; -.
DR   PeptideAtlas; Q9Y5I7; -.
DR   ProteomicsDB; 86416; -.
DR   Antibodypedia; 19357; 219 antibodies from 25 providers.
DR   DNASU; 10686; -.
DR   Ensembl; ENST00000264734.3; ENSP00000264734.3; ENSG00000113946.4.
DR   GeneID; 10686; -.
DR   KEGG; hsa:10686; -.
DR   MANE-Select; ENST00000264734.3; ENSP00000264734.3; NM_006580.4; NP_006571.2.
DR   UCSC; uc003fsi.3; human.
DR   AGR; HGNC:2037; -.
DR   CTD; 10686; -.
DR   DisGeNET; 10686; -.
DR   GeneCards; CLDN16; -.
DR   HGNC; HGNC:2037; CLDN16.
DR   HPA; ENSG00000113946; Tissue enriched (kidney).
DR   MalaCards; CLDN16; -.
DR   MIM; 248250; phenotype.
DR   MIM; 603959; gene.
DR   neXtProt; NX_Q9Y5I7; -.
DR   OpenTargets; ENSG00000113946; -.
DR   Orphanet; 31043; Primary hypomagnesemia with hypercalciuria and nephrocalcinosis without severe ocular involvement.
DR   PharmGKB; PA26563; -.
DR   VEuPathDB; HostDB:ENSG00000113946; -.
DR   eggNOG; ENOG502QRY9; Eukaryota.
DR   GeneTree; ENSGT00730000111162; -.
DR   HOGENOM; CLU_079378_0_0_1; -.
DR   InParanoid; Q9Y5I7; -.
DR   OMA; GLHCVKF; -.
DR   PhylomeDB; Q9Y5I7; -.
DR   TreeFam; TF331936; -.
DR   PathwayCommons; Q9Y5I7; -.
DR   Reactome; R-HSA-420029; Tight junction interactions.
DR   SignaLink; Q9Y5I7; -.
DR   BioGRID-ORCS; 10686; 5 hits in 1135 CRISPR screens.
DR   ChiTaRS; CLDN16; human.
DR   GeneWiki; CLDN16; -.
DR   GenomeRNAi; 10686; -.
DR   Pharos; Q9Y5I7; Tbio.
DR   PRO; PR:Q9Y5I7; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q9Y5I7; Protein.
DR   Bgee; ENSG00000113946; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 81 other cell types or tissues.
DR   ExpressionAtlas; Q9Y5I7; baseline and differential.
DR   GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR   GO; GO:0015095; F:magnesium ion transmembrane transporter activity; TAS:ProtInc.
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:0010496; P:intercellular transport; TAS:ProtInc.
DR   GO; GO:0030003; P:intracellular monoatomic cation homeostasis; TAS:ProtInc.
DR   GO; GO:0030001; P:metal ion transport; TAS:UniProtKB.
DR   Gene3D; 1.20.140.150; -; 1.
DR   InterPro; IPR006187; Claudin.
DR   InterPro; IPR003927; Claudin16.
DR   InterPro; IPR017974; Claudin_CS.
DR   InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR   PANTHER; PTHR12002; CLAUDIN; 1.
DR   PANTHER; PTHR12002:SF56; CLAUDIN-16; 1.
DR   Pfam; PF00822; PMP22_Claudin; 1.
DR   PRINTS; PR01077; CLAUDIN.
DR   PRINTS; PR01447; CLAUDIN16.
DR   PROSITE; PS01346; CLAUDIN; 1.
DR   Genevisible; Q9Y5I7; HS.
PE   1: Evidence at protein level;
KW   Cell junction; Cell membrane; Disease variant; Ion transport; Magnesium;
KW   Membrane; Primary hypomagnesemia; Reference proteome; Tight junction;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..235
FT                   /note="Claudin-16"
FT                   /id="PRO_0000144774"
FT   TOPO_DOM        1..3
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        4..24
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        25..79
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        80..100
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        101..115
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        116..136
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        137..169
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        170..190
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        191..235
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   VARIANT         71
FT                   /note="H -> D (in HOMG3)"
FT                   /evidence="ECO:0000269|PubMed:10878661,
FT                   ECO:0000269|PubMed:11518780"
FT                   /id="VAR_017228"
FT   VARIANT         75
FT                   /note="L -> P (in HOMG3; dbSNP:rs104893731)"
FT                   /evidence="ECO:0000269|PubMed:10878661,
FT                   ECO:0000269|PubMed:11518780"
FT                   /id="VAR_017229"
FT   VARIANT         79
FT                   /note="R -> L (in HOMG3; dbSNP:rs968906940)"
FT                   /evidence="ECO:0000269|PubMed:11518780"
FT                   /id="VAR_017230"
FT   VARIANT         81
FT                   /note="L -> F (in HOMG3; dbSNP:rs104893729)"
FT                   /evidence="ECO:0000269|PubMed:10878661,
FT                   ECO:0000269|PubMed:11518780"
FT                   /id="VAR_017231"
FT   VARIANT         81
FT                   /note="L -> P (in HOMG3)"
FT                   /evidence="ECO:0000269|PubMed:10878661"
FT                   /id="VAR_017232"
FT   VARIANT         81
FT                   /note="L -> W (in HOMG3; dbSNP:rs104893730)"
FT                   /evidence="ECO:0000269|PubMed:10878661,
FT                   ECO:0000269|PubMed:11518780"
FT                   /id="VAR_017233"
FT   VARIANT         97
FT                   /note="L -> P (in HOMG3; dbSNP:rs104893725)"
FT                   /evidence="ECO:0000269|PubMed:10390358"
FT                   /id="VAR_008174"
FT   VARIANT         121
FT                   /note="G -> R (in HOMG3; dbSNP:rs104893722)"
FT                   /evidence="ECO:0000269|PubMed:10390358"
FT                   /id="VAR_008175"
FT   VARIANT         128
FT                   /note="G -> A (in HOMG3)"
FT                   /evidence="ECO:0000269|PubMed:11518780"
FT                   /id="VAR_017234"
FT   VARIANT         128
FT                   /note="G -> D (in HOMG3; dbSNP:rs104893723)"
FT                   /evidence="ECO:0000269|PubMed:10390358,
FT                   ECO:0000269|PubMed:10878661"
FT                   /id="VAR_008176"
FT   VARIANT         139
FT                   /note="A -> T (in HOMG3; dbSNP:rs1270704258)"
FT                   /evidence="ECO:0000269|PubMed:11518780"
FT                   /id="VAR_017235"
FT   VARIANT         146
FT                   /note="R -> T (in HOMG3)"
FT                   /evidence="ECO:0000269|PubMed:11518780"
FT                   /id="VAR_017236"
FT   VARIANT         162
FT                   /note="F -> C (in HOMG3; dbSNP:rs104893726)"
FT                   /evidence="ECO:0000269|PubMed:10390358"
FT                   /id="VAR_008177"
FT   VARIANT         163
FT                   /note="G -> D (in HOMG3; dbSNP:rs104893727)"
FT                   /evidence="ECO:0000269|PubMed:10390358"
FT                   /id="VAR_008178"
FT   VARIANT         165
FT                   /note="S -> F (in HOMG3; dbSNP:rs104893728)"
FT                   /evidence="ECO:0000269|PubMed:10390358"
FT                   /id="VAR_008179"
FT   VARIANT         165
FT                   /note="S -> P (in HOMG3)"
FT                   /evidence="ECO:0000269|PubMed:11518780"
FT                   /id="VAR_017237"
FT   VARIANT         169
FT                   /note="G -> R (in HOMG3; dbSNP:rs104893721)"
FT                   /evidence="ECO:0000269|PubMed:10390358,
FT                   ECO:0000269|PubMed:10878661, ECO:0000269|PubMed:11518780"
FT                   /id="VAR_008172"
SQ   SEQUENCE   235 AA;  26078 MW;  258633C2920B8807 CRC64;
     MRDLLQYIAC FFAFFSAGFL IVATWTDCWM VNADDSLEVS TKCRGLWWEC VTNAFDGIRT
     CDEYDSILAE HPLKLVVTRA LMITADILAG FGFLTLLLGL DCVKFLPDEP YIKVRICFVA
     GATLLIAGTP GIIGSVWYAV DVYVERSTLV LHNIFLGIQY KFGWSCWLGM AGSLGCFLAG
     AVLTCCLYLF KDVGPERNYP YSLRKAYSAA GVSMAKSYSA PRTETAKMYA VDTRV
//