CLD16_HUMAN
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 03-AUG-2022, entry version 174.
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; CCDS3296.1; -.
DR RefSeq; NP_006571.1; NM_006580.3.
DR AlphaFoldDB; 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; Q9Y5I7; -.
DR PeptideAtlas; Q9Y5I7; -.
DR PRIDE; Q9Y5I7; -.
DR ProteomicsDB; 86416; -.
DR Antibodypedia; 19357; 201 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 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 OrthoDB; 1169036at2759; -.
DR PhylomeDB; Q9Y5I7; -.
DR TreeFam; TF331936; -.
DR PathwayCommons; Q9Y5I7; -.
DR Reactome; R-HSA-420029; Tight junction interactions.
DR SignaLink; Q9Y5I7; -.
DR BioGRID-ORCS; 10686; 4 hits in 1058 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 olfactory segment of nasal mucosa and 81 other tissues.
DR ExpressionAtlas; Q9Y5I7; baseline and differential.
DR Genevisible; Q9Y5I7; HS.
DR GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0006875; P:cellular metal ion homeostasis; TAS:ProtInc.
DR GO; GO:0010496; P:intercellular transport; TAS:ProtInc.
DR GO; GO:0030001; P:metal ion transport; TAS:UniProtKB.
DR InterPro; IPR006187; Claudin.
DR InterPro; IPR003927; Claudin16.
DR InterPro; IPR017974; Claudin_CS.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR PANTHER; PTHR12002; PTHR12002; 1.
DR PANTHER; PTHR12002:SF56; PTHR12002:SF56; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PRINTS; PR01447; CLAUDIN16.
DR PROSITE; PS01346; CLAUDIN; 1.
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
