CLD15_HUMAN
ID CLD15_HUMAN Reviewed; 228 AA.
AC P56746; B3KPB5;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Claudin-15;
GN Name=CLDN15;
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].
RC TISSUE=Kidney;
RA Keen T.J., Inglehearn C.F.;
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP GLU-46; ASP-55 AND GLU-64.
RX PubMed=12055082; DOI=10.1152/ajpcell.00038.2002;
RA Colegio O.R., Van Itallie C.M., McCrea H.J., Rahner C., Anderson J.M.;
RT "Claudins create charge-selective channels in the paracellular pathway
RT between epithelial cells.";
RL Am. J. Physiol. 283:C142-C147(2002).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=13129853; DOI=10.1152/ajprenal.00116.2003;
RA Van Itallie C.M., Fanning A.S., Anderson J.M.;
RT "Reversal of charge selectivity in cation or anion-selective epithelial
RT lines by expression of different claudins.";
RL Am. J. Physiol. 285:F1078-F1084(2003).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
CC -!- FUNCTION: Claudins function as major constituents of the tight junction
CC complexes that regulate the permeability of epithelia. While some
CC claudin family members function as impermeable barriers, others mediate
CC the permeability to ions and small molecules. Often, several claudin
CC family members are coexpressed and interact with each other, and this
CC determines the overall permeability. CLDN15 forms tight junctions that
CC mediate the paracellular transport of small monovalent cations along a
CC concentration gradient, due to selective permeability for Na(+), Li(+)
CC and K(+) ions, but selects against Cl(-) ions. Plays an important role
CC in paracellular Na(+) transport in the intestine and in Na(+)
CC homeostasis. Required for normal Na(+)-dependent intestinal nutrient
CC uptake. {ECO:0000269|PubMed:12055082, ECO:0000269|PubMed:13129853}.
CC -!- SUBUNIT: Can form linear homooligomers in the membrane, giving rise to
CC tight junction strand-like structures.
CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction. Cell membrane;
CC Multi-pass membrane protein. Note=Tight junctions form continuous
CC circumferential cell-cell contacts at the borders of apical and lateral
CC cell membranes that seal the intercellular space and show up as strand-
CC like structures in electron microscopy.
CC -!- TISSUE SPECIFICITY: Detected in colon (at protein level).
CC {ECO:0000269|PubMed:12055082}.
CC -!- PTM: Palmitoylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
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DR EMBL; AJ245738; CAB52587.1; -; mRNA.
DR EMBL; AK056103; BAG51627.1; -; mRNA.
DR EMBL; CH471197; EAW50211.1; -; Genomic_DNA.
DR CCDS; CCDS5717.1; -.
DR RefSeq; NP_001172009.1; NM_001185080.1.
DR RefSeq; NP_055158.1; NM_014343.2.
DR AlphaFoldDB; P56746; -.
DR SMR; P56746; -.
DR BioGRID; 117296; 4.
DR IntAct; P56746; 1.
DR STRING; 9606.ENSP00000385300; -.
DR TCDB; 1.H.1.1.9; the claudin tight junction (claudin1) family.
DR iPTMnet; P56746; -.
DR PhosphoSitePlus; P56746; -.
DR BioMuta; CLDN15; -.
DR DMDM; 6685306; -.
DR jPOST; P56746; -.
DR MassIVE; P56746; -.
DR PaxDb; P56746; -.
DR PeptideAtlas; P56746; -.
DR PRIDE; P56746; -.
DR ProteomicsDB; 56942; -.
DR Antibodypedia; 16744; 201 antibodies from 21 providers.
DR DNASU; 24146; -.
DR Ensembl; ENST00000308344.10; ENSP00000308870.5; ENSG00000106404.14.
DR Ensembl; ENST00000401528.5; ENSP00000385300.1; ENSG00000106404.14.
DR GeneID; 24146; -.
DR KEGG; hsa:24146; -.
DR MANE-Select; ENST00000308344.10; ENSP00000308870.5; NM_014343.3; NP_055158.1.
DR UCSC; uc003uyg.2; human.
DR CTD; 24146; -.
DR DisGeNET; 24146; -.
DR GeneCards; CLDN15; -.
DR HGNC; HGNC:2036; CLDN15.
DR HPA; ENSG00000106404; Tissue enriched (intestine).
DR MIM; 615778; gene.
DR neXtProt; NX_P56746; -.
DR OpenTargets; ENSG00000106404; -.
DR PharmGKB; PA26562; -.
DR VEuPathDB; HostDB:ENSG00000106404; -.
DR eggNOG; ENOG502RYAR; Eukaryota.
DR GeneTree; ENSGT00940000157650; -.
DR InParanoid; P56746; -.
DR OMA; FYPGIKY; -.
DR OrthoDB; 1375597at2759; -.
DR PhylomeDB; P56746; -.
DR TreeFam; TF331936; -.
DR PathwayCommons; P56746; -.
DR Reactome; R-HSA-420029; Tight junction interactions.
DR SignaLink; P56746; -.
DR BioGRID-ORCS; 24146; 19 hits in 1079 CRISPR screens.
DR GeneWiki; CLDN15; -.
DR GenomeRNAi; 24146; -.
DR Pharos; P56746; Tbio.
DR PRO; PR:P56746; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P56746; protein.
DR Bgee; ENSG00000106404; Expressed in jejunal mucosa and 137 other tissues.
DR ExpressionAtlas; P56746; baseline and differential.
DR Genevisible; P56746; 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:0016328; C:lateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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:0006811; P:ion transport; IEA:UniProtKB-KW.
DR InterPro; IPR006187; Claudin.
DR InterPro; IPR008094; Claudin15.
DR InterPro; IPR017974; Claudin_CS.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR PANTHER; PTHR12002; PTHR12002; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PRINTS; PR01718; CLAUDIN15.
DR PROSITE; PS01346; CLAUDIN; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Disulfide bond; Ion transport; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Reference proteome; Tight junction;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..228
FT /note="Claudin-15"
FT /id="PRO_0000144771"
FT TOPO_DOM 1
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 2..24
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 25..74
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 75..99
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 100..115
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 116..140
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 141..159
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 160..182
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 183..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 146..147
FT /note="Important for the formation of tight-junction
FT strand-like structures"
FT /evidence="ECO:0000250"
FT REGION 208..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 55
FT /note="Important for Na(+)-selective paracellular ion
FT transport"
FT SITE 64
FT /note="Important for Na(+)-selective paracellular ion
FT transport"
FT SITE 68
FT /note="Important for the formation of tight-junction
FT strand-like structures"
FT /evidence="ECO:0000250"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:D3ZQJ0"
FT MOD_RES 218
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0S5"
FT DISULFID 52..62
FT /evidence="ECO:0000250"
FT MUTAGEN 46
FT /note="E->K: No effect on charge selectivity for
FT paracellular ion transport."
FT /evidence="ECO:0000269|PubMed:12055082"
FT MUTAGEN 55
FT /note="D->R: Reverses the charge selectivity for
FT paracellular ion transport, favoring Cl(-) transport."
FT /evidence="ECO:0000269|PubMed:12055082"
FT MUTAGEN 64
FT /note="E->K: Impairs the charge selectivity for
FT paracellular ion transport, favoring Cl(-) transport."
FT /evidence="ECO:0000269|PubMed:12055082"
SQ SEQUENCE 228 AA; 24356 MW; D502E2CD9116F4B1 CRC64;
MSMAVETFGF FMATVGLLML GVTLPNSYWR VSTVHGNVIT TNTIFENLWF SCATDSLGVY
NCWEFPSMLA LSGYIQACRA LMITAILLGF LGLLLGIAGL RCTNIGGLEL SRKAKLAATA
GALHILAGIC GMVAISWYAF NITRDFFDPL YPGTKYELGP ALYLGWSASL ISILGGLCLC
SACCCGSDED PAASARRPYQ APVSVMPVAT SDQEGDSSFG KYGRNAYV
