CLD15_MOUSE
ID CLD15_MOUSE Reviewed; 227 AA.
AC Q9Z0S5; Q9D7Z0; Q9D8A6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Claudin-15;
GN Name=Cldn15;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Small intestine, and Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-122.
RC TISSUE=Lung;
RA Morita K., Furuse M., Tsukita S.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=16505581; DOI=10.1679/aohc.68.349;
RA Inai T., Sengoku A., Guan X., Hirose E., Iida H., Shibata Y.;
RT "Heterogeneity in expression and subcellular localization of tight junction
RT proteins, claudin-10 and -15, examined by RT-PCR and immunofluorescence
RT microscopy.";
RL Arch. Histol. Cytol. 68:349-360(2005).
RN [5]
RP DISRUPTION, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18242218; DOI=10.1053/j.gastro.2007.11.040;
RA Tamura A., Kitano Y., Hata M., Katsuno T., Moriwaki K., Sasaki H.,
RA Hayashi H., Suzuki Y., Noda T., Furuse M., Tsukita S., Tsukita S.;
RT "Megaintestine in claudin-15-deficient mice.";
RL Gastroenterology 134:523-534(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214 AND SER-217, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=20727355; DOI=10.1053/j.gastro.2010.08.006;
RA Tamura A., Hayashi H., Imasato M., Yamazaki Y., Hagiwara A., Wada M.,
RA Noda T., Watanabe M., Suzuki Y., Tsukita S.;
RT "Loss of claudin-15, but not claudin-2, causes Na+ deficiency and glucose
RT malabsorption in mouse small intestine.";
RL Gastroenterology 140:913-923(2011).
RN [8]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23089202; DOI=10.1053/j.gastro.2012.10.035;
RA Wada M., Tamura A., Takahashi N., Tsukita S.;
RT "Loss of claudins 2 and 15 from mice causes defects in paracellular Na+
RT flow and nutrient transport in gut and leads to death from malnutrition.";
RL Gastroenterology 144:369-380(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-194 OF MUTANT
RP ALA-102/ALA-183/ALA-184/ALA-185, SUBCELLULAR LOCATION, SUBUNIT, MUTAGENESIS
RP OF MET-68; CYS-102; 146-PHE-PHE-147 AND 183-CYS--CYS-185, TOPOLOGY,
RP DISULFIDE BOND, AND PALMITOYLATION.
RX PubMed=24744376; DOI=10.1126/science.1248571;
RA Suzuki H., Nishizawa T., Tani K., Yamazaki Y., Tamura A., Ishitani R.,
RA Dohmae N., Tsukita S., Nureki O., Fujiyoshi Y.;
RT "Crystal structure of a claudin provides insight into the architecture of
RT tight junctions.";
RL Science 344:304-307(2014).
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:18242218, ECO:0000269|PubMed:20727355,
CC ECO:0000269|PubMed:23089202}.
CC -!- SUBUNIT: Can form linear homooligomers in the membrane, giving rise to
CC tight junction strand-like structures. {ECO:0000269|PubMed:24744376}.
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 duodenum, jejunum and ileum. Detected
CC on intestinal villi and crypts (at protein level). Ubiquitous. Detected
CC in small intestine, colon, jejunum, heart, kidney and lung.
CC {ECO:0000269|PubMed:16505581, ECO:0000269|PubMed:18242218,
CC ECO:0000269|PubMed:20727355, ECO:0000269|PubMed:23089202}.
CC -!- PTM: Palmitoylated when heterogeneously expressed in S.frugiperda
CC cells. {ECO:0000269|PubMed:24744376}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth and during the
CC first four weeks after birth. After about eight weeks, the upper part
CC of the small intestine is abnormally increased both in length and in
CC thickness with enlarged villi and crypts. The villi are about two times
CC larger than normal, and each is associated with about forty abnormally
CC large crypts instead of the normally observed ratio of ten crypts per
CC villus. In contrast, there is no difference in the size of the lower
CC part of the small intestine. The body weight of mutant mice does not
CC differ from that of wild-type littermates (PubMed:18242218). According
CC to PubMed:20727355, the intestinal mucosa from newborn and adult mutant
CC mice displays strongly decreased transepithelial conductance with
CC strongly reduced paracellular Na(+) permeability, but no major changes
CC in paracellular permeability to Cl(-). Adults show strongly decreased
CC Na(+) levels in the lumen of the small intestine. Mutant mice also
CC display decreased intestinal glucose uptake, probably due to decreased
CC Na(+) levels. According to PubMed:23089202, mutant mice lacking both
CC Cldn2 and Cldn15 display no visible phenotype at birth, but show
CC decreased growth after about 10 days, severe developmental retardation
CC about 14 days after birth, and then die from malnutrition. None survive
CC more than 25 days after birth. Mice lacking both Cldn2 and Cldn15 show
CC abnormally low Na(+) levels in the intestine, leading to decreased
CC intestinal glucose uptake; glucose uptake can be restored to normal
CC levels by addition of Na(+). Likewise, mice lacking both Cldn2 and
CC Cldn15 show decreased intestinal uptake of milk fat, fatty acids, bile
CC acids and amino acids; again, normal bile acid and amino acid uptake
CC can be restored by the addition of Na(+). {ECO:0000269|PubMed:18242218,
CC ECO:0000269|PubMed:20727355, ECO:0000269|PubMed:23089202}.
CC -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
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DR EMBL; AK008227; BAB25544.1; -; mRNA.
DR EMBL; AK008683; BAB25831.1; -; mRNA.
DR EMBL; BC023428; AAH23428.1; -; mRNA.
DR EMBL; AF124427; AAD17331.1; -; mRNA.
DR CCDS; CCDS19758.1; -.
DR RefSeq; NP_068365.1; NM_021719.4.
DR PDB; 4P79; X-ray; 2.40 A; A=2-194.
DR PDBsum; 4P79; -.
DR AlphaFoldDB; Q9Z0S5; -.
DR SMR; Q9Z0S5; -.
DR STRING; 10090.ENSMUSP00000106722; -.
DR TCDB; 1.H.1.1.12; the claudin tight junction (claudin1) family.
DR iPTMnet; Q9Z0S5; -.
DR PhosphoSitePlus; Q9Z0S5; -.
DR MaxQB; Q9Z0S5; -.
DR PaxDb; Q9Z0S5; -.
DR PeptideAtlas; Q9Z0S5; -.
DR PRIDE; Q9Z0S5; -.
DR ProteomicsDB; 283578; -.
DR Antibodypedia; 16744; 201 antibodies from 21 providers.
DR DNASU; 60363; -.
DR Ensembl; ENSMUST00000001790; ENSMUSP00000001790; ENSMUSG00000001739.
DR Ensembl; ENSMUST00000111093; ENSMUSP00000106722; ENSMUSG00000001739.
DR GeneID; 60363; -.
DR KEGG; mmu:60363; -.
DR UCSC; uc009abg.2; mouse.
DR CTD; 24146; -.
DR MGI; MGI:1913103; Cldn15.
DR VEuPathDB; HostDB:ENSMUSG00000001739; -.
DR eggNOG; ENOG502RYAR; Eukaryota.
DR GeneTree; ENSGT00940000157650; -.
DR HOGENOM; CLU_076370_0_2_1; -.
DR InParanoid; Q9Z0S5; -.
DR OMA; FYPGIKY; -.
DR OrthoDB; 1375597at2759; -.
DR PhylomeDB; Q9Z0S5; -.
DR TreeFam; TF331936; -.
DR BioGRID-ORCS; 60363; 7 hits in 72 CRISPR screens.
DR ChiTaRS; Cldn15; mouse.
DR PRO; PR:Q9Z0S5; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9Z0S5; protein.
DR Bgee; ENSMUSG00000001739; Expressed in small intestine Peyer's patch and 117 other tissues.
DR Genevisible; Q9Z0S5; MM.
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; IDA:MGI.
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 3D-structure; Cell junction; Cell membrane; Disulfide bond; Ion transport;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Reference proteome;
KW Tight junction; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..227
FT /note="Claudin-15"
FT /id="PRO_0000144772"
FT TOPO_DOM 1
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24744376"
FT TRANSMEM 2..24
FT /note="Helical"
FT TOPO_DOM 25..74
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24744376"
FT TRANSMEM 75..99
FT /note="Helical"
FT TOPO_DOM 100..115
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24744376"
FT TRANSMEM 116..140
FT /note="Helical"
FT TOPO_DOM 141..159
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24744376"
FT TRANSMEM 160..182
FT /note="Helical"
FT TOPO_DOM 183..227
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24744376"
FT REGION 146..147
FT /note="Important for the formation of tight-junction
FT strand-like structures"
FT SITE 55
FT /note="Important for Na(+)-selective paracellular ion
FT transport"
FT /evidence="ECO:0000250"
FT SITE 64
FT /note="Important for Na(+)-selective paracellular ion
FT transport"
FT /evidence="ECO:0000250"
FT SITE 68
FT /note="Important for the formation of tight-junction
FT strand-like structures"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56746"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:D3ZQJ0"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT DISULFID 52..62
FT /evidence="ECO:0000269|PubMed:24744376"
FT MUTAGEN 68
FT /note="M->A,E: Abolishes formation of tight-junction
FT strand-like structures."
FT /evidence="ECO:0000269|PubMed:24744376"
FT MUTAGEN 68
FT /note="M->I,L: No effect on formation of tight-junction
FT strand-like structures."
FT /evidence="ECO:0000269|PubMed:24744376"
FT MUTAGEN 102
FT /note="C->A: Abolishes palmitoylation; when associated with
FT 183-A--A-185."
FT /evidence="ECO:0000269|PubMed:24744376"
FT MUTAGEN 146..147
FT /note="FF->AA: Abolishes formation of tight-junction
FT strand-like structures."
FT /evidence="ECO:0000269|PubMed:24744376"
FT MUTAGEN 183..185
FT /note="CCC->AAA: Abolishes palmitoylation; when associated
FT with A-102."
FT /evidence="ECO:0000269|PubMed:24744376"
FT CONFLICT 2
FT /note="S -> L (in Ref. 1; BAB25544)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="D -> N (in Ref. 1; BAB25544)"
FT /evidence="ECO:0000305"
FT HELIX 2..24
FT /evidence="ECO:0007829|PDB:4P79"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:4P79"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:4P79"
FT STRAND 48..54
FT /evidence="ECO:0007829|PDB:4P79"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:4P79"
FT HELIX 67..72
FT /evidence="ECO:0007829|PDB:4P79"
FT HELIX 75..99
FT /evidence="ECO:0007829|PDB:4P79"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:4P79"
FT HELIX 110..146
FT /evidence="ECO:0007829|PDB:4P79"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:4P79"
FT HELIX 160..184
FT /evidence="ECO:0007829|PDB:4P79"
SQ SEQUENCE 227 AA; 24280 MW; 7112FE8A6EEF2941 CRC64;
MSVAVETFGF FMSALGLLML GLTLSNSYWR VSTVHGNVIT TNTIFENLWY SCATDSLGVS
NCWDFPSMLA LSGYVQGCRA LMITAILLGF LGLFLGMVGL RCTNVGNMDL SKKAKLLAIA
GTLHILAGAC GMVAISWYAV NITTDFFNPL YAGTKYELGP ALYLGWSASL LSILGGICVF
STCCCSSKEE PATRAGLPYK PSTVVIPRAT SDESDISFGK YGKNAYV
