CLD18_HUMAN
ID CLD18_HUMAN Reviewed; 261 AA.
AC P56856; A5PL21; Q96PH4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Claudin-18;
GN Name=CLDN18; ORFNames=UNQ778/PRO1572;
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 ALTERNATIVE SPLICING.
RX PubMed=11585919; DOI=10.1128/mcb.21.21.7380-7390.2001;
RA Niimi T., Nagashima K., Ward J.M., Minoo P., Zimonjic D.B., Popescu N.C.,
RA Kimura S.;
RT "Claudin-18, a novel downstream target gene for the T/EBP/NKX2.1
RT homeodomain transcription factor, encodes lung- and stomach-specific
RT isoforms through alternative splicing.";
RL Mol. Cell. Biol. 21:7380-7390(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A1).
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].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A1).
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 TISSUE SPECIFICITY.
RX PubMed=19047087; DOI=10.1158/1078-0432.ccr-08-1547;
RA Sahin U., Koslowski M., Dhaene K., Usener D., Brandenburg G., Seitz G.,
RA Huber C., Tuereci O.;
RT "Claudin-18 splice variant 2 is a pan-cancer target suitable for
RT therapeutic antibody development.";
RL Clin. Cancer Res. 14:7624-7634(2008).
CC -!- FUNCTION: Plays a major role in tight junction-specific obliteration of
CC the intercellular space, through calcium-independent cell-adhesion
CC activity. {ECO:0000250}.
CC -!- INTERACTION:
CC P56856; Q08426: EHHADH; NbExp=3; IntAct=EBI-16354902, EBI-2339219;
CC P56856; Q01453: PMP22; NbExp=3; IntAct=EBI-16354902, EBI-2845982;
CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction
CC {ECO:0000250|UniProtKB:P56857}. Cell membrane
CC {ECO:0000250|UniProtKB:P56857}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localizes to tight junctions in epithelial cells.
CC {ECO:0000250|UniProtKB:P56857}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A1 {ECO:0000303|PubMed:11585919}; Synonyms=CLDN18.1
CC {ECO:0000303|PubMed:19047087};
CC IsoId=P56856-1; Sequence=Displayed;
CC Name=A2 {ECO:0000303|PubMed:11585919}; Synonyms=CLDN18.2
CC {ECO:0000303|PubMed:19047087};
CC IsoId=P56856-2; Sequence=VSP_001102;
CC -!- TISSUE SPECIFICITY: Isoform A1: Expression is restricted to the lung
CC (PubMed:19047087). Isoform A2: Expression is restricted to the stomach
CC mucosa where it is predominantly observed in the epithelial cells of
CC the pit region and the base of the gastric glands including exocrine
CC and endocrine cells (at protein level) (PubMed:19047087).
CC {ECO:0000269|PubMed:19047087}.
CC -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
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DR EMBL; AF221069; AAF26448.1; -; mRNA.
DR EMBL; AF349452; AAL15637.1; -; mRNA.
DR EMBL; AY358479; AAQ88843.1; -; mRNA.
DR EMBL; CH471052; EAW79092.1; -; Genomic_DNA.
DR EMBL; BC142708; AAI42709.1; -; mRNA.
DR EMBL; BC146668; AAI46669.1; -; mRNA.
DR CCDS; CCDS3095.1; -. [P56856-1]
DR CCDS; CCDS33862.1; -. [P56856-2]
DR RefSeq; NP_001002026.1; NM_001002026.2. [P56856-2]
DR RefSeq; NP_057453.1; NM_016369.3. [P56856-1]
DR AlphaFoldDB; P56856; -.
DR SMR; P56856; -.
DR BioGRID; 119381; 37.
DR DIP; DIP-48955N; -.
DR IntAct; P56856; 6.
DR STRING; 9606.ENSP00000183605; -.
DR ChEMBL; CHEMBL3712859; -.
DR GlyConnect; 2029; 1 N-Linked glycan (1 site).
DR GlyGen; P56856; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; P56856; -.
DR PhosphoSitePlus; P56856; -.
DR BioMuta; CLDN18; -.
DR DMDM; 7387578; -.
DR MassIVE; P56856; -.
DR PaxDb; P56856; -.
DR PeptideAtlas; P56856; -.
DR PRIDE; P56856; -.
DR ProteomicsDB; 56953; -. [P56856-1]
DR ProteomicsDB; 56954; -. [P56856-2]
DR ABCD; P56856; 1 sequenced antibody.
DR Antibodypedia; 4575; 209 antibodies from 29 providers.
DR DNASU; 51208; -.
DR Ensembl; ENST00000183605.10; ENSP00000183605.5; ENSG00000066405.13. [P56856-1]
DR Ensembl; ENST00000343735.8; ENSP00000340939.4; ENSG00000066405.13. [P56856-2]
DR GeneID; 51208; -.
DR KEGG; hsa:51208; -.
DR MANE-Select; ENST00000183605.10; ENSP00000183605.5; NM_016369.4; NP_057453.1.
DR UCSC; uc003ero.2; human. [P56856-1]
DR CTD; 51208; -.
DR DisGeNET; 51208; -.
DR GeneCards; CLDN18; -.
DR HGNC; HGNC:2039; CLDN18.
DR HPA; ENSG00000066405; Group enriched (lung, stomach).
DR MIM; 609210; gene.
DR neXtProt; NX_P56856; -.
DR OpenTargets; ENSG00000066405; -.
DR PharmGKB; PA26565; -.
DR VEuPathDB; HostDB:ENSG00000066405; -.
DR eggNOG; ENOG502QTRB; Eukaryota.
DR GeneTree; ENSGT00940000158655; -.
DR HOGENOM; CLU_076370_2_1_1; -.
DR InParanoid; P56856; -.
DR OMA; TICQVMG; -.
DR OrthoDB; 1079889at2759; -.
DR PhylomeDB; P56856; -.
DR TreeFam; TF331936; -.
DR PathwayCommons; P56856; -.
DR Reactome; R-HSA-420029; Tight junction interactions.
DR SignaLink; P56856; -.
DR BioGRID-ORCS; 51208; 12 hits in 1063 CRISPR screens.
DR ChiTaRS; CLDN18; human.
DR GeneWiki; CLDN18; -.
DR GenomeRNAi; 51208; -.
DR Pharos; P56856; Tbio.
DR PRO; PR:P56856; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P56856; protein.
DR Bgee; ENSG00000066405; Expressed in pylorus and 136 other tissues.
DR ExpressionAtlas; P56856; baseline and differential.
DR Genevisible; P56856; 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: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:0048565; P:digestive tract development; IEA:Ensembl.
DR GO; GO:0045779; P:negative regulation of bone resorption; IEA:Ensembl.
DR GO; GO:2001205; P:negative regulation of osteoclast development; IEA:Ensembl.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0071847; P:TNFSF11-mediated signaling pathway; IEA:Ensembl.
DR InterPro; IPR006187; Claudin.
DR InterPro; IPR003928; Claudin18.
DR InterPro; IPR017974; Claudin_CS.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR PANTHER; PTHR12002; PTHR12002; 1.
DR PANTHER; PTHR12002:SF9; PTHR12002:SF9; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PRINTS; PR01448; CLAUDIN18.
DR PROSITE; PS01346; CLAUDIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Membrane;
KW Phosphoprotein; Reference proteome; Tight junction; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..261
FT /note="Claudin-18"
FT /id="PRO_0000144779"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..80
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 102..122
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 144..174
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 196..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 242..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56857"
FT VAR_SEQ 1..69
FT /note="MSTTTCQVVAFLLSILGLAGCIAATGMDMWSTQDLYDNPVTSVFQYEGLWRS
FT CVRQSSGFTECRPYFTI -> MAVTACQGLGFVVSLIGIAGIIAATCMDQWSTQDLYNN
FT PVTAVFNYQGLWRSCVRESSGFTECRGYFTL (in isoform A2)"
FT /evidence="ECO:0000305"
FT /id="VSP_001102"
FT VARIANT 149
FT /note="M -> L (in dbSNP:rs17204075)"
FT /id="VAR_033775"
SQ SEQUENCE 261 AA; 27856 MW; 4362B590D3C2B387 CRC64;
MSTTTCQVVA FLLSILGLAG CIAATGMDMW STQDLYDNPV TSVFQYEGLW RSCVRQSSGF
TECRPYFTIL GLPAMLQAVR ALMIVGIVLG AIGLLVSIFA LKCIRIGSME DSAKANMTLT
SGIMFIVSGL CAIAGVSVFA NMLVTNFWMS TANMYTGMGG MVQTVQTRYT FGAALFVGWV
AGGLTLIGGV MMCIACRGLA PEETNYKAVS YHASGHSVAY KPGGFKASTG FGSNTKNKKI
YDGGARTEDE VQSYPSKHDY V
