ID   CLD8_HUMAN              Reviewed;         225 AA.
AC   P56748; D3DSE3; Q53EX7;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 176.
DE   RecName: Full=Claudin-8;
GN   Name=CLDN8 {ECO:0000312|HGNC:HGNC:2050};
GN   ORFNames=UNQ779/PRO1573 {ECO:0000303|Ref.1};
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 [GENOMIC DNA].
RA   Keen T.J., Inglehearn C.F.;
RL   Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 MRNA], AND VARIANT PRO-151.
RC   TISSUE=Colon;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10830953; DOI=10.1038/35012518;
RA   Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA   Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA   Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA   Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA   Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA   Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA   Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA   Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA   Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA   Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA   Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT   "The DNA sequence of human chromosome 21.";
RL   Nature 405:311-319(2000).
RN   [5]
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
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   [7]
RP   TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=17287494; DOI=10.1095/biolreprod.106.059246;
RA   Dube E., Chan P.T.K., Hermo L., Cyr D.G.;
RT   "Gene expression profiling and its relevance to the blood-epididymal
RT   barrier in the human epididymis.";
RL   Biol. Reprod. 76:1034-1044(2007).
RN   [8]
RP   MISCELLANEOUS.
RX   PubMed=22042635; DOI=10.1074/mcp.m111.013458;
RA   Uhlen M., Oksvold P., Algenas C., Hamsten C., Fagerberg L., Klevebring D.,
RA   Lundberg E., Odeberg J., Ponten F., Kondo T., Sivertsson A.;
RT   "Antibody-based protein profiling of the human chromosome 21.";
RL   Mol. Cell. Proteomics 11:M111.013458-M111.013458(2012).
CC   -!- FUNCTION: Tight-junction protein required for paracellular chloride
CC       transport in the kidney. Mediates recruitment of CLDN4 to tight
CC       junction in the kidney. Claudins play a major role in tight junction-
CC       specific obliteration of the intercellular space, through calcium-
CC       independent cell-adhesion activity. {ECO:0000250|UniProtKB:Q9Z260}.
CC   -!- SUBUNIT: Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3.
CC       Interacts with CLDN4. Interacts with KLHL3.
CC       {ECO:0000250|UniProtKB:Q9Z260}.
CC   -!- INTERACTION:
CC       P56748; Q8TC27: ADAM32; NbExp=3; IntAct=EBI-10215641, EBI-18273040;
CC       P56748; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-10215641, EBI-11343438;
CC       P56748; Q6ZS10: CLEC17A; NbExp=3; IntAct=EBI-10215641, EBI-11977093;
CC       P56748; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-10215641, EBI-781551;
CC       P56748; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-10215641, EBI-749265;
CC       P56748; P35372-10: OPRM1; NbExp=3; IntAct=EBI-10215641, EBI-12807478;
CC       P56748; Q99640-2: PKMYT1; NbExp=3; IntAct=EBI-10215641, EBI-12257782;
CC       P56748; Q9BZL3: SMIM3; NbExp=3; IntAct=EBI-10215641, EBI-741850;
CC       P56748; Q8N205: SYNE4; NbExp=3; IntAct=EBI-10215641, EBI-7131783;
CC       P56748; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-10215641, EBI-11742770;
CC       P56748; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-10215641, EBI-11988865;
CC   -!- SUBCELLULAR LOCATION: Cell junction, tight junction
CC       {ECO:0000269|PubMed:17287494}. Cell membrane
CC       {ECO:0000250|UniProtKB:Q9Z260}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Localizes to tight junctions in all 3 segments of
CC       the epididymis, in the caput found in the lateral margins of principal
CC       cells, and in the corpus at the interface between basal and principal
CC       cells. {ECO:0000269|PubMed:17287494}.
CC   -!- TISSUE SPECIFICITY: Expressed in the epididymis, mainly in the caput
CC       segment. {ECO:0000269|PubMed:17287494}.
CC   -!- PTM: Ubiquitinated by the BCR(KLHL3) E3 ubiquitin ligase complex in the
CC       kidney, leading to its degradation. {ECO:0000250|UniProtKB:Q9Z260}.
CC   -!- MISCELLANEOUS: A protein of the expected size has been detected by
CC       antibody binding and Western blot in at least one of the analyzed
CC       tissues or cells. {ECO:0000305|PubMed:22042635}.
CC   -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
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DR   EMBL; AJ250711; CAB60615.1; -; Genomic_DNA.
DR   EMBL; AY358707; AAQ89070.1; -; mRNA.
DR   EMBL; AK223512; BAD97232.1; -; mRNA.
DR   EMBL; AP001707; BAA95567.1; -; Genomic_DNA.
DR   EMBL; CH471079; EAX09901.1; -; Genomic_DNA.
DR   EMBL; CH471079; EAX09902.1; -; Genomic_DNA.
DR   EMBL; BC020866; AAH20866.1; -; mRNA.
DR   EMBL; BC058004; AAH58004.1; -; mRNA.
DR   CCDS; CCDS13587.1; -.
DR   RefSeq; NP_955360.1; NM_199328.2.
DR   AlphaFoldDB; P56748; -.
DR   SMR; P56748; -.
DR   BioGRID; 114530; 14.
DR   IntAct; P56748; 11.
DR   STRING; 9606.ENSP00000382783; -.
DR   TCDB; 1.H.1.1.7; the claudin tight junction (claudin1) family.
DR   iPTMnet; P56748; -.
DR   PhosphoSitePlus; P56748; -.
DR   BioMuta; CLDN8; -.
DR   DMDM; 6685307; -.
DR   MassIVE; P56748; -.
DR   PaxDb; 9606-ENSP00000382783; -.
DR   PeptideAtlas; P56748; -.
DR   ProteomicsDB; 56944; -.
DR   Antibodypedia; 6589; 281 antibodies from 28 providers.
DR   DNASU; 9073; -.
DR   Ensembl; ENST00000399899.2; ENSP00000382783.1; ENSG00000156284.6.
DR   GeneID; 9073; -.
DR   KEGG; hsa:9073; -.
DR   MANE-Select; ENST00000399899.2; ENSP00000382783.1; NM_199328.3; NP_955360.1.
DR   UCSC; uc002ynu.3; human.
DR   AGR; HGNC:2050; -.
DR   CTD; 9073; -.
DR   DisGeNET; 9073; -.
DR   GeneCards; CLDN8; -.
DR   HGNC; HGNC:2050; CLDN8.
DR   HPA; ENSG00000156284; Tissue enhanced (breast, intestine, kidney, salivary gland).
DR   MIM; 611231; gene.
DR   neXtProt; NX_P56748; -.
DR   OpenTargets; ENSG00000156284; -.
DR   PharmGKB; PA26576; -.
DR   VEuPathDB; HostDB:ENSG00000156284; -.
DR   eggNOG; ENOG502RTNJ; Eukaryota.
DR   GeneTree; ENSGT00940000159077; -.
DR   HOGENOM; CLU_076370_1_2_1; -.
DR   InParanoid; P56748; -.
DR   OMA; WMNCMRH; -.
DR   OrthoDB; 4040914at2759; -.
DR   PhylomeDB; P56748; -.
DR   TreeFam; TF331936; -.
DR   PathwayCommons; P56748; -.
DR   Reactome; R-HSA-420029; Tight junction interactions.
DR   SignaLink; P56748; -.
DR   BioGRID-ORCS; 9073; 8 hits in 1148 CRISPR screens.
DR   GeneWiki; CLDN8; -.
DR   GenomeRNAi; 9073; -.
DR   Pharos; P56748; Tbio.
DR   PRO; PR:P56748; -.
DR   Proteomes; UP000005640; Chromosome 21.
DR   RNAct; P56748; Protein.
DR   Bgee; ENSG00000156284; Expressed in mucosa of sigmoid colon and 80 other cell types or tissues.
DR   ExpressionAtlas; P56748; baseline and differential.
DR   GO; GO:0016327; C:apicolateral plasma membrane; IEA:Ensembl.
DR   GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR   GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; HDA:UniProtKB.
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   Gene3D; 1.20.140.150; -; 1.
DR   InterPro; IPR006187; Claudin.
DR   InterPro; IPR017974; Claudin_CS.
DR   InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR   PANTHER; PTHR12002; CLAUDIN; 1.
DR   PANTHER; PTHR12002:SF24; CLAUDIN-8; 1.
DR   Pfam; PF00822; PMP22_Claudin; 1.
DR   PRINTS; PR01077; CLAUDIN.
DR   PRINTS; PR01446; CLAUDIN8.
DR   PROSITE; PS01346; CLAUDIN; 1.
DR   Genevisible; P56748; HS.
PE   1: Evidence at protein level;
KW   Cell junction; Cell membrane; Membrane; Reference proteome; Tight junction;
KW   Transmembrane; Transmembrane helix; Ubl conjugation.
FT   CHAIN           1..225
FT                   /note="Claudin-8"
FT                   /id="PRO_0000144753"
FT   TOPO_DOM        1..7
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        8..28
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        29..81
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        82..102
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        103..117
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        118..138
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        139..166
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        167..187
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        188..225
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          206..225
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          224..225
FT                   /note="Interactions with TJP1, TJP2 and TJP3"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z260"
FT   VARIANT         25
FT                   /note="T -> A (in dbSNP:rs1557294)"
FT                   /id="VAR_048739"
FT   VARIANT         129
FT                   /note="T -> A (in dbSNP:rs685967)"
FT                   /id="VAR_024417"
FT   VARIANT         151
FT                   /note="S -> P (in dbSNP:rs686364)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_020387"
FT   CONFLICT        170
FT                   /note="T -> A (in Ref. 3; BAD97232)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   225 AA;  24845 MW;  F7920E8E71682473 CRC64;
     MATHALEIAG LFLGGVGMVG TVAVTVMPQW RVSAFIENNI VVFENFWEGL WMNCVRQANI
     RMQCKIYDSL LALSPDLQAA RGLMCAASVM SFLAFMMAIL GMKCTRCTGD NEKVKAHILL
     TAGIIFIITG MVVLIPVSWV ANAIIRDFYN SIVNVAQKRE LGEALYLGWT TALVLIVGGA
     LFCCVFCCNE KSSSYRYSIP SHRTTQKSYH TGKKSPSVYS RSQYV
//