CLD8_HUMAN
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 03-AUG-2022, entry version 168.
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; P56748; -.
DR PeptideAtlas; P56748; -.
DR PRIDE; P56748; -.
DR ProteomicsDB; 56944; -.
DR Antibodypedia; 6589; 252 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 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; VVFENLW; -.
DR OrthoDB; 1314055at2759; -.
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 1070 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 tissues.
DR ExpressionAtlas; P56748; baseline and differential.
DR Genevisible; P56748; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 InterPro; IPR006187; Claudin.
DR InterPro; IPR003926; Claudin8.
DR InterPro; IPR017974; Claudin_CS.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR PANTHER; PTHR12002; PTHR12002; 1.
DR PANTHER; PTHR12002:SF24; PTHR12002:SF24; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PROSITE; PS01346; CLAUDIN; 1.
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
