CLD6_HUMAN
ID CLD6_HUMAN Reviewed; 220 AA.
AC P56747; B3KQP9; D3DUA5;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Claudin-6;
DE AltName: Full=Skullin;
GN Name=CLDN6; ORFNames=UNQ757/PRO1488;
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], AND VARIANT VAL-143.
RA Keen T.J., Inglehearn C.F.;
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-143.
RA Troy T., Wisco V., Turksen K.;
RT "Skullin: a novel membrane molecule marks formation of epithelium.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-143.
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-143.
RC TISSUE=Placenta;
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 [8]
RP TISSUE SPECIFICITY, AND FUNCTION (MICROBIAL INFECTION).
RX PubMed=17804490; DOI=10.1128/jvi.01457-07;
RA Zheng A., Yuan F., Li Y., Zhu F., Hou P., Li J., Song X., Ding M., Deng H.;
RT "Claudin-6 and claudin-9 function as additional coreceptors for hepatitis C
RT virus.";
RL J. Virol. 81:12465-12471(2007).
RN [9]
RP FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, AND INTERACTION WITH
RP CLDN1; CD81 AND OCLN.
RX PubMed=20375010; DOI=10.1074/jbc.m110.104836;
RA Harris H.J., Davis C., Mullins J.G., Hu K., Goodall M., Farquhar M.J.,
RA Mee C.J., McCaffrey K., Young S., Drummer H., Balfe P., McKeating J.A.;
RT "Claudin association with CD81 defines hepatitis C virus entry.";
RL J. Biol. Chem. 285:21092-21102(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-201; SER-203; SER-208 AND
RP SER-212, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Plays a major role in tight junction-specific obliteration of
CC the intercellular space. {ECO:0000250}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C
CC virus (HCV) entry into hepatic cells. {ECO:0000269|PubMed:17804490,
CC ECO:0000269|PubMed:20375010}.
CC -!- SUBUNIT: Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3 (By
CC similarity). Interacts with CLDN1, CD81 and OCLN (PubMed:20375010).
CC {ECO:0000250|UniProtKB:Q9Z262, ECO:0000269|PubMed:20375010}.
CC -!- INTERACTION:
CC P56747; P24593: IGFBP5; NbExp=3; IntAct=EBI-12955011, EBI-720480;
CC P56747; Q96HJ5: MS4A3; NbExp=5; IntAct=EBI-12955011, EBI-12806656;
CC P56747; P15941-11: MUC1; NbExp=3; IntAct=EBI-12955011, EBI-17263240;
CC P56747; Q01453: PMP22; NbExp=3; IntAct=EBI-12955011, EBI-2845982;
CC P56747; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-12955011, EBI-10262251;
CC P56747; Q7Z7N9: TMEM179B; NbExp=3; IntAct=EBI-12955011, EBI-11724423;
CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction
CC {ECO:0000250|UniProtKB:Q9Z262}. Cell membrane
CC {ECO:0000269|PubMed:20375010}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the liver, in peripheral blood
CC mononuclear cells and hepatocarcinoma cell lines.
CC {ECO:0000269|PubMed:17804490}.
CC -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CLDN6ID50974ch16p13.html";
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DR EMBL; AJ249735; CAB56533.1; -; Genomic_DNA.
DR EMBL; AF125306; AAK02013.1; -; mRNA.
DR EMBL; AY358480; AAQ88844.1; -; mRNA.
DR EMBL; BT007399; AAP36063.1; -; mRNA.
DR EMBL; AK075329; BAG52111.1; -; mRNA.
DR EMBL; CH471112; EAW85431.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85432.1; -; Genomic_DNA.
DR EMBL; BC008934; AAH08934.1; -; mRNA.
DR CCDS; CCDS10488.1; -.
DR RefSeq; NP_067018.2; NM_021195.4.
DR AlphaFoldDB; P56747; -.
DR SMR; P56747; -.
DR BioGRID; 114531; 6.
DR IntAct; P56747; 6.
DR STRING; 9606.ENSP00000380131; -.
DR iPTMnet; P56747; -.
DR PhosphoSitePlus; P56747; -.
DR SwissPalm; P56747; -.
DR BioMuta; CLDN6; -.
DR DMDM; 90183180; -.
DR EPD; P56747; -.
DR jPOST; P56747; -.
DR MassIVE; P56747; -.
DR MaxQB; P56747; -.
DR PaxDb; P56747; -.
DR PeptideAtlas; P56747; -.
DR PRIDE; P56747; -.
DR ProteomicsDB; 56943; -.
DR ABCD; P56747; 8 sequenced antibodies.
DR Antibodypedia; 23973; 578 antibodies from 31 providers.
DR DNASU; 9074; -.
DR Ensembl; ENST00000328796.5; ENSP00000328674.4; ENSG00000184697.7.
DR Ensembl; ENST00000396925.1; ENSP00000380131.1; ENSG00000184697.7.
DR GeneID; 9074; -.
DR KEGG; hsa:9074; -.
DR MANE-Select; ENST00000328796.5; ENSP00000328674.4; NM_021195.5; NP_067018.2.
DR UCSC; uc002csu.5; human.
DR CTD; 9074; -.
DR DisGeNET; 9074; -.
DR GeneCards; CLDN6; -.
DR HGNC; HGNC:2048; CLDN6.
DR HPA; ENSG00000184697; Tissue enhanced (brain, pancreas).
DR MIM; 615798; gene.
DR neXtProt; NX_P56747; -.
DR OpenTargets; ENSG00000184697; -.
DR PharmGKB; PA26574; -.
DR VEuPathDB; HostDB:ENSG00000184697; -.
DR eggNOG; ENOG502QSCN; Eukaryota.
DR GeneTree; ENSGT00940000163060; -.
DR HOGENOM; CLU_076370_1_2_1; -.
DR InParanoid; P56747; -.
DR OMA; HYLARYS; -.
DR OrthoDB; 1231389at2759; -.
DR PhylomeDB; P56747; -.
DR TreeFam; TF331936; -.
DR PathwayCommons; P56747; -.
DR Reactome; R-HSA-420029; Tight junction interactions.
DR SignaLink; P56747; -.
DR BioGRID-ORCS; 9074; 24 hits in 1029 CRISPR screens.
DR GeneWiki; CLDN6; -.
DR GenomeRNAi; 9074; -.
DR Pharos; P56747; Tbio.
DR PRO; PR:P56747; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P56747; protein.
DR Bgee; ENSG00000184697; Expressed in cortical plate and 105 other tissues.
DR ExpressionAtlas; P56747; baseline and differential.
DR Genevisible; P56747; HS.
DR GO; GO:0016327; C:apicolateral plasma membrane; IEA:Ensembl.
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; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0001618; F:virus receptor activity; IMP:UniProtKB.
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; IPR003925; Claudin6.
DR InterPro; IPR017974; Claudin_CS.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR PANTHER; PTHR12002; PTHR12002; 1.
DR PANTHER; PTHR12002:SF41; PTHR12002:SF41; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PRINTS; PR01445; CLAUDIN6.
DR PROSITE; PS01346; CLAUDIN; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Host cell receptor for virus entry;
KW Host-virus interaction; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Tight junction; Transmembrane; Transmembrane helix.
FT CHAIN 1..220
FT /note="Claudin-6"
FT /id="PRO_0000144748"
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..116
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..160
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 161..181
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 182..220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 219..220
FT /note="Interactions with TJP1, TJP2 and TJP3"
FT /evidence="ECO:0000250"
FT MOD_RES 201
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 208
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VARIANT 143
FT /note="I -> V (in dbSNP:rs2257295)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16303743, ECO:0000269|Ref.1,
FT ECO:0000269|Ref.2"
FT /id="VAR_017151"
SQ SEQUENCE 220 AA; 23292 MW; D80AECB5681502AA CRC64;
MASAGMQILG VVLTLLGWVN GLVSCALPMW KVTAFIGNSI VVAQVVWEGL WMSCVVQSTG
QMQCKVYDSL LALPQDLQAA RALCVIALLV ALFGLLVYLA GAKCTTCVEE KDSKARLVLT
SGIVFVISGV LTLIPVCWTA HAIIRDFYNP LVAEAQKREL GASLYLGWAA SGLLLLGGGL
LCCTCPSGGS QGPSHYMARY STSAPAISRG PSEYPTKNYV
