PCD19_HUMAN
ID PCD19_HUMAN Reviewed; 1148 AA.
AC Q8TAB3; B0LDS4; E9PAM6; Q5JTG1; Q5JTG2; Q68DT7; Q9P2N3;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Protocadherin-19;
DE Flags: Precursor;
GN Name=PCDH19; Synonyms=KIAA1313;
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] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND VARIANTS DEE9 GLU-441 AND LYS-557.
RX PubMed=18469813; DOI=10.1038/ng.149;
RA Dibbens L.M., Tarpey P.S., Hynes K., Bayly M.A., Scheffer I.E., Smith R.,
RA Bomar J., Sutton E., Vandeleur L., Shoubridge C., Edkins S., Turner S.J.,
RA Stevens C., O'Meara S., Tofts C., Barthorpe S., Buck G., Cole J.,
RA Halliday K., Jones D., Lee R., Madison M., Mironenko T., Varian J.,
RA West S., Widaa S., Wray P., Teague J., Dicks E., Butler A., Menzies A.,
RA Jenkinson A., Shepherd R., Gusella J.F., Afawi Z., Mazarib A.,
RA Neufeld M.Y., Kivity S., Lev D., Lerman-Sagie T., Korczyn A.D., Derry C.P.,
RA Sutherland G.R., Friend K., Shaw M., Corbett M., Kim H.-G., Geschwind D.H.,
RA Thomas P., Haan E., Ryan S., McKee S., Berkovic S.F., Futreal P.A.,
RA Stratton M.R., Mulley J.C., Gecz J.;
RT "X-linked protocadherin 19 mutations cause female-limited epilepsy and
RT cognitive impairment.";
RL Nat. Genet. 40:776-781(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 482-1148 (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 704-1148 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [5]
RP GENE STRUCTURE, AND TISSUE SPECIFICITY.
RX PubMed=11549318; DOI=10.1006/geno.2001.6592;
RA Wolverton T., Lalande M.;
RT "Identification and characterization of three members of a novel subclass
RT of protocadherins.";
RL Genomics 76:66-72(2001).
RN [6]
RP INVOLVEMENT IN DEE9.
RX PubMed=20830798; DOI=10.1002/ajmg.a.33611;
RA Jamal S.M., Basran R.K., Newton S., Wang Z., Milunsky J.M.;
RT "Novel de novo PCDH19 mutations in three unrelated females with epilepsy
RT female restricted mental retardation syndrome.";
RL Am. J. Med. Genet. A 152:2475-2481(2010).
RN [7]
RP VARIANTS DEE9 ASN-121; GLN-199; SER-340 AND PRO-543, AND VARIANT GLY-1107.
RX PubMed=19214208; DOI=10.1371/journal.pgen.1000381;
RA Depienne C., Bouteiller D., Keren B., Cheuret E., Poirier K.,
RA Trouillard O., Benyahia B., Quelin C., Carpentier W., Julia S., Afenjar A.,
RA Gautier A., Rivier F., Meyer S., Berquin P., Helias M., Py I., Rivera S.,
RA Bahi-Buisson N., Gourfinkel-An I., Cazeneuve C., Ruberg M., Brice A.,
RA Nabbout R., Leguern E.;
RT "Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19
RT resembles Dravet syndrome but mainly affects females.";
RL PLoS Genet. 5:E1000381-E1000381(2009).
RN [8]
RP VARIANTS DEE9 PRO-276 AND LYS-557, AND VARIANTS GLN-958 AND GLY-1107.
RX PubMed=19752159; DOI=10.1136/jmg.2009.068817;
RA Hynes K., Tarpey P., Dibbens L.M., Bayly M.A., Berkovic S.F., Smith R.,
RA Raisi Z.A., Turner S.J., Brown N.J., Desai T.D., Haan E., Turner G.,
RA Christodoulou J., Leonard H., Gill D., Stratton M.R., Gecz J.,
RA Scheffer I.E.;
RT "Epilepsy and mental retardation limited to females with PCDH19 mutations
RT can present de novo or in single generation families.";
RL J. Med. Genet. 47:211-216(2010).
RN [9]
RP VARIANTS DEE9 PRO-203; CYS-206; SER-340; HIS-377; ILE-404 AND GLN-414.
RX PubMed=20713952; DOI=10.1212/wnl.0b013e3181ed9e67;
RA Marini C., Mei D., Parmeggiani L., Norci V., Calado E., Ferrari A.,
RA Moreira A., Pisano T., Specchio N., Vigevano F., Battaglia D., Guerrini R.;
RT "Protocadherin 19 mutations in girls with infantile-onset epilepsy.";
RL Neurology 75:646-653(2010).
RN [10]
RP VARIANTS DEE9 SER-236; SER-340; PRO-433 AND ARG-513.
RX PubMed=21480887; DOI=10.1111/j.1528-1167.2011.03063.x;
RA Specchio N., Marini C., Terracciano A., Mei D., Trivisano M., Sicca F.,
RA Fusco L., Cusmai R., Darra F., Bernardina B.D., Bertini E., Guerrini R.,
RA Vigevano F.;
RT "Spectrum of phenotypes in female patients with epilepsy due to
RT protocadherin 19 mutations.";
RL Epilepsia 52:1251-1257(2011).
RN [11]
RP VARIANTS DEE9 ARG-81; SER-GLU-ALA-141 INS; ARG-146; TYR-206; ASP-249;
RP GLU-341; ARG-561; LEU-567 AND ASN-618.
RX PubMed=21053371; DOI=10.1002/humu.21373;
RA Depienne C., Trouillard O., Bouteiller D., Gourfinkel-An I., Poirier K.,
RA Rivier F., Berquin P., Nabbout R., Chaigne D., Steschenko D., Gautier A.,
RA Hoffman-Zacharska D., Lannuzel A., Lackmy-Port-Lis M., Maurey H.,
RA Dusser A., Bru M., Gilbert-Dussardier B., Roubertie A., Kaminska A.,
RA Whalen S., Mignot C., Baulac S., Lesca G., Arzimanoglou A., LeGuern E.;
RT "Mutations and deletions in PCDH19 account for various familial or isolated
RT epilepsies in females.";
RL Hum. Mutat. 32:E1959-E1975(2011).
RN [12]
RP VARIANTS DEE9 PRO-25 AND SER-340.
RX PubMed=21519002; DOI=10.1212/wnl.0b013e318217e7b6;
RA Dibbens L.M., Kneen R., Bayly M.A., Heron S.E., Arsov T., Damiano J.A.,
RA Desai T., Gibbs J., McKenzie F., Mulley J.C., Ronan A., Scheffer I.E.;
RT "Recurrence risk of epilepsy and mental retardation in females due to
RT parental mosaicism of PCDH19 mutations.";
RL Neurology 76:1514-1519(2011).
RN [13]
RP VARIANTS DEE9 GLY-72; LEU-191 AND SER-340, AND VARIANTS HIS-1107 AND
RP HIS-1134.
RX PubMed=22050978; DOI=10.1016/j.eplepsyres.2011.10.014;
RA Higurashi N., Shi X., Yasumoto S., Oguni H., Sakauchi M., Itomi K.,
RA Miyamoto A., Shiraishi H., Kato T., Makita Y., Hirose S.;
RT "PCDH19 mutation in Japanese females with epilepsy.";
RL Epilepsy Res. 99:28-37(2012).
RN [14]
RP VARIANTS DEE9 THR-153; ARG-190; SER-232; SER-234; ASP-262; ARG-344; GLU-377
RP AND MET-642, AND VARIANTS CYS-980; VAL-1094 AND HIS-1134.
RX PubMed=22267240; DOI=10.1002/humu.22029;
RA Depienne C., Leguern E.;
RT "PCDH19-related infantile epileptic encephalopathy: An unusual X-linked
RT inheritance disorder.";
RL Hum. Mutat. 33:627-634(2012).
RN [15]
RP VARIANT DEE9 158-SER--LEU-1148 DEL.
RX PubMed=25818041; DOI=10.1111/epi.12954;
RA Mercimek-Mahmutoglu S., Patel J., Cordeiro D., Hewson S., Callen D.,
RA Donner E.J., Hahn C.D., Kannu P., Kobayashi J., Minassian B.A., Moharir M.,
RA Siriwardena K., Weiss S.K., Weksberg R., Snead O.C. III;
RT "Diagnostic yield of genetic testing in epileptic encephalopathy in
RT childhood.";
RL Epilepsia 56:707-716(2015).
RN [16]
RP VARIANTS DEE9 ASN-230 AND LEU-236.
RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263;
RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A.,
RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A.,
RA Scott R.H.;
RT "Improving diagnosis and broadening the phenotypes in early-onset seizure
RT and severe developmental delay disorders through gene panel analysis.";
RL J. Med. Genet. 53:310-317(2016).
RN [17]
RP VARIANT HIS-447.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
CC -!- FUNCTION: Potential calcium-dependent cell-adhesion protein.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8TAB3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TAB3-2; Sequence=VSP_015081;
CC Name=3;
CC IsoId=Q8TAB3-3; Sequence=VSP_015081, VSP_054046;
CC -!- TISSUE SPECIFICITY: Moderately expressed in all regions of the brain
CC examined, with lowest levels found in the cerebellum. Moderate
CC expression is also found in ovary, and low expression in all other
CC tissues tested. Also detected in primary skin fibroblast.
CC {ECO:0000269|PubMed:11549318, ECO:0000269|PubMed:18469813}.
CC -!- DEVELOPMENTAL STAGE: Expressed in developing cortical plate, amygdala
CC and subcortical regions and in the ganglionic eminence.
CC {ECO:0000269|PubMed:18469813}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 9 (DEE9)
CC [MIM:300088]: A condition characterized by seizure with onset in
CC infancy or early childhood, cognitive impairment, and delayed
CC development of variable severity in some patients. Additional features
CC include autistic signs and psychosis. The disorder is sex-limited, with
CC the phenotype being restricted to females.
CC {ECO:0000269|PubMed:18469813, ECO:0000269|PubMed:19214208,
CC ECO:0000269|PubMed:19752159, ECO:0000269|PubMed:20713952,
CC ECO:0000269|PubMed:20830798, ECO:0000269|PubMed:21053371,
CC ECO:0000269|PubMed:21480887, ECO:0000269|PubMed:21519002,
CC ECO:0000269|PubMed:22050978, ECO:0000269|PubMed:22267240,
CC ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26993267}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH18133.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=X-chromosome gene database Protocadherin 19
CC (PCDH19); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/PCDH19";
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DR EMBL; EF676096; ABX58058.1; -; mRNA.
DR EMBL; AL355593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR749278; CAH18133.1; ALT_INIT; mRNA.
DR EMBL; AB037734; BAA92551.1; -; mRNA.
DR CCDS; CCDS43976.1; -. [Q8TAB3-2]
DR CCDS; CCDS48141.1; -. [Q8TAB3-3]
DR CCDS; CCDS55462.1; -. [Q8TAB3-1]
DR RefSeq; NP_001098713.1; NM_001105243.1. [Q8TAB3-2]
DR RefSeq; NP_001171809.1; NM_001184880.1. [Q8TAB3-1]
DR RefSeq; NP_065817.2; NM_020766.2. [Q8TAB3-3]
DR PDB; 6VFU; X-ray; 3.50 A; A/B/C=22-445.
DR PDBsum; 6VFU; -.
DR AlphaFoldDB; Q8TAB3; -.
DR SMR; Q8TAB3; -.
DR BioGRID; 121586; 23.
DR IntAct; Q8TAB3; 4.
DR STRING; 9606.ENSP00000362125; -.
DR DrugBank; DB01373; Calcium.
DR GlyGen; Q8TAB3; 6 sites.
DR iPTMnet; Q8TAB3; -.
DR PhosphoSitePlus; Q8TAB3; -.
DR BioMuta; PCDH19; -.
DR DMDM; 73620979; -.
DR EPD; Q8TAB3; -.
DR jPOST; Q8TAB3; -.
DR MassIVE; Q8TAB3; -.
DR MaxQB; Q8TAB3; -.
DR PaxDb; Q8TAB3; -.
DR PeptideAtlas; Q8TAB3; -.
DR PRIDE; Q8TAB3; -.
DR ProteomicsDB; 19048; -.
DR ProteomicsDB; 73850; -. [Q8TAB3-1]
DR ProteomicsDB; 73851; -. [Q8TAB3-2]
DR TopDownProteomics; Q8TAB3-3; -. [Q8TAB3-3]
DR Antibodypedia; 429; 46 antibodies from 16 providers.
DR DNASU; 57526; -.
DR Ensembl; ENST00000255531.8; ENSP00000255531.7; ENSG00000165194.15. [Q8TAB3-2]
DR Ensembl; ENST00000373034.8; ENSP00000362125.4; ENSG00000165194.15. [Q8TAB3-1]
DR Ensembl; ENST00000420881.6; ENSP00000400327.2; ENSG00000165194.15. [Q8TAB3-3]
DR GeneID; 57526; -.
DR KEGG; hsa:57526; -.
DR MANE-Select; ENST00000373034.8; ENSP00000362125.4; NM_001184880.2; NP_001171809.1.
DR UCSC; uc004efw.5; human. [Q8TAB3-1]
DR CTD; 57526; -.
DR DisGeNET; 57526; -.
DR GeneCards; PCDH19; -.
DR HGNC; HGNC:14270; PCDH19.
DR HPA; ENSG00000165194; Tissue enriched (brain).
DR MalaCards; PCDH19; -.
DR MIM; 300088; phenotype.
DR MIM; 300460; gene.
DR neXtProt; NX_Q8TAB3; -.
DR OpenTargets; ENSG00000165194; -.
DR Orphanet; 33069; Dravet syndrome.
DR Orphanet; 101039; Female restricted epilepsy with intellectual disability.
DR PharmGKB; PA33003; -.
DR VEuPathDB; HostDB:ENSG00000165194; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT00940000159162; -.
DR HOGENOM; CLU_006480_1_1_1; -.
DR InParanoid; Q8TAB3; -.
DR OMA; CWMPRGA; -.
DR OrthoDB; 64478at2759; -.
DR PhylomeDB; Q8TAB3; -.
DR TreeFam; TF352008; -.
DR PathwayCommons; Q8TAB3; -.
DR SignaLink; Q8TAB3; -.
DR SIGNOR; Q8TAB3; -.
DR BioGRID-ORCS; 57526; 10 hits in 687 CRISPR screens.
DR ChiTaRS; PCDH19; human.
DR GenomeRNAi; 57526; -.
DR Pharos; Q8TAB3; Tbio.
DR PRO; PR:Q8TAB3; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q8TAB3; protein.
DR Bgee; ENSG00000165194; Expressed in cortical plate and 132 other tissues.
DR ExpressionAtlas; Q8TAB3; baseline and differential.
DR Genevisible; Q8TAB3; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0007420; P:brain development; IEA:InterPro.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR013164; Cadherin_N.
DR InterPro; IPR030716; Protocadherin-19.
DR PANTHER; PTHR24028:SF40; PTHR24028:SF40; 1.
DR Pfam; PF00028; Cadherin; 5.
DR Pfam; PF08266; Cadherin_2; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 6.
DR SUPFAM; SSF49313; SSF49313; 5.
DR PROSITE; PS00232; CADHERIN_1; 5.
DR PROSITE; PS50268; CADHERIN_2; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell adhesion; Cell membrane;
KW Disease variant; Epilepsy; Glycoprotein; Intellectual disability; Membrane;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1148
FT /note="Protocadherin-19"
FT /id="PRO_0000004003"
FT TOPO_DOM 22..678
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 679..699
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 700..1148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 22..129
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 130..238
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 239..346
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 350..453
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 454..563
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 569..672
FT /note="Cadherin 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REGION 901..921
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1100..1148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 902..921
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1112..1148
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 485
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 570
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 676
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 716..762
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10718198,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_015081"
FT VAR_SEQ 892
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054046"
FT VARIANT 25
FT /note="L -> P (in DEE9)"
FT /evidence="ECO:0000269|PubMed:21519002"
FT /id="VAR_067472"
FT VARIANT 72
FT /note="V -> G (in DEE9)"
FT /evidence="ECO:0000269|PubMed:22050978"
FT /id="VAR_067473"
FT VARIANT 81
FT /note="L -> R (in DEE9; dbSNP:rs1569316056)"
FT /evidence="ECO:0000269|PubMed:21053371"
FT /id="VAR_064840"
FT VARIANT 121
FT /note="D -> N (in DEE9; disease features overlapping with
FT Dravet syndrome; dbSNP:rs796052795)"
FT /evidence="ECO:0000269|PubMed:19214208"
FT /id="VAR_064481"
FT VARIANT 141
FT /note="A -> ASEA (in DEE9)"
FT /id="VAR_064841"
FT VARIANT 146
FT /note="T -> R (in DEE9; dbSNP:rs796052799)"
FT /evidence="ECO:0000269|PubMed:21053371"
FT /id="VAR_064842"
FT VARIANT 153
FT /note="A -> T (in DEE9)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067474"
FT VARIANT 158..1148
FT /note="Missing (in DEE9)"
FT /evidence="ECO:0000269|PubMed:25818041"
FT /id="VAR_078722"
FT VARIANT 190
FT /note="L -> R (in DEE9)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067475"
FT VARIANT 191
FT /note="V -> L (in DEE9; dbSNP:rs753757730)"
FT /evidence="ECO:0000269|PubMed:22050978"
FT /id="VAR_067476"
FT VARIANT 199
FT /note="E -> Q (in DEE9; disease features overlapping with
FT Dravet syndrome)"
FT /evidence="ECO:0000269|PubMed:19214208"
FT /id="VAR_064482"
FT VARIANT 203
FT /note="H -> P (in DEE9; disease features overlapping with
FT Dravet syndrome; associated with Cys-206)"
FT /evidence="ECO:0000269|PubMed:20713952"
FT /id="VAR_064483"
FT VARIANT 206
FT /note="F -> C (in DEE9; disease features overlapping with
FT Dravet syndrome; associated with Pro-203;
FT dbSNP:rs746274631)"
FT /evidence="ECO:0000269|PubMed:20713952"
FT /id="VAR_064484"
FT VARIANT 206
FT /note="F -> Y (in DEE9)"
FT /evidence="ECO:0000269|PubMed:21053371"
FT /id="VAR_064843"
FT VARIANT 230
FT /note="D -> N (in DEE9; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078723"
FT VARIANT 232
FT /note="N -> S (in DEE9; dbSNP:rs587784299)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067477"
FT VARIANT 234
FT /note="N -> S (in DEE9; dbSNP:rs1555985475)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067478"
FT VARIANT 236
FT /note="P -> L (in DEE9; dbSNP:rs1060502176)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078724"
FT VARIANT 236
FT /note="P -> S (in DEE9)"
FT /evidence="ECO:0000269|PubMed:21480887"
FT /id="VAR_067479"
FT VARIANT 249
FT /note="E -> D (in DEE9)"
FT /evidence="ECO:0000269|PubMed:21053371"
FT /id="VAR_064844"
FT VARIANT 262
FT /note="A -> D (in DEE9; dbSNP:rs1555985448)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067480"
FT VARIANT 276
FT /note="S -> P (in DEE9)"
FT /evidence="ECO:0000269|PubMed:19752159"
FT /id="VAR_064485"
FT VARIANT 340
FT /note="N -> S (in DEE9; disease features overlapping with
FT Dravet syndrome; dbSNP:rs796052839)"
FT /evidence="ECO:0000269|PubMed:19214208,
FT ECO:0000269|PubMed:20713952, ECO:0000269|PubMed:21480887,
FT ECO:0000269|PubMed:21519002, ECO:0000269|PubMed:22050978"
FT /id="VAR_064486"
FT VARIANT 341
FT /note="D -> E (in DEE9)"
FT /evidence="ECO:0000269|PubMed:21053371"
FT /id="VAR_064845"
FT VARIANT 344
FT /note="P -> R (in DEE9)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067481"
FT VARIANT 377
FT /note="D -> E (in DEE9)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067482"
FT VARIANT 377
FT /note="D -> H (in DEE9; disease features overlapping with
FT Dravet syndrome)"
FT /evidence="ECO:0000269|PubMed:20713952"
FT /id="VAR_064487"
FT VARIANT 404
FT /note="T -> I (in DEE9; disease features overlapping with
FT Dravet syndrome)"
FT /evidence="ECO:0000269|PubMed:20713952"
FT /id="VAR_064488"
FT VARIANT 414
FT /note="E -> Q (in DEE9; disease features overlapping with
FT Dravet syndrome)"
FT /evidence="ECO:0000269|PubMed:20713952"
FT /id="VAR_064489"
FT VARIANT 433
FT /note="L -> P (in DEE9)"
FT /evidence="ECO:0000269|PubMed:21480887"
FT /id="VAR_067483"
FT VARIANT 441
FT /note="V -> E (in DEE9; dbSNP:rs132630323)"
FT /evidence="ECO:0000269|PubMed:18469813"
FT /id="VAR_046484"
FT VARIANT 447
FT /note="N -> H (probable disease-associated variant found in
FT a patient with drug-resistant epilepsy)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078227"
FT VARIANT 513
FT /note="G -> R (in DEE9)"
FT /evidence="ECO:0000269|PubMed:21480887"
FT /id="VAR_067484"
FT VARIANT 543
FT /note="L -> P (in DEE9; disease features overlapping with
FT Dravet syndrome)"
FT /evidence="ECO:0000269|PubMed:19214208"
FT /id="VAR_064490"
FT VARIANT 557
FT /note="N -> K (in DEE9; dbSNP:rs267606933)"
FT /evidence="ECO:0000269|PubMed:18469813,
FT ECO:0000269|PubMed:19752159"
FT /id="VAR_046485"
FT VARIANT 561
FT /note="P -> R (in DEE9; dbSNP:rs796052819)"
FT /evidence="ECO:0000269|PubMed:21053371"
FT /id="VAR_064846"
FT VARIANT 567
FT /note="P -> L (in DEE9; dbSNP:rs201989363)"
FT /evidence="ECO:0000269|PubMed:21053371"
FT /id="VAR_064847"
FT VARIANT 618
FT /note="D -> N (in DEE9)"
FT /evidence="ECO:0000269|PubMed:21053371"
FT /id="VAR_064848"
FT VARIANT 642
FT /note="V -> M (in DEE9; dbSNP:rs1221643775)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067485"
FT VARIANT 958
FT /note="R -> Q (in dbSNP:rs748581653)"
FT /evidence="ECO:0000269|PubMed:19752159"
FT /id="VAR_064491"
FT VARIANT 980
FT /note="R -> C (in dbSNP:rs3764758)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067486"
FT VARIANT 1094
FT /note="L -> V (in dbSNP:rs184545774)"
FT /evidence="ECO:0000269|PubMed:22267240"
FT /id="VAR_067487"
FT VARIANT 1107
FT /note="R -> G (in dbSNP:rs191333060)"
FT /evidence="ECO:0000269|PubMed:19214208,
FT ECO:0000269|PubMed:19752159"
FT /id="VAR_064492"
FT VARIANT 1107
FT /note="R -> H (in dbSNP:rs200021840)"
FT /evidence="ECO:0000269|PubMed:22050978"
FT /id="VAR_067488"
FT VARIANT 1134
FT /note="N -> H (in dbSNP:rs141816797)"
FT /evidence="ECO:0000269|PubMed:22050978,
FT ECO:0000269|PubMed:22267240"
FT /id="VAR_067489"
FT CONFLICT 868
FT /note="V -> A (in Ref. 3; CAH18133)"
FT /evidence="ECO:0000305"
FT STRAND 23..32
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:6VFU"
FT HELIX 42..49
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 61..67
FT /evidence="ECO:0007829|PDB:6VFU"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:6VFU"
FT TURN 76..78
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:6VFU"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 100..107
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 112..120
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 130..139
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:6VFU"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 172..184
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 186..192
FT /evidence="ECO:0007829|PDB:6VFU"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 203..212
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 219..229
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 241..248
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 253..259
FT /evidence="ECO:0007829|PDB:6VFU"
FT HELIX 268..271
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:6VFU"
FT HELIX 284..288
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:6VFU"
FT TURN 293..295
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 297..300
FT /evidence="ECO:0007829|PDB:6VFU"
FT TURN 306..308
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 310..324
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 328..337
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 345..349
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 356..361
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 367..374
FT /evidence="ECO:0007829|PDB:6VFU"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 384..388
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 393..399
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 402..407
FT /evidence="ECO:0007829|PDB:6VFU"
FT TURN 413..415
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 417..431
FT /evidence="ECO:0007829|PDB:6VFU"
FT STRAND 434..445
FT /evidence="ECO:0007829|PDB:6VFU"
SQ SEQUENCE 1148 AA; 126253 MW; AF8721355A33C1C2 CRC64;
MESLLLPVLL LLAILWTQAA ALINLKYSVE EEQRAGTVIA NVAKDAREAG FALDPRQASA
FRVVSNSAPH LVDINPSSGL LVTKQKIDRD LLCRQSPKCI ISLEVMSSSM EICVIKVEIK
DLNDNAPSFP AAQIELEISE AASPGTRIPL DSAYDPDSGS FGVQTYELTP NELFGLEIKT
RGDGSRFAEL VVEKSLDRET QSHYSFRITA LDGGDPPRLG TVGLSIKVTD SNDNNPVFSE
STYAVSVPEN SPPNTPVIRL NASDPDEGTN GQVVYSFYGY VNDRTRELFQ IDPHSGLVTV
TGALDYEEGH VYELDVQAKD LGPNSIPAHC KVTVSVLDTN DNPPVINLLS VNSELVEVSE
SAPPGYVIAL VRVSDRDSGL NGRVQCRLLG NVPFRLQEYE SFSTILVDGR LDREQHDQYN
LTIQARDGGV PMLQSAKSFT VLITDENDNH PHFSKPYYQV IVQENNTPGA YLLSVSARDP
DLGLNGSVSY QIVPSQVRDM PVFTYVSINP NSGDIYALRS FNHEQTKAFE FKVLAKDGGL
PSLQSNATVR VIILDVNDNT PVITAPPLIN GTAEVYIPRN SGIGYLVTVV KAEDYDEGEN
GRVTYDMTEG DRGFFEIDQV NGEVRTTRTF GESSKSSYEL IVVAHDHGKT SLSASALVLI
YLSPALDAQE SMGSVNLSLI FIIALGSIAG ILFVTMIFVA IKCKRDNKEI RTYNCSNCLT
ITCLLGCFIK GQNSKCLHCI SVSPISEEQD KKTEEKVSLR GKRIAEYSYG HQKKSSKKKK
ISKNDIRLVP RDVEETDKMN VVSCSSLTSS LNYFDYHQQT LPLGCRRSES TFLNVENQNT
RNTSANHIYH HSFNSQGPQQ PDLIINGVPL PETENYSFDS NYVNSRAHLI KSSSTFKDLE
GNSLKDSGHE ESDQTDSEHD VQRSLYCDTA VNDVLNTSVT SMGSQMPDHD QNEGFHCREE
CRILGHSDRC WMPRNPMPIR SKSPEHVRNI IALSIEATAA DVEAYDDCGP TKRTFATFGK
DVSDHPAEER PTLKGKRTVD VTICSPKVNS VIREAGNGCE AISPVTSPLH LKSSLPTKPS
VSYTIALAPP ARDLEQYVNN VNNGPTRPSE AEPRGADSEK VMHEVSPILK EGRNKESPGV
KRLKDIVL
