ID   EVPL_HUMAN              Reviewed;        2033 AA.
AC   Q92817; A0AUV5;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=Envoplakin;
DE   AltName: Full=210 kDa cornified envelope precursor protein;
DE   AltName: Full=210 kDa paraneoplastic pemphigus antigen;
DE   AltName: Full=p210;
GN   Name=EVPL;
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].
RC   TISSUE=Keratinocyte;
RX   PubMed=8707850; DOI=10.1083/jcb.134.3.715;
RA   Ruhrberg C., Hajibagheri M.A.N., Simon M., Dooley T.P., Watt F.M.;
RT   "Envoplakin, a novel precursor of the cornified envelope that has homology
RT   to desmoplakin.";
RL   J. Cell Biol. 134:715-729(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10409435; DOI=10.1006/geno.1999.5857;
RA   Risk J.M., Ruhrberg C., Hennies H.-C., Mills H.S., Di Colandrea T.,
RA   Evans K.E., Ellis A., Watt F.M., Bishop D.T., Spurr N.K., Stevens H.P.,
RA   Leigh I.M., Reis A., Kelsell D.P., Field J.K.;
RT   "Envoplakin, a possible candidate gene for focal NEPPK/esophageal cancer
RT   (TOC): the integration of genetic and physical maps of the TOC region on
RT   17q25.";
RL   Genomics 59:234-242(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-1814.
RC   TISSUE=Cerebellum;
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1799, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2025, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
CC   -!- FUNCTION: Component of the cornified envelope of keratinocytes. May
CC       link the cornified envelope to desmosomes and intermediate filaments.
CC   -!- SUBUNIT: May form a homodimer or a heterodimer with PPL.
CC   -!- SUBCELLULAR LOCATION: Cell junction, desmosome. Cornified envelope.
CC       Cytoplasm, cytoskeleton. Note=Colocalized with DSP at desmosomes and
CC       along intermediate filaments.
CC   -!- TISSUE SPECIFICITY: Exclusively expressed in stratified squamous
CC       epithelia.
CC   -!- INDUCTION: During differentiation of epidermal keratinocytes.
CC   -!- SIMILARITY: Belongs to the plakin or cytolinker family. {ECO:0000305}.
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DR   EMBL; U53786; AAC64662.1; -; mRNA.
DR   EMBL; U72849; AAD00186.1; -; Genomic_DNA.
DR   EMBL; U72843; AAD00186.1; JOINED; Genomic_DNA.
DR   EMBL; U72845; AAD00186.1; JOINED; Genomic_DNA.
DR   EMBL; U72846; AAD00186.1; JOINED; Genomic_DNA.
DR   EMBL; U72847; AAD00186.1; JOINED; Genomic_DNA.
DR   EMBL; U72848; AAD00186.1; JOINED; Genomic_DNA.
DR   EMBL; AC040980; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC126103; AAI26104.1; -; mRNA.
DR   EMBL; BC126105; AAI26106.1; -; mRNA.
DR   CCDS; CCDS11737.1; -.
DR   RefSeq; NP_001307676.1; NM_001320747.1.
DR   RefSeq; NP_001979.2; NM_001988.3.
DR   PDB; 4QMD; X-ray; 1.60 A; A/B=1822-2014.
DR   PDBsum; 4QMD; -.
DR   AlphaFoldDB; Q92817; -.
DR   SMR; Q92817; -.
DR   BioGRID; 108426; 122.
DR   IntAct; Q92817; 25.
DR   MINT; Q92817; -.
DR   STRING; 9606.ENSP00000465630; -.
DR   GlyGen; Q92817; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q92817; -.
DR   PhosphoSitePlus; Q92817; -.
DR   SwissPalm; Q92817; -.
DR   BioMuta; EVPL; -.
DR   DMDM; 296439359; -.
DR   EPD; Q92817; -.
DR   jPOST; Q92817; -.
DR   MassIVE; Q92817; -.
DR   MaxQB; Q92817; -.
DR   PaxDb; 9606-ENSP00000301607; -.
DR   PeptideAtlas; Q92817; -.
DR   PRIDE; Q92817; -.
DR   ProteomicsDB; 75494; -.
DR   Pumba; Q92817; -.
DR   Antibodypedia; 46112; 79 antibodies from 19 providers.
DR   DNASU; 2125; -.
DR   Ensembl; ENST00000301607.8; ENSP00000301607.3; ENSG00000167880.8.
DR   GeneID; 2125; -.
DR   KEGG; hsa:2125; -.
DR   MANE-Select; ENST00000301607.8; ENSP00000301607.3; NM_001988.4; NP_001979.2.
DR   UCSC; uc002jqi.3; human.
DR   AGR; HGNC:3503; -.
DR   CTD; 2125; -.
DR   DisGeNET; 2125; -.
DR   GeneCards; EVPL; -.
DR   HGNC; HGNC:3503; EVPL.
DR   HPA; ENSG00000167880; Tissue enhanced (esophagus, skin, vagina).
DR   MIM; 601590; gene.
DR   neXtProt; NX_Q92817; -.
DR   OpenTargets; ENSG00000167880; -.
DR   PharmGKB; PA27916; -.
DR   VEuPathDB; HostDB:ENSG00000167880; -.
DR   eggNOG; KOG0516; Eukaryota.
DR   GeneTree; ENSGT00940000153578; -.
DR   HOGENOM; CLU_001780_0_0_1; -.
DR   InParanoid; Q92817; -.
DR   OMA; TEHACGA; -.
DR   OrthoDB; 5357436at2759; -.
DR   PhylomeDB; Q92817; -.
DR   TreeFam; TF342779; -.
DR   PathwayCommons; Q92817; -.
DR   Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR   SignaLink; Q92817; -.
DR   BioGRID-ORCS; 2125; 17 hits in 1148 CRISPR screens.
DR   ChiTaRS; EVPL; human.
DR   GeneWiki; Envoplakin; -.
DR   GenomeRNAi; 2125; -.
DR   Pharos; Q92817; Tbio.
DR   PRO; PR:Q92817; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q92817; Protein.
DR   Bgee; ENSG00000167880; Expressed in lower esophagus mucosa and 136 other cell types or tissues.
DR   ExpressionAtlas; Q92817; baseline and differential.
DR   GO; GO:0001533; C:cornified envelope; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0030057; C:desmosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR   GO; GO:0005198; F:structural molecule activity; IBA:GO_Central.
DR   GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR   GO; GO:0045104; P:intermediate filament cytoskeleton organization; IBA:GO_Central.
DR   GO; GO:0031424; P:keratinization; IEA:UniProtKB-KW.
DR   GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB.
DR   GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB.
DR   GO; GO:0042060; P:wound healing; IBA:GO_Central.
DR   Gene3D; 1.20.58.60; -; 4.
DR   Gene3D; 3.30.160.780; -; 1.
DR   Gene3D; 3.90.1290.10; Plakin repeat; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 1.
DR   InterPro; IPR041615; Desmoplakin_SH3.
DR   InterPro; IPR049538; PCN-like_spectrin-like_rpt.
DR   InterPro; IPR043197; Plakin.
DR   InterPro; IPR035915; Plakin_repeat_sf.
DR   InterPro; IPR001101; Plectin_repeat.
DR   InterPro; IPR001452; SH3_domain.
DR   InterPro; IPR018159; Spectrin/alpha-actinin.
DR   PANTHER; PTHR23169; ENVOPLAKIN; 1.
DR   PANTHER; PTHR23169:SF7; ENVOPLAKIN; 1.
DR   Pfam; PF00681; Plectin; 4.
DR   Pfam; PF17902; SH3_10; 1.
DR   Pfam; PF21020; Spectrin_4; 1.
DR   SMART; SM00250; PLEC; 8.
DR   SMART; SM00150; SPEC; 1.
DR   SUPFAM; SSF75399; Plakin repeat; 2.
DR   SUPFAM; SSF46966; Spectrin repeat; 1.
DR   PROSITE; PS50002; SH3; 1.
DR   Genevisible; Q92817; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cell junction; Coiled coil; Cytoplasm; Cytoskeleton;
KW   Keratinization; Phosphoprotein; Reference proteome; Repeat; SH3 domain.
FT   CHAIN           1..2033
FT                   /note="Envoplakin"
FT                   /id="PRO_0000078147"
FT   REPEAT          229..330
FT                   /note="Spectrin"
FT   DOMAIN          413..470
FT                   /note="SH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   REPEAT          1185..1226
FT                   /note="Plectin 1"
FT   REPEAT          1678..1713
FT                   /note="Plectin 2"
FT   REPEAT          1818..1855
FT                   /note="Plectin 3"
FT   REPEAT          1856..1893
FT                   /note="Plectin 4"
FT   REPEAT          1894..1931
FT                   /note="Plectin 5"
FT   REPEAT          1932..1969
FT                   /note="Plectin 6"
FT   REPEAT          1970..2007
FT                   /note="Plectin 7"
FT   REGION          1..841
FT                   /note="Globular 1"
FT   REGION          1..37
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          12..28
FT                   /note="4 X 4 AA tandem repeats of K-G-S-P"
FT   REGION          65..85
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          388..418
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          842..1673
FT                   /note="Central fibrous rod domain"
FT   REGION          891..916
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1614..1636
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1674..2033
FT                   /note="Globular 2"
FT   COILED          845..1135
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        67..83
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        388..404
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1620..1636
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         1575
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9D952"
FT   MOD_RES         1799
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:20068231"
FT   MOD_RES         2025
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VARIANT         49
FT                   /note="N -> S (in dbSNP:rs397833081)"
FT                   /id="VAR_024579"
FT   VARIANT         168
FT                   /note="Y -> C (in dbSNP:rs10445216)"
FT                   /id="VAR_057698"
FT   VARIANT         433
FT                   /note="Q -> R (in dbSNP:rs2071192)"
FT                   /id="VAR_033863"
FT   VARIANT         1814
FT                   /note="P -> S (in dbSNP:rs7342883)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_057699"
FT   CONFLICT        444
FT                   /note="D -> E (in Ref. 1; AAC64662 and 2; AAD00186)"
FT                   /evidence="ECO:0000305"
FT   STRAND          1829..1832
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   TURN            1833..1836
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   STRAND          1837..1839
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1841..1846
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1852..1863
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   TURN            1864..1866
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   STRAND          1867..1869
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   TURN            1871..1873
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1879..1884
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1890..1892
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1893..1904
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   TURN            1909..1911
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1917..1922
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1928..1940
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1955..1960
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1966..1973
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1975..1977
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   TURN            1985..1987
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   HELIX           1993..1999
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   TURN            2004..2006
FT                   /evidence="ECO:0007829|PDB:4QMD"
FT   STRAND          2009..2013
FT                   /evidence="ECO:0007829|PDB:4QMD"
SQ   SEQUENCE   2033 AA;  231604 MW;  0A994627703393E0 CRC64;
     MFKGLSKGSQ GKGSPKGSPA KGSPKGSPSR HSRAATQELA LLISRMQANA DQVERDILET
     QKRLQQDRLN SEQSQALQHQ QETGRSLKEA EVLLKDLFLD VDKARRLKHP QAEEIEKDIK
     QLHERVTQEC AEYRALYEKM VLPPDVGPRV DWARVLEQKQ KQVCAGQYGP GMAELEQQIA
     EHNILQKEID AYGQQLRSLV GPDAATIRSQ YRDLLKAASW RGQSLGSLYT HLQGCTRQLS
     ALAEQQRRIL QQDWSDLMAD PAGVRREYEH FKQHELLSQE QSVNQLEDDG ERMVELRHPA
     VGPIQAHQEA LKMEWQNFLN LCICQETQLQ HVEDYRRFQE EADSVSQTLA KLNSNLDAKY
     SPAPGGPPGA PTELLQQLEA EEKRLAVTER ATGDLQRRSR DVAPLPQRRN PPQQPLHVDS
     ICDWDSGEVQ LLQGERYKLV DNTDPHAWVV QGPGGETKRA PAACFCIPAP DPDAVARASR
     LASELQALKQ KLATVQSRLK ASAVESLRPS QQAPSGSDLA NPQAQKLLTQ MTRLDGDLGQ
     IERQVLAWAR APLSRPTPLE DLEGRIHSHE GTAQRLQSLG TEKETAQKEC EAFLSTRPVG
     PAALQLPVAL NSVKNKFSDV QVLCSLYGEK AKAALDLERQ IQDADRVIRG FEATLVQEAP
     IPAEPGALQE RVSELQRQRR ELLEQQTCVL RLHRALKASE HACAALQNNF QEFCQDLPRQ
     QRQVRALTDR YHAVGDQLDL REKVVQDAAL TYQQFKNCKD NLSSWLEHLP RSQVRPSDGP
     SQIAYKLQAQ KRLTQEIQSR ERDRATASHL SQALQAALQD YELQADTYRC SLEPTLAVSA
     PKRPRVAPLQ ESIQAQEKNL AKAYTEVAAA QQQLLQQLEF ARKMLEKKEL SEDIRRTHDA
     KQGSESPAQA GRESEALKAQ LEEERKRVAR VQHELEAQRS QLLQLRTQRP LERLEEKEVV
     EFYRDPQLEG SLSRVKAQVE EEGKRRAGLQ ADLEVAAQKV VQLESKRKTM QPHLLTKEVT
     QVERDPGLDS QAAQLRIQIQ QLRGEDAVIS ARLEGLKKEL LALEKREVDV KEKVVVKEVV
     KVEKNLEMVK AAQALRLQME EDAARRKQAE EAVAKLQARI EDLERAISSV EPKVIVKEVK
     KVEQDPGLLQ ESSRLRSLLE EERTKNATLA RELSDLHSKY SVVEKQRPKV QLQERVHEIF
     QVDPETEQEI TRLKAKLQEM AGKRSGVEKE VEKLLPDLEV LRAQKPTVEY KEVTQEVVRH
     ERSPEVLREI DRLKAQLNEL VNSHGRSQEQ LIRLQGERDE WRRERAKVET KTVSKEVVRH
     EKDPVLEKEA ERLRQEVREA AQKRRAAEDA VYELQSKRLL LERRKPEEKV VVQEVVVTQK
     DPKLREEHSR LSGSLDEEVG RRRQLELEVQ QLRAGVEEQE GLLSFQEDRS KKLAVERELR
     QLTLRIQELE KRPPTVQEKI IMEEVVKLEK DPDLEKSTEA LRWDLDQEKT QVTELNRECK
     NLQVQIDVLQ KAKSQEKTIY KEVIRVQKDR VLEDERARVW EMLNRERTAR QAREEEARRL
     RERIDRAETL GRTWSREESE LQRARDQADQ ECGRLQQELR ALERQKQQQT LQLQEESKLL
     SQKTESERQK AAQRGQELSR LEAAILREKD QIYEKERTLR DLHAKVSREE LSQETQTRET
     NLSTKISILE PETGKDMSPY EAYKRGIIDR GQYLQLQELE CDWEEVTTSG PCGEESVLLD
     RKSGKQYSIE AALRCRRISK EEYHLYKDGH LPISEFALLV AGETKPSSSL SIGSIISKSP
     LASPAPQSTS FFSPSFSLGL GDDSFPIAGI YDTTTDNKCS IKTAVAKNML DPITGQKLLE
     AQAATGGIVD LLSRERYSVH KAMERGLIEN TSTQRLLNAQ KAFTGIEDPV TKKRLSVGEA
     VQKGWMPRES VLPHLQVQHL TGGLIDPKRT GRIPIQQALL SGMISEELAQ LLQDESSYEK
     DLTDPISKER LSYKEAMGRC RKDPLSGLLL LPAALEGYRC YRSASPTVPR SLR
//