EVPL_HUMAN
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 03-AUG-2022, entry version 179.
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; 112.
DR IntAct; Q92817; 25.
DR MINT; Q92817; -.
DR STRING; 9606.ENSP00000301607; -.
DR GlyGen; Q92817; 1 site, 1 O-linked glycan (1 site).
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; Q92817; -.
DR PeptideAtlas; Q92817; -.
DR PRIDE; Q92817; -.
DR ProteomicsDB; 75494; -.
DR Antibodypedia; 46112; 65 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 CTD; 2125; -.
DR DisGeNET; 2125; -.
DR GeneCards; EVPL; -.
DR HGNC; HGNC:3503; EVPL.
DR HPA; ENSG00000167880; Group enriched (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; VRHEKNP; -.
DR OrthoDB; 68483at2759; -.
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 1070 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 135 other tissues.
DR ExpressionAtlas; Q92817; baseline and differential.
DR Genevisible; Q92817; HS.
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:0019215; F:intermediate filament binding; IEA:InterPro.
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; 3.90.1290.10; -; 1.
DR InterPro; IPR041615; Desmoplakin_SH3.
DR InterPro; IPR030460; Envoplakin.
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; PTHR23169; 1.
DR PANTHER; PTHR23169:SF7; PTHR23169:SF7; 1.
DR Pfam; PF00681; Plectin; 4.
DR Pfam; PF17902; SH3_10; 1.
DR SMART; SM00250; PLEC; 8.
DR SMART; SM00150; SPEC; 1.
DR SUPFAM; SSF75399; SSF75399; 2.
DR PROSITE; PS50002; SH3; 1.
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
