Full text data of PPL
PPL
(KIAA0568)
[Confidence: low (only semi-automatic identification from reviews)]
Periplakin (190 kDa paraneoplastic pemphigus antigen; 195 kDa cornified envelope precursor protein)
Periplakin (190 kDa paraneoplastic pemphigus antigen; 195 kDa cornified envelope precursor protein)
UniProt
O60437
ID PEPL_HUMAN Reviewed; 1756 AA.
AC O60437; O60314; O60454; Q14C98;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-JAN-2011, sequence version 4.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Periplakin;
DE AltName: Full=190 kDa paraneoplastic pemphigus antigen;
DE AltName: Full=195 kDa cornified envelope precursor protein;
GN Name=PPL; Synonyms=KIAA0568;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, INDUCTION, INTERACTION WITH EVPL, AND VARIANTS GLN-589 AND
RP SER-819.
RC TISSUE=Keratinocyte;
RX PubMed=9412476; DOI=10.1083/jcb.139.7.1835;
RA Ruhrberg C., Hajibagheri M.A.N., Parry D.A.D., Watt F.M.;
RT "Periplakin, a novel component of cornified envelopes and desmosomes
RT that belongs to the plakin family and forms complexes with
RT envoplakin.";
RL J. Cell Biol. 139:1835-1849(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT SER-819.
RC TISSUE=Keratinocyte;
RX PubMed=9521878; DOI=10.1006/geno.1997.5188;
RA Aho S., McLean W.H.I., Li K., Uitto J.;
RT "cDNA cloning, mRNA expression, and chromosomal mapping of human and
RT mouse periplakin genes.";
RL Genomics 48:242-247(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-819.
RX PubMed=10051401; DOI=10.1006/geno.1998.5704;
RA Aho S., Rothenberger K., Tan E.M.L., Ryoo Y.W., Cho B.H.,
RA McLean W.H.I., Uitto J.;
RT "Human periplakin: genomic organization in a clonally unstable region
RT of chromosome 16p with an abundance of repetitive sequence elements.";
RL Genomics 56:160-168(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS GLN-589;
RP SER-819 AND GLU-1573.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLN-589; SER-819
RP AND GLU-1573.
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 331-1756, AND VARIANTS
RP GLN-589; SER-819 AND GLU-1573.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [8]
RP INTERACTION WITH AKT1.
RC TISSUE=Embryo;
RX PubMed=12244133; DOI=10.1242/jcs.00069;
RA van den Heuvel A.P., de Vries-Smits A.M.M., van Weeren P.C.,
RA Dijkers P.F., de Bruyn K.M., Riedl J.A., Burgering B.M.T.;
RT "Binding of protein kinase B to the plakin family member periplakin.";
RL J. Cell Sci. 115:3957-3966(2002).
RN [9]
RP INTERACTION WITH FCGR1A.
RX PubMed=15229321; DOI=10.1073/pnas.0401217101;
RA Beekman J.M., Bakema J.E., van de Winkel J.G.J., Leusen J.H.W.;
RT "Direct interaction between FcgammaRI (CD64) and periplakin controls
RT receptor endocytosis and ligand binding capacity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10392-10397(2004).
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.,
RA Buerckstuemmer T., 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-14; SER-887 AND
RP SER-1657, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Component of the cornified envelope of keratinocytes.
CC May link the cornified envelope to desmosomes and intermediate
CC filaments. May act as a localization signal in PKB/AKT-mediated
CC signaling.
CC -!- SUBUNIT: Homodimer or a heterodimer with EVPL. Interacts with
CC PPHLN1 and VIM. Binds to the PH domain of AKT1. Interacts with
CC FCGR1A.
CC -!- INTERACTION:
CC P31749:AKT1; NbExp=2; IntAct=EBI-368321, EBI-296087;
CC O76027:ANXA9; NbExp=6; IntAct=EBI-368321, EBI-720960;
CC -!- SUBCELLULAR LOCATION: Cell junction, desmosome. Cytoplasm,
CC cytoskeleton. Cell membrane (By similarity). Nucleus (By
CC similarity). Mitochondrion (By similarity). Note=Associated with
CC desmosomes and intermediate filaments.
CC -!- TISSUE SPECIFICITY: Expressed in stratified squamous epithelia and
CC in some other epithelia.
CC -!- INDUCTION: During differentiation of epidermal keratinocytes.
CC -!- SIMILARITY: Belongs to the plakin or cytolinker family.
CC -!- SIMILARITY: Contains 2 plectin repeats.
CC -!- SIMILARITY: Contains 4 spectrin repeats.
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DR EMBL; AF001691; AAC17738.1; -; mRNA.
DR EMBL; AF013717; AAC39668.1; -; mRNA.
DR EMBL; AF041004; AAD17459.1; -; Genomic_DNA.
DR EMBL; AF040999; AAD17459.1; JOINED; Genomic_DNA.
DR EMBL; AF041000; AAD17459.1; JOINED; Genomic_DNA.
DR EMBL; AF041002; AAD17459.1; JOINED; Genomic_DNA.
DR EMBL; AF041003; AAD17459.1; JOINED; Genomic_DNA.
DR EMBL; AC027687; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85248.1; -; Genomic_DNA.
DR EMBL; BC114620; AAI14621.1; -; mRNA.
DR EMBL; AB011140; BAA25494.1; -; mRNA.
DR PIR; T00337; T00337.
DR RefSeq; NP_002696.3; NM_002705.4.
DR UniGene; Hs.192233; -.
DR ProteinModelPortal; O60437; -.
DR IntAct; O60437; 6.
DR MINT; MINT-1181651; -.
DR STRING; 9606.ENSP00000340510; -.
DR PhosphoSite; O60437; -.
DR PaxDb; O60437; -.
DR PRIDE; O60437; -.
DR Ensembl; ENST00000345988; ENSP00000340510; ENSG00000118898.
DR GeneID; 5493; -.
DR KEGG; hsa:5493; -.
DR UCSC; uc002cyd.1; human.
DR CTD; 5493; -.
DR GeneCards; GC16M004872; -.
DR H-InvDB; HIX0012794; -.
DR HGNC; HGNC:9273; PPL.
DR HPA; HPA042550; -.
DR MIM; 602871; gene.
DR neXtProt; NX_O60437; -.
DR PharmGKB; PA33602; -.
DR eggNOG; NOG280386; -.
DR HOGENOM; HOG000168302; -.
DR HOVERGEN; HBG053564; -.
DR InParanoid; O60437; -.
DR KO; K10386; -.
DR OMA; DGGQEYV; -.
DR OrthoDB; EOG7XM2WT; -.
DR PhylomeDB; O60437; -.
DR GeneWiki; Periplakin; -.
DR GenomeRNAi; 5493; -.
DR NextBio; 21238; -.
DR PRO; PR:O60437; -.
DR ArrayExpress; O60437; -.
DR Bgee; O60437; -.
DR CleanEx; HS_PPL; -.
DR Genevestigator; O60437; -.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0030057; C:desmosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0031424; P:keratinization; IEA:UniProtKB-KW.
DR InterPro; IPR001101; Plectin_repeat.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR Pfam; PF00681; Plectin; 1.
DR SMART; SM00250; PLEC; 2.
DR SMART; SM00150; SPEC; 5.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Coiled coil; Complete proteome;
KW Cytoplasm; Cytoskeleton; Keratinization; Membrane; Mitochondrion;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat.
FT CHAIN 1 1756 Periplakin.
FT /FTId=PRO_0000078149.
FT REPEAT 216 317 Spectrin 1.
FT REPEAT 323 485 Spectrin 2.
FT REPEAT 505 612 Spectrin 3.
FT REPEAT 733 861 Spectrin 4.
FT REPEAT 1651 1685 Plectin 1.
FT REPEAT 1700 1735 Plectin 2.
FT COILED 16 125 Potential.
FT COILED 188 389 Potential.
FT COILED 585 820 Potential.
FT COILED 886 1645 Potential.
FT MOD_RES 14 14 Phosphoserine.
FT MOD_RES 887 887 Phosphoserine.
FT MOD_RES 1657 1657 Phosphoserine.
FT VARIANT 520 520 R -> Q (in dbSNP:rs8063727).
FT /FTId=VAR_055125.
FT VARIANT 572 572 A -> S (in dbSNP:rs35300633).
FT /FTId=VAR_055126.
FT VARIANT 589 589 R -> Q (in dbSNP:rs1049205).
FT /FTId=VAR_055127.
FT VARIANT 631 631 H -> Y (in dbSNP:rs34936263).
FT /FTId=VAR_055128.
FT VARIANT 819 819 R -> S (in dbSNP:rs2734742).
FT /FTId=VAR_055129.
FT VARIANT 891 891 E -> Q (in dbSNP:rs35869286).
FT /FTId=VAR_055130.
FT VARIANT 1007 1007 A -> V (in dbSNP:rs2075639).
FT /FTId=VAR_055131.
FT VARIANT 1199 1199 E -> Q (in dbSNP:rs12446946).
FT /FTId=VAR_055132.
FT VARIANT 1573 1573 Q -> E (in dbSNP:rs2037912).
FT /FTId=VAR_055133.
FT VARIANT 1754 1754 G -> R (in dbSNP:rs35865314).
FT /FTId=VAR_055134.
FT CONFLICT 657 657 A -> P (in Ref. 2; AAC39668 and 3;
FT AAD17459).
FT CONFLICT 994 994 V -> F (in Ref. 1; AAC17738).
FT CONFLICT 1663 1663 P -> L (in Ref. 1; AAC17738).
SQ SEQUENCE 1756 AA; 204747 MW; EA7EAF3E756D78B4 CRC64;
MNSLFRKRNK GKYSPTVQTR SISNKELSEL IEQLQKNADQ VEKNIVDTEA KMQSDLARLQ
EGRQPEHRDV TLQKVLDSEK LLYVLEADAA IAKHMKHPQG DMIAEDIRQL KERVTNLRGK
HKQIYRLAVK EVDPQVNWAA LVEEKLDKLN NQSFGTDLPL VDHQVEEHNI FHNEVKAIGP
HLAKDGDKEQ NSELRAKYQK LLAASQARQQ HLSSLQDYMQ RCTNELYWLD QQAKGRMQYD
WSDRNLDYPS RRRQYENFIN RNLEAKEERI NKLHSEGDQL LAAEHPGRNS IEAHMEAVHA
DWKEYLNLLI CEESHLKYME DYHQFHEDVK DAQELLRKVD SDLNQKYGPD FKDRYQIELL
LRELDDQEKV LDKYEDVVQG LQKRGQQVVP LKYRRETPLK PIPVEALCDF EGEQGLISRG
YSYTLQKNNG ESWELMDSAG NKLIAPAVCF VIPPTDPEAL ALADSLGSQY RSVRQKAAGS
KRTLQQRYEV LKTENPGDAS DLQGRQLLAG LDKVASDLDR QEKAITGILR PPLEQGRAVQ
DSAERAKDLK NITNELLRIE PEKTRSTAEG EAFIQALPGS GTTPLLRTRV EDTNRKYEHL
LQLLDLAQEK VDVANRLEKS LQQSWELLAT HENHLNQDDT VPESSRVLDS KGQELAAMAC
ELQAQKSLLG EVEQNLQAAK QCSSTLASRF QEHCPDLERQ EAEVHKLGQR FNNLRQQVER
RAQSLQSAKA AYEHFHRGHD HVLQFLVSIP SYEPQETDSL SQMETKLKNQ KNLLDEIASR
EQEVQKICAN SQQYQQAVKD YELEAEKLRS LLDLENGRRS HVSKRARLQS PATKVKEEEA
ALAAKFTEVY AINRQRLQNL EFALNLLRQQ PEVEVTHETL QRNRPDSGVE EAWKIRKELD
EETERRRQLE NEVKSTQEEI WTLRNQGPQE SVVRKEVLKK VPDPVLEESF QQLQRTLAEE
QHKNQLLQEE LEALQLQLRA LEQETRDGGQ EYVVKEVLRI EPDRAQADEV LQLREELEAL
RRQKGAREAE VLLLQQRVAA LAEEKSRAQE KVTEKEVVKL QNDPQLEAEY QQLQEDHQRQ
DQLREKQEEE LSFLQDKLKR LEKERAMAEG KITVKEVLKV EKDAATEREV SDLTRQYEDE
AAKARASQRE KTELLRKIWA LEEENAKVVV QEKVREIVRP DPKAESEVAN LRLELVEQER
KYRGAEEQLR SYQSELEALR RRGPQVEVKE VTKEVIKYKT DPEMEKELQR LREEIVDKTR
LIERCDLEIY QLKKEIQALK DTKPQVQTKE VVQEILQFQE DPQTKEEVAS LRAKLSEEQK
KQVDLERERA SQEEQIARKE EELSRVKERV VQQEVVRYEE EPGLRAEASA FAESIDVELR
QIDKLRAELR RLQRRRTELE RQLEELERER QARREAEREV QRLQQRLAAL EQEEAEAREK
VTHTQKVVLQ QDPQQAREHA LLRLQLEEEQ HRRQLLEGEL ETLRRKLAAL EKAEVKEKVV
LSESVQVEKG DTEQEIQRLK SSLEEESRSK RELDVEVSRL EARLSELEFH NSKSSKELDF
LREENHKLQL ERQNLQLETR RLQSEINMAA TETRDLRNMT VADSGTNHDS RLWSLERELD
DLKRLSKDKD LEIDELQKRL GSVAVKREQR ENHLRRSIVV IHPDTGRELS PEEAHRAGLI
DWNMFVKLRS QECDWEEISV KGPNGESSVI HDRKSGKKFS IEEALQSGRL TPAQYDRYVN
KDMSIQELAV LVSGQK
//
ID PEPL_HUMAN Reviewed; 1756 AA.
AC O60437; O60314; O60454; Q14C98;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-JAN-2011, sequence version 4.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Periplakin;
DE AltName: Full=190 kDa paraneoplastic pemphigus antigen;
DE AltName: Full=195 kDa cornified envelope precursor protein;
GN Name=PPL; Synonyms=KIAA0568;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, INDUCTION, INTERACTION WITH EVPL, AND VARIANTS GLN-589 AND
RP SER-819.
RC TISSUE=Keratinocyte;
RX PubMed=9412476; DOI=10.1083/jcb.139.7.1835;
RA Ruhrberg C., Hajibagheri M.A.N., Parry D.A.D., Watt F.M.;
RT "Periplakin, a novel component of cornified envelopes and desmosomes
RT that belongs to the plakin family and forms complexes with
RT envoplakin.";
RL J. Cell Biol. 139:1835-1849(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT SER-819.
RC TISSUE=Keratinocyte;
RX PubMed=9521878; DOI=10.1006/geno.1997.5188;
RA Aho S., McLean W.H.I., Li K., Uitto J.;
RT "cDNA cloning, mRNA expression, and chromosomal mapping of human and
RT mouse periplakin genes.";
RL Genomics 48:242-247(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-819.
RX PubMed=10051401; DOI=10.1006/geno.1998.5704;
RA Aho S., Rothenberger K., Tan E.M.L., Ryoo Y.W., Cho B.H.,
RA McLean W.H.I., Uitto J.;
RT "Human periplakin: genomic organization in a clonally unstable region
RT of chromosome 16p with an abundance of repetitive sequence elements.";
RL Genomics 56:160-168(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS GLN-589;
RP SER-819 AND GLU-1573.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLN-589; SER-819
RP AND GLU-1573.
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 331-1756, AND VARIANTS
RP GLN-589; SER-819 AND GLU-1573.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [8]
RP INTERACTION WITH AKT1.
RC TISSUE=Embryo;
RX PubMed=12244133; DOI=10.1242/jcs.00069;
RA van den Heuvel A.P., de Vries-Smits A.M.M., van Weeren P.C.,
RA Dijkers P.F., de Bruyn K.M., Riedl J.A., Burgering B.M.T.;
RT "Binding of protein kinase B to the plakin family member periplakin.";
RL J. Cell Sci. 115:3957-3966(2002).
RN [9]
RP INTERACTION WITH FCGR1A.
RX PubMed=15229321; DOI=10.1073/pnas.0401217101;
RA Beekman J.M., Bakema J.E., van de Winkel J.G.J., Leusen J.H.W.;
RT "Direct interaction between FcgammaRI (CD64) and periplakin controls
RT receptor endocytosis and ligand binding capacity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10392-10397(2004).
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.,
RA Buerckstuemmer T., 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-14; SER-887 AND
RP SER-1657, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Component of the cornified envelope of keratinocytes.
CC May link the cornified envelope to desmosomes and intermediate
CC filaments. May act as a localization signal in PKB/AKT-mediated
CC signaling.
CC -!- SUBUNIT: Homodimer or a heterodimer with EVPL. Interacts with
CC PPHLN1 and VIM. Binds to the PH domain of AKT1. Interacts with
CC FCGR1A.
CC -!- INTERACTION:
CC P31749:AKT1; NbExp=2; IntAct=EBI-368321, EBI-296087;
CC O76027:ANXA9; NbExp=6; IntAct=EBI-368321, EBI-720960;
CC -!- SUBCELLULAR LOCATION: Cell junction, desmosome. Cytoplasm,
CC cytoskeleton. Cell membrane (By similarity). Nucleus (By
CC similarity). Mitochondrion (By similarity). Note=Associated with
CC desmosomes and intermediate filaments.
CC -!- TISSUE SPECIFICITY: Expressed in stratified squamous epithelia and
CC in some other epithelia.
CC -!- INDUCTION: During differentiation of epidermal keratinocytes.
CC -!- SIMILARITY: Belongs to the plakin or cytolinker family.
CC -!- SIMILARITY: Contains 2 plectin repeats.
CC -!- SIMILARITY: Contains 4 spectrin repeats.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AF001691; AAC17738.1; -; mRNA.
DR EMBL; AF013717; AAC39668.1; -; mRNA.
DR EMBL; AF041004; AAD17459.1; -; Genomic_DNA.
DR EMBL; AF040999; AAD17459.1; JOINED; Genomic_DNA.
DR EMBL; AF041000; AAD17459.1; JOINED; Genomic_DNA.
DR EMBL; AF041002; AAD17459.1; JOINED; Genomic_DNA.
DR EMBL; AF041003; AAD17459.1; JOINED; Genomic_DNA.
DR EMBL; AC027687; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85248.1; -; Genomic_DNA.
DR EMBL; BC114620; AAI14621.1; -; mRNA.
DR EMBL; AB011140; BAA25494.1; -; mRNA.
DR PIR; T00337; T00337.
DR RefSeq; NP_002696.3; NM_002705.4.
DR UniGene; Hs.192233; -.
DR ProteinModelPortal; O60437; -.
DR IntAct; O60437; 6.
DR MINT; MINT-1181651; -.
DR STRING; 9606.ENSP00000340510; -.
DR PhosphoSite; O60437; -.
DR PaxDb; O60437; -.
DR PRIDE; O60437; -.
DR Ensembl; ENST00000345988; ENSP00000340510; ENSG00000118898.
DR GeneID; 5493; -.
DR KEGG; hsa:5493; -.
DR UCSC; uc002cyd.1; human.
DR CTD; 5493; -.
DR GeneCards; GC16M004872; -.
DR H-InvDB; HIX0012794; -.
DR HGNC; HGNC:9273; PPL.
DR HPA; HPA042550; -.
DR MIM; 602871; gene.
DR neXtProt; NX_O60437; -.
DR PharmGKB; PA33602; -.
DR eggNOG; NOG280386; -.
DR HOGENOM; HOG000168302; -.
DR HOVERGEN; HBG053564; -.
DR InParanoid; O60437; -.
DR KO; K10386; -.
DR OMA; DGGQEYV; -.
DR OrthoDB; EOG7XM2WT; -.
DR PhylomeDB; O60437; -.
DR GeneWiki; Periplakin; -.
DR GenomeRNAi; 5493; -.
DR NextBio; 21238; -.
DR PRO; PR:O60437; -.
DR ArrayExpress; O60437; -.
DR Bgee; O60437; -.
DR CleanEx; HS_PPL; -.
DR Genevestigator; O60437; -.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0030057; C:desmosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0031424; P:keratinization; IEA:UniProtKB-KW.
DR InterPro; IPR001101; Plectin_repeat.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR Pfam; PF00681; Plectin; 1.
DR SMART; SM00250; PLEC; 2.
DR SMART; SM00150; SPEC; 5.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Coiled coil; Complete proteome;
KW Cytoplasm; Cytoskeleton; Keratinization; Membrane; Mitochondrion;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat.
FT CHAIN 1 1756 Periplakin.
FT /FTId=PRO_0000078149.
FT REPEAT 216 317 Spectrin 1.
FT REPEAT 323 485 Spectrin 2.
FT REPEAT 505 612 Spectrin 3.
FT REPEAT 733 861 Spectrin 4.
FT REPEAT 1651 1685 Plectin 1.
FT REPEAT 1700 1735 Plectin 2.
FT COILED 16 125 Potential.
FT COILED 188 389 Potential.
FT COILED 585 820 Potential.
FT COILED 886 1645 Potential.
FT MOD_RES 14 14 Phosphoserine.
FT MOD_RES 887 887 Phosphoserine.
FT MOD_RES 1657 1657 Phosphoserine.
FT VARIANT 520 520 R -> Q (in dbSNP:rs8063727).
FT /FTId=VAR_055125.
FT VARIANT 572 572 A -> S (in dbSNP:rs35300633).
FT /FTId=VAR_055126.
FT VARIANT 589 589 R -> Q (in dbSNP:rs1049205).
FT /FTId=VAR_055127.
FT VARIANT 631 631 H -> Y (in dbSNP:rs34936263).
FT /FTId=VAR_055128.
FT VARIANT 819 819 R -> S (in dbSNP:rs2734742).
FT /FTId=VAR_055129.
FT VARIANT 891 891 E -> Q (in dbSNP:rs35869286).
FT /FTId=VAR_055130.
FT VARIANT 1007 1007 A -> V (in dbSNP:rs2075639).
FT /FTId=VAR_055131.
FT VARIANT 1199 1199 E -> Q (in dbSNP:rs12446946).
FT /FTId=VAR_055132.
FT VARIANT 1573 1573 Q -> E (in dbSNP:rs2037912).
FT /FTId=VAR_055133.
FT VARIANT 1754 1754 G -> R (in dbSNP:rs35865314).
FT /FTId=VAR_055134.
FT CONFLICT 657 657 A -> P (in Ref. 2; AAC39668 and 3;
FT AAD17459).
FT CONFLICT 994 994 V -> F (in Ref. 1; AAC17738).
FT CONFLICT 1663 1663 P -> L (in Ref. 1; AAC17738).
SQ SEQUENCE 1756 AA; 204747 MW; EA7EAF3E756D78B4 CRC64;
MNSLFRKRNK GKYSPTVQTR SISNKELSEL IEQLQKNADQ VEKNIVDTEA KMQSDLARLQ
EGRQPEHRDV TLQKVLDSEK LLYVLEADAA IAKHMKHPQG DMIAEDIRQL KERVTNLRGK
HKQIYRLAVK EVDPQVNWAA LVEEKLDKLN NQSFGTDLPL VDHQVEEHNI FHNEVKAIGP
HLAKDGDKEQ NSELRAKYQK LLAASQARQQ HLSSLQDYMQ RCTNELYWLD QQAKGRMQYD
WSDRNLDYPS RRRQYENFIN RNLEAKEERI NKLHSEGDQL LAAEHPGRNS IEAHMEAVHA
DWKEYLNLLI CEESHLKYME DYHQFHEDVK DAQELLRKVD SDLNQKYGPD FKDRYQIELL
LRELDDQEKV LDKYEDVVQG LQKRGQQVVP LKYRRETPLK PIPVEALCDF EGEQGLISRG
YSYTLQKNNG ESWELMDSAG NKLIAPAVCF VIPPTDPEAL ALADSLGSQY RSVRQKAAGS
KRTLQQRYEV LKTENPGDAS DLQGRQLLAG LDKVASDLDR QEKAITGILR PPLEQGRAVQ
DSAERAKDLK NITNELLRIE PEKTRSTAEG EAFIQALPGS GTTPLLRTRV EDTNRKYEHL
LQLLDLAQEK VDVANRLEKS LQQSWELLAT HENHLNQDDT VPESSRVLDS KGQELAAMAC
ELQAQKSLLG EVEQNLQAAK QCSSTLASRF QEHCPDLERQ EAEVHKLGQR FNNLRQQVER
RAQSLQSAKA AYEHFHRGHD HVLQFLVSIP SYEPQETDSL SQMETKLKNQ KNLLDEIASR
EQEVQKICAN SQQYQQAVKD YELEAEKLRS LLDLENGRRS HVSKRARLQS PATKVKEEEA
ALAAKFTEVY AINRQRLQNL EFALNLLRQQ PEVEVTHETL QRNRPDSGVE EAWKIRKELD
EETERRRQLE NEVKSTQEEI WTLRNQGPQE SVVRKEVLKK VPDPVLEESF QQLQRTLAEE
QHKNQLLQEE LEALQLQLRA LEQETRDGGQ EYVVKEVLRI EPDRAQADEV LQLREELEAL
RRQKGAREAE VLLLQQRVAA LAEEKSRAQE KVTEKEVVKL QNDPQLEAEY QQLQEDHQRQ
DQLREKQEEE LSFLQDKLKR LEKERAMAEG KITVKEVLKV EKDAATEREV SDLTRQYEDE
AAKARASQRE KTELLRKIWA LEEENAKVVV QEKVREIVRP DPKAESEVAN LRLELVEQER
KYRGAEEQLR SYQSELEALR RRGPQVEVKE VTKEVIKYKT DPEMEKELQR LREEIVDKTR
LIERCDLEIY QLKKEIQALK DTKPQVQTKE VVQEILQFQE DPQTKEEVAS LRAKLSEEQK
KQVDLERERA SQEEQIARKE EELSRVKERV VQQEVVRYEE EPGLRAEASA FAESIDVELR
QIDKLRAELR RLQRRRTELE RQLEELERER QARREAEREV QRLQQRLAAL EQEEAEAREK
VTHTQKVVLQ QDPQQAREHA LLRLQLEEEQ HRRQLLEGEL ETLRRKLAAL EKAEVKEKVV
LSESVQVEKG DTEQEIQRLK SSLEEESRSK RELDVEVSRL EARLSELEFH NSKSSKELDF
LREENHKLQL ERQNLQLETR RLQSEINMAA TETRDLRNMT VADSGTNHDS RLWSLERELD
DLKRLSKDKD LEIDELQKRL GSVAVKREQR ENHLRRSIVV IHPDTGRELS PEEAHRAGLI
DWNMFVKLRS QECDWEEISV KGPNGESSVI HDRKSGKKFS IEEALQSGRL TPAQYDRYVN
KDMSIQELAV LVSGQK
//
MIM
602871
*RECORD*
*FIELD* NO
602871
*FIELD* TI
*602871 PERIPLAKIN; PPL
*FIELD* TX
DESCRIPTION
The intermediate filament cytoskeleton of keratinocytes, composed of
read morekeratins (see 139350) that are expressed in specific expression pairs
according to tissue and differentiation state, are interconnected
through transmembrane protein complexes called desmosomes and connect
with the basement membrane via hemidesmosomes. The proteins thought to
make contact with the intermediate filaments of keratinocytes belong to
a family of proteins known as plakins, of which desmoplakin (125647),
envoplakin (601590), and periplakin are members. These proteins have a
similar overall domain structure that includes an N-terminal globular
domain, a central coiled-coil rod domain, and a C-terminal tail with
characteristic repeat sequences.
CLONING
Ruhrberg et al. (1997) cloned PPL from a keratinocyte expression library
using antibody to PPL as the probe. The deduced 1,666-amino acid protein
has a calculated molecular mass of about 205 kD. PPL shares extensive
sequence homology with other proteins of the plakin family, with highest
identities found in the N- and C-terminal domains. Immunoblots of
keratinocyte extracts revealed a protein with an apparent molecular mass
of 195 kD. Immunogold electron microscopy revealed association of PPL
with the desmosomal plaque and with keratin filaments in the
differentiated layers of the epidermis.
Aho et al. (1998) isolated PPL in a yeast 2-hybrid system by its
interactions with type XVII collagen, a component of hemidesmosomes. The
PPL clones from human keratinocyte and placenta libraries span
approximately 6.2 kb. The predicted 1,756-amino acid periplakin
polypeptide has a computed molecular mass of approximately 204 kD. PPL
shares 50.3% amino acid sequence similarity with envoplakin. Northern
blot analysis revealed that a 6.5-kb PPL message is expressed
predominantly in keratinocytes compared to fibroblasts; dot blot
analysis detected expression in tissues containing epithelial cells,
with the highest expression in trachea, and in nonepithelial tissues,
most notably in many areas of the brain.
By RT-PCR, Kazerounian et al. (2002) detected significant expression of
PPL in brain, heart, liver, pancreas, placenta, skeletal muscle, colon,
and small intestine.
GENE FUNCTION
Ruhrberg et al. (1997) noted that the influx of Ca(2+) that occurs
following treatment of confluent keratinocyte cultures with a detergent
or with a calcium ionophore stimulates the cross-linking of cornified
envelope precursors by transglutaminases (190195). PPL became
cross-linked following exposure of keratinocytes to these agents, and a
transglutaminase inhibitor blocked PPL cross-linking.
Coimmunoprecipitation experiments revealed interaction between PPL and
envoplakin. Analysis of putative ionic interactions between the rod
domains suggested that both PPL and envoplakin could form homodimers and
heterodimers. Confocal immunofluorescent microscopy of cultured
epidermal keratinocytes suggested that envoplakin and PPL form a network
radiating from desmosomes.
Using a yeast 2-hybrid assay, Kazerounian et al. (2002) found that a
linker region within the C-terminal globular domain of periplakin
interacts with keratin-8 (K8; 148060) and vimentin (193060). In an in
vitro pull-down assay, K18 (148070) also coprecipitated with K8 with the
periplakin C-terminal tail, suggesting that periplakin can interact with
K8 within the K8/K18 heterodimer.
GENE STRUCTURE
Aho et al. (1999) determined that the PPL gene contains 22 exons and
spans 60 kb. The 5-prime flanking sequence is GC rich (80%) and contains
multiple AP2 (107580) and SP1 (189906) sites, but no canonical TATA or
CCAAT boxes. The gene also has multiple Alu repeats and numerous MIR and
L1 elements.
MAPPING
By radiation hybrid analysis, Aho et al. (1998) assigned the PPL gene to
chromosome 16p13. By use of an interspecific backcross panel, they
mapped the mouse periplakin gene to the proximal part of mouse
chromosome 16, a region syntenic with human chromosome 16. By somatic
cell hybrid analysis and FISH, Ruhrberg et al. (1998) mapped the PPL
gene to chromosome 16p13.3. They mapped the mouse Ppl gene to chromosome
16A-B1.
ANIMAL MODEL
Aho et al. (2004) found that Ppl -/- mice were born in the expected
mendelian frequency, developed normally, possessed grossly normal
epidermis and hair, and were healthy and fertile. The epidermal barrier
developed normally during embryonic days 15.5 to 16.5, and the cornified
envelope and desmosomes in the newborn mice were ultrastructurally
normal. No compensatory increase in the expression of other epithelial
proteins was detected in neonatal mouse epidermis lacking periplakin.
Aho et al. (2004) concluded that the primary role of periplakin may not
relate to the physiology of the cornified cell envelope in epidermal
keratinocytes.
*FIELD* RF
1. Aho, S.; Li, K.; Ryoo, Y.; McGee, C.; Ishida-Yamamoto, A.; Uitto,
J.; Klement, J. F.: Periplakin gene targeting reveals a constituent
of the cornified cell envelope dispensable for normal mouse development. Molec.
Cell. Biol. 24: 6410-6418, 2004.
2. Aho, S.; McLean, W. H. I.; Li, K.; Uitto, J.: cDNA cloning, mRNA
expression, and chromosomal mapping of human and mouse periplakin
genes. Genomics 48: 242-247, 1998.
3. Aho, S.; Rothenberger, K.; Tan, E. M. L.; Ryoo, Y. W.; Cho, B.
H.; McLean, W. H. I.; Uitto, J.: Human periplakin: genomic organization
in a clonally unstable region of chromosome 16p with an abundance
of repetitive sequence elements. Genomics 56: 160-168, 1999.
4. Kazerounian, S.; Uitto, J.; Aho, S.: Unique role for the periplakin
tail in intermediate filament association: specific binding to keratin
8 and vimentin. Exp. Derm. 11: 428-438, 2002.
5. Ruhrberg, C.; Hajibagheri, M. A. N.; Parry, D. A. D.; Watt, F.
A.: Periplakin, a novel component of cornified envelopes and desmosomes
that belongs to the plakin family and forms complexes with envoplakin. J.
Cell Biol. 139: 1835-1849, 1997.
6. Ruhrberg, C.; Williamson, J. A.; Maatta, A.; Watt, F. A.: The
periplakin gene maps to 16p13.3 in human and 16A-B1 in mouse. Genomics 49:
157-159, 1998.
*FIELD* CN
Patricia A. Hartz - updated: 8/16/2004
Patricia A. Hartz - updated: 10/7/2003
Patricia A. Hartz - updated: 11/21/2002
*FIELD* CD
Sheryl A. Jankowski: 7/21/1998
*FIELD* ED
mgross: 09/07/2004
terry: 8/16/2004
mgross: 10/7/2003
mgross: 11/21/2002
carol: 7/24/1998
carol: 7/23/1998
dholmes: 7/23/1998
dholmes: 7/22/1998
*RECORD*
*FIELD* NO
602871
*FIELD* TI
*602871 PERIPLAKIN; PPL
*FIELD* TX
DESCRIPTION
The intermediate filament cytoskeleton of keratinocytes, composed of
read morekeratins (see 139350) that are expressed in specific expression pairs
according to tissue and differentiation state, are interconnected
through transmembrane protein complexes called desmosomes and connect
with the basement membrane via hemidesmosomes. The proteins thought to
make contact with the intermediate filaments of keratinocytes belong to
a family of proteins known as plakins, of which desmoplakin (125647),
envoplakin (601590), and periplakin are members. These proteins have a
similar overall domain structure that includes an N-terminal globular
domain, a central coiled-coil rod domain, and a C-terminal tail with
characteristic repeat sequences.
CLONING
Ruhrberg et al. (1997) cloned PPL from a keratinocyte expression library
using antibody to PPL as the probe. The deduced 1,666-amino acid protein
has a calculated molecular mass of about 205 kD. PPL shares extensive
sequence homology with other proteins of the plakin family, with highest
identities found in the N- and C-terminal domains. Immunoblots of
keratinocyte extracts revealed a protein with an apparent molecular mass
of 195 kD. Immunogold electron microscopy revealed association of PPL
with the desmosomal plaque and with keratin filaments in the
differentiated layers of the epidermis.
Aho et al. (1998) isolated PPL in a yeast 2-hybrid system by its
interactions with type XVII collagen, a component of hemidesmosomes. The
PPL clones from human keratinocyte and placenta libraries span
approximately 6.2 kb. The predicted 1,756-amino acid periplakin
polypeptide has a computed molecular mass of approximately 204 kD. PPL
shares 50.3% amino acid sequence similarity with envoplakin. Northern
blot analysis revealed that a 6.5-kb PPL message is expressed
predominantly in keratinocytes compared to fibroblasts; dot blot
analysis detected expression in tissues containing epithelial cells,
with the highest expression in trachea, and in nonepithelial tissues,
most notably in many areas of the brain.
By RT-PCR, Kazerounian et al. (2002) detected significant expression of
PPL in brain, heart, liver, pancreas, placenta, skeletal muscle, colon,
and small intestine.
GENE FUNCTION
Ruhrberg et al. (1997) noted that the influx of Ca(2+) that occurs
following treatment of confluent keratinocyte cultures with a detergent
or with a calcium ionophore stimulates the cross-linking of cornified
envelope precursors by transglutaminases (190195). PPL became
cross-linked following exposure of keratinocytes to these agents, and a
transglutaminase inhibitor blocked PPL cross-linking.
Coimmunoprecipitation experiments revealed interaction between PPL and
envoplakin. Analysis of putative ionic interactions between the rod
domains suggested that both PPL and envoplakin could form homodimers and
heterodimers. Confocal immunofluorescent microscopy of cultured
epidermal keratinocytes suggested that envoplakin and PPL form a network
radiating from desmosomes.
Using a yeast 2-hybrid assay, Kazerounian et al. (2002) found that a
linker region within the C-terminal globular domain of periplakin
interacts with keratin-8 (K8; 148060) and vimentin (193060). In an in
vitro pull-down assay, K18 (148070) also coprecipitated with K8 with the
periplakin C-terminal tail, suggesting that periplakin can interact with
K8 within the K8/K18 heterodimer.
GENE STRUCTURE
Aho et al. (1999) determined that the PPL gene contains 22 exons and
spans 60 kb. The 5-prime flanking sequence is GC rich (80%) and contains
multiple AP2 (107580) and SP1 (189906) sites, but no canonical TATA or
CCAAT boxes. The gene also has multiple Alu repeats and numerous MIR and
L1 elements.
MAPPING
By radiation hybrid analysis, Aho et al. (1998) assigned the PPL gene to
chromosome 16p13. By use of an interspecific backcross panel, they
mapped the mouse periplakin gene to the proximal part of mouse
chromosome 16, a region syntenic with human chromosome 16. By somatic
cell hybrid analysis and FISH, Ruhrberg et al. (1998) mapped the PPL
gene to chromosome 16p13.3. They mapped the mouse Ppl gene to chromosome
16A-B1.
ANIMAL MODEL
Aho et al. (2004) found that Ppl -/- mice were born in the expected
mendelian frequency, developed normally, possessed grossly normal
epidermis and hair, and were healthy and fertile. The epidermal barrier
developed normally during embryonic days 15.5 to 16.5, and the cornified
envelope and desmosomes in the newborn mice were ultrastructurally
normal. No compensatory increase in the expression of other epithelial
proteins was detected in neonatal mouse epidermis lacking periplakin.
Aho et al. (2004) concluded that the primary role of periplakin may not
relate to the physiology of the cornified cell envelope in epidermal
keratinocytes.
*FIELD* RF
1. Aho, S.; Li, K.; Ryoo, Y.; McGee, C.; Ishida-Yamamoto, A.; Uitto,
J.; Klement, J. F.: Periplakin gene targeting reveals a constituent
of the cornified cell envelope dispensable for normal mouse development. Molec.
Cell. Biol. 24: 6410-6418, 2004.
2. Aho, S.; McLean, W. H. I.; Li, K.; Uitto, J.: cDNA cloning, mRNA
expression, and chromosomal mapping of human and mouse periplakin
genes. Genomics 48: 242-247, 1998.
3. Aho, S.; Rothenberger, K.; Tan, E. M. L.; Ryoo, Y. W.; Cho, B.
H.; McLean, W. H. I.; Uitto, J.: Human periplakin: genomic organization
in a clonally unstable region of chromosome 16p with an abundance
of repetitive sequence elements. Genomics 56: 160-168, 1999.
4. Kazerounian, S.; Uitto, J.; Aho, S.: Unique role for the periplakin
tail in intermediate filament association: specific binding to keratin
8 and vimentin. Exp. Derm. 11: 428-438, 2002.
5. Ruhrberg, C.; Hajibagheri, M. A. N.; Parry, D. A. D.; Watt, F.
A.: Periplakin, a novel component of cornified envelopes and desmosomes
that belongs to the plakin family and forms complexes with envoplakin. J.
Cell Biol. 139: 1835-1849, 1997.
6. Ruhrberg, C.; Williamson, J. A.; Maatta, A.; Watt, F. A.: The
periplakin gene maps to 16p13.3 in human and 16A-B1 in mouse. Genomics 49:
157-159, 1998.
*FIELD* CN
Patricia A. Hartz - updated: 8/16/2004
Patricia A. Hartz - updated: 10/7/2003
Patricia A. Hartz - updated: 11/21/2002
*FIELD* CD
Sheryl A. Jankowski: 7/21/1998
*FIELD* ED
mgross: 09/07/2004
terry: 8/16/2004
mgross: 10/7/2003
mgross: 11/21/2002
carol: 7/24/1998
carol: 7/23/1998
dholmes: 7/23/1998
dholmes: 7/22/1998