Reviewed, UniProtKB/Swiss-Prot O60437 (PEPL_HUMAN)

Names and origin

Protein names

Recommended name:
    Periplakin
Alternative name(s):
    195 kDa cornified envelope precursor protein
    190 kDa paraneoplastic pemphigus antigen

Gene names

Name:	PPL
Synonyms:	KIAA0568

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1756 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. May act as a localization signal in PKB/AKT-mediated signaling. Ref.1
Subunit structure	Homodimer or a heterodimer with EVPL. Interacts with PPHLN1 and VIM. Binds to the PH domain of AKT1. Interacts with FCGR1A. Ref.1 Ref.8 Ref.9
Subcellular location	Cell junction › desmosome. Cytoplasm › cytoskeleton. Cell membrane By similarity. Nucleus By similarity. Mitochondrion By similarity. Note: Associated with desmosomes and intermediate filaments. Ref.1
Tissue specificity	Expressed in stratified squamous epithelia and in some other epithelia. Ref.1 Ref.2
Induction	During differentiation of epidermal keratinocytes. Ref.1
Sequence similarities	Belongs to the plakin or cytolinker family. Contains 2 plectin repeats. Contains 4 spectrin repeats.

Ontologies

Keywords
Biological process	Keratinization
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane Mitochondrion Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil Repeat
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	keratinization Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoskeleton Ref.2 Traceable author statement. Source: ProtInc desmosome Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: IntAct structural constituent of cytoskeleton Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AKT1	P31749	1	EBI-368321,EBI-296087

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1756	1756	Periplakin		PRO_0000078149
Regions
	Repeat	216 – 317	102	Spectrin 1
	Repeat	323 – 485	163	Spectrin 2
	Repeat	505 – 612	108	Spectrin 3
	Repeat	733 – 861	129	Spectrin 4
	Repeat	1651 – 1685	35	Plectin 1
	Repeat	1700 – 1735	36	Plectin 2
	Coiled coil	16 – 125	110	Potential
	Coiled coil	188 – 389	202	Potential
	Coiled coil	585 – 820	236	Potential
	Coiled coil	886 – 1645	760	Potential
Amino acid modifications
	Modified residue	14	1	Phosphoserine By similarity
	Modified residue	1331	1	Phosphoserine Ref.10
	Modified residue	1579	1	Phosphothreonine Ref.11
	Modified residue	1657	1	Phosphoserine By similarity
Natural variations
	Natural variant	520	1	R → Q: dbSNP rs8063727.		VAR_055125
	Natural variant	572	1	A → S: dbSNP rs35300633.		VAR_055126
	Natural variant	589	1	R → Q: dbSNP rs1049205. Ref.1 Ref.5 Ref.6 Ref.7		VAR_055127
	Natural variant	631	1	H → Y: dbSNP rs34936263.		VAR_055128
	Natural variant	819	1	S → R: dbSNP rs2734742. Ref.4		VAR_055129
	Natural variant	891	1	E → Q: dbSNP rs35869286.		VAR_055130
	Natural variant	1007	1	A → V: dbSNP rs2075639.		VAR_055131
	Natural variant	1199	1	E → Q: dbSNP rs12446946.		VAR_055132
	Natural variant	1573	1	Q → E: dbSNP rs2037912. Ref.5 Ref.6 Ref.7		VAR_055133
	Natural variant	1754	1	G → R: dbSNP rs35865314.		VAR_055134
Experimental info
	Sequence conflict	657	1	A → P in AAC39668. Ref.2
	Sequence conflict	657	1	A → P in AAD17459. Ref.3
	Sequence conflict	994	1	V → F in AAC17738. Ref.1
	Sequence conflict	1663	1	P → L in AAC17738. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O60437-1 [UniParc]. Last modified May 5, 2009. Version 3. Checksum: 2821D0711F06F105	FASTA	1,756	204,678
	10 20 30 40 50 60 MNSLFRKRNK GKYSPTVQTR SISNKELSEL IEQLQKNADQ VEKNIVDTEA KMQSDLARLQ 70 80 90 100 110 120 EGRQPEHRDV TLQKVLDSEK LLYVLEADAA IAKHMKHPQG DMIAEDIRQL KERVTNLRGK 130 140 150 160 170 180 HKQIYRLAVK EVDPQVNWAA LVEEKLDKLN NQSFGTDLPL VDHQVEEHNI FHNEVKAIGP 190 200 210 220 230 240 HLAKDGDKEQ NSELRAKYQK LLAASQARQQ HLSSLQDYMQ RCTNELYWLD QQAKGRMQYD 250 260 270 280 290 300 WSDRNLDYPS RRRQYENFIN RNLEAKEERI NKLHSEGDQL LAAEHPGRNS IEAHMEAVHA 310 320 330 340 350 360 DWKEYLNLLI CEESHLKYME DYHQFHEDVK DAQELLRKVD SDLNQKYGPD FKDRYQIELL 370 380 390 400 410 420 LRELDDQEKV LDKYEDVVQG LQKRGQQVVP LKYRRETPLK PIPVEALCDF EGEQGLISRG 430 440 450 460 470 480 YSYTLQKNNG ESWELMDSAG NKLIAPAVCF VIPPTDPEAL ALADSLGSQY RSVRQKAAGS 490 500 510 520 530 540 KRTLQQRYEV LKTENPGDAS DLQGRQLLAG LDKVASDLDR QEKAITGILR PPLEQGRAVQ 550 560 570 580 590 600 DSAERAKDLK NITNELLRIE PEKTRSTAEG EAFIQALPGS GTTPLLRTRV EDTNRKYEHL 610 620 630 640 650 660 LQLLDLAQEK VDVANRLEKS LQQSWELLAT HENHLNQDDT VPESSRVLDS KGQELAAMAC 670 680 690 700 710 720 ELQAQKSLLG EVEQNLQAAK QCSSTLASRF QEHCPDLERQ EAEVHKLGQR FNNLRQQVER 730 740 750 760 770 780 RAQSLQSAKA AYEHFHRGHD HVLQFLVSIP SYEPQETDSL SQMETKLKNQ KNLLDEIASR 790 800 810 820 830 840 EQEVQKICAN SQQYQQAVKD YELEAEKLRS LLDLENGRSS HVSKRARLQS PATKVKEEEA 850 860 870 880 890 900 ALAAKFTEVY AINRQRLQNL EFALNLLRQQ PEVEVTHETL QRNRPDSGVE EAWKIRKELD 910 920 930 940 950 960 EETERRRQLE NEVKSTQEEI WTLRNQGPQE SVVRKEVLKK VPDPVLEESF QQLQRTLAEE 970 980 990 1000 1010 1020 QHKNQLLQEE LEALQLQLRA LEQETRDGGQ EYVVKEVLRI EPDRAQADEV LQLREELEAL 1030 1040 1050 1060 1070 1080 RRQKGAREAE VLLLQQRVAA LAEEKSRAQE KVTEKEVVKL QNDPQLEAEY QQLQEDHQRQ 1090 1100 1110 1120 1130 1140 DQLREKQEEE LSFLQDKLKR LEKERAMAEG KITVKEVLKV EKDAATEREV SDLTRQYEDE 1150 1160 1170 1180 1190 1200 AAKARASQRE KTELLRKIWA LEEENAKVVV QEKVREIVRP DPKAESEVAN LRLELVEQER 1210 1220 1230 1240 1250 1260 KYRGAEEQLR SYQSELEALR RRGPQVEVKE VTKEVIKYKT DPEMEKELQR LREEIVDKTR 1270 1280 1290 1300 1310 1320 LIERCDLEIY QLKKEIQALK DTKPQVQTKE VVQEILQFQE DPQTKEEVAS LRAKLSEEQK 1330 1340 1350 1360 1370 1380 KQVDLERERA SQEEQIARKE EELSRVKERV VQQEVVRYEE EPGLRAEASA FAESIDVELR 1390 1400 1410 1420 1430 1440 QIDKLRAELR RLQRRRTELE RQLEELERER QARREAEREV QRLQQRLAAL EQEEAEAREK 1450 1460 1470 1480 1490 1500 VTHTQKVVLQ QDPQQAREHA LLRLQLEEEQ HRRQLLEGEL ETLRRKLAAL EKAEVKEKVV 1510 1520 1530 1540 1550 1560 LSESVQVEKG DTEQEIQRLK SSLEEESRSK RELDVEVSRL EARLSELEFH NSKSSKELDF 1570 1580 1590 1600 1610 1620 LREENHKLQL ERQNLQLETR RLQSEINMAA TETRDLRNMT VADSGTNHDS RLWSLERELD 1630 1640 1650 1660 1670 1680 DLKRLSKDKD LEIDELQKRL GSVAVKREQR ENHLRRSIVV IHPDTGRELS PEEAHRAGLI 1690 1700 1710 1720 1730 1740 DWNMFVKLRS QECDWEEISV KGPNGESSVI HDRKSGKKFS IEEALQSGRL TPAQYDRYVN 1750 KDMSIQELAV LVSGQK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin." Ruhrberg C., Hajibagheri M.A.N., Parry D.A.D., Watt F.M. J. Cell Biol. 139:1835-1849(1997) [PubMed: 9412476] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION, INTERACTION WITH EVPL, VARIANT GLN-589. Tissue: Keratinocyte.
[2]	"cDNA cloning, mRNA expression, and chromosomal mapping of human and mouse periplakin genes." Aho S., McLean W.H.I., Li K., Uitto J. Genomics 48:242-247(1998) [PubMed: 9521878] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Keratinocyte.
[3]	"Human periplakin: genomic organization in a clonally unstable region of chromosome 16p with an abundance of repetitive sequence elements." Aho S., Rothenberger K., Tan E.M.L., Ryoo Y.W., Cho B.H., McLean W.H.I., Uitto J. Genomics 56:160-168(1999) [PubMed: 10051401] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ARG-819.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS GLN-589 AND GLU-1573.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLN-589 AND GLU-1573.
[7]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed: 9628581] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 331-1756, VARIANTS GLN-589 AND GLU-1573. Tissue: Brain.
[8]	"Binding of protein kinase B to the plakin family member periplakin." van den Heuvel A.P., de Vries-Smits A.M.M., van Weeren P.C., Dijkers P.F., de Bruyn K.M., Riedl J.A., Burgering B.M.T. J. Cell Sci. 115:3957-3966(2002) [PubMed: 12244133] [Abstract] Cited for: INTERACTION WITH AKT1. Tissue: Embryo.
[9]	"Direct interaction between FcgammaRI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity." Beekman J.M., Bakema J.E., van de Winkel J.G.J., Leusen J.H.W. Proc. Natl. Acad. Sci. U.S.A. 101:10392-10397(2004) [PubMed: 15229321] [Abstract] Cited for: INTERACTION WITH FCGR1A.
[10]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1331, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1579, MASS SPECTROMETRY. Tissue: Epithelium.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF001691 mRNA. Translation: AAC17738.1. AF013717 mRNA. Translation: AAC39668.1. AF041004 , AF040999, AF041000, AF041002, AF041003 Genomic DNA. Translation: AAD17459.1. AC027687 Genomic DNA. No translation available. CH471112 Genomic DNA. Translation: EAW85248.1. BC114620 mRNA. Translation: AAI14621.1. AB011140 mRNA. Translation: BAA25494.1.
IPI	IPI00298057.
PIR	T00337.
RefSeq	NP_002696.3.
UniGene	Hs.192233
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O60437. 3 interactions.
STRING	O60437.
PTM databases
PhosphoSite	O60437.
Proteomic databases
PRIDE	O60437.
Genome annotation databases
Ensembl	ENST00000345988; ENSP00000340510; ENSG00000118898; Homo sapiens. [Genome view]
GeneID	5493.
KEGG	hsa:5493.
Organism-specific databases
CTD	5493.
GeneCards	GC16M004872.
H-InvDB	HIX0012794.
HGNC	HGNC:9273. PPL.
MIM	602871. gene.
PharmGKB	PA142671174.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11981.
HOGENOM	HBG716998.
HOVERGEN	O60437.
InParanoid	O60437.
Gene expression databases
ArrayExpress	O60437.
Bgee	O60437.
CleanEx	HS_PPL.
Genevestigator	O60437.
GermOnline	ENSG00000118898. Homo sapiens.
Family and domain databases
InterPro	IPR001101. Plectin_repeat. IPR018159. Spectrin/alpha-actinin. [Graphical view]
Pfam	PF00681. Plectin. 1 hit. [Graphical view]
SMART	SM00250. PLEC. 2 hits. SM00150. SPEC. 5 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	21238.
SOURCE	Search...

Entry information

Entry name

PEPL_HUMAN

Accession

Primary (citable) accession number: O60437
Secondary accession number(s): O60314, O60454, Q14C98

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	May 5, 2009
Last modified:	January 19, 2010
This is version 92 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.