Full text data of PREP
PREP
(PEP)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Prolyl endopeptidase; PE; 3.4.21.26 (Post-proline cleaving enzyme)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Prolyl endopeptidase; PE; 3.4.21.26 (Post-proline cleaving enzyme)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00008164
IPI00008164 Prolyl endopeptidase Cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long, blood, proteolysis soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00008164 Prolyl endopeptidase Cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long, blood, proteolysis soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P48147
ID PPCE_HUMAN Reviewed; 710 AA.
AC P48147; Q8N6D4;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 2.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Prolyl endopeptidase;
DE Short=PE;
DE EC=3.4.21.26;
DE AltName: Full=Post-proline cleaving enzyme;
GN Name=PREP; Synonyms=PEP;
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].
RC TISSUE=Blood;
RX PubMed=7959018; DOI=10.1016/0378-1119(94)90177-5;
RA Vanhoof G., Goossens F., Hendriks L., De Meester I., Hendriks D.,
RA Vriend G., van Broeckhoven C., Scharpe S.;
RT "Cloning and sequence analysis of the gene encoding human lymphocyte
RT prolyl endopeptidase.";
RL Gene 149:363-366(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-706.
RX PubMed=8089089;
RA Shirasawa Y., Osawa T., Hirashima A.;
RT "Molecular cloning and characterization of prolyl endopeptidase from
RT human T cells.";
RL J. Biochem. 115:724-729(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tarrago T., Giralt E.;
RT "cDNA cloning and recombinant expression of human brain prolyl
RT oligopeptidase.";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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].
RC TISSUE=Skin;
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 PROTEIN SEQUENCE OF 136-149, SUBUNIT, AND CHARACTERIZATION.
RC TISSUE=Lymphocyte;
RX PubMed=7588785; DOI=10.1111/j.1432-1033.1995.432_2.x;
RA Goossens F., De Meester I., Vanhoof G., Hendriks D., Vriend G.,
RA Scharpe S.;
RT "The purification, characterization and analysis of primary and
RT secondary-structure of prolyl oligopeptidase from human lymphocytes.
RT Evidence that the enzyme belongs to the alpha/beta hydrolase fold
RT family.";
RL Eur. J. Biochem. 233:432-441(1995).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-157, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [9]
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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 2-710 IN COMPLEX WITH
RP INHIBITOR.
RX PubMed=18606544; DOI=10.1016/j.bmcl.2008.06.067;
RA Haffner C.D., Diaz C.J., Miller A.B., Reid R.A., Madauss K.P.,
RA Hassell A., Hanlon M.H., Porter D.J., Becherer J.D., Carter L.H.;
RT "Pyrrolidinyl pyridone and pyrazinone analogues as potent inhibitors
RT of prolyl oligopeptidase (POP).";
RL Bioorg. Med. Chem. Lett. 18:4360-4363(2008).
CC -!- FUNCTION: Cleaves peptide bonds on the C-terminal side of prolyl
CC residues within peptides that are up to approximately 30 amino
CC acids long.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in
CC oligopeptides.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the peptidase S9A family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X74496; CAA52605.1; -; mRNA.
DR EMBL; D21102; BAA04661.1; -; mRNA.
DR EMBL; AY660966; AAV70495.1; -; mRNA.
DR EMBL; AL590871; CAH72545.1; -; Genomic_DNA.
DR EMBL; AL133406; CAH72545.1; JOINED; Genomic_DNA.
DR EMBL; AL139191; CAH72545.1; JOINED; Genomic_DNA.
DR EMBL; AL139191; CAI21416.1; -; Genomic_DNA.
DR EMBL; AL133406; CAI21416.1; JOINED; Genomic_DNA.
DR EMBL; AL590871; CAI21416.1; JOINED; Genomic_DNA.
DR EMBL; AL133406; CAI42689.1; -; Genomic_DNA.
DR EMBL; AL139191; CAI42689.1; JOINED; Genomic_DNA.
DR EMBL; AL590871; CAI42689.1; JOINED; Genomic_DNA.
DR EMBL; CH471051; EAW48426.1; -; Genomic_DNA.
DR EMBL; BC030636; AAH30636.1; -; mRNA.
DR PIR; I38134; I38134.
DR PIR; JC2257; JC2257.
DR RefSeq; NP_002717.3; NM_002726.4.
DR UniGene; Hs.436564; -.
DR PDB; 3DDU; X-ray; 1.56 A; A=2-710.
DR PDBsum; 3DDU; -.
DR ProteinModelPortal; P48147; -.
DR SMR; P48147; 2-710.
DR MINT; MINT-5004282; -.
DR STRING; 9606.ENSP00000358106; -.
DR BindingDB; P48147; -.
DR ChEMBL; CHEMBL3202; -.
DR DrugBank; DB00107; Oxytocin.
DR GuidetoPHARMACOLOGY; 2395; -.
DR MEROPS; S09.001; -.
DR PhosphoSite; P48147; -.
DR DMDM; 215273868; -.
DR PaxDb; P48147; -.
DR PRIDE; P48147; -.
DR DNASU; 5550; -.
DR Ensembl; ENST00000369110; ENSP00000358106; ENSG00000085377.
DR GeneID; 5550; -.
DR KEGG; hsa:5550; -.
DR UCSC; uc003prc.3; human.
DR CTD; 5550; -.
DR GeneCards; GC06M105725; -.
DR HGNC; HGNC:9358; PREP.
DR HPA; CAB025414; -.
DR MIM; 600400; gene.
DR neXtProt; NX_P48147; -.
DR PharmGKB; PA33730; -.
DR eggNOG; COG1505; -.
DR HOGENOM; HOG000238967; -.
DR HOVERGEN; HBG007251; -.
DR InParanoid; P48147; -.
DR KO; K01322; -.
DR OMA; PAHSFKF; -.
DR OrthoDB; EOG78PV88; -.
DR PhylomeDB; P48147; -.
DR EvolutionaryTrace; P48147; -.
DR GeneWiki; Prolyl_endopeptidase; -.
DR GenomeRNAi; 5550; -.
DR NextBio; 21508; -.
DR PMAP-CutDB; Q8N6D4; -.
DR PRO; PR:P48147; -.
DR Bgee; P48147; -.
DR CleanEx; HS_PREP; -.
DR Genevestigator; P48147; -.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0070008; F:serine-type exopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR Gene3D; 2.130.10.120; -; 1.
DR InterPro; IPR002471; Pept_S9_AS.
DR InterPro; IPR023302; Pept_S9A_N.
DR InterPro; IPR001375; Peptidase_S9.
DR InterPro; IPR002470; Peptidase_S9A.
DR PANTHER; PTHR11757; PTHR11757; 1.
DR Pfam; PF00326; Peptidase_S9; 1.
DR Pfam; PF02897; Peptidase_S9_N; 1.
DR PRINTS; PR00862; PROLIGOPTASE.
DR PROSITE; PS00708; PRO_ENDOPEP_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Polymorphism; Protease;
KW Reference proteome; Serine protease.
FT CHAIN 1 710 Prolyl endopeptidase.
FT /FTId=PRO_0000122401.
FT ACT_SITE 554 554 Charge relay system (By similarity).
FT ACT_SITE 641 641 Charge relay system (By similarity).
FT ACT_SITE 680 680 Charge relay system (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 157 157 N6-acetyllysine.
FT VARIANT 351 351 L -> V (in dbSNP:rs12192054).
FT /FTId=VAR_047790.
FT VARIANT 706 706 V -> I (in dbSNP:rs1051484).
FT /FTId=VAR_047791.
FT CONFLICT 4 4 L -> F (in Ref. 1; CAA52605 and 2;
FT BAA04661).
FT CONFLICT 16 16 V -> I (in Ref. 2; BAA04661).
FT CONFLICT 245 245 R -> C (in Ref. 2; BAA04661).
FT CONFLICT 298 298 T -> A (in Ref. 2; BAA04661).
FT CONFLICT 319 319 R -> W (in Ref. 1; CAA52605).
FT CONFLICT 440 440 I -> L (in Ref. 2; BAA04661).
FT CONFLICT 459 459 G -> S (in Ref. 2; BAA04661).
FT STRAND 16 19
FT STRAND 22 25
FT HELIX 29 32
FT HELIX 37 55
FT HELIX 59 70
FT STRAND 80 82
FT STRAND 85 91
FT STRAND 99 105
FT STRAND 111 114
FT HELIX 116 119
FT STRAND 121 123
FT STRAND 125 132
FT STRAND 136 145
FT STRAND 151 157
FT TURN 158 161
FT STRAND 162 171
FT STRAND 176 178
FT STRAND 182 189
FT STRAND 198 200
FT STRAND 209 214
FT HELIX 219 221
FT STRAND 223 226
FT STRAND 235 240
FT STRAND 246 257
FT STRAND 260 265
FT HELIX 266 268
FT STRAND 270 273
FT STRAND 280 283
FT STRAND 285 288
FT STRAND 290 296
FT STRAND 299 304
FT STRAND 312 317
FT HELIX 323 325
FT STRAND 327 330
FT STRAND 337 344
FT TURN 345 347
FT STRAND 348 355
FT STRAND 358 365
FT TURN 366 368
FT STRAND 371 375
FT STRAND 379 386
FT STRAND 392 399
FT STRAND 401 403
FT STRAND 406 411
FT STRAND 414 416
FT STRAND 420 423
FT HELIX 432 434
FT STRAND 435 443
FT STRAND 449 457
FT STRAND 468 471
FT HELIX 486 495
FT STRAND 498 502
FT HELIX 511 516
FT HELIX 520 523
FT HELIX 524 539
FT HELIX 545 547
FT STRAND 548 553
FT HELIX 555 566
FT HELIX 568 570
FT STRAND 572 578
FT TURN 583 585
FT HELIX 586 588
FT HELIX 592 595
FT HELIX 596 599
FT HELIX 605 614
FT HELIX 616 618
FT STRAND 632 638
FT HELIX 647 659
FT TURN 660 662
FT STRAND 670 677
FT HELIX 686 704
SQ SEQUENCE 710 AA; 80700 MW; 139072B990820B90 CRC64;
MLSLQYPDVY RDETAVQDYH GHKICDPYAW LEDPDSEQTK AFVEAQNKIT VPFLEQCPIR
GLYKERMTEL YDYPKYSCHF KKGKRYFYFY NTGLQNQRVL YVQDSLEGEA RVFLDPNILS
DDGTVALRGY AFSEDGEYFA YGLSASGSDW VTIKFMKVDG AKELPDVLER VKFSCMAWTH
DGKGMFYNSY PQQDGKSDGT ETSTNLHQKL YYHVLGTDQS EDILCAEFPD EPKWMGGAEL
SDDGRYVLLS IREGCDPVNR LWYCDLQQES SGIAGILKWV KLIDNFEGEY DYVTNEGTVF
TFKTNRQSPN YRVINIDFRD PEESKWKVLV PEHEKDVLEW IACVRSNFLV LCYLHDVKNI
LQLHDLTTGA LLKTFPLDVG SIVGYSGQKK DTEIFYQFTS FLSPGIIYHC DLTKEELEPR
VFREVTVKGI DASDYQTVQI FYPSKDGTKI PMFIVHKKGI KLDGSHPAFL YGYGGFNISI
TPNYSVSRLI FVRHMGGILA VANIRGGGEY GETWHKGGIL ANKQNCFDDF QCAAEYLIKE
GYTSPKRLTI NGGSNGGLLV AACANQRPDL FGCVIAQVGV MDMLKFHKYT IGHAWTTDYG
CSDSKQHFEW LVKYSPLHNV KLPEADDIQY PSMLLLTADH DDRVVPLHSL KFIATLQYIV
GRSRKQSNPL LIHVDTKAGH GAGKPTAKVI EEVSDMFAFI ARCLNVDWIP
//
ID PPCE_HUMAN Reviewed; 710 AA.
AC P48147; Q8N6D4;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 2.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Prolyl endopeptidase;
DE Short=PE;
DE EC=3.4.21.26;
DE AltName: Full=Post-proline cleaving enzyme;
GN Name=PREP; Synonyms=PEP;
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].
RC TISSUE=Blood;
RX PubMed=7959018; DOI=10.1016/0378-1119(94)90177-5;
RA Vanhoof G., Goossens F., Hendriks L., De Meester I., Hendriks D.,
RA Vriend G., van Broeckhoven C., Scharpe S.;
RT "Cloning and sequence analysis of the gene encoding human lymphocyte
RT prolyl endopeptidase.";
RL Gene 149:363-366(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-706.
RX PubMed=8089089;
RA Shirasawa Y., Osawa T., Hirashima A.;
RT "Molecular cloning and characterization of prolyl endopeptidase from
RT human T cells.";
RL J. Biochem. 115:724-729(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tarrago T., Giralt E.;
RT "cDNA cloning and recombinant expression of human brain prolyl
RT oligopeptidase.";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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].
RC TISSUE=Skin;
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 PROTEIN SEQUENCE OF 136-149, SUBUNIT, AND CHARACTERIZATION.
RC TISSUE=Lymphocyte;
RX PubMed=7588785; DOI=10.1111/j.1432-1033.1995.432_2.x;
RA Goossens F., De Meester I., Vanhoof G., Hendriks D., Vriend G.,
RA Scharpe S.;
RT "The purification, characterization and analysis of primary and
RT secondary-structure of prolyl oligopeptidase from human lymphocytes.
RT Evidence that the enzyme belongs to the alpha/beta hydrolase fold
RT family.";
RL Eur. J. Biochem. 233:432-441(1995).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-157, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [9]
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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 2-710 IN COMPLEX WITH
RP INHIBITOR.
RX PubMed=18606544; DOI=10.1016/j.bmcl.2008.06.067;
RA Haffner C.D., Diaz C.J., Miller A.B., Reid R.A., Madauss K.P.,
RA Hassell A., Hanlon M.H., Porter D.J., Becherer J.D., Carter L.H.;
RT "Pyrrolidinyl pyridone and pyrazinone analogues as potent inhibitors
RT of prolyl oligopeptidase (POP).";
RL Bioorg. Med. Chem. Lett. 18:4360-4363(2008).
CC -!- FUNCTION: Cleaves peptide bonds on the C-terminal side of prolyl
CC residues within peptides that are up to approximately 30 amino
CC acids long.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in
CC oligopeptides.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the peptidase S9A family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X74496; CAA52605.1; -; mRNA.
DR EMBL; D21102; BAA04661.1; -; mRNA.
DR EMBL; AY660966; AAV70495.1; -; mRNA.
DR EMBL; AL590871; CAH72545.1; -; Genomic_DNA.
DR EMBL; AL133406; CAH72545.1; JOINED; Genomic_DNA.
DR EMBL; AL139191; CAH72545.1; JOINED; Genomic_DNA.
DR EMBL; AL139191; CAI21416.1; -; Genomic_DNA.
DR EMBL; AL133406; CAI21416.1; JOINED; Genomic_DNA.
DR EMBL; AL590871; CAI21416.1; JOINED; Genomic_DNA.
DR EMBL; AL133406; CAI42689.1; -; Genomic_DNA.
DR EMBL; AL139191; CAI42689.1; JOINED; Genomic_DNA.
DR EMBL; AL590871; CAI42689.1; JOINED; Genomic_DNA.
DR EMBL; CH471051; EAW48426.1; -; Genomic_DNA.
DR EMBL; BC030636; AAH30636.1; -; mRNA.
DR PIR; I38134; I38134.
DR PIR; JC2257; JC2257.
DR RefSeq; NP_002717.3; NM_002726.4.
DR UniGene; Hs.436564; -.
DR PDB; 3DDU; X-ray; 1.56 A; A=2-710.
DR PDBsum; 3DDU; -.
DR ProteinModelPortal; P48147; -.
DR SMR; P48147; 2-710.
DR MINT; MINT-5004282; -.
DR STRING; 9606.ENSP00000358106; -.
DR BindingDB; P48147; -.
DR ChEMBL; CHEMBL3202; -.
DR DrugBank; DB00107; Oxytocin.
DR GuidetoPHARMACOLOGY; 2395; -.
DR MEROPS; S09.001; -.
DR PhosphoSite; P48147; -.
DR DMDM; 215273868; -.
DR PaxDb; P48147; -.
DR PRIDE; P48147; -.
DR DNASU; 5550; -.
DR Ensembl; ENST00000369110; ENSP00000358106; ENSG00000085377.
DR GeneID; 5550; -.
DR KEGG; hsa:5550; -.
DR UCSC; uc003prc.3; human.
DR CTD; 5550; -.
DR GeneCards; GC06M105725; -.
DR HGNC; HGNC:9358; PREP.
DR HPA; CAB025414; -.
DR MIM; 600400; gene.
DR neXtProt; NX_P48147; -.
DR PharmGKB; PA33730; -.
DR eggNOG; COG1505; -.
DR HOGENOM; HOG000238967; -.
DR HOVERGEN; HBG007251; -.
DR InParanoid; P48147; -.
DR KO; K01322; -.
DR OMA; PAHSFKF; -.
DR OrthoDB; EOG78PV88; -.
DR PhylomeDB; P48147; -.
DR EvolutionaryTrace; P48147; -.
DR GeneWiki; Prolyl_endopeptidase; -.
DR GenomeRNAi; 5550; -.
DR NextBio; 21508; -.
DR PMAP-CutDB; Q8N6D4; -.
DR PRO; PR:P48147; -.
DR Bgee; P48147; -.
DR CleanEx; HS_PREP; -.
DR Genevestigator; P48147; -.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0070008; F:serine-type exopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR Gene3D; 2.130.10.120; -; 1.
DR InterPro; IPR002471; Pept_S9_AS.
DR InterPro; IPR023302; Pept_S9A_N.
DR InterPro; IPR001375; Peptidase_S9.
DR InterPro; IPR002470; Peptidase_S9A.
DR PANTHER; PTHR11757; PTHR11757; 1.
DR Pfam; PF00326; Peptidase_S9; 1.
DR Pfam; PF02897; Peptidase_S9_N; 1.
DR PRINTS; PR00862; PROLIGOPTASE.
DR PROSITE; PS00708; PRO_ENDOPEP_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Polymorphism; Protease;
KW Reference proteome; Serine protease.
FT CHAIN 1 710 Prolyl endopeptidase.
FT /FTId=PRO_0000122401.
FT ACT_SITE 554 554 Charge relay system (By similarity).
FT ACT_SITE 641 641 Charge relay system (By similarity).
FT ACT_SITE 680 680 Charge relay system (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 157 157 N6-acetyllysine.
FT VARIANT 351 351 L -> V (in dbSNP:rs12192054).
FT /FTId=VAR_047790.
FT VARIANT 706 706 V -> I (in dbSNP:rs1051484).
FT /FTId=VAR_047791.
FT CONFLICT 4 4 L -> F (in Ref. 1; CAA52605 and 2;
FT BAA04661).
FT CONFLICT 16 16 V -> I (in Ref. 2; BAA04661).
FT CONFLICT 245 245 R -> C (in Ref. 2; BAA04661).
FT CONFLICT 298 298 T -> A (in Ref. 2; BAA04661).
FT CONFLICT 319 319 R -> W (in Ref. 1; CAA52605).
FT CONFLICT 440 440 I -> L (in Ref. 2; BAA04661).
FT CONFLICT 459 459 G -> S (in Ref. 2; BAA04661).
FT STRAND 16 19
FT STRAND 22 25
FT HELIX 29 32
FT HELIX 37 55
FT HELIX 59 70
FT STRAND 80 82
FT STRAND 85 91
FT STRAND 99 105
FT STRAND 111 114
FT HELIX 116 119
FT STRAND 121 123
FT STRAND 125 132
FT STRAND 136 145
FT STRAND 151 157
FT TURN 158 161
FT STRAND 162 171
FT STRAND 176 178
FT STRAND 182 189
FT STRAND 198 200
FT STRAND 209 214
FT HELIX 219 221
FT STRAND 223 226
FT STRAND 235 240
FT STRAND 246 257
FT STRAND 260 265
FT HELIX 266 268
FT STRAND 270 273
FT STRAND 280 283
FT STRAND 285 288
FT STRAND 290 296
FT STRAND 299 304
FT STRAND 312 317
FT HELIX 323 325
FT STRAND 327 330
FT STRAND 337 344
FT TURN 345 347
FT STRAND 348 355
FT STRAND 358 365
FT TURN 366 368
FT STRAND 371 375
FT STRAND 379 386
FT STRAND 392 399
FT STRAND 401 403
FT STRAND 406 411
FT STRAND 414 416
FT STRAND 420 423
FT HELIX 432 434
FT STRAND 435 443
FT STRAND 449 457
FT STRAND 468 471
FT HELIX 486 495
FT STRAND 498 502
FT HELIX 511 516
FT HELIX 520 523
FT HELIX 524 539
FT HELIX 545 547
FT STRAND 548 553
FT HELIX 555 566
FT HELIX 568 570
FT STRAND 572 578
FT TURN 583 585
FT HELIX 586 588
FT HELIX 592 595
FT HELIX 596 599
FT HELIX 605 614
FT HELIX 616 618
FT STRAND 632 638
FT HELIX 647 659
FT TURN 660 662
FT STRAND 670 677
FT HELIX 686 704
SQ SEQUENCE 710 AA; 80700 MW; 139072B990820B90 CRC64;
MLSLQYPDVY RDETAVQDYH GHKICDPYAW LEDPDSEQTK AFVEAQNKIT VPFLEQCPIR
GLYKERMTEL YDYPKYSCHF KKGKRYFYFY NTGLQNQRVL YVQDSLEGEA RVFLDPNILS
DDGTVALRGY AFSEDGEYFA YGLSASGSDW VTIKFMKVDG AKELPDVLER VKFSCMAWTH
DGKGMFYNSY PQQDGKSDGT ETSTNLHQKL YYHVLGTDQS EDILCAEFPD EPKWMGGAEL
SDDGRYVLLS IREGCDPVNR LWYCDLQQES SGIAGILKWV KLIDNFEGEY DYVTNEGTVF
TFKTNRQSPN YRVINIDFRD PEESKWKVLV PEHEKDVLEW IACVRSNFLV LCYLHDVKNI
LQLHDLTTGA LLKTFPLDVG SIVGYSGQKK DTEIFYQFTS FLSPGIIYHC DLTKEELEPR
VFREVTVKGI DASDYQTVQI FYPSKDGTKI PMFIVHKKGI KLDGSHPAFL YGYGGFNISI
TPNYSVSRLI FVRHMGGILA VANIRGGGEY GETWHKGGIL ANKQNCFDDF QCAAEYLIKE
GYTSPKRLTI NGGSNGGLLV AACANQRPDL FGCVIAQVGV MDMLKFHKYT IGHAWTTDYG
CSDSKQHFEW LVKYSPLHNV KLPEADDIQY PSMLLLTADH DDRVVPLHSL KFIATLQYIV
GRSRKQSNPL LIHVDTKAGH GAGKPTAKVI EEVSDMFAFI ARCLNVDWIP
//
MIM
600400
*RECORD*
*FIELD* NO
600400
*FIELD* TI
*600400 PROLYL ENDOPEPTIDASE; PREP
;;PROLYL OLIGOPEPTIDASE
*FIELD* TX
CLONING
Prolyl endopeptidase (EC 3.4.21.26) is a large cytosolic enzyme that
read morebelongs to a distinct class of serine peptidases. The enzyme is involved
in the maturation and degradation of peptide hormones and neuropeptides.
PREP cleaves peptide bonds at the C-terminal side of proline residues.
Its activity is confined to action on oligopeptides of less than 10 kD
and it has an absolute requirement for the trans-configuration of the
peptide bond preceding proline. Vanhoof et al. (1994) sequenced the
human cDNA encoding prolyl endopeptidase. A complete cDNA was 2,562
nucleotides long and contained an open reading frame coding for a
protein of 710 amino acids. Comparison of the sequences from human
lymphocyte PREP and that of pig brain showed 97% identity. Also known as
prolyl oligopeptidase, this enzyme shows sequence similarity with
dipeptidyl peptidase IV (102720) and acylaminoacyl peptidase (102645)
(Goossens et al., 1996).
BIOCHEMICAL FEATURES
- Crystal Structure
Fulop et al. (1998) reported the 1.4-angstrom resolution crystal
structure of the porcine PREP enzyme. The enzyme contains a peptidase
domain with an alpha/beta hydrolase fold, and its catalytic triad
(ser554, his680, asp641) is covered by the central tunnel of an unusual
beta propeller. This domain makes PREP an oligopeptidase by excluding
large structured peptides from the active site. In this way, the
propeller protects larger peptides and proteins from proteolysis in the
cytosol.
GENE FUNCTION
Using fluorimetric analysis of PREP and pyroglutamyl peptidase I
(PGPEP1; 610694) enzyme activity in seminal fractions from fertile men
and subfertile patients, Valdivia et al. (2004) showed increased
specific activities of both enzymes in necrozoospermic semen (defined as
having more that 50% dead spermatozoa) in comparison to normozoospermic
semen. PGEP1 activity was highest in the particulate sperm fraction,
whereas PREP activity was highest in the soluble sperm fraction.
Valdivia et al. (2004) hypothesized that PGPEP1 and PREP may play a role
in mediating sperm death by regulating the levels of
thyrotropin-releasing hormone (TRH; 613879) analogs and in mediating
sperm death associated with necrozoospermia.
MAPPING
By fluorescence in situ hybridization, Goossens et al. (1996) mapped the
PREP gene to 6q22.
*FIELD* RF
1. Fulop, V.; Bocskei, Z.; Polgar, L.: Prolyl oligopeptidase: an
unusual beta-propeller domain regulates proteolysis. Cell 94: 161-170,
1998.
2. Goossens, F. J.; Wauters, J. G.; Vanhoof, G. C.; Bossuyt, P. J.;
Schatteman, K. A.; Loens, K.; Scharpe, S. L.: Subregional mapping
of the human lymphocyte prolyl oligopeptidase gene (PREP) to human
chromosome 6q22. Cytogenet. Cell Genet. 74: 99-101, 1996.
3. Valdivia, A.; Irazusta, J.; Fernandez, D.; Mugica, J.; Ochoa, C.;
Casis, L.: Pyroglutamyl peptidase I and prolyl endopeptidase in human
semen: increased activity in necrozoospermia. Regulatory Peptides 122:
79-84, 2004.
4. Vanhoof, G.; Goossens, F.; Hendriks, L.; De Meester, I.; Hendriks,
D.; Vriend, G.; Van Broeckhoven, C.; Scharpe, S.: Cloning and sequence
analysis of the gene encoding human lymphocyte prolyl endopeptidase. Gene 149:
363-366, 1994.
*FIELD* CN
Dorothy S. Reilly - updated: 1/10/2007
Stylianos E. Antonarakis - updated: 8/3/1998
*FIELD* CD
Victor A. McKusick: 2/13/1995
*FIELD* ED
carol: 04/20/2011
carol: 1/10/2007
alopez: 5/30/2002
terry: 11/13/1998
carol: 8/4/1998
terry: 8/3/1998
jenny: 12/16/1996
terry: 12/9/1996
carol: 2/13/1995
*RECORD*
*FIELD* NO
600400
*FIELD* TI
*600400 PROLYL ENDOPEPTIDASE; PREP
;;PROLYL OLIGOPEPTIDASE
*FIELD* TX
CLONING
Prolyl endopeptidase (EC 3.4.21.26) is a large cytosolic enzyme that
read morebelongs to a distinct class of serine peptidases. The enzyme is involved
in the maturation and degradation of peptide hormones and neuropeptides.
PREP cleaves peptide bonds at the C-terminal side of proline residues.
Its activity is confined to action on oligopeptides of less than 10 kD
and it has an absolute requirement for the trans-configuration of the
peptide bond preceding proline. Vanhoof et al. (1994) sequenced the
human cDNA encoding prolyl endopeptidase. A complete cDNA was 2,562
nucleotides long and contained an open reading frame coding for a
protein of 710 amino acids. Comparison of the sequences from human
lymphocyte PREP and that of pig brain showed 97% identity. Also known as
prolyl oligopeptidase, this enzyme shows sequence similarity with
dipeptidyl peptidase IV (102720) and acylaminoacyl peptidase (102645)
(Goossens et al., 1996).
BIOCHEMICAL FEATURES
- Crystal Structure
Fulop et al. (1998) reported the 1.4-angstrom resolution crystal
structure of the porcine PREP enzyme. The enzyme contains a peptidase
domain with an alpha/beta hydrolase fold, and its catalytic triad
(ser554, his680, asp641) is covered by the central tunnel of an unusual
beta propeller. This domain makes PREP an oligopeptidase by excluding
large structured peptides from the active site. In this way, the
propeller protects larger peptides and proteins from proteolysis in the
cytosol.
GENE FUNCTION
Using fluorimetric analysis of PREP and pyroglutamyl peptidase I
(PGPEP1; 610694) enzyme activity in seminal fractions from fertile men
and subfertile patients, Valdivia et al. (2004) showed increased
specific activities of both enzymes in necrozoospermic semen (defined as
having more that 50% dead spermatozoa) in comparison to normozoospermic
semen. PGEP1 activity was highest in the particulate sperm fraction,
whereas PREP activity was highest in the soluble sperm fraction.
Valdivia et al. (2004) hypothesized that PGPEP1 and PREP may play a role
in mediating sperm death by regulating the levels of
thyrotropin-releasing hormone (TRH; 613879) analogs and in mediating
sperm death associated with necrozoospermia.
MAPPING
By fluorescence in situ hybridization, Goossens et al. (1996) mapped the
PREP gene to 6q22.
*FIELD* RF
1. Fulop, V.; Bocskei, Z.; Polgar, L.: Prolyl oligopeptidase: an
unusual beta-propeller domain regulates proteolysis. Cell 94: 161-170,
1998.
2. Goossens, F. J.; Wauters, J. G.; Vanhoof, G. C.; Bossuyt, P. J.;
Schatteman, K. A.; Loens, K.; Scharpe, S. L.: Subregional mapping
of the human lymphocyte prolyl oligopeptidase gene (PREP) to human
chromosome 6q22. Cytogenet. Cell Genet. 74: 99-101, 1996.
3. Valdivia, A.; Irazusta, J.; Fernandez, D.; Mugica, J.; Ochoa, C.;
Casis, L.: Pyroglutamyl peptidase I and prolyl endopeptidase in human
semen: increased activity in necrozoospermia. Regulatory Peptides 122:
79-84, 2004.
4. Vanhoof, G.; Goossens, F.; Hendriks, L.; De Meester, I.; Hendriks,
D.; Vriend, G.; Van Broeckhoven, C.; Scharpe, S.: Cloning and sequence
analysis of the gene encoding human lymphocyte prolyl endopeptidase. Gene 149:
363-366, 1994.
*FIELD* CN
Dorothy S. Reilly - updated: 1/10/2007
Stylianos E. Antonarakis - updated: 8/3/1998
*FIELD* CD
Victor A. McKusick: 2/13/1995
*FIELD* ED
carol: 04/20/2011
carol: 1/10/2007
alopez: 5/30/2002
terry: 11/13/1998
carol: 8/4/1998
terry: 8/3/1998
jenny: 12/16/1996
terry: 12/9/1996
carol: 2/13/1995