P48147 (PPCE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prolyl endopeptidase
Short name=PE
EC=3.4.21.26

Alternative name(s):
Post-proline cleaving enzyme

Gene names

Name:	PREP
Synonyms:	PEP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	710 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long.
Catalytic activity	Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in oligopeptides.
Subunit structure	Monomer. Ref.7
Subcellular location	Cytoplasm.
Post-translational modification	The N-terminus is blocked.
Sequence similarities	Belongs to the peptidase S9A family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Protease Serine protease
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Traceable author statement PubMed 9695945. Source: ProtInc
Cellular_component	cytoplasm Traceable author statement PubMed 9695945. Source: ProtInc nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	serine-type endopeptidase activity Traceable author statement PubMed 9695945. Source: ProtInc serine-type exopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 710

710

Prolyl endopeptidase

PRO_0000122401

Sites

Active site

554

1

Charge relay system By similarity

Active site

641

1

Charge relay system By similarity

Active site

680

1

Charge relay system By similarity

Amino acid modifications

Modified residue

157

1

N6-acetyllysine Ref.8

Natural variations

Natural variant

351

1

L → V.
Corresponds to variant rs12192054 [ dbSNP | Ensembl ].

VAR_047790

Natural variant

706

1

V → I. Ref.2
Corresponds to variant rs1051484 [ dbSNP | Ensembl ].

VAR_047791

Experimental info

Sequence conflict

4

1

L → F in CAA52605. Ref.1

Sequence conflict

4

1

L → F in BAA04661. Ref.2

Sequence conflict

16

1

V → I in BAA04661. Ref.2

Sequence conflict

245

1

R → C in BAA04661. Ref.2

Sequence conflict

298

1

T → A in BAA04661. Ref.2

Sequence conflict

319

1

R → W in CAA52605. Ref.1

Sequence conflict

440

1

I → L in BAA04661. Ref.2

Sequence conflict

459

1

G → S in BAA04661. Ref.2

Secondary structure

1

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710

Helix Strand Turn

Details...

Beta strand

16 – 19

4

Beta strand

22 – 25

4

Helix

29 – 32

4

Helix

37 – 55

19

Helix

59 – 70

12

Beta strand

80 – 82

3

Beta strand

85 – 91

7

Beta strand

99 – 105

7

Beta strand

111 – 114

4

Helix

116 – 119

4

Beta strand

121 – 123

3

Beta strand

125 – 132

8

Beta strand

136 – 145

10

Beta strand

151 – 157

7

Turn

158 – 161

4

Beta strand

162 – 171

10

Beta strand

176 – 178

3

Beta strand

182 – 189

8

Beta strand

198 – 200

3

Beta strand

209 – 214

6

Helix

219 – 221

3

Beta strand

223 – 226

4

Beta strand

235 – 240

6

Beta strand

246 – 257

12

Beta strand

260 – 265

6

Helix

266 – 268

3

Beta strand

270 – 273

4

Beta strand

280 – 283

4

Beta strand

285 – 288

4

Beta strand

290 – 296

7

Beta strand

299 – 304

6

Beta strand

312 – 317

6

Helix

323 – 325

3

Beta strand

327 – 330

4

Beta strand

337 – 344

8

Turn

345 – 347

3

Beta strand

348 – 355

8

Beta strand

358 – 365

8

Turn

366 – 368

3

Beta strand

371 – 375

5

Beta strand

379 – 386

8

Beta strand

392 – 399

8

Beta strand

401 – 403

3

Beta strand

406 – 411

6

Beta strand

414 – 416

3

Beta strand

420 – 423

4

Helix

432 – 434

3

Beta strand

435 – 443

9

Beta strand

449 – 457

9

Beta strand

468 – 471

4

Helix

486 – 495

10

Beta strand

498 – 502

5

Helix

511 – 516

6

Helix

520 – 523

4

Helix

524 – 539

16

Helix

545 – 547

3

Beta strand

548 – 553

6

Helix

555 – 566

12

Helix

568 – 570

3

Beta strand

572 – 578

7

Turn

583 – 585

3

Helix

586 – 588

3

Helix

592 – 595

4

Helix

596 – 599

4

Helix

605 – 614

10

Helix

616 – 618

3

Beta strand

632 – 638

7

Helix

647 – 659

13

Turn

660 – 662

3

Beta strand

670 – 677

8

Helix

686 – 704

19

Sequences

	Sequence		Length	Mass (Da)
	P48147 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 139072B990820B90	FASTA	710	80,700
	10 20 30 40 50 60 MLSLQYPDVY RDETAVQDYH GHKICDPYAW LEDPDSEQTK AFVEAQNKIT VPFLEQCPIR 70 80 90 100 110 120 GLYKERMTEL YDYPKYSCHF KKGKRYFYFY NTGLQNQRVL YVQDSLEGEA RVFLDPNILS 130 140 150 160 170 180 DDGTVALRGY AFSEDGEYFA YGLSASGSDW VTIKFMKVDG AKELPDVLER VKFSCMAWTH 190 200 210 220 230 240 DGKGMFYNSY PQQDGKSDGT ETSTNLHQKL YYHVLGTDQS EDILCAEFPD EPKWMGGAEL 250 260 270 280 290 300 SDDGRYVLLS IREGCDPVNR LWYCDLQQES SGIAGILKWV KLIDNFEGEY DYVTNEGTVF 310 320 330 340 350 360 TFKTNRQSPN YRVINIDFRD PEESKWKVLV PEHEKDVLEW IACVRSNFLV LCYLHDVKNI 370 380 390 400 410 420 LQLHDLTTGA LLKTFPLDVG SIVGYSGQKK DTEIFYQFTS FLSPGIIYHC DLTKEELEPR 430 440 450 460 470 480 VFREVTVKGI DASDYQTVQI FYPSKDGTKI PMFIVHKKGI KLDGSHPAFL YGYGGFNISI 490 500 510 520 530 540 TPNYSVSRLI FVRHMGGILA VANIRGGGEY GETWHKGGIL ANKQNCFDDF QCAAEYLIKE 550 560 570 580 590 600 GYTSPKRLTI NGGSNGGLLV AACANQRPDL FGCVIAQVGV MDMLKFHKYT IGHAWTTDYG 610 620 630 640 650 660 CSDSKQHFEW LVKYSPLHNV KLPEADDIQY PSMLLLTADH DDRVVPLHSL KFIATLQYIV 670 680 690 700 710 GRSRKQSNPL LIHVDTKAGH GAGKPTAKVI EEVSDMFAFI ARCLNVDWIP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence analysis of the gene encoding human lymphocyte prolyl endopeptidase." Vanhoof G., Goossens F., Hendriks L., De Meester I., Hendriks D., Vriend G., van Broeckhoven C., Scharpe S. Gene 149:363-366(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[2]	"Molecular cloning and characterization of prolyl endopeptidase from human T cells." Shirasawa Y., Osawa T., Hirashima A. J. Biochem. 115:724-729(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-706.
[3]	"cDNA cloning and recombinant expression of human brain prolyl oligopeptidase." Tarrago T., Giralt E. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[7]	"The purification, characterization and analysis of primary and secondary-structure of prolyl oligopeptidase from human lymphocytes. Evidence that the enzyme belongs to the alpha/beta hydrolase fold family." Goossens F., De Meester I., Vanhoof G., Hendriks D., Vriend G., Scharpe S. Eur. J. Biochem. 233:432-441(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 136-149, SUBUNIT, CHARACTERIZATION. Tissue: Lymphocyte.
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-157, MASS SPECTROMETRY.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X74496 mRNA. Translation: CAA52605.1.
D21102 mRNA. Translation: BAA04661.1.
AY660966 mRNA. Translation: AAV70495.1.
AL590871, AL133406, AL139191 Genomic DNA. Translation: CAH72545.1.
AL139191, AL133406, AL590871 Genomic DNA. Translation: CAI21416.1.
AL133406, AL139191, AL590871 Genomic DNA. Translation: CAI42689.1.
CH471051 Genomic DNA. Translation: EAW48426.1.
BC030636 mRNA. Translation: AAH30636.1.

IPI

IPI00008164.

PIR

I38134.
JC2257.

RefSeq

NP_002717.3. NM_002726.4.

UniGene

Hs.436564.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DDU	X-ray	1.56	A	2-710	[»]

ProteinModelPortal

P48147.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000358106.

Protein family/group databases

MEROPS

S09.001.

PTM databases

PhosphoSite

P48147.

Polymorphism databases

DMDM

215273868.

Proteomic databases

PaxDb

P48147.

PRIDE

P48147.

Protocols and materials databases

DNASU

5550.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000369110; ENSP00000358106; ENSG00000085377.

GeneID

5550.

KEGG

hsa:5550.

UCSC

uc003prc.3. human.

Organism-specific databases

CTD

5550.

GeneCards

GC06M105725.

HGNC

HGNC:9358. PREP.

HPA

CAB025414.

MIM

600400. gene.

neXtProt

NX_P48147.

PharmGKB

PA33730.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1505.

HOGENOM

HOG000238967.

HOVERGEN

HBG007251.

InParanoid

P48147.

KO

K01322.

OMA

PFLEQCP.

OrthoDB

EOG4548Z1.

PhylomeDB

P48147.

Gene expression databases

ArrayExpress

P48147.

Bgee

P48147.

CleanEx

HS_PREP.

Genevestigator

P48147.

GermOnline

ENSG00000085377. Homo sapiens.

Family and domain databases

Gene3D

2.130.10.120. 1 hit.

InterPro

IPR002471. Pept_S9_AS.
IPR023302. Pept_S9A_oligopept_N.
IPR001375. Peptidase_S9.
IPR002470. Peptidase_S9A.
IPR004106. Peptidase_S9A_B_C_N.
[Graphical view]

PANTHER

PTHR11757. PTHR11757. 1 hit.

Pfam

PF00326. Peptidase_S9. 1 hit.
PF02897. Peptidase_S9_N. 1 hit.
[Graphical view]

PRINTS

PR00862. PROLIGOPTASE.

SUPFAM

SSF50993. Peptidase_S9A_N. 1 hit.

PROSITE

PS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P48147.

ChEMBL

CHEMBL3202.

DrugBank

DB00107. Oxytocin.

EvolutionaryTrace

P48147.

GenomeRNAi

5550.

NextBio

21508.

PMAP-CutDB

Q8N6D4.

SOURCE

Search...

Entry information

Entry name

PPCE_HUMAN

Accession

Primary (citable) accession number: P48147
Secondary accession number(s): Q8N6D4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.