Reviewed, UniProtKB/Swiss-Prot P48147 (PPCE_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	710 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Traceable author statement. Source: ProtInc
Molecular function	serine-type endopeptidase activity Traceable author statement. Source: ProtInc
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
Natural variations
	Natural variant	351	1	L → V: dbSNP rs12192054.		VAR_047790
	Natural variant	706	1	V → I: dbSNP rs1051484. Ref.2		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

Sequences

	Sequence		Length	Mass (Da)
	P48147-1 [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: 7959018] [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: 8089089] [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: 14574404] [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: 15489334] [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: 7588785] [Abstract] Cited for: PROTEIN SEQUENCE OF 136-149, SUBUNIT, CHARACTERIZATION. Tissue: Lymphocyte.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

UniGene

Hs.436564

3D structure databases

PDBPDBe

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

SMR

P48147. Positions 1-710.

ModBase

Search...

Protein-protein interaction databases

IntAct

P48147. 3 interactions.

Protein family/group databases

MEROPS

S09.001.

PTM databases

PhosphoSite

P48147.

Proteomic databases

PRIDE

P48147.

Genome annotation databases

Ensembl

ENSG00000085377. Homo sapiens. [Contig view]

GeneID

5550.

KEGG

hsa:5550.

Organism-specific databases

GeneCards

GC06M105832.

HGNC

HGNC:9358. PREP.

MIM

600400. gene.

PharmGKB

PA33730.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P48147.

HOVERGEN

P48147.

OMA

P48147. LEWVACV.

Enzyme and pathway databases

BRENDA

3.4.21.26. 247.

Gene expression databases

ArrayExpress

P48147.

Bgee

P48147.

CleanEx

HS_PREP.

GermOnline

ENSG00000085377. Homo sapiens.

Family and domain databases

InterPro

IPR002471. Pept_S9_AS.
IPR001375. Peptidase_S9.
IPR002470. Peptidase_S9A.
IPR004106. Peptidase_S9A_N.
[Graphical view]

PANTHER

PTHR11757. Peptidase_S9A. 1 hit.

Pfam

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

PRINTS

PR00862. PROLIGOPTASE.

PROSITE

PS00708. PRO_ENDOPEP_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00107. Oxytocin.

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:	June 16, 2009
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)