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P12955 (PEPD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 170. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Xaa-Pro dipeptidase

Short name=X-Pro dipeptidase
EC=3.4.13.9
Alternative name(s):
Imidodipeptidase
Peptidase D
Proline dipeptidase
Short name=Prolidase
Gene names
Name:PEPD
Synonyms:PRD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length493 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Splits dipeptides with a prolyl or hydroxyprolyl residue in the C-terminal position. Plays an important role in collagen metabolism because the high level of iminoacids in collagen.

Catalytic activity

Hydrolysis of Xaa-|-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-|-Pro.

Cofactor

Binds 2 manganese ions per subunit. Ref.10

Subunit structure

Homodimer.

Involvement in disease

Prolidase deficiency (PD) [MIM:170100]: A multisystem disorder associated with massive iminodipeptiduria and lack of or reduced prolidase activity in erythrocytes, leukocytes, or cultured fibroblasts. Clinical features include skin ulcers, developmental delay, recurrent infections, and a characteristic facies.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Ref.13 Ref.14

Sequence similarities

Belongs to the peptidase M24B family. Eukaryotic-type prolidase subfamily.

Mass spectrometry

Molecular mass is 54251.73 Da from positions 2 - 493. Determined by MALDI. Ref.6

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P12955-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P12955-2)

The sequence of this isoform differs from the canonical sequence as follows:
     184-224: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P12955-3)

The sequence of this isoform differs from the canonical sequence as follows:
     68-131: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 493492Xaa-Pro dipeptidase
PRO_0000185087

Sites

Metal binding2761Manganese 1
Metal binding2871Manganese 1
Metal binding2871Manganese 2
Metal binding3701Manganese 2
Metal binding4121Manganese 2
Metal binding4521Manganese 1
Metal binding4521Manganese 2

Amino acid modifications

Modified residue21N-acetylalanine Ref.7 Ref.9

Natural variations

Alternative sequence68 – 13164Missing in isoform 3.
VSP_045370
Alternative sequence184 – 22441Missing in isoform 2.
VSP_042629
Natural variant1841R → Q in PD. Ref.13
VAR_011614
Natural variant2761D → N in PD. Ref.11
VAR_004404
Natural variant2781G → D in PD. Ref.13
VAR_011615
Natural variant3881R → H.
Corresponds to variant rs2230062 [ dbSNP | Ensembl ].
VAR_051574
Natural variant4351L → F. Ref.3 Ref.5
Corresponds to variant rs17570 [ dbSNP | Ensembl ].
VAR_014723
Natural variant4481G → R in PD. Ref.12 Ref.13 Ref.14
VAR_004405
Natural variant4521Missing in PD. Ref.12 Ref.13
VAR_004406

Experimental info

Sequence conflict481L → R in BAF84250. Ref.3
Sequence conflict661R → L in AAA60064. Ref.1
Sequence conflict1071W → R in BAF83470. Ref.3
Sequence conflict1081M → I in BAF83445. Ref.3
Sequence conflict1831C → S in AAA60064. Ref.1
Sequence conflict2211E → G in AAA60064. Ref.1
Sequence conflict283 – 2842CF → SV in AAA60064. Ref.1
Sequence conflict2941A → R in AAA60064. Ref.1
Sequence conflict3111R → L in AAA60064. Ref.1
Sequence conflict3241V → D in AAA60064. Ref.1
Sequence conflict329 – 3302MH → ID in AAA60064. Ref.1
Sequence conflict4081V → A in BAG56678. Ref.3
Sequence conflict4581T → I in AAA60064. Ref.1
Sequence conflict4781C → R in BAF83470. Ref.3

Secondary structure

............................................................................ 493
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E8C4A2497E44BA22

FASTA49354,548
        10         20         30         40         50         60 
MAAATGPSFW LGNETLKVPL ALFALNRQRL CERLRKNPAV QAGSIVVLQG GEETQRYCTD 

        70         80         90        100        110        120 
TGVLFRQESF FHWAFGVTEP GCYGVIDVDT GKSTLFVPRL PASHATWMGK IHSKEHFKEK 

       130        140        150        160        170        180 
YAVDDVQYVD EIASVLTSQK PSVLLTLRGV NTDSGSVCRE ASFDGISKFE VNNTILHPEI 

       190        200        210        220        230        240 
VECRVFKTDM ELEVLRYTNK ISSEAHREVM KAVKVGMKEY ELESLFEHYC YSRGGMRHSS 

       250        260        270        280        290        300 
YTCICGSGEN SAVLHYGHAG APNDRTIQNG DMCLFDMGGE YYCFASDITC SFPANGKFTA 

       310        320        330        340        350        360 
DQKAVYEAVL RSSRAVMGAM KPGVWWPDMH RLADRIHLEE LAHMGILSGS VDAMVQAHLG 

       370        380        390        400        410        420 
AVFMPHGLGH FLGIDVHDVG GYPEGVERID EPGLRSLRTA RHLQPGMVLT VEPGIYFIDH 

       430        440        450        460        470        480 
LLDEALADPA RASFLNREVL QRFRGFGGVR IEEDVVVTDS GIELLTCVPR TVEEIEACMA 

       490 
GCDKAFTPFS GPK 

« Hide

Isoform 2 [UniParc].

Checksum: EA1B0DFBE694A180
Show »

FASTA45249,691
Isoform 3 [UniParc].

Checksum: 2D094B4069E39CF5
Show »

FASTA42947,261

References

« Hide 'large scale' references
[1]"Primary structure and gene localization of human prolidase."
Endo F., Tanoue A., Nakai H., Hata A., Indo Y., Titani K., Matsuda I.
J. Biol. Chem. 264:4476-4481(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
Tissue: Liver and Placenta.
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT PHE-435.
Tissue: Brain and Kidney.
[4]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM 1), VARIANT PHE-435.
Tissue: Kidney, Skin and Uterus.
[6]"Cluster analysis of an extensive human breast cancer cell line protein expression map database."
Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., Zvelebil M.J.
Proteomics 2:212-223(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MASS SPECTROMETRY.
Tissue: Mammary cancer.
[7]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[8]"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].
[9]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Crystal structure of human prolidase: the molecular basis of PD disease."
Protein structure factory (PSF)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS, COFACTOR.
[11]"A single nucleotide change in the prolidase gene in fibroblasts from two patients with polypeptide positive prolidase deficiency. Expression of the mutant enzyme in NIH 3T3 cells."
Tanoue A., Endo F., Kitano A., Matsuda I.
J. Clin. Invest. 86:351-355(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PD ASN-276.
[12]"Four novel PEPD alleles causing prolidase deficiency."
Ledoux P., Scriver C.R., Hechtman P.
Am. J. Hum. Genet. 54:1014-1021(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PD ARG-448 AND GLU-452 DEL.
[13]"Expression and molecular analysis of mutations in prolidase deficiency."
Ledoux P., Scriver C.R., Hechtman P.
Am. J. Hum. Genet. 59:1035-1039(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PD GLN-184; ASP-278; ARG-448 AND GLU-452 DEL.
[14]"Mutation analysis of five new patients affected by prolidase deficiency: the lack of enzyme activity causes necrosis-like cell death in cultured fibroblasts."
Forlino A., Lupi A., Vaghi P., Icaro Cornaglia A., Calligaro A., Campari E., Cetta G.
Hum. Genet. 111:314-322(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PD ARG-448.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04605 mRNA. Translation: AAA60064.1.
BT006692 mRNA. Translation: AAP35338.1.
AK290756 mRNA. Translation: BAF83445.1.
AK290781 mRNA. Translation: BAF83470.1.
AK291561 mRNA. Translation: BAF84250.1.
AK293126 mRNA. Translation: BAG56678.1.
AK294619 mRNA. Translation: BAG57802.1.
AC008744 Genomic DNA. No translation available.
AC010485 Genomic DNA. No translation available.
BC004305 mRNA. Translation: AAH04305.1.
BC015027 mRNA. Translation: AAH15027.1.
BC028295 mRNA. Translation: AAH28295.1.
CCDSCCDS42544.1. [P12955-1]
CCDS54244.1. [P12955-3]
CCDS54245.1. [P12955-2]
PIRA32454.
RefSeqNP_000276.2. NM_000285.3. [P12955-1]
NP_001159528.1. NM_001166056.1. [P12955-2]
NP_001159529.1. NM_001166057.1. [P12955-3]
UniGeneHs.36473.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2IW2X-ray1.82A/B2-493[»]
2OKNX-ray2.45A/B2-493[»]
ProteinModelPortalP12955.
SMRP12955. Positions 6-482.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111208. 30 interactions.
IntActP12955. 8 interactions.
MINTMINT-5000488.
STRING9606.ENSP00000244137.

Chemistry

BindingDBP12955.
ChEMBLCHEMBL4185.

Protein family/group databases

MEROPSM24.007.

PTM databases

PhosphoSiteP12955.

Polymorphism databases

DMDM50403718.

2D gel databases

REPRODUCTION-2DPAGEIPI00257882.

Proteomic databases

MaxQBP12955.
PaxDbP12955.
PeptideAtlasP12955.
PRIDEP12955.

Protocols and materials databases

DNASU5184.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000244137; ENSP00000244137; ENSG00000124299. [P12955-1]
ENST00000397032; ENSP00000380226; ENSG00000124299. [P12955-2]
ENST00000436370; ENSP00000391890; ENSG00000124299. [P12955-3]
GeneID5184.
KEGGhsa:5184.
UCSCuc002nur.4. human. [P12955-1]
uc010xrr.2. human. [P12955-2]

Organism-specific databases

CTD5184.
GeneCardsGC19M033877.
HGNCHGNC:8840. PEPD.
HPAHPA015599.
MIM170100. phenotype.
613230. gene.
neXtProtNX_P12955.
Orphanet742. Prolidase deficiency.
PharmGKBPA33181.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0006.
HOGENOMHOG000008763.
HOVERGENHBG053562.
InParanoidP12955.
KOK14213.
OMAPIVACGE.
OrthoDBEOG7FNC76.
PhylomeDBP12955.
TreeFamTF313396.

Gene expression databases

ArrayExpressP12955.
BgeeP12955.
CleanExHS_PEPD.
GenevestigatorP12955.

Family and domain databases

Gene3D3.40.350.10. 1 hit.
3.90.230.10. 1 hit.
InterProIPR007865. Aminopep_P_N.
IPR029149. Creatin/AminoP/Spt16_NTD.
IPR028980. Creatinase/Aminopeptidase_P_N.
IPR000994. Pept_M24_structural-domain.
IPR001131. Peptidase_M24B_aminopep-P_CS.
[Graphical view]
PfamPF05195. AMP_N. 1 hit.
PF00557. Peptidase_M24. 1 hit.
[Graphical view]
SMARTSM01011. AMP_N. 1 hit.
[Graphical view]
SUPFAMSSF53092. SSF53092. 1 hit.
SSF55920. SSF55920. 1 hit.
PROSITEPS00491. PROLINE_PEPTIDASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPEPD. human.
EvolutionaryTraceP12955.
GeneWikiPEPD.
GenomeRNAi5184.
NextBio20054.
PROP12955.
SOURCESearch...

Entry information

Entry namePEPD_HUMAN
AccessionPrimary (citable) accession number: P12955
Secondary accession number(s): A8K3Z1 expand/collapse secondary AC list , A8K416, A8K696, A8MX47, B4DDB7, B4DGJ1, E9PCE8, Q8TBN9, Q9BT75
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 170 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM