P42785 (PCP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lysosomal Pro-X carboxypeptidase
EC=3.4.16.2

Alternative name(s):
Angiotensinase C
Lysosomal carboxypeptidase C
Proline carboxypeptidase
Prolylcarboxypeptidase
Short name=PRCP

Gene names

Name:	PRCP
Synonyms:	PCP

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	496 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin. This cleavage occurs at acidic pH, but enzymatic activity is retained with some substrates at neutral pH.
Catalytic activity	Cleavage of a -Pro-|-Xaa bond to release a C-terminal amino acid.
Subunit structure	Homodimer. Ref.11
Subcellular location	Lysosome.
Tissue specificity	Highest levels in placenta, lung and liver. Also present in heart, brain, pancreas and kidney.
Sequence similarities	Belongs to the peptidase S28 family.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Carboxypeptidase Hydrolase Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation, intrinsic pathway Traceable author statement. Source: Reactome proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Traceable author statement. Source: Reactome
Molecular_function	serine-type carboxypeptidase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GPR37L1	O60883	2	EBI-2803892,EBI-2927498

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P42785-1)

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: P42785-2)

The sequence of this isoform differs from the canonical sequence as follows:
     56-56: K → KALAAGQLHICIIQLNHYKTPL

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Propeptide

22 – 45

24

PRO_0000027308

Chain

46 – 496

451

Lysosomal Pro-X carboxypeptidase

PRO_0000027309

Regions

Region

194 – 334

141

SKS domain

Sites

Active site

179

1

Charge relay system Ref.11

Active site

430

1

Charge relay system Ref.11

Active site

455

1

Charge relay system Ref.11

Amino acid modifications

Glycosylation

47

1

N-linked (GlcNAc...) Potential

Glycosylation

101

1

N-linked (GlcNAc...) Ref.11

Glycosylation

317

1

N-linked (GlcNAc...) Ref.9 Ref.11

Glycosylation

336

1

N-linked (GlcNAc...) Ref.11

Glycosylation

345

1

N-linked (GlcNAc...) Ref.11

Glycosylation

415

1

N-linked (GlcNAc...) Ref.9 Ref.11

Disulfide bond

215 ↔ 372

Ref.11

Disulfide bond

233 ↔ 310

Ref.11

Disulfide bond

264 ↔ 343

Ref.11

Disulfide bond

364 ↔ 394

Ref.11

Natural variations

Alternative sequence

56

1

K → KALAAGQLHICIIQLNHYKT PL in isoform 2.

VSP_045799

Natural variant

112

1

E → D. Ref.3
Corresponds to variant rs2298668 [ dbSNP | Ensembl ].

VAR_020464

Natural variant

444

1

T → S.
Corresponds to variant rs2228312 [ dbSNP | Ensembl ].

VAR_029329

Experimental info

Sequence conflict

104

1

G → E in BAG52417. Ref.3

Sequence conflict

248

1

S → L in BAG52417. Ref.3

Sequence conflict

304

1

W → R in BAG52417. Ref.3

Secondary structure

1

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496

Helix Strand Turn

Details...

Beta strand

49 – 57

9

Beta strand

67 – 75

9

Turn

81 – 83

3

Beta strand

85 – 90

6

Helix

96 – 102

7

Helix

104 – 113

10

Beta strand

115 – 120

6

Helix

132 – 136

5

Turn

139 – 141

3

Helix

147 – 164

18

Helix

168 – 170

3

Beta strand

173 – 178

6

Helix

180 – 191

12

Turn

193 – 195

3

Beta strand

197 – 202

6

Helix

217 – 227

11

Helix

233 – 247

15

Helix

251 – 260

10

Beta strand

263 – 265

3

Helix

272 – 288

17

Beta strand

295 – 301

7

Helix

305 – 312

8

Helix

320 – 336

17

Beta strand

342 – 344

3

Helix

354 – 365

12

Beta strand

375 – 380

6

Helix

387 – 398

12

Helix

406 – 411

6

Beta strand

422 – 429

8

Helix

431 – 435

5

Beta strand

441 – 450

10

Helix

457 – 459

3

Helix

468 – 489

22

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: FC5DD570D3D3AB4F	FASTA	496	55,800
	10 20 30 40 50 60 MGRRALLLLL LSFLAPWATI ALRPALRALG SLHLPTNPTS LPAVAKNYSV LYFQQKVDHF 70 80 90 100 110 120 GFNTVKTFNQ RYLVADKYWK KNGGSILFYT GNEGDIIWFC NNTGFMWDVA EELKAMLVFA 130 140 150 160 170 180 EHRYYGESLP FGDNSFKDSR HLNFLTSEQA LADFAELIKH LKRTIPGAEN QPVIAIGGSY 190 200 210 220 230 240 GGMLAAWFRM KYPHMVVGAL AASAPIWQFE DLVPCGVFMK IVTTDFRKSG PHCSESIHRS 250 260 270 280 290 300 WDAINRLSNT GSGLQWLTGA LHLCSPLTSQ DIQHLKDWIS ETWVNLAMVD YPYASNFLQP 310 320 330 340 350 360 LPAWPIKVVC QYLKNPNVSD SLLLQNIFQA LNVYYNYSGQ VKCLNISETA TSSLGTLGWS 370 380 390 400 410 420 YQACTEVVMP FCTNGVDDMF EPHSWNLKEL SDDCFQQWGV RPRPSWITTM YGGKNISSHT 430 440 450 460 470 480 NIVFSNGELD PWSGGGVTKD ITDTLVAVTI SEGAHHLDLR TKNALDPMSV LLARSLEVRH 490 MKNWIRDFYD SAGKQH
	Isoform 2 [UniParc]. Checksum: A2490258A57E6F23	FASTA	517	58,100
	10 20 30 40 50 60 MGRRALLLLL LSFLAPWATI ALRPALRALG SLHLPTNPTS LPAVAKNYSV LYFQQKALAA 70 80 90 100 110 120 GQLHICIIQL NHYKTPLVDH FGFNTVKTFN QRYLVADKYW KKNGGSILFY TGNEGDIIWF 130 140 150 160 170 180 CNNTGFMWDV AEELKAMLVF AEHRYYGESL PFGDNSFKDS RHLNFLTSEQ ALADFAELIK 190 200 210 220 230 240 HLKRTIPGAE NQPVIAIGGS YGGMLAAWFR MKYPHMVVGA LAASAPIWQF EDLVPCGVFM 250 260 270 280 290 300 KIVTTDFRKS GPHCSESIHR SWDAINRLSN TGSGLQWLTG ALHLCSPLTS QDIQHLKDWI 310 320 330 340 350 360 SETWVNLAMV DYPYASNFLQ PLPAWPIKVV CQYLKNPNVS DSLLLQNIFQ ALNVYYNYSG 370 380 390 400 410 420 QVKCLNISET ATSSLGTLGW SYQACTEVVM PFCTNGVDDM FEPHSWNLKE LSDDCFQQWG 430 440 450 460 470 480 VRPRPSWITT MYGGKNISSH TNIVFSNGEL DPWSGGGVTK DITDTLVAVT ISEGAHHLDL 490 500 510 RTKNALDPMS VLLARSLEVR HMKNWIRDFY DSAGKQH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequencing and cloning of human prolylcarboxypeptidase (angiotensinase C). Similarity to both serine carboxypeptidase and prolylendopeptidase families." Tan F., Morris P.W., Skidgel R.A., Erdoes E.G. J. Biol. Chem. 268:16631-16638(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. Tissue: Kidney.
[2]	Erratum Tan F., Morris P.W., Skidgel R.A., Erdoes E.G. J. Biol. Chem. 268:26032-26032(1993)
[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. , 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 AND 2), VARIANT ASP-112. Tissue: Kidney and Lung.
[4]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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). Tissue: Brain.
[8]	"Purification and properties of prolylcarboxypeptidase (angiotensinase C) from human kidney." Odya C.E., Marinkovic D.V., Hammon K.J., Stewart T.A., Erdos E.G. J. Biol. Chem. 253:5927-5931(1978) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION. Tissue: Kidney.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-317 AND ASN-415, MASS SPECTROMETRY. Tissue: Liver.
[10]	"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].
[11]	"Structural definition and substrate specificity of the S28 protease family: the crystal structure of human prolylcarboxypeptidase." Soisson S.M., Patel S.B., Abeywickrema P.D., Byrne N.J., Diehl R.E., Hall D.L., Ford R.E., Reid J.C., Rickert K.W., Shipman J.M., Sharma S., Lumb K.J. BMC Struct. Biol. 10:16-16(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) OF 46-491, SUBUNIT, DISULFIDE BONDS, ACTIVE SITE, GLYCOSYLATION AT ASN-101; ASN-317; ASN-336; ASN-345 AND ASN-415.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L13977 mRNA. Translation: AAA99891.1.
AK091786 mRNA. Translation: BAG52417.1.
AK312919 mRNA. Translation: BAG35764.1.
AB451270 mRNA. Translation: BAG70084.1.
AB451397 mRNA. Translation: BAG70211.1.
AP000893 Genomic DNA. No translation available.
AP001646 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW75074.1.
CH471076 Genomic DNA. Translation: EAW75075.1.
BC001500 mRNA. Translation: AAH01500.1.

IPI

IPI00001593.
IPI00399307.

PIR

A47352.

RefSeq

NP_005031.1. NM_005040.2.
NP_955450.2. NM_199418.2.

UniGene

Hs.523936.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3N2Z	X-ray	2.79	B	46-491	[»]

ProteinModelPortal

P42785.

ModBase

Search...

Protein-protein interaction databases

IntAct

P42785. 4 interactions.

STRING

9606.ENSP00000377055.

Protein family/group databases

MEROPS

S28.001.

PTM databases

PhosphoSite

P42785.

Polymorphism databases

DMDM

1172047.

Proteomic databases

PaxDb

P42785.

PRIDE

P42785.

Protocols and materials databases

DNASU

5547.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000313010; ENSP00000317362; ENSG00000137509.
ENST00000393399; ENSP00000377055; ENSG00000137509.

GeneID

5547.

KEGG

hsa:5547.

UCSC

uc001ozs.3. human.

Organism-specific databases

CTD

5547.

GeneCards

GC11M082535.

HGNC

HGNC:9344. PRCP.

HPA

HPA017065.

MIM

176785. gene.

neXtProt

NX_P42785.

PharmGKB

PA33705.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG290141.

HOGENOM

HOG000238311.

HOVERGEN

HBG005526.

KO

K01285.

PhylomeDB

P42785.

Enzyme and pathway databases

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P42785.

Bgee

P42785.

CleanEx

HS_PRCP.

Genevestigator

P42785.

GermOnline

ENSG00000137509. Homo sapiens.

Family and domain databases

InterPro

IPR008758. Peptidase_S28.
[Graphical view]

PANTHER

PTHR11010. PTHR11010. 1 hit.

Pfam

PF05577. Peptidase_S28. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P42785.

ChEMBL

CHEMBL2335.

ChiTaRS

PRCP. human.

EvolutionaryTrace

P42785.

GenomeRNAi

5547.

NextBio

21494.

SOURCE

Search...

Entry information

Entry name

PCP_HUMAN

Accession

Primary (citable) accession number: P42785
Secondary accession number(s): A8MU24 , B2R7B7, B3KRK5, B5BU34

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 122 of the entry and version 1 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.