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P16870 (CBPE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Carboxypeptidase E

Short name=CPE
EC=3.4.17.10
Alternative name(s):
Carboxypeptidase H
Short name=CPH
Enkephalin convertase
Prohormone-processing carboxypeptidase
Gene names
Name:CPE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length476 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Removes residual C-terminal Arg or Lys remaining after initial endoprotease cleavage during prohormone processing. Processes proinsulin.

Catalytic activity

Release of C-terminal arginine or lysine residues from polypeptides.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

Isoform 2 interacts with HDAC1 and HDAC2. Ref.6

Subcellular location

Isoform 1: Cytoplasmic vesiclesecretory vesicle membrane; Peripheral membrane protein By similarity. Secreted By similarity. Note: Associated with the secretory granule membrane through direct binding to lipid rafts in intragranular conditions By similarity. Ref.6

Isoform 2: Nucleus Ref.6.

Tissue specificity

Isoform 2, but not isoform 1, is overexpressed in hepatocellular carcinoma (at protein level), as well as in other tumors, including pheochromocytomas and paragangliomas. Ref.6

Sequence similarities

Belongs to the peptidase M14 family.

Sequence caution

The sequence BAG52254.1 differs from that shown. Reason: Frameshift at position 415.

Ontologies

Keywords
   Cellular componentCytoplasmic vesicle
Membrane
Nucleus
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   LigandMetal-binding
Zinc
   Molecular functionCarboxypeptidase
Hydrolase
Metalloprotease
Protease
   PTMCleavage on pair of basic residues
Glycoprotein
Zymogen
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac left ventricle morphogenesis

Inferred from mutant phenotype PubMed 19593212. Source: BHF-UCL

cellular protein modification process

Non-traceable author statement Ref.1. Source: UniProtKB

insulin processing

Inferred from electronic annotation. Source: Ensembl

neuropeptide signaling pathway

Non-traceable author statement Ref.1. Source: UniProtKB

protein localization to membrane

Inferred from direct assay PubMed 19166515. Source: BHF-UCL

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 19166515. Source: BHF-UCL

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Traceable author statement PubMed 9019408. Source: ProtInc

secretory granule membrane

Traceable author statement. Source: Reactome

transport vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncarboxypeptidase activity

Traceable author statement PubMed 9019408. Source: ProtInc

metallocarboxypeptidase activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PRKAA1Q131311EBI-711320,EBI-1181405

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P16870-1)

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: P16870-2)

Also known as: CPE delta-N;

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Propeptide26 – 4217Activation peptide
PRO_0000004384
Chain43 – 476434Carboxypeptidase E
PRO_0000004385

Sites

Active site3421Nucleophile By similarity
Metal binding1141Zinc By similarity
Metal binding1171Zinc By similarity
Metal binding2481Zinc By similarity

Amino acid modifications

Glycosylation1391N-linked (GlcNAc...) Potential
Glycosylation3901N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 3636Missing in isoform 2.
VSP_040959
Natural variant2351W → R.
Corresponds to variant rs34516004 [ dbSNP | Ensembl ].
VAR_048599
Natural variant2971R → Q in a colorectal cancer sample; somatic mutation. Ref.7
VAR_036011

Experimental info

Sequence conflict2871S → P in BAG52254. Ref.3
Sequence conflict3911A → R in BAA86053. Ref.2

Sequences

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

Last modified August 1, 1990. Version 1.
Checksum: D561AC0285A51E86

FASTA47653,151
        10         20         30         40         50         60 
MAGRGGSALL ALCGALAACG WLLGAEAQEP GAPAAGMRRR RRLQQEDGIS FEYHRYPELR 

        70         80         90        100        110        120 
EALVSVWLQC TAISRIYTVG RSFEGRELLV IELSDNPGVH EPGEPEFKYI GNMHGNEAVG 

       130        140        150        160        170        180 
RELLIFLAQY LCNEYQKGNE TIVNLIHSTR IHIMPSLNPD GFEKAASQPG ELKDWFVGRS 

       190        200        210        220        230        240 
NAQGIDLNRN FPDLDRIVYV NEKEGGPNNH LLKNMKKIVD QNTKLAPETK AVIHWIMDIP 

       250        260        270        280        290        300 
FVLSANLHGG DLVANYPYDE TRSGSAHEYS SSPDDAIFQS LARAYSSFNP AMSDPNRPPC 

       310        320        330        340        350        360 
RKNDDDSSFV DGTTNGGAWY SVPGGMQDFN YLSSNCFEIT VELSCEKFPP EETLKTYWED 

       370        380        390        400        410        420 
NKNSLISYLE QIHRGVKGFV RDLQGNPIAN ATISVEGIDH DVTSAKDGDY WRLLIPGNYK 

       430        440        450        460        470 
LTASAPGYLA ITKKVAVPYS PAAGVDFELE SFSERKEEEK EELMEWWKMM SETLNF 

« Hide

Isoform 2 (CPE delta-N) [UniParc].

Checksum: DF064F491F278611
Show »

FASTA44049,886

References

« Hide 'large scale' references
[1]"Human carboxypeptidase E. Isolation and characterization of the cDNA, sequence conservation, expression and processing in vitro."
Manser E., Fernandez D., Loo L., Goh P.Y., Monfries C., Hall C., Lim L.
Biochem. J. 267:517-525(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"Organization of the human carboxypeptidase E gene and molecular scanning for mutations in Japanese subjects with NIDDM or obesity."
Utsunomiya N., Ohagi S., Sanke T., Tatsuta H., Hanabusa T., Nanjo K.
Diabetologia 41:701-705(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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 AND 2).
Tissue: Amygdala and Teratocarcinoma.
[4]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. expand/collapse author list , 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].
[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).
Tissue: Colon and Eye.
[6]"An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers."
Lee T.K., Murthy S.R., Cawley N.X., Dhanvantari S., Hewitt S.M., Lou H., Lau T., Ma S., Huynh T., Wesley R.A., Ng I.O., Pacak K., Poon R.T., Loh Y.P.
J. Clin. Invest. 121:880-892(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION (ISOFORM 2), INTERACTION WITH HDAC1 AND HDAC2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-297.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X51405 mRNA. Translation: CAA35767.1.
AB006898 Genomic DNA. Translation: BAA86053.1.
AK090962 mRNA. Translation: BAG52254.1. Frameshift.
AK290996 mRNA. Translation: BAF83685.1.
AK294175 mRNA. Translation: BAG57495.1.
CH471056 Genomic DNA. Translation: EAX04817.1.
CH471056 Genomic DNA. Translation: EAX04818.1.
BC033866 mRNA. Translation: AAH33866.1.
BC053612 mRNA. Translation: AAH53612.1.
PIRS09489.
RefSeqNP_001864.1. NM_001873.2.
UniGeneHs.75360.

3D structure databases

ProteinModelPortalP16870.
SMRP16870. Positions 49-449.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107755. 11 interactions.
IntActP16870. 10 interactions.
MINTMINT-1374084.
STRING9606.ENSP00000386104.

Chemistry

DrugBankDB00040. Glucagon recombinant.
DB00047. Insulin Glargine recombinant.
DB00046. Insulin Lyspro recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.

Protein family/group databases

MEROPSM14.005.

PTM databases

PhosphoSiteP16870.

Polymorphism databases

DMDM115892.

Proteomic databases

PaxDbP16870.
PRIDEP16870.

Protocols and materials databases

DNASU1363.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000402744; ENSP00000386104; ENSG00000109472. [P16870-1]
GeneID1363.
KEGGhsa:1363.
UCSCuc003irg.4. human. [P16870-1]

Organism-specific databases

CTD1363.
GeneCardsGC04P166300.
HGNCHGNC:2303. CPE.
HPACAB024907.
HPA003819.
MIM114855. gene.
neXtProtNX_P16870.
PharmGKBPA26824.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG322453.
HOGENOMHOG000232185.
HOVERGENHBG003410.
InParanoidP16870.
KOK01294.
OMATIVNLIH.
PhylomeDBP16870.
TreeFamTF315592.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressP16870.
BgeeP16870.
CleanExHS_CPE.
GenevestigatorP16870.

Family and domain databases

Gene3D2.60.40.1120. 1 hit.
InterProIPR008969. CarboxyPept-like_regulatory.
IPR014766. CarboxyPept_regulatory_dom.
IPR000834. Peptidase_M14.
[Graphical view]
PfamPF00246. Peptidase_M14. 1 hit.
[Graphical view]
PRINTSPR00765. CRBOXYPTASEA.
SMARTSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMSSF49464. SSF49464. 1 hit.
PROSITEPS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCPE. human.
GeneWikiCarboxypeptidase_E.
GenomeRNAi1363.
NextBio35471538.
PROP16870.
SOURCESearch...

Entry information

Entry nameCBPE_HUMAN
AccessionPrimary (citable) accession number: P16870
Secondary accession number(s): A8K4N1 expand/collapse secondary AC list , B3KR42, B4DFN4, D3DP33, Q9UIU9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: March 19, 2014
This is version 150 of the entry and version 1 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

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 4

Human chromosome 4: entries, gene names and cross-references to MIM