P16870 (CBPE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	476 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	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 vesicle › secretory 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 component	Cytoplasmic vesicle Membrane Nucleus Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac 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: Compara 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_component	Golgi 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 Traceable author statement. Source: Reactome transport vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carboxypeptidase 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
PRKAA1	Q13131	1	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Propeptide	26 – 42	17	Activation peptide		PRO_0000004384
	Chain	43 – 476	434	Carboxypeptidase E		PRO_0000004385
Sites
	Active site	342	1	Nucleophile By similarity
	Metal binding	114	1	Zinc By similarity
	Metal binding	117	1	Zinc By similarity
	Metal binding	248	1	Zinc By similarity
Amino acid modifications
	Glycosylation	139	1	N-linked (GlcNAc...) Potential
	Glycosylation	390	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 36	36	Missing in isoform 2.		VSP_040959
	Natural variant	235	1	W → R. Corresponds to variant rs34516004 [ dbSNP | Ensembl ].		VAR_048599
	Natural variant	297	1	R → Q in a colorectal cancer sample; somatic mutation. Ref.7		VAR_036011
Experimental info
	Sequence conflict	287	1	S → P in BAG52254. Ref.3
	Sequence conflict	391	1	A → R in BAA86053. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: D561AC0285A51E86	FASTA	476	53,151
	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
	Isoform 2 (CPE delta-N) [UniParc]. Checksum: DF064F491F278611	FASTA	440	49,886
	10 20 30 40 50 60 MRRRRRLQQE DGISFEYHRY PELREALVSV WLQCTAISRI YTVGRSFEGR ELLVIELSDN 70 80 90 100 110 120 PGVHEPGEPE FKYIGNMHGN EAVGRELLIF LAQYLCNEYQ KGNETIVNLI HSTRIHIMPS 130 140 150 160 170 180 LNPDGFEKAA SQPGELKDWF VGRSNAQGID LNRNFPDLDR IVYVNEKEGG PNNHLLKNMK 190 200 210 220 230 240 KIVDQNTKLA PETKAVIHWI MDIPFVLSAN LHGGDLVANY PYDETRSGSA HEYSSSPDDA 250 260 270 280 290 300 IFQSLARAYS SFNPAMSDPN RPPCRKNDDD SSFVDGTTNG GAWYSVPGGM QDFNYLSSNC 310 320 330 340 350 360 FEITVELSCE KFPPEETLKT YWEDNKNSLI SYLEQIHRGV KGFVRDLQGN PIANATISVE 370 380 390 400 410 420 GIDHDVTSAK DGDYWRLLIP GNYKLTASAP GYLAITKKVA VPYSPAAGVD FELESFSERK 430 440 EEEKEELMEW WKMMSETLNF

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00031121. IPI00967442.
PIR	S09489.
RefSeq	NP_001864.1. NM_001873.2.
UniGene	Hs.75360.
3D structure databases
ProteinModelPortal	P16870.
ModBase	Search...
Protein-protein interaction databases
IntAct	P16870. 10 interactions.
MINT	MINT-1374084.
STRING	9606.ENSP00000386104.
Protein family/group databases
MEROPS	M14.005.
PTM databases
PhosphoSite	P16870.
Polymorphism databases
DMDM	115892.
Proteomic databases
PaxDb	P16870.
PRIDE	P16870.
Protocols and materials databases
DNASU	1363.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000402744; ENSP00000386104; ENSG00000109472.
GeneID	1363.
KEGG	hsa:1363.
UCSC	uc003irg.4. human.
Organism-specific databases
CTD	1363.
GeneCards	GC04P166300.
HGNC	HGNC:2303. CPE.
HPA	CAB024907.
MIM	114855. gene.
neXtProt	NX_P16870.
PharmGKB	PA26824.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG322453.
HOGENOM	HOG000232185.
HOVERGEN	HBG003410.
InParanoid	P16870.
KO	K01294.
OMA	TIVNLIH.
PhylomeDB	P16870.
Enzyme and pathway databases
Pathway_Interaction_DB	arf6_traffickingpathway. Arf6 trafficking events.
Reactome	REACT_116125. Disease.
Gene expression databases
ArrayExpress	P16870.
Bgee	P16870.
CleanEx	HS_CPE.
Genevestigator	P16870.
GermOnline	ENSG00000109472. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.1120. 1 hit.
InterPro	IPR008969. CarboxyPept-like_regulatory. IPR014766. CarboxyPept_regulatory_dom. IPR000834. Peptidase_M14. [Graphical view]
Pfam	PF00246. Peptidase_M14. 1 hit. [Graphical view]
PRINTS	PR00765. CRBOXYPTASEA.
SMART	SM00631. Zn_pept. 1 hit. [Graphical view]
SUPFAM	SSF49464. CarboxypepD_reg. 1 hit.
PROSITE	PS00132. CARBOXYPEPT_ZN_1. 1 hit. PS00133. CARBOXYPEPT_ZN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CPE. human.
DrugBank	DB00040. Glucagon recombinant. DB00047. Insulin Glargine recombinant. DB00046. Insulin Lyspro recombinant. DB00030. Insulin recombinant. DB00071. Insulin, porcine.
GenomeRNAi	1363.
NextBio	35471538.
SOURCE	Search...

Entry information

Entry name

CBPE_HUMAN

Accession

Primary (citable) accession number: P16870
Secondary accession number(s): A8K4N1 , B3KR42, B4DFN4, D3DP33, Q9UIU9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	May 1, 2013
This is version 142 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.