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P16870

- CBPE_HUMAN

UniProt

P16870 - CBPE_HUMAN

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Protein

Carboxypeptidase E

Gene

CPE

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

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

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi114 – 1141ZincBy similarity
Metal bindingi117 – 1171ZincBy similarity
Metal bindingi248 – 2481ZincBy similarity
Active sitei342 – 3421NucleophileBy similarity

GO - Molecular functioni

  1. carboxypeptidase activity Source: ProtInc
  2. cell adhesion molecule binding Source: BHF-UCL
  3. metallocarboxypeptidase activity Source: InterPro
  4. neurexin family protein binding Source: BHF-UCL
  5. zinc ion binding Source: InterPro

GO - Biological processi

  1. cardiac left ventricle morphogenesis Source: BHF-UCL
  2. cellular protein metabolic process Source: Reactome
  3. cellular protein modification process Source: UniProtKB
  4. insulin processing Source: Ensembl
  5. metabolic process Source: ProtInc
  6. neuropeptide signaling pathway Source: UniProtKB
  7. protein localization to membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_15550. Insulin processing.

Protein family/group databases

MEROPSiM14.005.

Names & Taxonomyi

Protein namesi
Recommended name:
Carboxypeptidase E (EC:3.4.17.10)
Short name:
CPE
Alternative name(s):
Carboxypeptidase H
Short name:
CPH
Enkephalin convertase
Prohormone-processing carboxypeptidase
Gene namesi
Name:CPE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:2303. CPE.

Subcellular locationi

Isoform 1 : Cytoplasmic vesiclesecretory vesicle membrane By similarity; 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

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProtKB
  2. Golgi apparatus Source: BHF-UCL
  3. nucleus Source: UniProtKB-KW
  4. plasma membrane Source: ProtInc
  5. secretory granule membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane, Nucleus, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26824.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence AnalysisAdd
BLAST
Propeptidei26 – 4217Activation peptidePRO_0000004384Add
BLAST
Chaini43 – 476434Carboxypeptidase EPRO_0000004385Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi139 – 1391N-linked (GlcNAc...)Sequence Analysis
Glycosylationi390 – 3901N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Zymogen

Proteomic databases

MaxQBiP16870.
PaxDbiP16870.
PRIDEiP16870.

PTM databases

PhosphoSiteiP16870.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiP16870.
CleanExiHS_CPE.
ExpressionAtlasiP16870. baseline and differential.
GenevestigatoriP16870.

Organism-specific databases

HPAiCAB024907.
HPA003819.

Interactioni

Subunit structurei

Isoform 2 interacts with HDAC1 and HDAC2.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
PRKAA1Q131311EBI-711320,EBI-1181405

Protein-protein interaction databases

BioGridi107755. 15 interactions.
IntActiP16870. 11 interactions.
MINTiMINT-1374084.
STRINGi9606.ENSP00000386104.

Structurei

3D structure databases

ProteinModelPortaliP16870.
SMRiP16870. Positions 49-449.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M14 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG322453.
GeneTreeiENSGT00760000119124.
HOGENOMiHOG000232185.
HOVERGENiHBG003410.
InParanoidiP16870.
KOiK01294.
OMAiTIVNLIH.
PhylomeDBiP16870.
TreeFamiTF315592.

Family and domain databases

Gene3Di2.60.40.1120. 1 hit.
InterProiIPR008969. CarboxyPept-like_regulatory.
IPR014766. CarboxyPept_regulatory_dom.
IPR000834. Peptidase_M14.
[Graphical view]
PfamiPF00246. Peptidase_M14. 1 hit.
[Graphical view]
PRINTSiPR00765. CRBOXYPTASEA.
SMARTiSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMiSSF49464. SSF49464. 1 hit.
PROSITEiPS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P16870-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MAGRGGSALL ALCGALAACG WLLGAEAQEP GAPAAGMRRR RRLQQEDGIS
60 70 80 90 100
FEYHRYPELR EALVSVWLQC TAISRIYTVG RSFEGRELLV IELSDNPGVH
110 120 130 140 150
EPGEPEFKYI GNMHGNEAVG RELLIFLAQY LCNEYQKGNE TIVNLIHSTR
160 170 180 190 200
IHIMPSLNPD GFEKAASQPG ELKDWFVGRS NAQGIDLNRN FPDLDRIVYV
210 220 230 240 250
NEKEGGPNNH LLKNMKKIVD QNTKLAPETK AVIHWIMDIP FVLSANLHGG
260 270 280 290 300
DLVANYPYDE TRSGSAHEYS SSPDDAIFQS LARAYSSFNP AMSDPNRPPC
310 320 330 340 350
RKNDDDSSFV DGTTNGGAWY SVPGGMQDFN YLSSNCFEIT VELSCEKFPP
360 370 380 390 400
EETLKTYWED NKNSLISYLE QIHRGVKGFV RDLQGNPIAN ATISVEGIDH
410 420 430 440 450
DVTSAKDGDY WRLLIPGNYK LTASAPGYLA ITKKVAVPYS PAAGVDFELE
460 470
SFSERKEEEK EELMEWWKMM SETLNF
Length:476
Mass (Da):53,151
Last modified:August 1, 1990 - v1
Checksum:iD561AC0285A51E86
GO
Isoform 2 (identifier: P16870-2) [UniParc]FASTAAdd to Basket

Also known as: CPE delta-N

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

Show »
Length:440
Mass (Da):49,886
Checksum:iDF064F491F278611
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti287 – 2871S → P in BAG52254. (PubMed:14702039)Curated
Sequence conflicti391 – 3911A → R in BAA86053. (PubMed:9662053)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti235 – 2351W → R.
Corresponds to variant rs34516004 [ dbSNP | Ensembl ].
VAR_048599
Natural varianti297 – 2971R → Q in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036011

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3636Missing in isoform 2. 1 PublicationVSP_040959Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3810.1. [P16870-1]
PIRiS09489.
RefSeqiNP_001864.1. NM_001873.2. [P16870-1]
UniGeneiHs.75360.

Genome annotation databases

EnsembliENST00000402744; ENSP00000386104; ENSG00000109472. [P16870-1]
GeneIDi1363.
KEGGihsa:1363.
UCSCiuc003irg.4. human. [P16870-1]

Polymorphism databases

DMDMi115892.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS3810.1. [P16870-1 ]
PIRi S09489.
RefSeqi NP_001864.1. NM_001873.2. [P16870-1 ]
UniGenei Hs.75360.

3D structure databases

ProteinModelPortali P16870.
SMRi P16870. Positions 49-449.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107755. 15 interactions.
IntActi P16870. 11 interactions.
MINTi MINT-1374084.
STRINGi 9606.ENSP00000386104.

Chemistry

DrugBanki DB00071. "Insulin.
DB00030. Insulin Regular.

Protein family/group databases

MEROPSi M14.005.

PTM databases

PhosphoSitei P16870.

Polymorphism databases

DMDMi 115892.

Proteomic databases

MaxQBi P16870.
PaxDbi P16870.
PRIDEi P16870.

Protocols and materials databases

DNASUi 1363.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000402744 ; ENSP00000386104 ; ENSG00000109472 . [P16870-1 ]
GeneIDi 1363.
KEGGi hsa:1363.
UCSCi uc003irg.4. human. [P16870-1 ]

Organism-specific databases

CTDi 1363.
GeneCardsi GC04P166300.
HGNCi HGNC:2303. CPE.
HPAi CAB024907.
HPA003819.
MIMi 114855. gene.
neXtProti NX_P16870.
PharmGKBi PA26824.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG322453.
GeneTreei ENSGT00760000119124.
HOGENOMi HOG000232185.
HOVERGENi HBG003410.
InParanoidi P16870.
KOi K01294.
OMAi TIVNLIH.
PhylomeDBi P16870.
TreeFami TF315592.

Enzyme and pathway databases

Reactomei REACT_15550. Insulin processing.

Miscellaneous databases

ChiTaRSi CPE. human.
GeneWikii Carboxypeptidase_E.
GenomeRNAii 1363.
NextBioi 35471538.
PROi P16870.
SOURCEi Search...

Gene expression databases

Bgeei P16870.
CleanExi HS_CPE.
ExpressionAtlasi P16870. baseline and differential.
Genevestigatori P16870.

Family and domain databases

Gene3Di 2.60.40.1120. 1 hit.
InterProi IPR008969. CarboxyPept-like_regulatory.
IPR014766. CarboxyPept_regulatory_dom.
IPR000834. Peptidase_M14.
[Graphical view ]
Pfami PF00246. Peptidase_M14. 1 hit.
[Graphical view ]
PRINTSi PR00765. CRBOXYPTASEA.
SMARTi SM00631. Zn_pept. 1 hit.
[Graphical view ]
SUPFAMi SSF49464. SSF49464. 1 hit.
PROSITEi PS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-297.

Entry informationi

Entry nameiCBPE_HUMAN
AccessioniPrimary (citable) accession number: P16870
Secondary accession number(s): A8K4N1
, B3KR42, B4DFN4, D3DP33, Q9UIU9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 26, 2014
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3