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P16870

- CBPE_HUMAN

UniProt

P16870 - CBPE_HUMAN

Protein

Carboxypeptidase E

Gene

CPE

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 155 (01 Oct 2014)
      Sequence version 1 (01 Aug 1990)
      Previous versions | rss
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    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

    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

    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: UniProt
    2. Golgi apparatus Source: BHF-UCL
    3. nucleus Source: UniProtKB-SubCell
    4. plasma membrane Source: ProtInc
    5. secretory granule membrane Source: Reactome
    6. transport vesicle membrane Source: UniProtKB-SubCell

    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

    ArrayExpressiP16870.
    BgeeiP16870.
    CleanExiHS_CPE.
    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. 11 interactions.
    IntActiP16870. 10 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.
    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

    MAGRGGSALL ALCGALAACG WLLGAEAQEP GAPAAGMRRR RRLQQEDGIS    50
    FEYHRYPELR EALVSVWLQC TAISRIYTVG RSFEGRELLV IELSDNPGVH 100
    EPGEPEFKYI GNMHGNEAVG RELLIFLAQY LCNEYQKGNE TIVNLIHSTR 150
    IHIMPSLNPD GFEKAASQPG ELKDWFVGRS NAQGIDLNRN FPDLDRIVYV 200
    NEKEGGPNNH LLKNMKKIVD QNTKLAPETK AVIHWIMDIP FVLSANLHGG 250
    DLVANYPYDE TRSGSAHEYS SSPDDAIFQS LARAYSSFNP AMSDPNRPPC 300
    RKNDDDSSFV DGTTNGGAWY SVPGGMQDFN YLSSNCFEIT VELSCEKFPP 350
    EETLKTYWED NKNSLISYLE QIHRGVKGFV RDLQGNPIAN ATISVEGIDH 400
    DVTSAKDGDY WRLLIPGNYK LTASAPGYLA ITKKVAVPYS PAAGVDFELE 450
    SFSERKEEEK EELMEWWKMM SETLNF 476
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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. 11 interactions.
    IntActi P16870. 10 interactions.
    MINTi MINT-1374084.
    STRINGi 9606.ENSP00000386104.

    Chemistry

    DrugBanki DB00040. Glucagon recombinant.
    DB00047. Insulin Glargine recombinant.
    DB00046. Insulin Lyspro recombinant.
    DB00030. Insulin recombinant.
    DB00071. Insulin, porcine.

    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.
    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

    ArrayExpressi P16870.
    Bgeei P16870.
    CleanExi HS_CPE.
    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

    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: October 1, 2014
    This is version 155 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