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Protein

Carboxypeptidase A4

Gene

CPA4

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

Functioni

Metalloprotease that could be involved in the histone hyperacetylation pathway (PubMed:10383164). Releases a C-terminal amino acid, with preference for -Phe, -Leu, -Ile, -Met, -Tyr and -Val (PubMed:20385563).2 Publications

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Enzyme regulationi

Inhibited by interaction with the metallocarboxypeptidase inhibitor (MCPI) from N.versicolor that binds to the catalytic zinc ion.1 Publication

Kineticsi

  1. KM=55.6 µM for 3-(2-furyl)acryloyl-Phe-Phe1 Publication
  2. KM=19.4 µM for 3-(2-furyl)acryloyl-Phe-Leu1 Publication
  3. KM=23.3 µM for 3-(2-furyl)acryloyl-Phe-Ile1 Publication
  4. KM=40.4 µM for 3-(2-furyl)acryloyl-Phe-Met1 Publication
  5. KM=57.3 µM for 3-(2-furyl)acryloyl-Phe-Val1 Publication
  6. KM=0.329 µM for neurotensin1 Publication
  7. KM=9.23 µM for Met-enkephalin-Arg-Phe1 Publication

    pH dependencei

    Optimum pH is 8.5-9.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi181Zinc; catalytic1 Publication1
    Metal bindingi184Zinc; catalytic1 Publication1
    Binding sitei239SubstrateBy similarity1
    Metal bindingi308Zinc; catalytic1 Publication1
    Binding sitei360SubstrateBy similarity1
    Active sitei382Proton donor/acceptorBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    • histone acetylation Source: UniProtKB

    Keywordsi

    Molecular functionCarboxypeptidase, Hydrolase, Metalloprotease, Protease
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi3.4.17.1 2681

    Protein family/group databases

    MEROPSiM14.017

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carboxypeptidase A4 (EC:3.4.17.-)
    Alternative name(s):
    Carboxypeptidase A3
    Gene namesi
    Name:CPA4
    Synonyms:CPA3
    ORF Names:UNQ694/PRO1339
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 7

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000128510.10
    HGNCiHGNC:15740 CPA4
    MIMi607635 gene
    neXtProtiNX_Q9UI42

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi51200
    OpenTargetsiENSG00000128510
    PharmGKBiPA26819

    Polymorphism and mutation databases

    BioMutaiCPA4
    DMDMi61252703

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 16Sequence analysisAdd BLAST16
    PropeptideiPRO_000000435717 – 113Activation peptideSequence analysisAdd BLAST97
    ChainiPRO_0000004358114 – 421Carboxypeptidase A4Add BLAST308

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi250 ↔ 2733 Publications
    Glycosylationi260N-linked (GlcNAc...) asparagine2 Publications1

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    EPDiQ9UI42
    PaxDbiQ9UI42
    PeptideAtlasiQ9UI42
    PRIDEiQ9UI42

    PTM databases

    iPTMnetiQ9UI42
    PhosphoSitePlusiQ9UI42
    SwissPalmiQ9UI42

    Expressioni

    Tissue specificityi

    Fetal expression in the adrenal gland, brain, heart, intestine, kidney, liver and lung. Except for fetal brain that shows no imprinting, expression was found preferentially from the maternal allele.

    Inductioni

    Up-regulated by inhibitors of histone dacetylation.1 Publication

    Gene expression databases

    BgeeiENSG00000128510
    CleanExiHS_CPA3
    HS_CPA4
    ExpressionAtlasiQ9UI42 baseline and differential

    Organism-specific databases

    HPAiHPA021030

    Interactioni

    Subunit structurei

    Monomer. Interacts with LXN.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    P848753EBI-16060275,EBI-16060264From Sabellastarte magnifica.

    Protein-protein interaction databases

    BioGridi119373, 38 interactors
    DIPiDIP-60558N
    IntActiQ9UI42, 1 interactor
    STRINGi9606.ENSP00000222482

    Structurei

    Secondary structure

    1421
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi25 – 29Combined sources5
    Helixi34 – 43Combined sources10
    Turni44 – 47Combined sources4
    Helixi48 – 50Combined sources3
    Beta strandi52 – 55Combined sources4
    Beta strandi59 – 62Combined sources4
    Beta strandi64 – 68Combined sources5
    Helixi70 – 72Combined sources3
    Helixi73 – 82Combined sources10
    Beta strandi87 – 92Combined sources6
    Helixi94 – 115Combined sources22
    Beta strandi120 – 122Combined sources3
    Helixi126 – 139Combined sources14
    Turni141 – 143Combined sources3
    Beta strandi144 – 151Combined sources8
    Beta strandi157 – 163Combined sources7
    Beta strandi173 – 178Combined sources6
    Helixi185 – 201Combined sources17
    Turni202 – 204Combined sources3
    Helixi206 – 214Combined sources9
    Beta strandi216 – 221Combined sources6
    Helixi225 – 233Combined sources9
    Beta strandi249 – 251Combined sources3
    Helixi255 – 257Combined sources3
    Beta strandi259 – 262Combined sources4
    Beta strandi265 – 270Combined sources6
    Helixi286 – 298Combined sources13
    Beta strandi301 – 308Combined sources8
    Beta strandi310 – 317Combined sources8
    Helixi328 – 343Combined sources16
    Turni344 – 346Combined sources3
    Beta strandi351 – 354Combined sources4
    Helixi355 – 358Combined sources4
    Helixi366 – 372Combined sources7
    Beta strandi377 – 382Combined sources6
    Beta strandi386 – 389Combined sources4
    Helixi390 – 392Combined sources3
    Helixi395 – 397Combined sources3
    Helixi398 – 417Combined sources20

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2BO9X-ray1.60A/C114-421[»]
    2BOAX-ray2.20A/B19-421[»]
    2PCUX-ray1.60A116-420[»]
    4A94X-ray1.70A/B112-421[»]
    4BD9X-ray2.20A112-421[»]
    ProteinModelPortaliQ9UI42
    SMRiQ9UI42
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UI42

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni181 – 184Substrate binding4
    Regioni256 – 257Substrate bindingBy similarity2
    Regioni275 – 276Substrate binding2
    Regioni309 – 310Substrate bindingBy similarity2

    Sequence similaritiesi

    Belongs to the peptidase M14 family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG2650 Eukaryota
    COG2866 LUCA
    GeneTreeiENSGT00760000119103
    HOGENOMiHOG000252967
    HOVERGENiHBG050815
    InParanoidiQ9UI42
    KOiK08637
    OMAiIQKHGNF
    OrthoDBiEOG091G0HUI
    PhylomeDBiQ9UI42
    TreeFamiTF317197

    Family and domain databases

    CDDicd03870 M14_CPA, 1 hit
    Gene3Di3.30.70.340, 1 hit
    InterProiView protein in InterPro
    IPR034248 CPA_M14_CPD
    IPR036990 M14A-like_propep
    IPR003146 M14A_act_pep
    IPR000834 Peptidase_M14
    PfamiView protein in Pfam
    PF00246 Peptidase_M14, 1 hit
    PF02244 Propep_M14, 1 hit
    PRINTSiPR00765 CRBOXYPTASEA
    SMARTiView protein in SMART
    SM00631 Zn_pept, 1 hit
    PROSITEiView protein in PROSITE
    PS00132 CARBOXYPEPT_ZN_1, 1 hit
    PS00133 CARBOXYPEPT_ZN_2, 1 hit

    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. AlignAdd to basket

    Isoform 1 (identifier: Q9UI42-1) [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
    MRWILFIGAL IGSSICGQEK FFGDQVLRIN VRNGDEISKL SQLVNSNNLK
    60 70 80 90 100
    LNFWKSPSSF NRPVDVLVPS VSLQAFKSFL RSQGLEYAVT IEDLQALLDN
    110 120 130 140 150
    EDDEMQHNEG QERSSNNFNY GAYHSLEAIY HEMDNIAADF PDLARRVKIG
    160 170 180 190 200
    HSFENRPMYV LKFSTGKGVR RPAVWLNAGI HSREWISQAT AIWTARKIVS
    210 220 230 240 250
    DYQRDPAITS ILEKMDIFLL PVANPDGYVY TQTQNRLWRK TRSRNPGSSC
    260 270 280 290 300
    IGADPNRNWN ASFAGKGASD NPCSEVYHGP HANSEVEVKS VVDFIQKHGN
    310 320 330 340 350
    FKGFIDLHSY SQLLMYPYGY SVKKAPDAEE LDKVARLAAK ALASVSGTEY
    360 370 380 390 400
    QVGPTCTTVY PASGSSIDWA YDNGIKFAFT FELRDTGTYG FLLPANQIIP
    410 420
    TAEETWLGLK TIMEHVRDNL Y
    Length:421
    Mass (Da):47,351
    Last modified:March 15, 2005 - v2
    Checksum:i52750CC50B470EC9
    GO
    Isoform 2 (identifier: Q9UI42-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         96-128: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:388
    Mass (Da):43,570
    Checksum:i088297ACC9D70264
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti18Q → R in AAF23230 (PubMed:10383164).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04859427L → F. Corresponds to variant dbSNP:rs34587586Ensembl.1
    Natural variantiVAR_020393157P → T. Corresponds to variant dbSNP:rs3735051Ensembl.1
    Natural variantiVAR_048595183R → L. Corresponds to variant dbSNP:rs3735053Ensembl.1
    Natural variantiVAR_020394303G → C. Corresponds to variant dbSNP:rs2171492Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_04289496 – 128Missing in isoform 2. 1 PublicationAdd BLAST33

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF095719 mRNA Translation: AAF23230.1
    AY358699 mRNA Translation: AAQ89062.1
    AK298550 mRNA Translation: BAH12812.1
    AC024085 Genomic DNA No translation available.
    BC052289 mRNA Translation: AAH52289.1
    CCDSiCCDS55163.1 [Q9UI42-2]
    CCDS5818.1 [Q9UI42-1]
    RefSeqiNP_001156918.1, NM_001163446.1 [Q9UI42-2]
    NP_057436.2, NM_016352.3 [Q9UI42-1]
    UniGeneiHs.93764

    Genome annotation databases

    EnsembliENST00000222482; ENSP00000222482; ENSG00000128510 [Q9UI42-1]
    ENST00000445470; ENSP00000412947; ENSG00000128510 [Q9UI42-2]
    GeneIDi51200
    KEGGihsa:51200
    UCSCiuc003vpr.4 human [Q9UI42-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiCBPA4_HUMAN
    AccessioniPrimary (citable) accession number: Q9UI42
    Secondary accession number(s): B7Z576, Q86UY9
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 13, 2001
    Last sequence update: March 15, 2005
    Last modified: March 28, 2018
    This is version 155 of the entry and version 2 of the sequence. See 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

    3D-structure, Complete proteome, Reference proteome
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    Main funding by: National Institutes of Health