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Q8N4T0

- CBPA6_HUMAN

UniProt

Q8N4T0 - CBPA6_HUMAN

Protein

Carboxypeptidase A6

Gene

CPA6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 2 (24 Jan 2006)
      Previous versions | rss
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    Functioni

    May be involved in the proteolytic inactivation of enkephalins and neurotensin in some brain areas. May convert inactive angiotensin I into the biologically active angiotensin II.1 Publication

    Catalytic activityi

    Release of a C-terminal amino acid, with preference for large hydrophobic C-terminal amino acids and only very weak activity toward small amino acids and histidine.1 Publication

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Kineticsi

    1. KM=266 µM for 3-(2-furyl)acryloyl-Phe-Phe1 Publication
    2. KM=100 µM for 3-(2-furyl)acryloyl-Phe-Tyr1 Publication
    3. KM=386 µM for 3-(2-furyl)acryloyl-Phe-Leu1 Publication
    4. KM=339 µM for 3-(2-furyl)acryloyl-Phe-Trp1 Publication
    5. KM=786 µM for 3-(2-furyl)acryloyl-Phe-Met1 Publication

    pH dependencei

    Optimum pH is 8.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi196 – 1961Zinc; catalyticBy similarity
    Metal bindingi199 – 1991Zinc; catalyticBy similarity
    Binding sitei254 – 2541SubstrateBy similarity
    Metal bindingi324 – 3241Zinc; catalyticBy similarity
    Active sitei398 – 3981NucleophileBy similarity

    GO - Molecular functioni

    1. metallocarboxypeptidase activity Source: UniProtKB
    2. zinc ion binding Source: InterPro

    Keywords - Molecular functioni

    Carboxypeptidase, Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Protein family/group databases

    MEROPSiM14.018.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carboxypeptidase A6 (EC:3.4.17.-)
    Gene namesi
    Name:CPA6
    Synonyms:CPAH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:17245. CPA6.

    Subcellular locationi

    Secretedextracellular spaceextracellular matrix 1 Publication

    GO - Cellular componenti

    1. proteinaceous extracellular matrix Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    A chromosomal aberration involving CPA6 was found in a patient with Duane retraction syndrome. Translocation t(6;8)(q26;q13).
    Epilepsy, familial temporal lobe, 5 (ETL5) [MIM:614417]: A focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti267 – 2671G → R in ETL5; affects protein secretion presumably by altering protein folding or stability. 1 Publication
    VAR_066946
    Febrile seizures, familial, 11 (FEB11) [MIM:614418]: Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti270 – 2701A → V in FEB11; affects protein secretion presumably by altering protein folding or stability. 1 Publication
    Corresponds to variant rs114402678 [ dbSNP | Ensembl ].
    VAR_066947

    Keywords - Diseasei

    Disease mutation, Epilepsy

    Organism-specific databases

    MIMi614417. phenotype.
    614418. phenotype.
    Orphaneti165805. Familial mesial temporal lobe epilepsy with febrile seizures.
    PharmGKBiPA38444.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3030Sequence AnalysisAdd
    BLAST
    Propeptidei31 – 12999Activation peptideBy similarityPRO_0000004365Add
    BLAST
    Chaini130 – 437308Carboxypeptidase A6PRO_0000004366Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi89 – 891N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi153 – 1531N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi265 ↔ 288By similarity
    Glycosylationi427 – 4271N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PaxDbiQ8N4T0.
    PRIDEiQ8N4T0.

    PTM databases

    PhosphoSiteiQ8N4T0.

    Expressioni

    Tissue specificityi

    Expressed in the hippocampus, nucleus raphe, and cortex.1 Publication

    Gene expression databases

    ArrayExpressiQ8N4T0.
    BgeeiQ8N4T0.
    CleanExiHS_CPA6.
    GenevestigatoriQ8N4T0.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000297770.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8N4T0.
    SMRiQ8N4T0. Positions 37-433.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni196 – 1994Substrate bindingBy similarity
    Regioni271 – 2722Substrate bindingBy similarity
    Regioni325 – 3262Substrate bindingBy similarity

    Sequence similaritiesi

    Belongs to the peptidase M14 family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiCOG2866.
    HOGENOMiHOG000252968.
    HOVERGENiHBG050815.
    InParanoidiQ8N4T0.
    KOiK08782.
    OMAiRKHIRAY.
    PhylomeDBiQ8N4T0.
    TreeFamiTF317197.

    Family and domain databases

    Gene3Di3.30.70.340. 1 hit.
    InterProiIPR000834. Peptidase_M14.
    IPR003146. Prot_inh_M14A.
    IPR009020. Prot_inh_propept.
    [Graphical view]
    PfamiPF00246. Peptidase_M14. 1 hit.
    PF02244. Propep_M14. 1 hit.
    [Graphical view]
    PRINTSiPR00765. CRBOXYPTASEA.
    SMARTiSM00631. Zn_pept. 1 hit.
    [Graphical view]
    SUPFAMiSSF54897. SSF54897. 1 hit.
    PROSITEiPS00133. CARBOXYPEPT_ZN_2. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8N4T0-1) [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

    MKCLGKRRGQ AAAFLPLCWL FLKILQPGHS HLYNNRYAGD KVIRFIPKTE    50
    EEAYALKKIS YQLKVDLWQP SSISYVSEGT VTDVHIPQNG SRALLAFLQE 100
    ANIQYKVLIE DLQKTLEKGS SLHTQRNRRS LSGYNYEVYH SLEEIQNWMH 150
    HLNKTHSGLI HMFSIGRSYE GRSLFILKLG RRSRLKRAVW IDCGIHAREW 200
    IGPAFCQWFV KEALLTYKSD PAMRKMLNHL YFYIMPVFNV DGYHFSWTND 250
    RFWRKTRSRN SRFRCRGVDA NRNWKVKWCD EGASMHPCDD TYCGPFPESE 300
    PEVKAVANFL RKHRKHIRAY LSFHAYAQML LYPYSYKYAT IPNFRCVESA 350
    AYKAVNALQS VYGVRYRYGP ASTTLYVSSG SSMDWAYKNG IPYAFAFELR 400
    DTGYFGFLLP EMLIKPTCTE TMLAVKNITM HLLKKCP 437
    Length:437
    Mass (Da):51,008
    Last modified:January 24, 2006 - v2
    Checksum:i9C21780D4B7D0A98
    GO
    Isoform 2 (identifier: Q8N4T0-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         280-437: DEGASMHPCD...ITMHLLKKCP → GKFGTNWDPD...SHGRLMFFCM

    Note: No experimental confirmation available.

    Show »
    Length:315
    Mass (Da):37,070
    Checksum:iECAA4B2F7F822684
    GO
    Isoform 3 (identifier: Q8N4T0-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-148: Missing.
         281-376: Missing.

    Show »
    Length:193
    Mass (Da):22,889
    Checksum:i3E8C11586C557024
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti45 – 451F → L.
    Corresponds to variant rs10957393 [ dbSNP | Ensembl ].
    VAR_024241
    Natural varianti173 – 1731S → C.2 Publications
    Corresponds to variant rs17853192 [ dbSNP | Ensembl ].
    VAR_025003
    Natural varianti249 – 2491N → S.
    Corresponds to variant rs17343819 [ dbSNP | Ensembl ].
    VAR_048597
    Natural varianti267 – 2671G → R in ETL5; affects protein secretion presumably by altering protein folding or stability. 1 Publication
    VAR_066946
    Natural varianti270 – 2701A → V in FEB11; affects protein secretion presumably by altering protein folding or stability. 1 Publication
    Corresponds to variant rs114402678 [ dbSNP | Ensembl ].
    VAR_066947

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 148148Missing in isoform 3. 1 PublicationVSP_017079Add
    BLAST
    Alternative sequencei280 – 437158DEGAS…LKKCP → GKFGTNWDPDPKVSAGFTLQ NMSPEDSHGRLMFFCM in isoform 2. 1 PublicationVSP_008808Add
    BLAST
    Alternative sequencei281 – 37696Missing in isoform 3. 1 PublicationVSP_017080Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF466284 Genomic DNA. Translation: AAM19307.1.
    BK000188 mRNA. Translation: DAA00037.1.
    AY044833 mRNA. Translation: AAK84941.1.
    AF221594 mRNA. Translation: AAF91231.1.
    BC033684 mRNA. Translation: AAH33684.1.
    CCDSiCCDS6200.1. [Q8N4T0-1]
    RefSeqiNP_065094.3. NM_020361.4. [Q8N4T0-1]
    UniGeneiHs.658850.

    Genome annotation databases

    EnsembliENST00000297770; ENSP00000297770; ENSG00000165078. [Q8N4T0-1]
    ENST00000518549; ENSP00000431112; ENSG00000165078. [Q8N4T0-2]
    GeneIDi57094.
    KEGGihsa:57094.
    UCSCiuc003xxq.4. human. [Q8N4T0-1]
    uc003xxr.4. human. [Q8N4T0-3]
    uc003xxs.2. human. [Q8N4T0-2]

    Polymorphism databases

    DMDMi85683250.

    Keywords - Coding sequence diversityi

    Alternative splicing, Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF466284 Genomic DNA. Translation: AAM19307.1 .
    BK000188 mRNA. Translation: DAA00037.1 .
    AY044833 mRNA. Translation: AAK84941.1 .
    AF221594 mRNA. Translation: AAF91231.1 .
    BC033684 mRNA. Translation: AAH33684.1 .
    CCDSi CCDS6200.1. [Q8N4T0-1 ]
    RefSeqi NP_065094.3. NM_020361.4. [Q8N4T0-1 ]
    UniGenei Hs.658850.

    3D structure databases

    ProteinModelPortali Q8N4T0.
    SMRi Q8N4T0. Positions 37-433.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000297770.

    Chemistry

    BindingDBi Q8N4T0.

    Protein family/group databases

    MEROPSi M14.018.

    PTM databases

    PhosphoSitei Q8N4T0.

    Polymorphism databases

    DMDMi 85683250.

    Proteomic databases

    PaxDbi Q8N4T0.
    PRIDEi Q8N4T0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000297770 ; ENSP00000297770 ; ENSG00000165078 . [Q8N4T0-1 ]
    ENST00000518549 ; ENSP00000431112 ; ENSG00000165078 . [Q8N4T0-2 ]
    GeneIDi 57094.
    KEGGi hsa:57094.
    UCSCi uc003xxq.4. human. [Q8N4T0-1 ]
    uc003xxr.4. human. [Q8N4T0-3 ]
    uc003xxs.2. human. [Q8N4T0-2 ]

    Organism-specific databases

    CTDi 57094.
    GeneCardsi GC08M068384.
    H-InvDB HIX0007565.
    HGNCi HGNC:17245. CPA6.
    MIMi 609562. gene.
    614417. phenotype.
    614418. phenotype.
    neXtProti NX_Q8N4T0.
    Orphaneti 165805. Familial mesial temporal lobe epilepsy with febrile seizures.
    PharmGKBi PA38444.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2866.
    HOGENOMi HOG000252968.
    HOVERGENi HBG050815.
    InParanoidi Q8N4T0.
    KOi K08782.
    OMAi RKHIRAY.
    PhylomeDBi Q8N4T0.
    TreeFami TF317197.

    Miscellaneous databases

    GeneWikii Carboxypeptidase_A6.
    GenomeRNAii 57094.
    NextBioi 62909.
    PROi Q8N4T0.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8N4T0.
    Bgeei Q8N4T0.
    CleanExi HS_CPA6.
    Genevestigatori Q8N4T0.

    Family and domain databases

    Gene3Di 3.30.70.340. 1 hit.
    InterProi IPR000834. Peptidase_M14.
    IPR003146. Prot_inh_M14A.
    IPR009020. Prot_inh_propept.
    [Graphical view ]
    Pfami PF00246. Peptidase_M14. 1 hit.
    PF02244. Propep_M14. 1 hit.
    [Graphical view ]
    PRINTSi PR00765. CRBOXYPTASEA.
    SMARTi SM00631. Zn_pept. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54897. SSF54897. 1 hit.
    PROSITEi PS00133. CARBOXYPEPT_ZN_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification and characterization of three members of the human metallocarboxypeptidase gene family."
      Wei S., Segura S., Vendrell J., Aviles F.X., Lanoue E., Day R., Feng Y., Fricker L.D.
      J. Biol. Chem. 277:14954-14964(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
    2. "A peptidase gene in chromosome 8q is disrupted by a balanced translocation in a duane syndrome patient."
      Pizzuti A., Calabrese G., Bozzali M., Telvi L., Morizio E., Guida V., Gatta V., Stuppia L., Ion A., Palka G., Dallapiccola B.
      Invest. Ophthalmol. Vis. Sci. 43:3609-3612(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), CHROMOSOMAL TRANSLOCATION.
      Tissue: Retina.
    3. "Novel genes expressed in hematopoietic stem/progenitor cells from myelodysplastic syndrome patients."
      Gu J., Huang Q., Yu Y., Xu S., Han Z., Fu G., Chen Z.
      Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT CYS-173.
      Tissue: Hematopoietic stem cell.
    4. "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), VARIANT CYS-173.
      Tissue: Brain.
    5. "Characterization of carboxypeptidase A6, an extracellular matrix peptidase."
      Lyons P.J., Callaway M.B., Fricker L.D.
      J. Biol. Chem. 283:7054-7063(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, SUBSTRATE SPECIFICITY.
    6. "Substrate specificity of human carboxypeptidase A6."
      Lyons P.J., Fricker L.D.
      J. Biol. Chem. 285:38234-38242(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
    7. "Carboxypeptidase A6 gene (CPA6) mutations in a recessive familial form of febrile seizures and temporal lobe epilepsy and in sporadic temporal lobe epilepsy."
      Salzmann A., Guipponi M., Lyons P.J., Fricker L.D., Sapio M., Lambercy C., Buresi C., Bencheikh B.O., Lahjouji F., Ouazzani R., Crespel A., Chaigne D., Malafosse A.
      Hum. Mutat. 33:124-135(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, VARIANT ETL5 ARG-267, VARIANT FEB11 VAL-270, CHARACTERIZATION OF VARIANT ETL5 ARG-267, CHARACTERIZATION OF VARIANT FEB11 VAL-270.

    Entry informationi

    Entry nameiCBPA6_HUMAN
    AccessioniPrimary (citable) accession number: Q8N4T0
    Secondary accession number(s): Q8NEX8, Q8TDE8, Q9NRI9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 7, 2003
    Last sequence update: January 24, 2006
    Last modified: October 1, 2014
    This is version 120 of the entry and version 2 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 8
      Human chromosome 8: 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