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Q8N4T0

- CBPA6_HUMAN

UniProt

Q8N4T0 - CBPA6_HUMAN

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Protein

Carboxypeptidase A6

Gene
CPA6, CPAH
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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-Tyr
  3. KM=386 µM for 3-(2-furyl)acryloyl-Phe-Leu
  4. KM=339 µM for 3-(2-furyl)acryloyl-Phe-Trp
  5. KM=786 µM for 3-(2-furyl)acryloyl-Phe-Met

pH dependencei

Optimum pH is 8.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi196 – 1961Zinc; catalytic By similarity
Metal bindingi199 – 1991Zinc; catalytic By similarity
Binding sitei254 – 2541Substrate By similarity
Metal bindingi324 – 3241Zinc; catalytic By similarity
Active sitei398 – 3981Nucleophile By similarity

GO - Molecular functioni

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

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
Complete GO annotation...

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.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
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 – 3030 Reviewed predictionAdd
BLAST
Propeptidei31 – 12999Activation peptide By similarityPRO_0000004365Add
BLAST
Chaini130 – 437308Carboxypeptidase A6PRO_0000004366Add
BLAST

Amino acid modifications

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

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.

Family & Domainsi

Region

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

Sequence similaritiesi

Belongs to the peptidase M14 family.

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. VSP_017079Add
BLAST
Alternative sequencei280 – 437158DEGAS…LKKCP → GKFGTNWDPDPKVSAGFTLQ NMSPEDSHGRLMFFCM in isoform 2. VSP_008808Add
BLAST
Alternative sequencei281 – 37696Missing in isoform 3. VSP_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

EnsembliENST00000297769; ENSP00000297769; ENSG00000165078. [Q8N4T0-3]
ENST00000297770; 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 ENST00000297769 ; ENSP00000297769 ; ENSG00000165078 . [Q8N4T0-3 ]
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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 119 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

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