Q8N4T0 (CBPA6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carboxypeptidase A6
EC=3.4.17.1

Alternative name(s):
Carboxypeptidase B

Gene names

Name:	CPA6
Synonyms:	CPAH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	437 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.5
Catalytic activity	Release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix Ref.5.
Tissue specificity	Expressed in the hippocampus, nucleus raphe, and cortex. Ref.6
Involvement in disease	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. Ref.6 Familial febrile convulsions 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. Ref.6
Sequence similarities	Belongs to the peptidase M14 family.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation Epilepsy
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metallocarboxypeptidase activity Non-traceable author statement Ref.1. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N4T0-1)

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.

Isoform 2 (identifier: Q8N4T0-2)

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

Note: No experimental confirmation available.

Isoform 3 (identifier: Q8N4T0-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30	Potential
	Propeptide	31 – 129	99	Activation peptide By similarity		PRO_0000004365
	Chain	130 – 437	308	Carboxypeptidase A6		PRO_0000004366
Regions
	Region	196 – 199	4	Substrate binding By similarity
	Region	271 – 272	2	Substrate binding By similarity
	Region	325 – 326	2	Substrate binding By similarity
Sites
	Active site	398	1	Nucleophile By similarity
	Metal binding	196	1	Zinc; catalytic By similarity
	Metal binding	199	1	Zinc; catalytic By similarity
	Metal binding	324	1	Zinc; catalytic By similarity
	Binding site	254	1	Substrate By similarity
Amino acid modifications
	Glycosylation	89	1	N-linked (GlcNAc...) Potential
	Glycosylation	153	1	N-linked (GlcNAc...) Potential
	Glycosylation	427	1	N-linked (GlcNAc...) Potential
	Disulfide bond	265 ↔ 288		By similarity
Natural variations
	Alternative sequence	1 – 148	148	Missing in isoform 3.		VSP_017079
	Alternative sequence	280 – 437	158	DEGAS…LKKCP → GKFGTNWDPDPKVSAGFTLQ NMSPEDSHGRLMFFCM in isoform 2.		VSP_008808
	Alternative sequence	281 – 376	96	Missing in isoform 3.		VSP_017080
	Natural variant	45	1	F → L. Corresponds to variant rs10957393 [ dbSNP | Ensembl ].		VAR_024241
	Natural variant	173	1	S → C. Ref.3 Ref.4 Corresponds to variant rs17853192 [ dbSNP | Ensembl ].		VAR_025003
	Natural variant	249	1	N → S. Corresponds to variant rs17343819 [ dbSNP | Ensembl ].		VAR_048597
	Natural variant	267	1	G → R in ETL5; affects protein secretion presumably by altering protein folding or stability. Ref.6		VAR_066946
	Natural variant	270	1	A → V in FEB11; affects protein secretion presumably by altering protein folding or stability. Ref.6		VAR_066947

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 24, 2006. Version 2. Checksum: 9C21780D4B7D0A98	FASTA	437	51,008
	10 20 30 40 50 60 MKCLGKRRGQ AAAFLPLCWL FLKILQPGHS HLYNNRYAGD KVIRFIPKTE EEAYALKKIS 70 80 90 100 110 120 YQLKVDLWQP SSISYVSEGT VTDVHIPQNG SRALLAFLQE ANIQYKVLIE DLQKTLEKGS 130 140 150 160 170 180 SLHTQRNRRS LSGYNYEVYH SLEEIQNWMH HLNKTHSGLI HMFSIGRSYE GRSLFILKLG 190 200 210 220 230 240 RRSRLKRAVW IDCGIHAREW IGPAFCQWFV KEALLTYKSD PAMRKMLNHL YFYIMPVFNV 250 260 270 280 290 300 DGYHFSWTND RFWRKTRSRN SRFRCRGVDA NRNWKVKWCD EGASMHPCDD TYCGPFPESE 310 320 330 340 350 360 PEVKAVANFL RKHRKHIRAY LSFHAYAQML LYPYSYKYAT IPNFRCVESA AYKAVNALQS 370 380 390 400 410 420 VYGVRYRYGP ASTTLYVSSG SSMDWAYKNG IPYAFAFELR DTGYFGFLLP EMLIKPTCTE 430 TMLAVKNITM HLLKKCP
	Isoform 2 [UniParc]. Checksum: ECAA4B2F7F822684	FASTA	315	37,070
	10 20 30 40 50 60 MKCLGKRRGQ AAAFLPLCWL FLKILQPGHS HLYNNRYAGD KVIRFIPKTE EEAYALKKIS 70 80 90 100 110 120 YQLKVDLWQP SSISYVSEGT VTDVHIPQNG SRALLAFLQE ANIQYKVLIE DLQKTLEKGS 130 140 150 160 170 180 SLHTQRNRRS LSGYNYEVYH SLEEIQNWMH HLNKTHSGLI HMFSIGRSYE GRSLFILKLG 190 200 210 220 230 240 RRSRLKRAVW IDCGIHAREW IGPAFCQWFV KEALLTYKSD PAMRKMLNHL YFYIMPVFNV 250 260 270 280 290 300 DGYHFSWTND RFWRKTRSRN SRFRCRGVDA NRNWKVKWCG KFGTNWDPDP KVSAGFTLQN 310 MSPEDSHGRL MFFCM
	Isoform 3 [UniParc]. Checksum: 3E8C11586C557024	FASTA	193	22,889
	10 20 30 40 50 60 MHHLNKTHSG LIHMFSIGRS YEGRSLFILK LGRRSRLKRA VWIDCGIHAR EWIGPAFCQW 70 80 90 100 110 120 FVKEALLTYK SDPAMRKMLN HLYFYIMPVF NVDGYHFSWT NDRFWRKTRS RNSRFRCRGV 130 140 150 160 170 180 DANRNWKVKW CDVSSGSSMD WAYKNGIPYA FAFELRDTGY FGFLLPEMLI KPTCTETMLA 190 VKNITMHLLK KCP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00166764. IPI00168794. IPI00386667.
RefSeq	NP_065094.3. NM_020361.4.
UniGene	Hs.658850.
3D structure databases
ProteinModelPortal	Q8N4T0.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000297770.
Protein family/group databases
MEROPS	M14.018.
PTM databases
PhosphoSite	Q8N4T0.
Polymorphism databases
DMDM	85683250.
Proteomic databases
PaxDb	Q8N4T0.
PRIDE	Q8N4T0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000297769; ENSP00000297769; ENSG00000165078. ENST00000297770; ENSP00000297770; ENSG00000165078. ENST00000518549; ENSP00000431112; ENSG00000165078.
GeneID	57094.
KEGG	hsa:57094.
UCSC	uc003xxq.4. human. uc003xxr.4. human. uc003xxs.2. human.
Organism-specific databases
CTD	57094.
GeneCards	GC08M068384.
H-InvDB	HIX0007565.
HGNC	HGNC:17245. CPA6.
MIM	609562. gene. 614417. phenotype. 614418. phenotype.
neXtProt	NX_Q8N4T0.
Orphanet	233. Duane syndrome. 165805. Familial mesial temporal lobe epilepsy with febrile seizures.
PharmGKB	PA38444.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2866.
HOGENOM	HOG000252968.
HOVERGEN	HBG050815.
InParanoid	Q8N4T0.
KO	K08782.
OMA	RKHIRAY.
OrthoDB	EOG4GB761.
Gene expression databases
ArrayExpress	Q8N4T0.
Bgee	Q8N4T0.
CleanEx	HS_CPA6.
Genevestigator	Q8N4T0.
GermOnline	ENSG00000165078. Homo sapiens.
Family and domain databases
Gene3D	3.30.70.340. 1 hit.
InterPro	IPR000834. Peptidase_M14. IPR003146. Prot_inh_M14A. IPR009020. Prot_inh_propept. [Graphical view]
Pfam	PF00246. Peptidase_M14. 1 hit. PF02244. Propep_M14. 1 hit. [Graphical view]
PRINTS	PR00765. CRBOXYPTASEA.
SMART	SM00631. Zn_pept. 1 hit. [Graphical view]
SUPFAM	SSF54897. Prot_inh_propept. 1 hit.
PROSITE	PS00132. CARBOXYPEPT_ZN_1. False negative. PS00133. CARBOXYPEPT_ZN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8N4T0.
ChEMBL	CHEMBL4496.
GenomeRNAi	57094.
NextBio	62909.
SOURCE	Search...

Entry information

Entry name

CBPA6_HUMAN

Accession

Primary (citable) accession number: Q8N4T0
Secondary accession number(s): Q8NEX8, Q8TDE8, Q9NRI9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 7, 2003
Last sequence update:	January 24, 2006
Last modified:	May 1, 2013
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.