Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
4  structures 5  species 0  interactions 15  sequences 1  architecture

Family: CarbpepA_inh (PF02977)

Summary: Carboxypeptidase A inhibitor

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Carboxypeptidase A inhibitor". More...

Carboxypeptidase A inhibitor Edit Wikipedia article

Carboxypeptidase A inhibitor
PDB 4cpa EBI.jpg
refined crystal structure of the potato inhibitor complex of carboxypeptidase a at 2.5 angstroms resolution
Identifiers
Symbol CarbpepA_inh
Pfam PF02977
Pfam clan CL0096
InterPro IPR004231
SCOP 4cpa
SUPERFAMILY 4cpa

In molecular biology, the carboxypeptidase A inhibitor family is a family of proteins which is represented by the well-characterised metallocarboxypeptidase A inhibitor (MCPI) from potatoes, which belongs to the MEROPS inhibitor family I37, clan IE. It inhibits metallopeptidases belonging to MEROPS peptidase family M14, carboxypeptidase A. In Russet Burbank potatoes, it is a mixture of approximately equal amounts of two polypeptide chains containing 38 or 39 amino acid residues. The chains differ in their amino terminal sequence only [1] and are resistant to fragmentation by proteases.[2] The structure of the complex between bovine carboxypeptidase A and the 39-amino-acid carboxypeptidase A inhibitor from potatoes has been determined at 2.5-Angstrom resolution.[3]

The potato inhibitor is synthesised as a precursor, having a 29 amino acid N-terminal signal peptide, a 27 amino acid pro-peptide, the 39 amino acid mature inhibitor region and a 7 amino acid C-terminal extension. The 7 amino acid C-terminal extension is involved in inhibitor inactivation and may be required for targeting to the vacuole where the mature active inhibitor accumulates.[4]

The N-terminal region and the mature inhibitor are weakly related to other solananaceous proteins found in this family, from potato, tomato and henbane, which have been incorrectly described as metallocarboxypeptidase inhibitors.[5]

References[edit]

  1. ^ Hass GM, Nau H, Biemann K, Grahn DT, Ericsson LH, Neurath H (March 1975). "The amino acid sequence of a carboxypeptidase inhibitor from potatoes". Biochemistry 14 (6): 1334–42. doi:10.1021/bi00677a036. PMID 1122280. 
  2. ^ Leary TR, Grahn DT, Neurath H, Hass GM (May 1979). "Structure of potato carboxypeptidase inhibitor: disulfide pairing and exposure of aromatic residues". Biochemistry 18 (11): 2252–6. doi:10.1021/bi00578a018. PMID 444453. 
  3. ^ Rees DC, Lipscomb WN (August 1980). "Structure of the potato inhibitor complex of carboxypeptidase A at 2.5-A resolution". Proc. Natl. Acad. Sci. U.S.A. 77 (8): 4633–7. doi:10.1073/pnas.77.8.4633. PMC 349899. PMID 6933511. 
  4. ^ Villanueva J, Canals F, Prat S, Ludevid D, Querol E, Aviles FX (November 1998). "Characterization of the wound-induced metallocarboxypeptidase inhibitor from potato. cDNA sequence, induction of gene expression, subcellular immunolocalization and potential roles of the C-terminal propeptide". FEBS Lett. 440 (1-2): 175–82. doi:10.1016/S0014-5793(98)01447-1. PMID 9862450. 
  5. ^ Molnar A, Lovas A, Banfalvi Z, Lakatos L, Polgar Z, Horvath S (June 2001). "Tissue-specific signal(s) activate the promoter of a metallocarboxypeptidase inhibitor gene family in potato tuber and berry". Plant Mol. Biol. 46 (3): 301–11. PMID 11488477. 

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR004231

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Carboxypeptidase A inhibitor Provide feedback

No Pfam abstract.

Literature references

  1. Rees DC, Lipscomb WN; , J Mol Biol 1982;160:475-498.: Refined crystal structure of the potato inhibitor complex of carboxypeptidase A at 2.5 A resolution. PUBMED:7154070 EPMC:7154070


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004231

Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties.

This family is represented by the well-characterised metallocarboxypeptidase A inhibitor (MCPI) from potatoes, which belongs to the MEROPS inhibitor family I37, clan IE. It inhibits metallopeptidases belonging to MEROPS peptidase family M14, carboxypeptidase A. In Russet Burbank potatoes, it is a mixture of approximately equal amounts of two polypeptide chains containing 38 or 39 amino acid residues. The chains differ in their amino terminal sequence only [PUBMED:1122280] and are resistant to fragmentation by proteases [PUBMED:444453]. The structure of the complex between bovine carboxypeptidase A and the 39-amino-acid carboxypeptidase A inhibitor from potatoes has been determined at 2.5-A resolution [PUBMED:6933511].

The potato inhibitor is synthesised as a precursor, having a 29 residue N-terminal signal peptide, a 27 residue pro-peptide, the 39 residue mature inhibitor region and a 7 residue C-terminal extension. The 7 residue C-terminal extension is involved in inhibitor inactivation and may be required for targeting to the vacuole where the mature active inhibitor accumulates [PUBMED:9862450].

The N-terminal region and the mature inhibitor are weakly related to other solananaceous proteins found in this entry, from potato, tomato and henbane, which have been incorrectly described as metallocarboxipeptidase inhibitors [PUBMED:11488477].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan Pept_Inhib_IE (CL0096), which has the following description:

The members of this clan are all cystine rich domains, which form a knottin scaffold. This clan should also contain alpha-amylase but currently this family is a singleton and can not be put into Pfam. Also see [1].

The clan contains the following 2 members:

CarbpepA_inh Squash

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(7)
Full
(15)
Representative proteomes NCBI
(18)
Meta
(0)
RP15
(0)
RP35
(0)
RP55
(0)
RP75
(0)
Jalview View  View          View   
HTML View  View             
PP/heatmap 1 View             
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(7)
Full
(15)
Representative proteomes NCBI
(18)
Meta
(0)
RP15
(0)
RP35
(0)
RP55
(0)
RP75
(0)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(7)
Full
(15)
Representative proteomes NCBI
(18)
Meta
(0)
RP15
(0)
RP35
(0)
RP55
(0)
RP75
(0)
Raw Stockholm Download   Download           Download    
Gzipped Download   Download           Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Structural domain
Previous IDs: none
Type: Domain
Author: Griffiths-Jones SR
Number in seed: 7
Number in full: 15
Average length of the domain: 45.30 aa
Average identity of full alignment: 45 %
Average coverage of the sequence by the domain: 51.05 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.5 21.5
Trusted cut-off 43.1 42.6
Noise cut-off 21.4 21.4
Model length: 46
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the CarbpepA_inh domain has been found. There are 4 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

Loading structure mapping...