PANDIT+

KeywordFamilyClanGene   

Entry: A1_Propeptide (PF07966)

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Pfam summary

Description

A1 Propeptide

Most eukaryotic endopeptidases (Merops Family A1) are synthesised with signal and propeptides. The animal pepsin-like endopeptidase propeptides form a distinct family of propeptides, which contain a conserved motif approximately 30 residues long. In pepsinogen A, the first 11 residues of the mature pepsin sequence are displaced by residues of the propeptide. The propeptide contains two helices that block the active site cleft, in particular the conserved Asp11 residue, in pepsin, hydrogen bonds to a conserved Arg residues in the propeptide. This hydrogen bond stabilises the propeptide conformation and is probably responsible for triggering the conversion of pepsinogen to pepsin under acidic conditions [1,2].
 
Literature1. Hartsuck JA, Koelsch G, Remington SJ; Proteins 1992;13:1-25.The high-resolution crystal structure of porcine pepsinogen. PUBMED:1594574
2. Sielecki AR, Fujinaga M, Read RJ, James MN; J Mol Biol 1991;219:671-692.Refined structure of porcine pepsinogen at 1.8 A resolution. PUBMED:2056534
 
 
InterPro entry
 

Alignment
New Hampshire tree

The seed alignment for this family in the PANDIT database contains 86 aligned sequences:

  ASPP_AEDAE/20-48   CATD_CHICK/21-49   CATD_CLUHA/19-47   CATD_HUMAN/21-49   CATE2_XENLA/17-45   CATE_CAVPO/21-49   CATE_RABIT/21-49   CATE_RANCA/17-45   CATE_RAT/23-51   CHYM_CALJA/19-47   O02723_SHEEP/16-44   O02725_SHEEP/16-44   O46496_BOVIN/16-44   O46498_BOVIN/16-44   O46499_BOVIN/16-44   O46523_EQUZE/16-44   O46524_FELCA/16-44   O57477_SPAAU/21-49   O57572_CHIHA/18-46   O76830_CAEEL/16-44   O93458_PODSI/19-47   O96906_ONCVO/33-61   P87370_ONCMY/19-47   P91802_SCHMA/14-42   PAG2_BOVIN/16-44   PAG2_PIG/16-44   PEP1_THUTO/1-29   PEP2_RABIT/17-45   PEP2_THUTO/1-29   PEPA_BOVIN/2-30   PEPA_CALJA/16-44   PEPA_CHICK/2-30   PEPA_MACMU/17-45   PEPA_PIG/16-44   PEPA_SUNMU/1-29   PEPC_CAVPO/18-46   PEPC_PIG/2-30   PEPC_RAT/18-46   PEPC_SUNMU/2-30   PEPE_CHICK/17-45   PEPF_RABIT/16-44   Q10735_PIG/1-29   Q21966_CAEEL/27-55   Q25037_HAECO/16-44   Q6DJB0_XENTR/18-46   Q6DJP1_XENLA/22-50   Q6HA04_PAGBE/15-43   Q6IMP1_FUGRU/24-52   Q6INM6_XENLA/24-52   Q6PGT7_BRARE/21-49   Q6R6N5_9CETA/16-44   More...

The full alignment for this family in the Pfam database contains 402 aligned sequences

Species in the seed alignment

List of species covered in the seed alignment. The number in brackets denotes the number of sequences taken from each organism.

  Bos taurus (5);   Gallus gallus (4);   Caenorhabditis elegans (4);   Danio rerio (4);   Sus scrofa (4);   Xenopus laevis (4);   Odocoileus virginianus (4);   Callithrix jacchus (3);   Ovis aries (3);   Rattus norvegicus (3);   Oryctolagus cuniculus (3);   Suncus murinus (2);   Rana catesbeiana (2);   Mus musculus (2);   Thunnus orientalis (2);   Cavia porcellus (2);   Drosophila melanogaster (2);   Haemonchus contortus (2);   Camelus dromedarius (2);   Canis lupus familiaris (2);   Takifugu rubripes (1);   Necator americanus (1);   Xenopus (Silurana) tropicalis (1);   Rhinolophus ferrumequinum (1);   Apriona germari (1);   Schistosoma mansoni (1);   Homo sapiens (1);   Onchocerca volvulus (1);   Silurus asotus (1);   Todarodes pacificus (1);   Sparus aurata (1);   Hynobius leechii (1);   Equus zebra (1);   Pseudopleuronectes americanus (1);   Trematomus bernacchii (1);   Sorex unguiculatus (1);   Macaca mulatta (1);   Clonorchis sinensis (1);   Oncorhynchus mykiss (1);   Clupea harengus (1);   Brugia malayi (1);   Podarcis sicula (1);   Aedes aegypti (1);   Bombyx mori (1);   Chionodraco hamatus (1);   Felis catus (1);   Capra hircus (1);  

The full alignment covers 106 species.

Pre-computed estimates from Markov codon substitution models (explanation)

Following are maximum-likelihood estimates and log-likelihood scores from codon models M0, M1, M2, M7 and M8, implemented in PAML v.4.1

Model name  

Model M0

Model M1

Model M2

Model M7

Model M8

Log-likelihood score  

-5780.93-5779.379736-5779.375176-5718.231554-5718.231567

Tree Length  

99.4199.410999.410999.410999.4109

κ  

1.621.6508361.649911.6451981.645197

ω-ratio  

ω=0.22801p0=0.933452 ~ ω0=0.244536
p1=0.0665480000000001 ~ ω1=1		p0=0.937127 ~ ω0=0.244972
p1=0.062869 ~ ω1=1
p2=4e-06 ~ ω2=999		ω~Β(1.952318,6.173314)p0=0.999999 ~ ω~Β(1.952322,6.173355)
p1=1e-06 ~ ω=2.239437

P-value for testing  
positive selection  

M1 vs M2: P-value=0.99545
motif classification: conserved		M7 vs M8: P-value=1
motif classification: conserved

Maximum-likelihood estimates and log-likelihood scores from codon models Nonsynonymous and Dual implemented in HYPHY

Model name  

Model Nonsynonymous

Model Dual

Log-likelihood score  

 -5716.50624-5712.53983

Mean ω-ratio  

ω = 0.24382ω = 0.27726

Coeff. of variation  
of ω-ratio  

 CVω = 0.43906CVω = 0.697
 

Annotations

InteractionsThis motif has 1 known interaction:
PF00026;
StructuresThis motif has 6 structures:
Notation: PDB_ID (PDB chain, PDB residues)
Gene Ontologies
Biological Process
 proteolysis[GO:0006508]
Molecular Function
 aspartic-type endopeptidase activity[GO:0004190]
KEGG Pathways - for genes coding for sequences from full alignment
Metabolism
Carbohydrate Metabolism
Aminosugars metabolism [KEGG]
Amino Acid Metabolism
Histidine metabolism [KEGG]
Metabolism of Other Amino Acids
Glutathione metabolism [KEGG]
Genetic Information Processing
Folding, Sorting and Degradation
Type III secretion system [KEGG]
Cellular Processes
Endocrine System
Renin - angiotensin system [KEGG]
 

Expression data (explanation)

 
Bgee expression data - for genes coding for sequences from seed alignment     Click here for overview of Bgee data

The numbers in brackets correspond to the number of genes that are associated with the selected family and are expressed in the corresponding tissue. Click on the tissue to see all the families that possibly have function in that tissue and click on the genes to see the corresponding genes.

Homo sapiens
Mus musculus
Xenopus (Silurana) tropicalis
Danio rerio
HumanProteinpedia expression data - for human genes coding for sequences from full alignment     Click here for overview of Human Proteinpedia data

The numbers in brackets correspond to the number of human genes that are associated with the selected family and are expressed in the corresponding tissue. Click on the tissue to see all the families that possibly have function in that tissue and click on the genes to see the corresponding genes.

Healthy tissues
Disease tissues

Human disease association

 
Genetic Association Database - data for human genes coding for sequences from full alignment

The numbers in brackets correspond to the number of genes that are associated with the selected family and are associated with the corresponding disease. Click on the disease name to see all the families possibly associated with that disease and click on the genes to see the corresponding genes.

Associated diseases and disorders
Links to OMIM - for human genes coding for sequences from full alignment
 
179820 (1) 116890 (1) 169710 (1) 169730 (1) 169720 (1) 169740 (1) 116840 (1)