Summary

Serine carboxypeptidase S28

These serine proteases include several eukaryotic enzymes such as lysosomal Pro-X carboxypeptidase, dipeptidyl-peptidase II, and thymus-specific serine peptidase.

Literature references

Skidgel RA, Erdos EG; , Immunol Rev 1998;161:129-141.: Cellular carboxypeptidases. PUBMED:9553770
Shariat-Madar Z, Mahdi F, Schmaier AH; , J Biol Chem 2002;277:17962-17969.: Identification and characterization of prolylcarboxypeptidase as an endothelial cell prekallikrein activator. PUBMED:11830581
Senten K, Van der Veken P, Bal G, De Meester I, Lambeir AM, Scharpe S, Bauvois B, Haemers A, Augustyns K; , Bioorg Med Chem Lett 2002;12:2825-2828.: Development of potent and selective dipeptidyl peptidase II inhibitors. PUBMED:12270155
Araki H, Li Y, Yamamoto Y, Haneda M, Nishi K, Kikkawa R, Ohkubo I; , J Biochem (Tokyo) 2001;129:279-288.: Purification, molecular cloning, and immunohistochemical localization of dipeptidyl peptidase II from the rat kidney and its identity with quiescent cell proline dipeptidase. PUBMED:11173530
Fukasawa KM, Fukasawa K, Higaki K, Shiina N, Ohno M, Ito S, Otogoto J, Ota N; , Biochem J 2001;353:283-290.: Cloning and functional expression of rat kidney dipeptidyl peptidase II. PUBMED:11139392
Carrier A, Wurbel MA, Mattei MG, Kissenpfennig A, Malissen M, Malissen B; , Immunogenetics 2000;51:984-986.: Chromosomal localization of two mouse genes encoding thymus-specific serine peptidase and thymus-expressed acidic protein. PUBMED:11003393
Bowlus CL, Ahn J, Chu T, Gruen JR; , Cell Immunol 1999;196:80-86.: Cloning of a novel MHC-encoded serine peptidase highly expressed by cortical epithelial cells of the thymus. PUBMED:10527559

InterPro entry IPR008758

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes PUBMED:7845208. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Over 20 families (denoted S1 - S66) of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence PUBMED:7845208. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases PUBMED:7845208.

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base PUBMED:7845208. The geometric orientations of the catalytic residues are similar between families, despite different protein folds PUBMED:7845208. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) PUBMED:7845208, PUBMED:8439290.

In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:

Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule.

In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.

This group of serine peptidases belong to MEROPS peptidase family S28 (clan SC). The predicted active site residues for members of this family and family S10 occur in the same order in the sequence: S, D, H.

These serine proteases include several eukaryotic enzymes such as lysosomal Pro-X carboxypeptidase, dipeptidyl-peptidase II, and thymus-specific serine peptidase PUBMED:10527559, PUBMED:11003393, PUBMED:11139392, PUBMED:11173530.

Clan

This family is a member of clan AB_hydrolase (CL0028), which contains the following 58 members:

Abhydrolase_1 Abhydrolase_2 Abhydrolase_3 Abhydrolase_4 Acyl_transf_2 Arb2 AXE1 BAAT_C Chlorophyllase COesterase Cutinase DLH DUF1023 DUF1057 DUF1100 DUF1234 DUF1350 DUF1400 DUF1749 DUF2048 DUF2305 DUF2424 DUF2920 DUF2974 DUF3141 DUF3530 DUF452 DUF676 DUF726 DUF818 DUF829 DUF900 DUF915 Esterase Esterase_phd FSH1 Hydrolase_4 LACT LIP Lipase Lipase_2 Lipase_3 Ndr PAF-AH_p_II Palm_thioest PE-PPE Peptidase_S10 Peptidase_S15 Peptidase_S28 Peptidase_S37 Peptidase_S9 PGAP1 PHB_depo_C PhoPQ_related Tannase Thioesterase UPF0227 VirJ

Gene Ontology

Molecular function	serine-type peptidase activity (GO:0008236)
Biological process	proteolysis (GO:0006508)

Internal database links

SCOOP:

UPF0227 DUF1023 Abhydrolase_4 BAAT_C

External database links

MEROPS:	S28
PANDIT:	PF05577
SYSTERS:	Peptidase_S28

Domain organisation

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

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (13) Full (570) NCBI (871) Metagenomics (71)
Viewer:

Formatting options

Alignment:	Seed (13) Full (570)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (13) Full (570) NCBI (871) Metagenomics (71)
Full length sequences	Full-sequences (570)

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 HMMER2.

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. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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

Seed source:

Merops

Previous IDs:

none

Type:

Family

Author:

Studholme DJ

Number in seed:

13

Number in full:

570

Average length of the domain:

341.70 aa

Average identity of full alignment:

23 %

Average coverage of the sequence by the domain:

70.09 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	19.9	19.9
Trusted cut-off	19.9	19.9
Noise cut-off	19.8	19.8

Model length:

433

Family (HMM) version:

5

Download:

download the raw HMM for this family

Species distribution

Tree controls

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

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Family: Peptidase_S28 (PF05577)

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