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83  structures 232  species 15  interactions 1427  sequences 138  architectures

Family: A2M_comp (PF07678)

Summary: A-macroglobulin complement component

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

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

A-macroglobulin complement component Provide feedback

This family includes the complement components region of the alpha-2-macroglobulin family.

Literature references

  1. Huang W, Dolmer K, Liao X, Gettins PG; , J Biol Chem 2000;275:1089-1094.: NMR solution structure of the receptor binding domain of human alpha(2)-macroglobulin. PUBMED:10625650 EPMC:10625650

  2. Xiao T, DeCamp DL, Spran SR; , Protein Sci 2000;9:1889-1897.: Structure of a rat alpha 1-macroglobulin receptor-binding domain dimer. PUBMED:11106161 EPMC:11106161

  3. Szakonyi G, Guthridge JM, Li D, Young K, Holers VM, Chen XS; , Science 2001;292:1725-1728.: Structure of complement receptor 2 in complex with its C3d ligand. PUBMED:11387479 EPMC:11387479

  4. Zanotti G, Bassetto A, Battistutta R, Folli C, Arcidiaco P, Stoppini M, Berni R; , Biochim Biophys Acta 2000;1478:232-238.: Structure at 1.44 A resolution of an N-terminally truncated form of the rat serum complement C3d fragment. PUBMED:10825534 EPMC:10825534


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR011626

This domain covers the complement component region of the alpha-2-macroglobulin family.

The alpha-macroglobulin (aM) family of proteins includes protease inhibitors [PUBMED:2473064], typified by the human tetrameric a2-macroglobulin (a2M); they belong to the MEROPS proteinase inhibitor family I39, clan IL. These protease inhibitors share several defining properties, which include (i) the ability to inhibit proteases from all catalytic classes, (ii) the presence of a 'bait region' and a thiol ester, (iii) a similar protease inhibitory mechanism and (iv) the inactivation of the inhibitory capacity by reaction of the thiol ester with small primary amines. aM protease inhibitors inhibit by steric hindrance [PUBMED:2472396]. The mechanism involves protease cleavage of the bait region, a segment of the aM that is particularly susceptible to proteolytic cleavage, which initiates a conformational change such that the aM collapses about the protease. In the resulting aM-protease complex, the active site of the protease is sterically shielded, thus substantially decreasing access to protein substrates. Two additional events occur as a consequence of bait region cleavage, namely (i) the h-cysteinyl-g-glutamyl thiol ester becomes highly reactive and (ii) a major conformational change exposes a conserved COOH-terminal receptor binding domain [PUBMED:2469470] (RBD). RBD exposure allows the aM protease complex to bind to clearance receptors and be removed from circulation [PUBMED:2430968]. Tetrameric, dimeric, and, more recently, monomeric aM protease inhibitors have been identified [PUBMED:9914899, PUBMED:10426429].

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...

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Pfam Clan

This family is a member of clan 6_Hairpin (CL0059), which has the following description:

This Clan includes CAZy clans GH-L, GH-M and GH-G. The members of this clan share a common structure composed of 6 helical hairpins. Most members of this superfamily are glycosyl hydrolase enzymes.

The clan contains the following 27 members:

A2M_comp Bac_rhamnosid C5-epim_C Cobalamin_bind DUF1237 DUF608 GDE_C GlcNAc_2-epim Glyco_hydro_100 Glyco_hydro_127 Glyco_hydro_15 Glyco_hydro_36 Glyco_hydro_47 Glyco_hydro_48 Glyco_hydro_63 Glyco_hydro_65m Glyco_hydro_76 Glyco_hydro_8 Glyco_hydro_88 Glyco_hydro_9 Glycoamylase LANC_like Pec_lyase Prenyltrans SQHop_cyclase_C SQHop_cyclase_N Trehalase

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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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
(25)
Full
(1427)
Representative proteomes UniProt
(3991)
NCBI
(6869)
Meta
(30)
RP15
(333)
RP35
(621)
RP55
(1006)
RP75
(1383)
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PP/heatmap 1 View               

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

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

Format an alignment

  Seed
(25)
Full
(1427)
Representative proteomes UniProt
(3991)
NCBI
(6869)
Meta
(30)
RP15
(333)
RP35
(621)
RP55
(1006)
RP75
(1383)
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
(25)
Full
(1427)
Representative proteomes UniProt
(3991)
NCBI
(6869)
Meta
(30)
RP15
(333)
RP35
(621)
RP55
(1006)
RP75
(1383)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

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

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: Prosite
Previous IDs: A2M3;
Type: Domain
Author: Studholme DJ, Sammut SJ
Number in seed: 25
Number in full: 1427
Average length of the domain: 217.60 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 16.60 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.5 20.5
Trusted cut-off 20.5 20.5
Noise cut-off 20.4 20.4
Model length: 249
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
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Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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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...

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Interactions

There are 15 interactions for this family. More...

Thiol-ester_cl Thiol-ester_cl Sushi Sushi A2M_recep A2M_N MACPF efb-c ANATO A2M_recep VWA A2M_N Sbi-IV A2M_comp TSP_1

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 A2M_comp domain has been found. There are 83 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.

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