Summary: MAM domain, meprin/A5/mu
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MAM domain Edit Wikipedia article
MAM domain is an evolutionary conserved protein domain. It is an extracellular domain found in many receptors.
A 170 amino acid domain, the so-called MAM domain, has been recognised in the extracellular region of functionally diverse proteins. These proteins have a modular, receptor-like architecture comprising a signal peptide, an N-terminal extracellular domain, a single transmembrane domain and an intracellular domain. Such proteins include meprin (a cell surface glycoprotein); A5 antigen (a developmentally-regulated cell surface protein); and receptor-like tyrosine protein phosphatase. The MAM domain is thought to have an adhesive function. It contains 4 conserved cysteine residues, which probably form disulphide bridges.
Human proteins containing this domain
- Bork P, Beckmann G (1993). "An adhesive domain detected in functionally diverse receptors". Trends Biochem. Sci. 18 (2): 40–41. doi:10.1016/0968-0004(93)90049-s. PMID 8387703.
- Grant GA, Jiang W, Gorbea CM, Flannery AV, Beynon RJ, Bond JS (1992). "The alpha subunit of meprin A. Molecular cloning and sequencing, differential expression in inbred mouse strains, and evidence for divergent evolution of the alpha and beta subunits". J. Biol. Chem. 267 (13): 9185–9193. PMID 1374387.
- Takagi S, Hirata T, Agata K, Eguchi G, Fujisawa H, Mochii M (1991). "The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors". Neuron. 7 (2): 295–307. doi:10.1016/0896-6273(91)90268-5. PMID 1908252.
- Gebbink MF, Hateboer G, Suijkerbuijk R, Beijersbergen RL, Moolenaar WH, van Etten I, Geurts van Kessel A (1991). "Cloning, expression and chromosomal localization of a new putative receptor-like protein tyrosine phosphatase". FEBS Lett. 290 (1): 123–130. doi:10.1016/0014-5793(91)81241-Y. PMID 1655529.
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MAM domain, meprin/A5/mu Provide feedback
An extracellular domain found in many receptors . The MAM domain along with the associated Ig domain in type IIB receptor protein tyrosine phosphatases forms a structural unit (termed MIg) with a seamless interdomain interface. It plays a major role in homodimerisation of the phosphatase ectoprotein and in cell adhesion [2,3]. MAM is a beta-sandwich consisting of two five-stranded antiparallel beta-sheets rotated away from each other by approx 25 degrees, and plays a similar role in meprin metalloproteinases .
Aricescu AR, Siebold C, Choudhuri K, Chang VT, Lu W, Davis SJ, van der Merwe PA, Jones EY;, Science. 2007;317:1217-1220.: Structure of a tyrosine phosphatase adhesive interaction reveals a spacer-clamp mechanism. PUBMED:17761881 EPMC:17761881
Aricescu AR, Hon WC, Siebold C, Lu W, van der Merwe PA, Jones EY;, EMBO J. 2006;25:701-712.: Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion. PUBMED:16456543 EPMC:16456543
Arolas JL, Broder C, Jefferson T, Guevara T, Sterchi EE, Bode W, Stocker W, Becker-Pauly C, Gomis-Ruth FX;, Proc Natl Acad Sci U S A. 2012;109:16131-16136.: Structural basis for the sheddase function of human meprin beta metalloproteinase at the plasma membrane. PUBMED:22988105 EPMC:22988105
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000998
MAM is an acronym derived from meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu. The MAM domain consists of approximately 170 amino acids. It occurs in several cell surface proteins and is likely to have an adhesive function [PUBMED:8387703]. The domain has been shown to play a role in homodimerization of protein-tyrosine phosphatase mu [PUBMED:7782276] and appears to help determine the specificity of these interactions. It contains four conserved cysteines which probably form two disulfide bridges. It has been reported that certain cysteine mutations in the MAM domain of murine meprin A result in the formation of monomeric meprin, which has altered stability and activity [PUBMED:8798668]. This indicates that these domain-domain interactions are critical for structure and function of the enzyme.
Proteins containing this domain are listed below.
- Meprin. This cell surface glycoprotein contains a zinc-metalloprotease domain capable of degrading a variety of polypeptides. Meprin is composed of two structurally related subunits (alpha and beta) that form homo- or heterotetramers by the non-covalent association of two disulfide-linked dimers. In both subunits, the MAM domain is located after the catalytic domain. It has also been shown that the MAM domain of meprins is necessary for correct folding and transport through the secretory pathway [PUBMED:9857066].
- Neuropilin (A5 antigen), a calcium-independent cell adhesion molecule that function during the formation of certain neuronal circuits. The sequence contains 2 CUB domains and a MAM domain.
- Receptor-like tyrosine protein phosphatases Mu, Kappa and PCP-2 (EC) . These PTPases have an extracellular region which consists of a MAM domain followed by an Ig-like domain and four fibronectin-type III domains.
- Vertebrate enteropeptidase (EC), a type II membrane protein of the intestinal brush border, which activates trypsinogen. It consists at least of a catalytic light chain and a multidomain heavy chain which has 2 LDL receptor class A domains, a MAM domain, a SRCR domain and a CUB domain.
- Apical endosomal glycoprotein from rat, a protein probably involved in the sorting and selective transport of receptors and ligands across polarized epithelia. This protein contains 6 MAM domains.
- Xenopus laevis thyroid hormone induced protein B. This protein contains 4 MAM domains.
- Pig zonadhesin, a protein that binds in a species-specific manner to the zona pellucida of the egg.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||membrane (GO:0016020)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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This superfamily includes a diverse range of carbohydrate binding domains and glycosyl hydrolase enzymes that share a common structure.
The clan contains the following 43 members:Alginate_lyase2 ArabFuran-catal Bac_rhamnosid Calreticulin Cleaved_Adhesin DUF1080 DUF1349 DUF1583 DUF1961 DUF2401 DUF3472 DUF4975 Exotox-A_bind Gal-bind_lectin Glyco_hydro_11 Glyco_hydro_12 Glyco_hydro_16 Glyco_hydro_32C Glyco_hydro_7 Laminin_G_1 Laminin_G_2 Laminin_G_3 Lectin_leg-like Lectin_legB MAM Methyltransf_FA Neuralized Pentaxin Peptidase_A4 Polysacc_lyase PRY Reoviridae_Vp9 Sial-lect-inser Sialidase SKN1 Spike_NTD SPRY TgMIC1 Toxin_R_bind_N TSP_C VP4_haemagglut XET_C YrpD
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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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.
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|Number in seed:||65|
|Number in full:||5270|
|Average length of the domain:||150.20 aa|
|Average identity of full alignment:||23 %|
|Average coverage of the sequence by the domain:||28.76 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||22|
|Download:||download the raw HMM for this family|
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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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.
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There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 MAM domain has been found. There are 7 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 sequence.
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