Summary: Lipid II flippase MurJ
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 "MOP flippase ". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at firstname.lastname@example.org and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
MOP flippase Edit Wikipedia article
The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) flippase superfamily (TC# 2.A.66) is a group of integral membrane protein families. The MOP flippase superfamily includes twelve distantly related families, six for which functional data are available:
- One ubiquitous family (MATE) specific for drugs - (TC# 2.A.66.1) The Multi Antimicrobial Extrusion (MATE) Family
- One (PST) specific for polysaccharides and/or their lipid-linked precursors in prokaryotes - (TC# 2.A.66.2) The Polysaccharide Transport (PST) Family
- One (OLF) specific for lipid-linked oligosaccharide precursors of glycoproteins in eukaryotes - (TC# 2.A.66.3) The Oligosaccharidyl-lipid Flippase (OLF) Family
- One (MVF) lipid-peptidoglycan precursor flippase involved in cell wall biosynthesis - (TC# 2.A.66.4) The Mouse Virulence Factor (MVF) Family
- One (AgnG) which includes a single functionally characterized member that extrudes the antibiotic, Agrocin 84 - (TC# 2.A.66.5) The Agrocin 84 Antibiotic Exporter (AgnG) Family
- And finally, one (Ank) that shuttles inorganic pyrophosphate (PPi) - (TC# 2.A.66.9) The Progressive Ankylosis (Ank) Family
- 1 Functionally characterized families
- 1.1 2.A.66.1 The Multi Antimicrobial Extrusion (MATE) Family
- 1.2 2.A.66.2 The Polysaccharide Transport (PST) Family
- 1.3 2.A.66.3 The Oligosaccharidyl-lipid Flippase (OLF) Family
- 1.4 2.A.66.4 The Mouse Virulence Factor (MVF) Family
- 1.5 2.A.66.5 The Agrocin 84 Antibiotic Exporter (AgnG) Family
- 1.6 2.A.66.9 The Progressive Ankylosis (Ank) Family
- 2 Other Families
- 3 See also
- 4 References
Functionally characterized families
2.A.66.1 The Multi Antimicrobial Extrusion (MATE) Family
|Multi-antimicrobial extrusion protein|
The MATE family is made up of several members and includes a functionally characterized multidrug efflux system from Vibrio parahaemolyticus NorM (TC# 2.A.66.1.1), and several homologues from other closely related bacteria that function by a drug:Na+ antiport mechanism, a putative ethionine resistance protein of Saccharomyces cerevisiae (ERC1 (YHR032w); TC# 2.A.66.1.5), a cationic drug efflux pump in A. thaliana (i.e., AtDTX1 aka AT2G04040; TC# 2.A.66.1.8) and the functionally uncharacterized DNA damage-inducible protein F (DinF; TC# 2.A.66.1.4) of E. coli.
The family includes hundreds of functionally uncharacterized but sequenced homologues from bacteria, archaea, and all eukaryotic kingdoms. A representative list of proteins belonging to the MATE family can be found in the Transporter Classification Database.
The bacterial proteins are of about 450 amino acyl residues in length and exhibit 12 putative transmembrane segments (TMSs). They arose by an internal gene duplication event from a primordial 6 TMS encoding genetic element. The yeast proteins are larger (up to about 700 residues) and exhibit about 12 TMSs.
Human MATE1 (hMATE1) is an electroneutral H+/organic cation (OC) exchanger responsible for the final excretion step of structurally unrelated toxic organic cations in kidney and liver. Glu273, Glu278, Glu300 and Glu389 are conserved in the transmembrane regions. Substitution with alanine or aspartate reduced export of tetraethylammonium (TEA) and cimetidine, and several had altered substrate affinities. Thus, all of these glutamate residues are involved in binding and/or transport of TEA and cimetidine, but their roles are different.
MATE (NorM) Transport Reaction
The probable transport reaction catalyzed by NorM, and possibly by other proteins of the MATE family is:
Antimicrobial (in) + nNa+ (out) â†’ Antimicrobial (out) + nNa+ (in).
2.A.66.2 The Polysaccharide Transport (PST) Family
Analyses conducted in 1997 showed that members of the PST family formed two major clusters. One is concerned with lipopolysaccharide O-antigen (undecaprenol pyrophosphate-linked O-antigen repeat unit) export (flipping from the cytoplasmic side to the periplasmic side of the inner membranes) in Gram-negative bacteria. On the periplasmic side, polymerization occurs catalyzed by Wzy. The other is concerned with exopolysaccharide or capsular polysaccharide export in both Gram-negative and Gram-positive bacteria. However, arachaeal and eukaryotic homologues are now recognized. The mechanism of energy coupling is not established, but homology with the MATE family suggests that they are secondary carriers. These transporters may function together with auxiliary proteins that allow passage across just the cytoplasmic membrane or both membranes of the Gram-negative bacterial envelope. They may also regulate transport. Thus, each Gram-negative bacterial PST system specific for an exo- or capsular polysaccharide functions in conjunction with a cytoplasmic membrane-periplasmic auxiliary (MPA) protein with a cytoplasmic ATP-binding domain (MPA1-C; TC# 3.C.3) as well as an outer membrane auxiliary protein (OMA; TC #3.C.5). Each Gram-positive bacterial PST system functions in conjunction with a homologous MPA1 + C pair of proteins equivalent to an MPA1-C proteins of Gram-negative bacteria. The C-domain has been shown to possess tyrosine protein kinase activity, so it may function in a regulatory capacity. The lipopolysaccharide exporters may function specifically in the translocation of the lipid-linked O-antigen side chain precursor from the inner leaflet of the cytoplasmic membrane to the outer leaflet. In this respect, they correlate in function with the flippase activities of members of the oligosaccharidyl-lipid flippase (OLF) family of the MVF families.
The protein members of the PST family are generally of 400-500 amino acyl residues in length and traverse the membrane as putative Î±-helical spanners twelve times.
PST Transport Reaction
The generalized transport reaction catalyzed by PST family proteins is:
Lipid-linked polysaccharide precursor (in) + energy â†’ Lipid-linked polysaccharide precursor (out).
2.A.66.3 The Oligosaccharidyl-lipid Flippase (OLF) Family
The OLF family is found in the endoplasmic reticular membranes of eukaryotes. N-linked glycosylation in eukaryotic cells follows a conserved pathway in which a tetradecasaccharide substrate (Glc3Man9GlcNAc2) is initially assembled in the ER membrane as a dolichylpyrophosphate (Dol-PP)-linked intermediate before being transferred to an asparaginyl residue in a lumenal protein. An intermediate, Man5GlcNAc2-PP-Dol is made on the cytoplasmic side of the membrane and translocated across the membrane so that the oligosaccharide chain faces the ER lumen where biosynthesis continues to completion. The flippase that catalyzes the translocation step is dependent on the Rft1 protein (TC# 2.A.66.3.1) of S. cerevisiae.
Homologues are found in plants, animals and fungi including C. elegans, D. melanogaster, H. sapiens, A. thaliana, S. cerevisiae and S. pombe. These proteins are distantly related to MATE and PST family members and therefore are believed to be secondary carriers.
The yeast protein, called the nuclear division Rft1 protein (TC# 2.A.66.3.1), is 574 aas with 12 putative TMSs. The homologue in A. thaliana is 401 aas in length with 8 or 9 putative TMSs while that in C. elegans is 522 aas long with 11 putative TMSs.
2.A.66.4 The Mouse Virulence Factor (MVF) Family
One member of the MVF family, MviN (TC# 2.A.66.4.1) of Salmonella typhimurium, has been shown to be an important virulence factor for this organism when infecting the mouse. In several bacteria, mviN genes occur in operons including glnD genes that encode the uridyl transferase that participates in the regulation of nitrogen metabolism. It is thought that MviN may flip the Lipid II peptidoglycan (PG) precursor from the cytoplasmic side of the inner membrane to the periplasmic surface acting as a putative lipid flippase in Salmonella typhimurium. In E. coli, MviN is an essential protein which when defective results in the accumulation of polyprenyl diphosphate-N-acetylmuramic acid-(pentapeptide)-N-acetyl-glucosamine, thought to be the peptidoglycan intermediated exported via MviN. In Mycobacterium tuberculosis, MviN is thought to play an essential role in peptidoglycan biosynthesis.
Another MVF protein, MurJ, functions as a peptidoglycan biosynthesis protein. A 3-d structureal model shows that MurJ contains a solvent-exposed cavity within the plane of the membrane. MurJ has 14 TMSs, and specific charged residues localized in the central cavity are essential for function. This structural homology model suggests that MurJ functions as an essential transporter in PG biosynthesis. Based on an in vivo assay, MurJ acts as a flippase for the lipid-linked cell wall precursor, polyisoprenoid-linked disaccharide-peptapeptide. There is controversy about the role of this porter and FtsW/RodA which on the basis of an in vitro assay, were thought to be flippases for the same intermediate.
2.A.66.5 The Agrocin 84 Antibiotic Exporter (AgnG) Family
Agrocin 84 is a disubstituted adenine nucleotide antibiotic made by and specific for Agrobacteria. It is encoded by the pAgK84 plasmid of A. tumefaciens  and targets a tRNA synthetase. The agnG gene encodes a protein of 496 aas with 12-13 putative TMSs and a short hydrophilic N-terminal domain of 80 residues. A TCDB Blast search with 2 iterations shows that members of the AgnG family are related to the U-MOP12 family (TC# 2.A.66.12) and the PST family (TC# 2.A.66.2) and more distantly related to the OLF (TC# 2.A.66.3), MVF (TC# 2.A.66.4), and LPS-F (TC# 2.A.66.10) families.
The reaction catalyzed by AgnG is:
agrocin (in) â†’ agrocin (out)
AgnG homologue 2 of Lyngbya sp. (TC# 2.A.66.5.3) is thought to be a polysaccharide exporter.
2.A.66.9 The Progressive Ankylosis (Ank) Family
Craniometaphyseal dysplasia (CMD) is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder has been linked to chromosome 5p15.2-p14.1 within a region harboring the human homolog (ANKH; TC# 2.A.66.9.1) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the cell membrane and shuttles inorganic pyrophosphate (PPi), a major inhibitor of physiologic and pathologic calcification, bone mineralization and bone resorption.
The ANK protein has 12 membrane-spanning helices with a central channel permitting the passage of PPi. Mutations occur at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. The PPi carrier ANK is concerned with bone formation and remodeling.
- 2.A.66.6 - The Putative Exopolysaccharide Exporter (EPS-E) Family
- 2.A.66.7 - Putative O-Unit Flippase (OUF) Family
- 2.A.66.8 - Unknown MOP-1 (U-MOP1) Family
- 2.A.66.10 - LPS Precursor Flippase (LPS-F) Family
- 2.A.66.11 - Uncharacterized MOP-11 (U-MOP11) Family
- 2.A.66.12 - Uncharacterized MOP-12 (U-MOP12) Family
- Multi-antimicrobial extrusion protein
- Capsular-polysaccharide-transporting ATPase
- Efflux (microbiology)
- Transporter Classification Database
- Hvorup RN, Winnen B, Chang AB, Jiang Y, Zhou XF, Saier MH (March 2003). "The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily". European Journal of Biochemistry. 270 (5): 799â€“813. doi:10.1046/j.1432-1033.2003.03418.x. PMID 12603313.
- Yen MR, Chen JS, Marquez JL, Sun EI, Saier MH (2010-01-01). Multidrug resistance: phylogenetic characterization of superfamilies of secondary carriers that include drug exporters. Methods in Molecular Biology. 637. pp. 47â€“64. doi:10.1007/978-1-60761-700-6_3. ISBN 978-1-60761-699-3. PMID 20419429.
- Saier, MH Jr. "2.A.66.1 The Multi Antimicrobial Extrusion (MATE) Family". Transporter Classification Database. Saier Lab Bioinformatics Group / SDSC.
- Kuroda T, Tsuchiya T (May 2009). "Multidrug efflux transporters in the MATE family". Biochimica et Biophysica Acta. 1794 (5): 763â€“8. doi:10.1016/j.bbapap.2008.11.012. PMID 19100867.
- Matsumoto T, Kanamoto T, Otsuka M, Omote H, Moriyama Y (April 2008). "Role of glutamate residues in substrate recognition by human MATE1 polyspecific H+/organic cation exporter". American Journal of Physiology. Cell Physiology. 294 (4): C1074â€“8. doi:10.1152/ajpcell.00504.2007. PMID 18305230.
- Paulsen IT, Beness AM, Saier MH (August 1997). "Computer-based analyses of the protein constituents of transport systems catalysing export of complex carbohydrates in bacteria". Microbiology. 143 ( Pt 8) (8): 2685â€“99. doi:10.1099/00221287-143-8-2685. PMID 9274022.
- Marolda CL, Tatar LD, Alaimo C, Aebi M, Valvano MA (July 2006). "Interplay of the Wzx translocase and the corresponding polymerase and chain length regulator proteins in the translocation and periplasmic assembly of lipopolysaccharide o antigen". Journal of Bacteriology. 188 (14): 5124â€“35. doi:10.1128/JB.00461-06. PMC 1539953. PMID 16816184.
- Islam ST, Lam JS (April 2013). "Wzx flippase-mediated membrane translocation of sugar polymer precursors in bacteria". Environmental Microbiology. 15 (4): 1001â€“15. doi:10.1111/j.1462-2920.2012.02890.x. PMID 23016929.
- Helenius J, Ng DT, Marolda CL, Walter P, Valvano MA, Aebi M (January 2002). "Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein". Nature. 415 (6870): 447â€“50. doi:10.1038/415447a. PMID 11807558.
- Kutsukake K, Okada T, Yokoseki T, Iino T (May 1994). "Sequence analysis of the flgA gene and its adjacent region in Salmonella typhimurium, and identification of another flagellar gene, flgN". Gene. 143 (1): 49â€“54. doi:10.1016/0378-1119(94)90603-3. PMID 8200538.
- Rudnick PA, ArcondÃ©guy T, Kennedy CK, Kahn D (April 2001). "glnD and mviN are genes of an essential operon in Sinorhizobium meliloti". Journal of Bacteriology. 183 (8): 2682â€“5. doi:10.1128/JB.183.8.2682-2685.2001. PMC 95188. PMID 11274131.
- Vasudevan P, McElligott J, Attkisson C, Betteken M, Popham DL (October 2009). "Homologues of the Bacillus subtilis SpoVB protein are involved in cell wall metabolism". Journal of Bacteriology. 191 (19): 6012â€“9. doi:10.1128/JB.00604-09. PMC 2747891. PMID 19648239.
- Fay A, Dworkin J (October 2009). "Bacillus subtilis homologs of MviN (MurJ), the putative Escherichia coli lipid II flippase, are not essential for growth". Journal of Bacteriology. 191 (19): 6020â€“8. doi:10.1128/JB.00605-09. PMC 2747889. PMID 19666716.
- Inoue A, Murata Y, Takahashi H, Tsuji N, Fujisaki S, Kato J (November 2008). "Involvement of an essential gene, mviN, in murein synthesis in Escherichia coli". Journal of Bacteriology. 190 (21): 7298â€“301. doi:10.1128/JB.00551-08. PMC 2580715. PMID 18708495.
- Gee CL, Papavinasasundaram KG, Blair SR, Baer CE, Falick AM, King DS, Griffin JE, Venghatakrishnan H, Zukauskas A, Wei JR, Dhiman RK, Crick DC, Rubin EJ, Sassetti CM, Alber T (January 2012). "A phosphorylated pseudokinase complex controls cell wall synthesis in mycobacteria". Science Signaling. 5 (208): ra7. doi:10.1126/scisignal.2002525. PMC 3664666. PMID 22275220.
- Ruiz N (October 2008). "Bioinformatics identification of MurJ (MviN) as the peptidoglycan lipid II flippase in Escherichia coli". Proceedings of the National Academy of Sciences of the United States of America. 105 (40): 15553â€“7. doi:10.1073/pnas.0808352105. PMC 2563115. PMID 18832143.
- Butler EK, Davis RM, Bari V, Nicholson PA, Ruiz N (October 2013). "Structure-function analysis of MurJ reveals a solvent-exposed cavity containing residues essential for peptidoglycan biogenesis in Escherichia coli". Journal of Bacteriology. 195 (20): 4639â€“49. doi:10.1128/JB.00731-13. PMC 3807429. PMID 23935042.
- Sham LT, Butler EK, Lebar MD, Kahne D, Bernhardt TG, Ruiz N (July 2014). "Bacterial cell wall. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis". Science. 345 (6193): 220â€“2. doi:10.1126/science.1254522. PMC 4163187. PMID 25013077.
- Young KD (July 2014). "Microbiology. A flipping cell wall ferry". Science. 345 (6193): 139â€“40. doi:10.1126/science.1256585. PMID 25013047.
- Kim JG, Park BK, Kim SU, Choi D, Nahm BH, Moon JS, Reader JS, Farrand SK, Hwang I (June 2006). "Bases of biocontrol: sequence predicts synthesis and mode of action of agrocin 84, the Trojan horse antibiotic that controls crown gall". Proceedings of the National Academy of Sciences of the United States of America. 103 (23): 8846â€“51. doi:10.1073/pnas.0602965103. PMC 1482666. PMID 16731618.
- Reader JS, Ordoukhanian PT, Kim JG, de CrÃ©cy-Lagard V, Hwang I, Farrand S, Schimmel P (September 2005). "Major biocontrol of plant tumors targets tRNA synthetase". Science. 309 (5740): 1533. doi:10.1126/science.1116841. PMID 16141066.
- "2.A.66.5: The Agrocin 84 Antibiotic Exporter (AgnG) Family". Transporter Classification Database. Retrieved 2016-03-08.
- NÃ¼rnberg P, Thiele H, Chandler D, HÃ¶hne W, Cunningham ML, Ritter H, Leschik G, Uhlmann K, Mischung C, Harrop K, Goldblatt J, Borochowitz ZU, Kotzot D, Westermann F, Mundlos S, Braun HS, Laing N, Tinschert S (May 2001). "Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia". Nature Genetics. 28 (1): 37â€“41. doi:10.1038/88236. PMID 11326272.
As of 19:37, 24 February 2016 (UTC), this article is derived in whole or in part from Transporter Classification Database. The copyright holder has licensed the content in a manner that permits reuse under CC BY-SA 3.0 and GFDL. All relevant terms must be followed. The original text was at "2.A.66 The Multidrug/Oligosaccharidyl-lipid/Polysaccharide (MOP) Flippase Superfamily".
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.
Lipid II flippase MurJ Provide feedback
Peptidoglycan synthesis (PG) biosynthesis involves the formation of peptidoglycan precursor lipid II (undecaprenyl-pyrophosphate-linked N-acetyl glucosamine-N-acetyl muramic acid-pentapeptide) on the cytosolic face of the cell membrane. Lipid II is then translocated across the membrane and its glycopeptide moiety becomes incorporated into the growing cell wall mesh. MviN, renamed as MurJ, is a lipid II flippase essential for cell wall peptidoglycan synthesis [1, 2]. MurJ belongs to the MVF (mouse virulence factor) family of MOP superfamily transporters, which also includes the MATE (multidrug and toxic compound extrusion) transporter and eukaryotic OLF (oligosaccharidyl-lipid flippase) families. In addition to the canonical MOP transporter core consisting of 12 transmembrane helices (TMs), MurJ has two additional C-terminal TMs (13 and 14) of unknown function. Structural analysis indicates that the N lobe (TMs 1â6) and C lobe (TMs 7â14) are arranged in an inward-facing N-shape conformation, rather than the outward-facing V-shape conformation observed in all existing MATE transporter structures. Furthermore, a hydrophobic groove is formed by two C-terminal transmembrane helices, which leads into a large central cavity that is mostly cationic. Mutagenesis studies, revealed a solvent-exposed cavity that is essential for function. Mutation of conserved residues (Ser17, Arg18, Arg24, Arg52, and Arg255) at the proximal site failed to complement MurJ function, consistent with the idea that these residues are important for recognizing the diphosphate and/or sugar moieties of lipid II. It has also been suggested that the chloride ion in the central cavity and a zinc ion at the beginning of TM 7 might be functionally important .
Mohamed YF, Valvano MA;, Glycobiology. 2014;24:564-576.: A Burkholderia cenocepacia MurJ (MviN) homolog is essential for cell wall peptidoglycan synthesis and bacterial viability. PUBMED:24688094 EPMC:24688094
Internal database links
|SCOOP:||MatE Polysacc_synt Polysacc_synt_3 Polysacc_synt_C|
|Similarity to PfamA using HHSearch:||MatE Polysacc_synt Polysacc_synt_3 Polysacc_synt_C|
This tab holds annotation information from the InterPro database.
InterPro entry IPR004268
Peptidoglycan synthesis (PG) biosynthesis involves the formation of peptidoglycan precursor lipid II (undecaprenyl-pyrophosphate-linked N-acetyl glucosamine-N-acetyl muramic acid-pentapeptide) on the cytosolic face of the cell membrane. Lipid II is then translocated across the membrane and its glycopeptide moiety becomes incorporated into the growing cell wall mesh.
MviN, renamed as MurJ, is a lipid II flippase essential for cell wall peptidoglycan synthesis [PUBMED:18832143, PUBMED:24688094]. Unlike most MviN proteins, the mycobacterial MviN orthologue possess an extended C-terminal region that contains an intracellular pseudo-kinase domain and an extracellular domain resembling carbohydrate-binding proteins [PUBMED:22275220].
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:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
This superfamily consists of a variety of integral membrane protein families. The MATE family are known to be transporters. Other proteins have been implicated in virulence and polysaccharide biosynthesis.
The clan contains the following 7 members:ANKH MatE MurJ Polysacc_synt Polysacc_synt_3 Polysacc_synt_C Rft-1
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...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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...
If you find these logos useful in your own work, please consider citing the following article:
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.
|Seed source:||Pfam-B_1348 (release 6.4)|
|Author:||Griffiths-Jones SR , Studholme DJ , El-Gebali S|
|Number in seed:||13|
|Number in full:||7198|
|Average length of the domain:||444.80 aa|
|Average identity of full alignment:||24 %|
|Average coverage of the sequence by the domain:||79.94 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||14|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
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.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
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.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
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.
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
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.
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 MurJ domain has been found. There are 1 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.
Loading structure mapping...