Summary: Major intrinsic protein
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 "Major intrinsic proteins". 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 email@example.com 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.
Major intrinsic proteins Edit Wikipedia article
|Major intrinsic protein|
Structure of a glycerol-conducting channel.
|SCOPe||1fx8 / SUPFAM|
Major intrinsic proteins comprise a large superfamily of transmembrane protein channels that are grouped together on the basis of homology. The MIP superfamily includes three subfamilies: aquaporins, aquaglyceroporins and S-aquaporins.
- The aquaporins (AQPs) are water selective.
- The aquaglyceroporins are permeable to water, but also to other small uncharged molecules such as glycerol.
- The third subfamily, with little conserved amino acid sequences around the NPA boxes, include 'superaquaporins' (S-aquaporins).
There are two families that belong to the MIP Superfamily.
- 1.A.8 - The Major Intrinsic Protein (MIP) Family
- 1.A.16 - The Formate-Nitrite Transporter (FNT) Family
The Major Intrinsic Protein Family (TC# 1.A.8)
The MIP family is large and diverse, possessing thousands of members that form transmembrane channels. These channel proteins function in transporting water, small carbohydrates (e.g., glycerol), urea, NH3, CO2, H2O2 and ions by energy-independent mechanisms. For example, the glycerol channel, FPS1p of Saccharomyces cerevisiae mediates uptake of arsenite and antimonite. Ion permeability appears to occur through a pathway different than that used for water/glycerol transport and may involve a channel at the 4 subunit interface rather than the channels through the subunits. MIP family members are found ubiquitously in bacteria, archaea and eukaryotes. Phylogenetic clustering of the proteins is primarily based according to phylum of the organisms of origin, but one or more clusters are observed for each phylogenetic kingdom (plants, animals, yeast, bacteria and archaea). MIPs are classified into five subfamilies in higher plants, including plasma membrane (PIPs), tonoplast (TIPs), NOD26-like (NIPs), small basic (SIPs) and unclassified X (XIPs) intrinsic proteins. One of the plant clusters includes only tonoplast (TIP) proteins, while another includes plasma membrane (PIP) proteins.
Major Intrinsic Protein
The Major Intrinsic Protein (MIP) of the human lens of the eye (Aqp0), after which the MIP family was named, represents about 60% of the protein in the lens cell. In the native form, it is an aquaporin (AQP), but during lens development, it becomes proteolytically truncated. The channel, which normally houses 6-9 water molecules, becomes constricted so only three remain, and these are trapped in a closed conformation. These truncated tetramers form intercellular adhesive junctions (head to head), yielding a crystalline array that mediates lens formation with cells tightly packed as required to form a clear lens. Lipids crystallize with the protein. Ion channel activity has been shown for Aquaporins 0, 1, and 6, Drosophila 'Big Brain' (bib) and plant Nodulin-26. Roles of aquaporins in human cancer have been reviewed as have their folding pathways. AQPs may act as transmembrane osmosensors in red cells, secretory granules and microorganisms. MIP superfamly proteins and variations of their selectivity filters have been reviewed.
The currently known aquaporins cluster loosely together as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport glycerol as well as water while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast Fps1 protein (TC# 1.A.8.5.1) and tobacco NtTIPa (TC# 1.A.8.10.2) may transport both water and small solutes.
A list of nearly 100 currently classified members of the MIP family can be found in the Transporter Classification Database. Some of the MIP family channels include:
- Mammalian major intrinsic protein (MIP). MIP is the major component of lens fibre gap junctions.
- Mammalian aquaporins. (InterPro: IPR012269) These proteins form water-specific channels that provide the plasma membranes of red cells, as well as kidney proximal and collecting tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient.
- Soybean nodulin-26, a major component of the peribacteroid membrane induced during nodulation in legume roots after Rhizobium infection.
- Plant tonoplast intrinsic proteins (TIP). There are various isoforms of TIP : alpha (seed), gamma, Rt (root), and Wsi (water-stress induced). These proteins may allow the diffusion of water, amino acids and/or peptides from the tonoplast interior to the cytoplasm.
- Bacterial glycerol facilitator protein (gene glpF), which facilitates the movement of glycerol non-specifically across the cytoplasmic membrane.
- Salmonella typhimurium propanediol diffusion facilitator (gene pduF).
- Yeast FPS1, a glycerol uptake/efflux facilitator protein.
- Drosophila neurogenic protein 'big brain' (bib). This protein may mediate intercellular communication; it may functions by allowing the transport of certain molecules(s) and thereby sending a signal for an exodermal cell to become an epidermoblast instead of a neuroblast.
- Yeast hypothetical protein YFL054c.
- A hypothetical protein from the pepX region of Lactococcus lactis.
MIP family channels consist of homotetramers (e.g., GlpF of E. coli; TC #1.A.8.1.1, AqpZ of E. coli; TC #1.A.8.3.1, and MIP or Aqp0 of Bos taurus; TC #1.A.8.8.1). Each subunit spans the membrane six times as putative Î±-helices. The 6 TMS domains are believed to have arisen from a 3-spanner-encoding genetic element by a tandem, intragenic duplication event. The two halves of the proteins are therefore of opposite orientation in the membrane. A well-conserved region between TMSs 2 and 3 and TMSs 5 and 6 dip into the membrane, each loop forming a half TMS. A common amino acyl motif in these transporters is an asparagineâ€“prolineâ€“alanine (NPA) motif. Aquaporins generally have the NPA motif in both halves, the glycerol facilitators generally have an NPA motif in the first haves and a DPA motif in the second halves, and the super-aquaporins have poorly conserved NPA motifs in both halves.
Glycerol Uptake Facilitator
The crystal structure of the glycerol facilitator of E. coli (TC# 1.A.8.1.1) was solved at 2.2 Ã… resolution ( ). Glycerol molecules create a single file within the channel and pass through a narrow selectivity filter. The two conserved D-P-A motifs in the loops between TMSs 2 and 3 and TMSs 5 and 6 form the interface between the two duplicated halves of each subunit. Thus each half of the protein forms 3.5 TMSs surrounding the channel. The structure explains why GlpF is selectively permeable to straight chain carbohydrates, and why water and ions are largely excluded. Aquaporin-1 (AQP1) and the bacterial glycerol facilitator, GlpF can transport O2, CO2, NH3, glycerol, urea, and water to varying degrees. For small solutes passing through AQP1, there is an anti-correlation between permeability and solute hydrophobicity. AQP1 is thus a selective filter for small polar solutes, whereas GlpF is highly permeable to small solutes and less permeable to larger solutes.
Aquaporin-1 (Aqp1) from the human red blood cell has been solved by electron crystallography to 3.8 Ã… resolution ( The aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport. Water selectivity is due to a constriction of the inner pore diameter to about 3 Ã… over the span of a single residue, superficially similar to that in the glycerol facilitator of E. coli. Several other more recently resolved crystal structures are available in RCSB, including but not limited to: , , .).
AqpZ, a homotetramer (tAqpZ) of four water-conducting channels that facilitate rapid water movements across the plasma membrane of E. coli, has been solved to 3.2 Ã… resolution ( Other resolved crystal structures for AqpZ include: , , .). All channel-lining residues in the four monomeric channels are orientated in nearly identical positions except at the narrowest channel constriction, where the side chain of a conserved Arg-189 adopts two distinct orientations. In one of the four monomers, the guanidino group of Arg-189 points toward the periplasmic vestibule, opening up the constriction to accommodate the binding of a water molecule through a tridentate H-bond. In the other three monomers, the Arg-189 guanidino group bends over to form an H-bond with carbonyl oxygen of Thr-183 occluding the channel. Therefore, the tAqpZ structure has two different Arg-189 conformations which provide water permeation through the channel. Alternating between the two Arg-189 conformations disrupts continuous flow of water, thus regulating the open probability of the water pore. Further, the difference in Arg-189 displacements is correlated with a strong electron density found between the first transmembrane helices of two open channels, suggesting that the observed Arg-189 conformations are stabilized by asymmetrical subunit interactions in tAqpZ.
PIP1 and PIP2
The 3-D structures of the open and closed forms of plant aquaporins, PIP1 and PIP2, have been solved (). In the closed conformation, loop D caps the channel from the cytoplasm and thereby occludes the pore. In the open conformation, loop D is displaced up to 16 Ã…, and this movement opens a hydrophobic gate blocking the channel entrance from the cytoplasm. These results reveal a molecular gating mechanism which appears conserved throughout all plant plasma membrane aquaporins. In plants it regulates water intake/export in response to water availability and cytoplasmic pH during anoxia.
Human proteins containing this domain
- MIP (gene)
- Integral membrane protein
- Transporter Classification Database
- Protein Superfamily
- Protein family
- Fu D, Libson A, Miercke LJ, et al. (October 2000). "Structure of a glycerol-conducting channel and the basis for its selectivity". Science. 290 (5491): 481â€“6. doi:10.1126/science.290.5491.481. PMID 11039922.
- Benga, Gheorghe (2012-12-01). "On the definition, nomenclature and classification of water channel proteins (aquaporins and relatives)". Molecular Aspects of Medicine. 33 (5â€“6): 514â€“517. doi:10.1016/j.mam.2012.04.003. ISSN 1872-9452. PMID 22542572.
- Reizer J, Reizer A, Saier Jr MH (1993). "The MIP family of integral membrane channel proteins: sequence comparisons, evolutionary relationships, reconstructed pathway of evolution, and proposed functional differentiation of the two repeated halves of the proteins". Crit. Rev. Biochem. Mol. Biol. 28 (3): 235â€“257. doi:10.3109/10409239309086796. PMID 8325040.
- Pao GM, Johnson KD, Chrispeels MJ, Sweet G, Sandal NN, Wu LF, Saier Jr MH, Hofte H (1991). "Evolution of the MIP family of integral membrane transport proteins". Mol. Microbiol. 5 (1): 33â€“37. doi:10.1111/j.1365-2958.1991.tb01823.x. PMID 2014003.
- Finn, Roderick Nigel; ChauvignÃ©, FranÃ§ois; Stavang, Jon Anders; Belles, Xavier; CerdÃ , Joan (2015-01-01). "Insect glycerol transporters evolved by functional co-option and gene replacement". Nature Communications. 6: 7814. doi:10.1038/ncomms8814. ISSN 2041-1723. PMC 4518291. PMID 26183829.
- Wysocki, R.; ChÃ©ry, C. C.; Wawrzycka, D.; Van Hulle, M.; Cornelis, R.; Thevelein, J. M.; TamÃ¡s, M. J. (2001-06-01). "The glycerol channel Fps1p mediates the uptake of arsenite and antimonite in Saccharomyces cerevisiae". Molecular Microbiology. 40 (6): 1391â€“1401. doi:10.1046/j.1365-2958.2001.02485.x. ISSN 0950-382X. PMID 11442837.
- Saparov, S. M.; Kozono, D.; Rothe, U.; Agre, P.; Pohl, P. (2001-08-24). "Water and ion permeation of aquaporin-1 in planar lipid bilayers. Major differences in structural determinants and stoichiometry". The Journal of Biological Chemistry. 276 (34): 31515â€“31520. doi:10.1074/jbc.M104267200. ISSN 0021-9258. PMID 11410596.
- Park, JH; Saier, MH Jr. (October 1996). "Phylogenetic Characterization of the MIP Family of Transmembrane Channel Proteins". The Journal of Membrane Biology. 153 (3): 171â€“180. doi:10.1007/s002329900120. PMID 8849412.
- Martins, Cristina de Paula Santos; Pedrosa, Andresa Muniz; Du, Dongliang; GonÃ§alves, Luana Pereira; Yu, Qibin; Gmitter, Frederick G.; Costa, Marcio Gilberto Cardoso (2015-01-01). "Genome-Wide Characterization and Expression Analysis of Major Intrinsic Proteins during Abiotic and Biotic Stresses in Sweet Orange (Citrus sinensis L. Osb.)". PLoS One. 10 (9): e0138786. doi:10.1371/journal.pone.0138786. ISSN 1932-6203. PMC 4580632. PMID 26397813.
- Gonen, Tamir; Cheng, Yifan; Kistler, Joerg; Walz, Thomas (2004-09-24). "Aquaporin-0 membrane junctions form upon proteolytic cleavage". Journal of Molecular Biology. 342 (4): 1337â€“1345. CiteSeerX 10.1.1.389.4773. doi:10.1016/j.jmb.2004.07.076. ISSN 0022-2836. PMID 15351655.
- Gonen, Tamir; Sliz, Piotr; Kistler, Joerg; Cheng, Yifan; Walz, Thomas (2004-05-13). "Aquaporin-0 membrane junctions reveal the structure of a closed water pore". Nature. 429 (6988): 193â€“197. doi:10.1038/nature02503. ISSN 1476-4687. PMID 15141214.
- Gonen, Tamir; Walz, Thomas (2006-11-01). "The structure of aquaporins". Quarterly Reviews of Biophysics. 39 (4): 361â€“396. doi:10.1017/S0033583506004458. ISSN 0033-5835. PMID 17156589.
- Gonen, Tamir; Cheng, Yifan; Sliz, Piotr; Hiroaki, Yoko; Fujiyoshi, Yoshinori; Harrison, Stephen C.; Walz, Thomas (2005-12-01). "Lipid-protein interactions in double-layered two-dimensional AQP0 crystals". Nature. 438 (7068): 633â€“638. doi:10.1038/nature04321. ISSN 1476-4687. PMC 1350984. PMID 16319884.
- Rao, Y.; Bodmer, R.; Jan, L. Y.; Jan, Y. N. (1992-09-01). "The big brain gene of Drosophila functions to control the number of neuronal precursors in the peripheral nervous system". Development. 116 (1): 31â€“40. ISSN 0950-1991. PMID 1483394.
- Yool, Andrea J.; Campbell, Ewan M. (2012-12-01). "Structure, function and translational relevance of aquaporin dual water and ion channels". Molecular Aspects of Medicine. 33 (5â€“6): 553â€“561. doi:10.1016/j.mam.2012.02.001. ISSN 1872-9452. PMC 3419283. PMID 22342689.
- Pareek, Gautam; Krishnamoorthy, Vivekanandhan; D'Silva, Patrick (2013-12-01). "Molecular insights revealing interaction of Tim23 and channel subunits of presequence translocase". Molecular and Cellular Biology. 33 (23): 4641â€“4659. doi:10.1128/MCB.00876-13. ISSN 1098-5549. PMC 3838011. PMID 24061477.
- Klein, Noreen; Neumann, Jennifer; O'Neil, Joe D.; Schneider, Dirk (2015-02-01). "Folding and stability of the aquaglyceroporin GlpF: Implications for human aqua(glycero)porin diseases". Biochimica et Biophysica Acta. 1848 (2): 622â€“633. doi:10.1016/j.bbamem.2014.11.015. ISSN 0006-3002. PMID 25462169.
- Hill, A. E.; Shachar-Hill, Y. (2015-08-01). "Are Aquaporins the Missing Transmembrane Osmosensors?". The Journal of Membrane Biology. 248 (4): 753â€“765. doi:10.1007/s00232-015-9790-0. ISSN 1432-1424. PMID 25791748.
- Verma, Ravi Kumar; Gupta, Anjali Bansal; Sankararamakrishnan, Ramasubbu (2015-01-01). Major intrinsic protein superfamily: channels with unique structural features and diverse selectivity filters. Methods in Enzymology. 557. pp. 485â€“520. doi:10.1016/bs.mie.2014.12.006. ISBN 9780128021835. ISSN 1557-7988. PMID 25950979.
- Chrispeels MJ, Agre P (1994). "Aquaporins: water channel proteins of plant and animal cells". Trends Biochem. Sci. 19 (10): 421â€“425. doi:10.1016/0968-0004(94)90091-4. PMID 7529436.
- Heller, K. B.; Lin, E. C.; Wilson, T. H. (1980-10-01). "Substrate specificity and transport properties of the glycerol facilitator of Escherichia coli". Journal of Bacteriology. 144 (1): 274â€“278. ISSN 0021-9193. PMC 294637. PMID 6998951.
- Wistow GJ, Pisano MM, Chepelinsky AB (1991). "Tandem sequence repeats in transmembrane channel proteins". Trends Biochem. Sci. 16 (5): 170â€“171. doi:10.1016/0968-0004(91)90065-4. PMID 1715617.
- Beese-Sims, Sara E.; Lee, Jongmin; Levin, David E. (2011-12-01). "Yeast Fps1 glycerol facilitator functions as a homotetramer". Yeast. 28 (12): 815â€“819. doi:10.1002/yea.1908. ISSN 1097-0061. PMC 3230664. PMID 22030956.
- Fu, D.; Libson, A.; Miercke, L. J.; Weitzman, C.; Nollert, P.; Krucinski, J.; Stroud, R. M. (2000-10-20). "Structure of a glycerol-conducting channel and the basis for its selectivity". Science. 290 (5491): 481â€“486. doi:10.1126/science.290.5491.481. ISSN 0036-8075. PMID 11039922.
- Hub, Jochen S.; de Groot, Bert L. (2008-01-29). "Mechanism of selectivity in aquaporins and aquaglyceroporins". Proceedings of the National Academy of Sciences of the United States of America. 105 (4): 1198â€“1203. doi:10.1073/pnas.0707662104. ISSN 1091-6490. PMC 2234115. PMID 18202181.
- Murata, K.; Mitsuoka, K.; Hirai, T.; Walz, T.; Agre, P.; Heymann, J. B.; Engel, A.; Fujiyoshi, Y. (2000-10-05). "Structural determinants of water permeation through aquaporin-1". Nature. 407 (6804): 599â€“605. doi:10.1038/35036519. ISSN 0028-0836. PMID 11034202.
- Jiang, Jiansheng; Daniels, Brenda V.; Fu, Dax (2006-01-06). "Crystal structure of AqpZ tetramer reveals two distinct Arg-189 conformations associated with water permeation through the narrowest constriction of the water-conducting channel". The Journal of Biological Chemistry. 281 (1): 454â€“460. doi:10.1074/jbc.M508926200. ISSN 0021-9258. PMID 16239219.
- TÃ¶rnroth-Horsefield, Susanna; Wang, Yi; Hedfalk, Kristina; Johanson, Urban; Karlsson, Maria; Tajkhorshid, Emad; Neutze, Richard; Kjellbom, Per (2006-02-09). "Structural mechanism of plant aquaporin gating". Nature. 439 (7077): 688â€“694. doi:10.1038/nature04316. ISSN 1476-4687. PMID 16340961.
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.
Major intrinsic protein Provide feedback
MIP (Major Intrinsic Protein) family proteins exhibit essentially two distinct types of channel properties: (1) specific water transport by the aquaporins, and (2) small neutral solutes transport, such as glycerol by the glycerol facilitators .
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000425
The major intrinsic protein (MIP) family is large and diverse, possessing over 100 members that form transmembrane channels. These channel proteins function in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2 and possibly ion transport, by an energy independent mechanism. They are found ubiquitously in bacteria, archaea and eukaryotes.
The MIP family contains two major groups of channels: aquaporins and glycerol facilitators. The known aquaporins cluster loosely together as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport water (but not glycerol) while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast FPS protein and tobacco NtTIPA may transport both water and small solutes.
The structures of various members of the MIP family have been determined by means of X-ray diffraction [ PUBMED:11780053 , PUBMED:10957645 , PUBMED:11039922 ], revealing the fold to comprise a right-handed bundle of 6 transmembrane (TM) alpha-helices [ PUBMED:11780053 , PUBMED:10957645 , PUBMED:11039922 ]. Similarities in the N-and C-terminal halves of the molecule suggest that the proteins may have arisen through tandem, intragenic duplication of an ancestral protein that contained 3 TM domains [ PUBMED:1715617 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||membrane (GO:0016020)|
|Molecular function||channel activity (GO:0015267)|
|Biological process||transmembrane transport (GO:0055085)|
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 clan groups families with an aquaporin-like structure comprising the canonical right-handed bundle of 6 transmembrane (TM) alpha-helices from aquaporins [1,2,3].
The clan contains the following 3 members:Form_Nir_trans MIP SpecificRecomb
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 and the UniProtKB 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
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.
|Author:||Finn RD , Delamarche C|
|Number in seed:||12|
|Number in full:||27928|
|Average length of the domain:||209.30 aa|
|Average identity of full alignment:||27 %|
|Average coverage of the sequence by the domain:||76.08 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||23|
|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 MIP domain has been found. There are 127 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...
AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.