Summary: V-ATPase subunit C
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V-ATPase Edit Wikipedia article
|V-ATPase, subunit c (Vo)|
|SCOP2||1aty / SCOPe / SUPFAM|
|V-ATPase, subunit C (V1)|
|SCOP2||1u7l / SCOPe / SUPFAM|
|V-ATPase, subunit I/a|
|SCOP2||3rrk / SCOPe / SUPFAM|
|V-ATPase, subunit E|
|V-ATPase, subunit d/d2|
|SCOP2||1r5z / SCOPe / SUPFAM|
|V-ATPase, subunit H, N-terminal|
|SCOP2||1ho8 / SCOPe / SUPFAM|
|V-ATPase, subunit G|
Vacuolar-type ATPase (V-ATPase) is a highly conserved evolutionarily ancient enzyme with remarkably diverse functions in eukaryotic organisms. V-ATPases acidify a wide array of intracellular organelles and pump protons across the plasma membranes of numerous cell types. V-ATPases couple the energy of ATP hydrolysis to proton transport across intracellular and plasma membranes of eukaryotic cells. It is generally seen as the polar opposite of ATP synthase because ATP synthase is a proton channel that uses the energy from a proton gradient to produce ATP. V-ATPase however, is a proton pump that uses the energy from ATP hydrolysis to produce a proton gradient.
The Archaea-type ATPase (A-ATPase) is a related group of ATPases found in Archaea that often work as an ATP synthase. It forms a clade V/A-ATPase with V-ATPase. Most members of either group shuttle protons (H+
), but a few members have evolved to use sodium ions (Na+
Roles played by V-ATPases
V-ATPases are found within the membranes of many organelles, such as endosomes, lysosomes, and secretory vesicles, where they play a variety of roles crucial for the function of these organelles. For example, the proton gradient across the yeast vacuolar membrane generated by V-ATPases drives calcium uptake into the vacuole through an H+
antiporter system. In synaptic transmission in neuronal cells, V-ATPase acidifies synaptic vesicles. Norepinephrine enters vesicles by V-ATPase.
V-ATPases are also found in the plasma membranes of a wide variety of cells such as intercalated cells of the kidney, osteoclasts (bone resorbing cells), macrophages, neutrophils, sperm, midgut cells of insects, and certain tumor cells. Plasma membrane V-ATPases are involved in processes such as pH homeostasis, coupled transport, and tumor metastasis. V-ATPases in the acrosomal membrane of sperm acidify the acrosome. This acidification activates proteases required to drill through the plasma membrane of the egg. V-ATPases in the osteoclast plasma membrane pump protons onto the bone surface, which is necessary for bone resorption. In the intercalated cells of the kidney, V-ATPases pump protons into the urine, allowing for bicarbonate reabsorption into the blood. In addition, other variety of biological processes, such as toxin delivery, viral entry, membrane targeting, apoptosis, regulation of cytoplasmic pH, proteolytic process, and acidification of intracellular systems, are important roles of V-ATPases.
V-ATPases also play a significant role in cell morphogenesis development. Disruption of the gene vma-1 gene which encodes for the catalytic subunit (A) of the enzyme severely impairs the rate of growth, differentiation, and the capacity to produce viable spores in fungus Neurospora crassa. 
The yeast V-ATPase is the best characterized. There are at least thirteen subunits identified to form a functional V-ATPase complex, which consists of two domains. The subunits belong to either the Vo domain (membrane associated subunits, lowercase letters on the figure) or the V1 domain (peripherally associated subunits, uppercase letters on the figure).
The V1 includes eight subunits, A-H, with three copies of the catalytic A and B subunits, three copies of the stator subunits E and G, and one copy of the regulatory C and H subunits. In addition, the V1 domain also contains the subunits D and F, which form a central rotor axle. The V1 domain contains tissue-specific subunit isoforms including B, C, E, and G. Mutations to the B1 isoform result in the human disease distal renal tubular acidosis and sensorineural deafness.
The Vo domain contains six different subunits, a, d, c, c', c", and e, with the stoichiometry of the c ring still a matter of debate with a decamer being postulated for the tobacco hornworm (Manduca sexta) V-ATPase. The mammalian Vo domain contains tissue-specific isoforms for subunits a and d, while yeast V-ATPase contains two organelle-specific subunit isoforms of a, Vph1p, and Stv1p. Mutations to the a3 isoform result in the human disease infantile malignant osteopetrosis, and mutations to the a4 isoform result in distal renal tubular acidosis, in some cases with sensorineural deafness.
The V1 domain is responsible for ATP hydrolysis, whereas the Vo domain is responsible for proton translocation. ATP hydrolysis at the catalytic nucleotide binding sites on subunit A drives rotation of a central stalk composed of subunits D and F, which in turn drives rotation of a barrel of c subunits relative to the a subunit. The complex structure of the V-ATPase has been revealed through the structure of the M. Sexta and Yeast complexes that were solved by single-particle cryo-EM and negative staining, respectively. These structures have revealed that the V-ATPase has a 3-stator network, linked by a collar of density formed by the C, H, and a subunits, which, while dividing the V1 and Vo domains, make no interactions with the central rotor axle formed by the F, D, and d subunits. Rotation of this central rotor axle caused by the hydrolysis of ATP within the catalytic AB domains results in the movement of the barrel of c subunits past the a subunit, which drives proton transport across the membrane. A stoichiometry of two protons translocated for each ATP hydrolyzed has been proposed by Johnson.
In addition to the structural subunits of yeast V-ATPase, associated proteins that are necessary for assembly have been identified. These associated proteins are essential for Vo domain assembly and are termed Vma12p, Vma21p, and Vma22p. Two of the three proteins, Vma12p and Vma22p, form a complex that binds transiently to Vph1p (subunit a) to aid its assembly and maturation. Vma21p coordinates assembly of the Vo subunits as well as escorting the Vo domain into vesicles for transport to the Golgi.
The V1 domain of the V-ATPase is the site of ATP hydrolysis. Unlike Vo, the V1 domain is hydrophilic. This soluble domain consists of a hexamer of alternating A and B subunits, a central rotor D, peripheral stators G and E, and regulatory subunits C and H. Hydrolysis of ATP drives a conformational change in the six A|B interfaces and with it rotation of the central rotor D. Unlike with the ATP synthase, the V1 domain is not an active ATPase when dissociated.
|A, B||ATP6V1A, ATP6V1B1, ATP6V1B2||Catalytic hexamer.|
|D||ATP6V1D||Central rotor stalk, responsible for ion specificity.|
|E, G||ATP6V1E1, ATP6V1E2, ATP6V1G1, ATP6V1G2, ATP6V1G3|
Subunit C function
The C subunit plays an essential role in controlling the assembly of V-ATPase, acting as a flexible stator that holds together the catalytic (V1) and membrane (VO) sectors of the enzyme . The release of subunit C from the ATPase complex results in the dissociation of the V1 and Vo subcomplexes, which is an important mechanism in controlling V-ATPase activity in cells. Essentially, by creating a high electrochemical gradient and low pH, this powers the enzyme to create more ATP.
Subunits E, G
These related subunits make up the stalk(s) of A/V-ATPase. They are important in assembly, and may function as pushrods in activity. E has a cap to connect to A/B, while G does not. They likely evolved from a single protein by gene duplication.
This subunit is only involved in activity and not in assembly. This subunit also acts as an inhibitor of free V1 subunits; it stops ATP hydrolysis when V1 and Vo are dissociated.
The Vo domain is responsible for proton translocation. Unlike the F-type ATP synthase, the Vo domain generally transports protons against their own concentration gradient. Rotation of the Vo domain transports the protons in movement coordinated with the V1 domain, which is responsible for ATP hydrolysis. The Vo domain is hydrophobic and composed of several dissociable subunits. These subunits are present in the Vo domain to make this a functional proton translocase; they are described below.
|a/I||ATP6V0A1, ATP6V0A2, ATP6V0A4|
|c||ATP6V0B, ATP6V0C||Ring of varied size.|
|e||ATP6V0E1, ATP6V0E2||9 kDa hydrophobic assembly protein.|
The 116kDa subunit (or subunit a) and subunit I are found in the Vo or Ao complex of V- or A-ATPases, respectively. The 116kDa subunit is a transmembrane glycoprotein required for the assembly and proton transport activity of the ATPase complex. Several isoforms of the 116kDa subunit exist, providing a potential role in the differential targeting and regulation of the V-ATPase for specific organelles.
The function of the 116-kDa subunit is not defined, but its predicted structure consists of 6â€“8 transmembranous sectors, suggesting that it may function similar to subunit a of FO.
Subunit d in V-ATPases, called subunit C in A-ATpases, is a part of the Vo complex. They fit onto the middle of the c ring, so are thought to function as a rotor. There are two versions of this subunit in eukaryotes, d/d1 and d2.
Similar to the F-type ATP synthase, the transmembrane region of the V-ATPase includes a ring of membrane-spanning subunits that are primarily responsible for proton translocation. Dissimilar from the F-type ATP synthase, however, the V-ATPase has multiple related subunits in the c-ring; in fungi such as yeast there are three related subunits (of varied stoichiometry) and in most other eukaryotes there are two.
Yeast V-ATPases fail to assemble when any of the genes that encode subunits are deleted except for subunits H and c". Without subunit H, the assembled V-ATPase is not active, and the loss of the c" subunit results in uncoupling of enzymatic activity.
The precise mechanisms by which V-ATPases assembly are still controversial, with evidence suggesting two different possibilities. Mutational analysis and in vitro assays have shown that preassembled Vo and V1 domains can combine to form one complex in a process called independent assembly. Support for independent assembly includes the findings that the assembled Vo domain can be found at the vacuole in the absence of the V1 domain, whereas free V1 domains can be found in the cytoplasm and not at the vacuole. In contrast, in vivo pulse-chase experiments have revealed early interactions between Vo and V1 subunits, to be specific, the a and B subunits, suggesting that subunits are added in a step-wise fashion to form a single complex in a concerted assembly process.
A relatively new technique called ancestral gene resurrection has shed new light on the evolutionary history of the V-ATPase. It has been shown how the V-ATPase structure of the ancestral form consisting of two different proteins evolves into the fungi version with three different proteins. The V-Type ATPase is similar to the archaeal (so called) A-Type ATP synthase, a fact that supports an archaeal origin of eukaryotes (like Eocyte Hypothesis, see also Lokiarchaeota). The exceptional occurrence of some lineages of archaea with F-type and of some lineages of bacteria with A-type ATPase respectively is regarded as a result of horizontal gene transfer.
Regulation of V-ATPase activity
V-ATPases are known to be specifically inhibited by macrolide antibiotics, such as concanamycin (CCA) and balifomycin A1. In vivo regulation of V-ATPase activity is accomplished by reversible dissociation of the V1 domain from the Vo domain. After initial assembly, both the insect Manduca sexta and yeast V-ATPases can reversibly disassemble into free Vo and V1 domains after a 2- to 5-minute deprivation of glucose. Reversible disassembly may be a general mechanism of regulating V-ATPase activity, since it exists in yeast and insects. Reassembly is proposed to be aided by a complex termed RAVE (regulator of H+
-ATPase of vacuolar and endosomal membranes). Disassembly and reassembly of V-ATPases does not require new protein synthesis but does need an intact microtubular network.
Osteopetrosis is generic name that represents a group of heritable conditions in which there is a defect in osteoclastic bone resorption. Both dominant and recessive osteopetrosis occur in humans. Autosomal dominant osteopetrosis shows mild symptoms in adults experiencing frequent bone fractures due to brittle bones. A more severe form of osteopetrosis is termed autosomal recessive infantile malignant osteopetrosis. Three genes that are responsible for recessive osteopetrosis in humans have been identified. They are all directly involved in the proton generation and secretion pathways that are essential for bone resorption. One gene is carbonic anhydrase II (CAII), which, when mutated, causes osteopetrosis with renal tubular acidosis(type 3). Mutations to the chloride channel ClC7 gene also lead to both dominant and recessive osteopetrosis. Approximately 50% of patients with recessive infantile malignant osteopetrosis have mutations to the a3 subunit isoform of V-ATPase.  In humans, 26 mutations have been identified in V-ATPase subunit isoform a3, found in osteoclasts, that result in the bone disease autosomal recessive osteopetrosis.
Distal renal tubular acidosis (dRTA)
The importance of V-ATPase activity in renal proton secretion is highlighted by the inherited disease distal renal tubular acidosis. In all cases, renal tubular acidosis results from a failure of the normal renal mechanisms that regulate systemic pH. There are four types of renal tubular acidosis. Type 1 is distal renal tubular acidosis and results from a failure of the cortical collecting duct to acidify the urine below pH 5. Some patients with autosomal recessive dRTA also have sensorineural hearing loss. Inheritance of this type of RTA results from either mutations to V-ATPase subunit isoform B1 or isoform a4 or mutations of band 3 (also called AE1), a Cl-/HCO3- exchanger. Twelve different mutations to V-ATPase isoform B1 and twenty-four different mutations in a4 lead to dRTA. Reverse transcription polymerase chain reaction studies have shown expression of the a4 subunit in the intercalated cell of the kidney and in the cochlea. dRTA caused by mutations in the a4 subunit gene in some cases can be associated with deafness due to a failure to normally acidify the endolymph of the inner ear.
X-linked myopathy with excessive autophagy is a rare genetic disease resulting from mutations in the VMA21 gene. The disease has a childhood onset and results in a slowly progressive muscle weakness, typically beginning in the legs, and some patients can eventually require wheelchair assistance with advanced age. The Vma21 protein assists in assembly of the V-ATPase, and XMEA associated mutations result in decreased activity of the V-ATPase and increased lysosomal pH.
The term Vo has a lowercase letter "o" (not the number "zero") in subscript. The "o" stands for oligomycin, which binds to the homologous region in F-ATPase. It is worth noting that the human gene notations at NCBI designate it as "zero" rather than the letter "o". For example, the gene for the human c subunit of Vo is listed in NCBI gene database as "ATP6V0C" (with a zero), rather than "ATP6VOC" (with an "o"). Many pieces of literature make this mistake as well.
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- Frattini A, Orchard PJ, Sobacchi C, Giliani S, Abinun M, Mattsson JP, Keeling DJ, Andersson AK, Wallbrandt P, Zecca L, Notarangelo LD, Vezzoni P, Villa A (July 2000). "Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis". Nature Genetics. 25 (3): 343â€“6. doi:10.1038/77131. PMIDÂ 10888887. S2CIDÂ 21316081.
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- Fasth A, Porras O (1999). "Human malignant osteopetrosis: pathophysiology, management and the role of bone marrow transplantation". Pediatric Transplantation. 3 Suppl 1 (Suppl 1): 102â€“7. doi:10.1034/j.1399-3046.1999.00063.x. PMIDÂ 10587979. S2CIDÂ 31745272.
- Sly WS, Hewett-Emmett D, Whyte MP, Yu YS, Tashian RE (May 1983). "Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification". Proceedings of the National Academy of Sciences of the United States of America. 80 (9): 2752â€“6. Bibcode:1983PNAS...80.2752S. doi:10.1073/pnas.80.9.2752. PMCÂ 393906. PMIDÂ 6405388.
- Kornak U, Schulz A, Friedrich W, Uhlhaas S, Kremens B, Voit T, Hasan C, Bode U, Jentsch TJ, Kubisch C (August 2000). "Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis". Human Molecular Genetics. 9 (13): 2059â€“63. doi:10.1093/hmg/9.13.2059. PMIDÂ 10942435.
- Frattini A, Pangrazio A, Susani L, Sobacchi C, Mirolo M, Abinun M, Andolina M, Flanagan A, Horwitz EM, Mihci E, Notarangelo LD, Ramenghi U, Teti A, Van Hove J, Vujic D, Young T, Albertini A, Orchard PJ, Vezzoni P, Villa A (October 2003). "Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis". Journal of Bone and Mineral Research. 18 (10): 1740â€“7. doi:10.1359/jbmr.2003.18.10.1740. PMIDÂ 14584882. S2CIDÂ 20966489.
- Susani L, Pangrazio A, Sobacchi C, Taranta A, Mortier G, Savarirayan R, Villa A, Orchard P, Vezzoni P, Albertini A, Frattini A, Pagani F (September 2004). "TCIRG1-dependent recessive osteopetrosis: mutation analysis, functional identification of the splicing defects, and in vitro rescue by U1 snRNA". Human Mutation. 24 (3): 225â€“35. doi:10.1002/humu.20076. PMIDÂ 15300850. S2CIDÂ 31788054.
- Alper SL (2002). "Genetic diseases of acid-base transporters". Annual Review of Physiology. 64: 899â€“923. doi:10.1146/annurev.physiol.64.092801.141759. PMIDÂ 11826292.
- Karet FE, Finberg KE, Nelson RD, Nayir A, Mocan H, Sanjad SA, etÂ al. (January 1999). "Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness". Nature Genetics. 21 (1): 84â€“90. doi:10.1038/5022. PMIDÂ 9916796. S2CIDÂ 34262548.
- Karet FE, Gainza FJ, GyÃ¶ry AZ, Unwin RJ, Wrong O, Tanner MJ, etÂ al. (May 1998). "Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis". Proceedings of the National Academy of Sciences of the United States of America. 95 (11): 6337â€“42. Bibcode:1998PNAS...95.6337K. doi:10.1073/pnas.95.11.6337. PMCÂ 27686. PMIDÂ 9600966.
- Stehberger PA, Schulz N, Finberg KE, Karet FE, Giebisch G, Lifton RP, Geibel JP, Wagner CA (December 2003). "Localization and regulation of the ATP6V0A4 (a4) vacuolar H+-ATPase subunit defective in an inherited form of distal renal tubular acidosis". Journal of the American Society of Nephrology. 14 (12): 3027â€“38. doi:10.1097/01.ASN.0000099375.74789.AB. PMIDÂ 14638902.
- Stover EH, Borthwick KJ, Bavalia C, Eady N, Fritz DM, Rungroj N, etÂ al. (November 2002). "Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss". Journal of Medical Genetics. 39 (11): 796â€“803. doi:10.1136/jmg.39.11.796. PMCÂ 1735017. PMIDÂ 12414817.
- Ramachandran N, Munteanu I, Wang P, Ruggieri A, Rilstone JJ, Israelian N, etÂ al. (March 2013). "VMA21 deficiency prevents vacuolar ATPase assembly and causes autophagic vacuolar myopathy". Acta Neuropathologica. 125 (3): 439â€“57. doi:10.1007/s00401-012-1073-6. PMIDÂ 23315026. S2CIDÂ 20528180.
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.
V-ATPase subunit C Provide feedback
No Pfam abstract.
This tab holds annotation information from the InterPro database.
InterPro entry IPR004907
V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra- and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release [ PUBMED:15629643 ]. V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins [ PUBMED:15907459 ].
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.
There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [ PUBMED:15473999 , PUBMED:15078220 ]. The different types include:
- F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).
- V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [ PUBMED:20450191 ]. They are also found in bacteria [ PUBMED:9741106 ].
- A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [ PUBMED:18937357 , PUBMED:1385979 ].
- P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
- E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.
This entry represents the C subunit that is part of the V1 complex, and is localised to the interface between the V1 and V0 complexes [ PUBMED:15951435 ]. This subunit does not show any homology with F-ATPase subunits. The C subunit plays an essential role in controlling the assembly of V-ATPase, acting as a flexible stator that holds together the catalytic (V1) and membrane (V0) sectors of the enzyme [ PUBMED:15540116 ]. The release of subunit C from the ATPase complex results in the dissociation of the V1 and V0 subcomplexes, which is an important mechanism in controlling V-ATPase activity in cells.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||proton-transporting V-type ATPase, V1 domain (GO:0033180)|
|Molecular function||proton transmembrane transporter activity (GO:0015078)|
|Biological process||proton transmembrane transport (GO:1902600)|
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.
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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.
|Seed source:||Pfam-B_2945 (release 6.5)|
|Number in seed:||113|
|Number in full:||2776|
|Average length of the domain:||324.70 aa|
|Average identity of full alignment:||40 %|
|Average coverage of the sequence by the domain:||91.07 %|
|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:||18|
|Download:||download the raw HMM for this family|
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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 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 V-ATPase_C domain has been found. There are 25 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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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.