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 "Hepcidin". 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.
Hepcidin Edit Wikipedia article
|, HEPC, HFE2B, LEAP1, PLTR, hepcidin antimicrobial peptide|
|RNA expression pattern|
|hepcidin antimicrobial peptide|
|Locus||Chr. 19 q13.1|
In states in which the hepcidin level is abnormally high such as inflammation, serum iron falls due to iron trapping within macrophages and liver cells and decreased gut iron absorption. This typically leads to anemia due to an inadequate amount of serum iron being available for developing red cells. When the hepcidin level is abnormally low such as in hemochromatosis, iron overload occurs due to increased ferroportin mediated iron efflux from storage and increased gut iron absorption.
In lab mice, hepcidin has been found to have anti-inflammatory properties. This is a negative feedback: it reduces the inflammation which caused the elevated hepcidin level.
It is a peptide hormone synthesized mainly in the liver which was discovered in 2000. It reduces dietary iron absorption by reducing iron transport across the gut mucosa (enterocytes); it reduces iron exit from macrophages, the main site of iron storage; and it reduces iron exit from the liver. In all three instances this is accomplished by reducing the transmembrane iron transporter ferroportin.
Hepcidin exists as a preprohormone (84 amino acids), prohormone (60 amino acids), and hormone (25 amino acids). Twenty- and 22-amino acid metabolites of hepcidin also exist in the urine. Deletion of 5 N-terminal amino acids results in loss of function. The conversion of prohepcidin to hepcidin is mediated by the prohormone convertase furin. This conversion may be regulated by alpha-1 antitrypsin.
Hepcidin is a tightly folded polypeptide with 32% beta sheet character and a hairpin structure stabilized by 4 disulfide bonds. The structure of hepcidin has been determined through solution NMR. NMR studies showed a new model for hepcidin: at ambient temperatures, the protein interconverts between two conformations, which could be individually resolved by temperature variation. The solution structure of hepcidin was determined at 325 K and 253 K in supercooled water. X-ray analysis of a co-crystal with Fab revealed a structure similar to the high-temperature NMR structure.
Hepcidin is a regulator of iron metabolism. Hepcidin inhibits iron transport by binding to the iron export channel ferroportin which is located on the basolateral surface of gut enterocytes and the plasma membrane of reticuloendothelial cells (macrophages). Hepcidin ultimately breaks down the transporter protein in the lysosome. Inhibiting ferroportin prevents iron from being exported and the iron is sequestered in the cells. By inhibiting ferroportin, hepcidin prevents enterocytes from allowing iron into the hepatic portal system, thereby reducing dietary iron absorption. The iron release from macrophages is also reduced by ferroportin inhibition. Increased hepcidin activity is partially responsible for reduced iron availability seen in anemia of chronic inflammation. such as renal failure.
Any one of several mutations in hepcidin result in juvenile hemochromatosis. The majority of juvenile hemochromatosis cases are due to mutations in hemojuvelin. Mutations in TMPRSS6 can cause anemia through dysregulation of Hepcidin
Hepcidin has strong antimicrobial activity against E.coli ML35P N.cinerea and weaker antimicrobial activity against S.epidermidis, S.aureus and Group B streptococcus bacteria. Active against the fungus C.albicans. No activity against P.aeruginosa.
Hepcidin synthesis and secretion by the liver is controlled by iron stores within macrophages, inflammation, hypoxia, and erythropoiesis. Macrophages communicate with the hepatocyte to regulate hepcidin release into the circulation via eight different proteins: hemojuvelin, heriditrary hemochromatosis protein, transferrin receptor 2, bone morphogenic protein 6 (BMP6), matriptase-2, neogenin, BMP receptors, and transferrin.
Vitamin D has been shown to decrease hepcidin, in cell models looking at transcription and when given in big doses to human volunteers. Optimal function of hepcidin may be predicated upon the adequate presence of vitamin D in the blood.
The peptide was initially named LEAP-1, for Liver-Expressed Antimicrobial Protein. Later, a peptide associated with inflammation was discovered, and named "hepcidin" after it was observed that it was produced in the liver ("hep-") and appeared to have bactericidal properties ("-cide" for "killing"). Although it is primarily synthesized in the liver, smaller amounts are synthesised in other tissues such as fat cells.
Soon after this discovery, researchers discovered that hepcidin production in mice increases in conditions of iron overload as well as in inflammation. Genetically modified mice engineered to overexpress hepcidin died shortly after birth with severe iron deficiency, again suggesting a central and not redundant role in iron regulation. The first evidence that linked hepcidin to the clinical condition known as the anemia of inflammation came from the lab of Nancy Andrews in Boston when researchers looked at tissue from two patients with liver tumors with a severe microcytic anemia that did not respond to iron supplements. The tumor tissue appeared to be overproducing hepcidin, and contained large quantities of hepcidin mRNA. Removing the tumors surgically cured the anemia.
Taken together, these discoveries suggested that hepcidin regulates the absorption of iron into the body.
There are many diseases where failure to adequately absorb iron contributes to iron deficiency and iron deficiency anaemia. The treatment will depend on the hepcidin levels that are present, as oral treatment will be unlikely to be effective if hepcidin is blocking enteral absorption, in which cases parenteral iron treatment would be appropriate. Studies have found that measuring hepcidin would be of benefit to establish optimal treatment, although as this is not widely available, C-reactive protein (CRP) is used as a surrogate marker.
β-thalassemia, one of the most common congenital anemias, arises from partial or complete lack of β-globin synthesis. Excessive iron absorption is one of the main features of β-thalassemia and can lead to severe morbidity and mortality. The serial analyses of β-thalassemic mice indicate hemoglobin levels decreases over time, while the concentration of iron in the liver, spleen, and kidneys markedly increases. The overload of iron is associated with low levels of hepcidin. Patients with β-thalassemia also have low hepcidin levels. The observations led researchers to hypothesize that more iron is absorbed in β-thalassemia than is required for erythropoiesis. Increasing expression of hepcidin in β-thalassemic mice limits iron overload, and also decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. From these data, researchers suggested that therapeutics to increase hepcidin levels or act as hepcidin agonists could help treat the abnormal iron absorption in individuals with β-thalassemia and related disorders. In later studies in mice, erythroferrone has been suggested to be the factor that is responsible for the hepcidin suppression. Correcting hepcidin and iron levels in these mice did not improve their anemia.
- "Human PubMed Reference:".
- doi:10.1074/jbc.M205305200. PMID 12138110.; Hunter HN, Fulton DB, Ganz T, Vogel HJ (October 2002). "The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis". J. Biol. Chem. 277 (40): 37597–603.
- Ganz T (August 2003). "Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation". Blood. 102 (3): 783–8. doi:10.1182/blood-2003-03-0672. PMID 12663437.
- De Domenico I, Zhang TY, Koening CL, Branch RW, London N, Lo E, Daynes RA, Kushner JP, Li D, Ward DM, Kaplan J (July 2010). "Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice". J. Clin. Invest. 120 (7): 2395–405. doi:10.1172/JCI42011. PMC . PMID 20530874.
- Valore EV, Ganz T (2008). "Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin". Blood Cells Mol. Dis. 40 (1): 132–8. doi:10.1016/j.bcmd.2007.07.009. PMC . PMID 17905609.
- Pandur E, Nagy J, Poór VS, Sarnyai A, Huszár A, Miseta A, Sipos K (April 2009). "Alpha-1 antitrypsin binds preprohepcidin intracellularly and prohepcidin in the serum". FEBS J. 276 (7): 2012–21. doi:10.1111/j.1742-4658.2009.06937.x. PMID 19292870.
- "Hepcidin revisited, disulfide connectivity, dynamics, and structure". J. Biol. Chem. 284 (36): 24155–67. doi:10.1074/jbc.M109.017764. PMC . PMID 19553669.; Jordan JB, Poppe L, Haniu M, Arvedson T, Syed R, Li V, Kohno H, Kim H, Schnier PD, Harvey TS, Miranda LP, Cheetham J, Sasu BJ (September 2009).
- Rossi E (August 2005). "Hepcidin--the iron regulatory hormone". Clin Biochem Rev. 26 (3): 47–9. PMC . PMID 16450011.
- Gulec S, Anderson GJ, Collins JF (Aug 2014). "Mechanistic and regulatory aspects of intestinal iron absorption.". AJP: Gastrointestinal and Liver Physiology. 307: G397–409. doi:10.1152/ajpgi.00348.2013. PMC . PMID 24994858.
- Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND, Cairns TD, Taube DH, Bloom SR, Tam FW, Chapman RS, Maxwell PH, Choi P (May 2009). "Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease". Kidney Int. 75 (9): 976–81. doi:10.1038/ki.2009.21. PMID 19212416.
- Core, AB; Canali, S; Babitt, JL (2014). "Hemojuvelin and bone morphogenetic protein (BMP) signaling in iron homeostasis.". Frontiers in Pharmacology. 5: 104. doi:10.3389/fphar.2014.00104. PMC . PMID 24860505.
- Iron-Deficiency Anemia: New Insights for the Healthcare Professional: 2011 Edition. Scholarly Media LLC. Dec 2012. ISBN 978-1-4649-8960-5.
- Zhao N, Zhang AS, Enns CA (2013). "Iron regulation by hepcidin.". J Clin Invest. 123 (6): 2337–43. doi:10.1172/JCI67225. PMC . PMID 23722909.
- Koury, M.J. "Erythroferrone: A Missing Link in Iron Regulation". The Hematologist. American Society of Hematology. Retrieved 26 August 2015.
- Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T (Jul 2014). "Identification of erythroferrone as an erythroid regulator of iron metabolism". Nature Genetics. 46 (7): 678–84. doi:10.1038/ng.2996. PMC . PMID 24880340.
- Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, Nayak A, Wesseling-Perry K, Westerman M, Hollis BW, Salusky IB, Hewison M (2014). "Suppression of iron-regulatory hepcidin by vitamin D". J. Am. Soc. Nephrol. 25 (3): 564–72. doi:10.1681/ASN.2013040355. PMC . PMID 24204002.
- Krause A, Neitz S, Mägert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K (September 2000). "LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity". FEBS Lett. 480 (2–3): 147–50. doi:10.1016/S0014-5793(00)01920-7. PMID 11034317.
- Park CH, Valore EV, Waring AJ, Ganz T (March 2001). "Hepcidin, a urinary antimicrobial peptide synthesized in the liver". J. Biol. Chem. 276 (11): 7806–10. doi:10.1074/jbc.M008922200. PMID 11113131.
- Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B, Iannelli A, Staccini-Myx A, Casanova D, Ben Amor I, Saint-Paul MC, Huet PM, Sadoul JL, Gugenheim J, Srai SK, Tran A, Le Marchand-Brustel Y (September 2006). "Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH". Gastroenterology. 131 (3): 788–96. doi:10.1053/j.gastro.2006.07.007. PMID 16952548.
- Kemna EH, Tjalsma H, Willems HL, Swinkels DW (January 2008). "Hepcidin: from discovery to differential diagnosis". Haematologica. 93 (1): 90–7. doi:10.3324/haematol.11705. PMID 18166790.
- Bregman DB, Morris D, Koch TA, He A, Goodnough LT (February 2013). "Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia". Am. J. Hematol. 88 (2): 97–101. doi:10.1002/ajh.23354. PMID 23335357.
- Gardenghi S, Ramos P, Marongiu MF, Melchiori L, Breda L, Guy E, Muirhead K, Rao N, Roy CN, Andrews NC, Nemeth E, Follenzi A, An X, Mohandas N, Ginzburg Y, Rachmilewitz EA, Giardina PJ, Grady RW, Rivella S (December 2010). "Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice". J. Clin. Invest. 120 (12): 4466–77. doi:10.1172/JCI41717. PMC . PMID 21099112.
- Kroot JJ, Tjalsma H, Fleming RE, Swinkels DW (December 2011). "Hepcidin in human iron disorders: diagnostic implications". Clin. Chem. 57 (12): 1650–69. doi:10.1373/clinchem.2009.140053. PMID 21989113.
- Moura IC, Hermine O (2015). "Erythroferrone: the missing link in β-thalassemia?". Blood. 126 (17): 1974–5. doi:10.1182/blood-2015-09-665596. PMID 26494918.
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.
Hepcidin Provide feedback
Hepcidin is a antibacterial and antifungal protein expressed in the liver and is also a signaling molecule in iron metabolism. The hepcidin protein is cysteine-rich and forms a distorted beta-sheet with an unusual disulphide bond found at the turn of the hairpin .
Hunter HN, Fulton DB, Ganz T, Vogel HJ; , J Biol Chem 2002;277:37597-37603.: The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. PUBMED:12138110 EPMC:12138110
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR010500
Hepcidin is a antibacterial and anti-fungal protein expressed in the liver and is also a signalling molecule in iron metabolism. The hepcidin protein is cysteine-rich and forms a distorted beta-sheet with an unusual disulphide bond found at the turn of the hairpin [PUBMED:12138110].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||extracellular region (GO:0005576)|
|Biological process||cellular iron ion homeostasis (GO:0006879)|
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...
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_41732 (release 9.0)|
|Number in seed:||19|
|Number in full:||57|
|Average length of the domain:||52.50 aa|
|Average identity of full alignment:||42 %|
|Average coverage of the sequence by the domain:||61.00 %|
|HMM build commands:||
build method: hmmbuild --amino -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||11|
|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 Hepcidin domain has been found. There are 11 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
Loading structure mapping...