Summary: Intermediate filament 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 "Intermediate filament". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at firstname.lastname@example.org and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Intermediate filament Edit Wikipedia article
|Intermediate filament tail domain|
|SCOP2||1ivt / SCOPe / SUPFAM|
|Intermediate filament rod domain|
|SCOP2||1gk7 / SCOPe / SUPFAM|
|Intermediate filament head (DNA binding) region|
|SCOP2||1gk7 / SCOPe / SUPFAM|
|Peripherin neuronal intermediate filament protein|
|Locus||Chr. 12 q13.12|
|Nestin neuronal stem cell intermediate filament protein|
|Locus||Chr. 1 q23.1|
Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate Branchiostoma.
Intermediate filaments are composed of a family of related proteins sharing common structural and sequence features. Initially designated 'intermediate' because their average diameter (10Â nm) is between those of narrower microfilaments (actin) and wider myosin filaments found in muscle cells, the diameter of intermediate filaments is now commonly compared to actin microfilaments (7Â nm) and microtubules (25Â nm). Animal intermediate filaments are subcategorized into six types based on similarities in amino acid sequence and protein structure. Most types are cytoplasmic, but one type, Type V is a nuclear lamin. Unlike microtubules, IF distribution in cells show no good correlation with the distribution of either mitochondria or endoplasmic reticulum.
The structure of proteins that form intermediate filaments (IF) was first predicted by computerized analysis of the amino acid sequence of a human epidermal keratin derived from cloned cDNAs. Analysis of a second keratin sequence revealed that the two types of keratins share only about 30% amino acid sequence homology but share similar patterns of secondary structure domains. As suggested by the first model, all IF proteins appear to have a central alpha-helical rod domain that is composed of four alpha-helical segments (named as 1A, 1B, 2A and 2B) separated by three linker regions.
The central building block of an intermediate filament is a pair of two intertwined proteins that is called a coiled-coil structure. This name reflects the fact that the structure of each protein is helical, and the intertwined pair is also a helical structure. Structural analysis of a pair of keratins shows that the two proteins that form the coiled-coil bind by hydrophobic. The charged residues in the central domain do not have a major role in the binding of the pair in the central domain.
Cytoplasmic IFs assemble into non-polar unit-length filaments (ULFs). Identical ULFs associate laterally into staggered, antiparallel, soluble tetramers, which associate head-to-tail into protofilaments that pair up laterally into protofibrils, four of which wind together into an intermediate filament. Part of the assembly process includes a compaction step, in which ULF tighten and assume a smaller diameter. The reasons for this compaction are not well understood, and IF are routinely observed to have diameters ranging between 6 and 12Â nm.
The N-terminus and the C-terminus of IF proteins are non-alpha-helical regions and show wide variation in their lengths and sequences across IF families. The N-terminal "head domain" binds DNA. Vimentin heads are able to alter nuclear architecture and chromatin distribution, and the liberation of heads by HIV-1 protease may play an important role in HIV-1 associated cytopathogenesis and carcinogenesis. Phosphorylation of the head region can affect filament stability. The head has been shown to interact with the rod domain of the same protein.
The anti-parallel orientation of tetramers means that, unlike microtubules and microfilaments, which have a plus end and a minus end, IFs lack polarity and cannot serve as basis for cell motility and intracellular transport.
IFs are rather deformable proteins that can be stretched several times their initial length. The key to facilitate this large deformation is due to their hierarchical structure, which facilitates a cascaded activation of deformation mechanisms at different levels of strain. Initially the coupled alpha-helices of unit-length filaments uncoil as they're strained, then as the strain increases they transition into beta-sheets, and finally at increased strain the hydrogen bonds between beta-sheets slip and the ULF monomers slide along each other.
There are about 70 different human genes coding for various intermediate filament proteins. However, different kinds of IFs share basic characteristics: In general, they are all polymers that measure between 9-11Â nm in diameter when fully assembled.
Types I and II â€“ acidic and basic keratins
- epithelial keratins (about 20) in epithelial cells (image to right)
- trichocytic keratins (about 13) (hair keratins), which make up hair, nails, horns and reptilian scales.
Regardless of the group, keratins are either acidic or basic. Acidic and basic keratins bind each other to form acidic-basic heterodimers and these heterodimers then associate to make a keratin filament.
Cytokeratin filaments laterally associate with each other to create a thick bundle of ~50nm radius. The optimal radius of such bundles is determined by the interplay between the long range electrostatic repulsion and short range hydrophobic attraction. Subsequently, these bundles would intersect through junctions to form a dynamic network, spanning the cytoplasm of epithelial cells.
- Desmin IFs are structural components of the sarcomeres in muscle cells and connect different cell organells like the desmosomes with the cytoskeleton.
- Glial fibrillary acidic protein (GFAP) is found in astrocytes and other glia.
- Peripherin found in peripheral neurons.
- Vimentin, the most widely distributed of all IF proteins, can be found in fibroblasts, leukocytes, and blood vessel endothelial cells. They support the cellular membranes, keep some organelles in a fixed place within the cytoplasm, and transmit membrane receptor signals to the nucleus.
- Syncoilin is an atypical type III IF protein.
- Neurofilaments - the type IV family of intermediate filaments that is found in high concentrations along the axons of vertebrate neurons.
Type V â€“ nuclear lamins
Lamins are fibrous proteins having structural function in the cell nucleus.
In metazoan cells, there are A and B type lamins, which differ in their length and pI. Human cells have three differentially regulated genes. B-type lamins are present in every cell. B type lamins, lamin B1 and B2, are expressed from the LMNB1 and LMNB2 genes on 5q23 and 19q13, respectively. A-type lamins are only expressed following gastrulation. Lamin A and C are the most common A-type lamins and are splice variants of the LMNA gene found at 1q21.
These proteins localize to two regions of the nuclear compartment, the nuclear laminaâ€”a proteinaceous structure layer subjacent to the inner surface of the nuclear envelope and throughout the nucleoplasm in the nucleoplasmic veil.
Comparison of the lamins to vertebrate cytoskeletal IFs shows that lamins have an extra 42 residues (six heptads) within coil 1b. The c-terminal tail domain contains a nuclear localization signal (NLS), an Ig-fold-like domain, and in most cases a carboxy-terminal CaaX box that is isoprenylated and carboxymethylated (lamin C does not have a CAAX box). Lamin A is further processed to remove the last 15 amino acids and its farnesylated cysteine.
During mitosis, lamins are phosphorylated by MPF, which drives the disassembly of the lamina and the nuclear envelope.
- Beaded filaments: Filensin, Phakinin.
- Nestin (was once proposed for reclassification but due to differences, remains as a type VI IF protein)
Vertebrate-only. Related to type I-IV. Used to contain other newly-discovered IF proteins not yet assigned to a type.
Filaggrin binds to keratin fibers in epidermal cells. Plectin links vimentin to other vimentin fibers, as well as to microfilaments, microtubules, and myosin II. Kinesin is being researched and is suggested to connect vimentin to tubulin via motor proteins.
Keratin filaments in epithelial cells link to desmosomes (desmosomes connect the cytoskeleton together) through plakoglobin, desmoplakin, desmogleins, and desmocollins; desmin filaments are connected in a similar way in heart muscle cells.
Diseases arising from mutations in IF genes
- Dilated cardiomyoathy (DCM), mutations in the DES gene
- Arrhythmogenic cardiomyopathy (ACM), mutations in the DES gene
- Restrictive cardiomyopathy (RCM), mutations in the DES gene
- Non-compaction cardiomyopathy, mutations in the DES genes
- Cardiomyopathy in combination with skeletal myopathy (DES)
- Epidermolysis bullosa simplex; keratin 5 or keratin 14 mutation
- Laminopathies are a family of diseases caused by mutations in nuclear lamins and include Hutchinson Gilford progeria syndrome and various lipodystrophies and cardiomyopathies among others.
In other organisms
IF proteins are universal among animals in the form of a nuclear lamin. The Hydra has an additional "nematocilin" derived from the lamin. Cytoplasmic IFs (type I-IV) found in humans are widespread in Bilateria; they also arose from a gene duplication event involving "type V" nuclear lamin. In addition, a few other diverse types of Eukaryotes have lamins, suggesting an early origin of the protein.
There was not really a concrete definition of an "intermediate filament protein", in the sense that the size or shape-based definition does not cover a monophyletic group. With the inclusion of unusual proteins like the network-forming beaded lamins (type VI), the current classification is moving to a clade containing nuclear lamin and its many descendents, characterized by sequence similarity as well as the exon structure. Functionally-similar proteins out of this clade, like crescentins, alveolins, tetrins, and epiplasmins, are therefore only "IF-like". They likely arose through convergent evolution.
- Herrmann H, BÃ¤r H, Kreplak L, Strelkov SV, Aebi U (July 2007). "Intermediate filaments: from cell architecture to nanomechanics". Nature Reviews. Molecular Cell Biology. 8 (7): 562â€“73. doi:10.1038/nrm2197. PMIDÂ 17551517. S2CIDÂ 27115011.
- Chang L, Goldman RD (August 2004). "Intermediate filaments mediate cytoskeletal crosstalk". Nature Reviews. Molecular Cell Biology. 5 (8): 601â€“13. doi:10.1038/nrm1438. PMIDÂ 15366704. S2CIDÂ 31835055.
- Traub, P. (2012), Intermediate Filaments: A Review, Springer Berlin Heidelberg, p.Â 33, ISBNÂ 9783642702303CS1 maint: uses authors parameter (link)
- Karabinos A, Riemer D, Erber A, Weber K (October 1998). "Homologues of vertebrate type I, II and III intermediate filament (IF) proteins in an invertebrate: the IF multigene family of the cephalochordate Branchiostoma". FEBS Letters. 437 (1â€“2): 15â€“8. doi:10.1016/S0014-5793(98)01190-9. PMIDÂ 9804163. S2CIDÂ 7886395.
- Ishikawa H, Bischoff R, Holtzer H (September 1968). "Mitosis and intermediate-sized filaments in developing skeletal muscle". The Journal of Cell Biology. 38 (3): 538â€“55. doi:10.1083/jcb.38.3.538. PMCÂ 2108373. PMIDÂ 5664223.
- Szeverenyi I, Cassidy AJ, Chung CW, Lee BT, Common JE, Ogg SC, etÂ al. (March 2008). "The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases". Human Mutation. 29 (3): 351â€“360. doi:10.1002/humu.20652. PMIDÂ 18033728.
- Soltys BJ, Gupta RS (1992). "Interrelationships of endoplasmic reticulum, mitochondria, intermediate filaments, and microtubules--a quadruple fluorescence labeling study". Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. 70 (10â€“11): 1174â€“86. doi:10.1139/o92-163. PMIDÂ 1363623.
- Hanukoglu I, Fuchs E (November 1982). "The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins". Cell. 31 (1): 243â€“52. doi:10.1016/0092-8674(82)90424-X. PMIDÂ 6186381. S2CIDÂ 35796315.
- Hanukoglu I, Fuchs E (July 1983). "The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins". Cell. 33 (3): 915â€“24. doi:10.1016/0092-8674(83)90034-X. PMIDÂ 6191871. S2CIDÂ 21490380.
- Lee CH, Kim MS, Chung BM, Leahy DJ, Coulombe PA (June 2012). "Structural basis for heteromeric assembly and perinuclear organization of keratin filaments". Nature Structural & Molecular Biology. 19 (7): 707â€“15. doi:10.1038/nsmb.2330. PMCÂ 3864793. PMIDÂ 22705788.
- Hanukoglu I, Ezra L (Jan 2014). "Proteopedia entry: coiled-coil structure of keratins". Biochemistry and Molecular Biology Education. 42 (1): 93â€“4. doi:10.1002/bmb.20746. PMIDÂ 24265184. S2CIDÂ 30720797.
- Qin Z, Kreplak L, Buehler MJ (October 2009). "Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments". PLOS ONE. 4 (10): e7294. Bibcode:2009PLoSO...4.7294Q. doi:10.1371/journal.pone.0007294. PMCÂ 2752800. PMIDÂ 19806221.
- Lodish H, Berk A, Zipursky SL, etÂ al. (2000). Molecular Cell Biology. New York: W. H. Freeman. p.Â Section 19.6, Intermediate Filaments. ISBNÂ 978-0-07-243940-3.
- Wang Q, Tolstonog GV, Shoeman R, Traub P (August 2001). "Sites of nucleic acid binding in type I-IV intermediate filament subunit proteins". Biochemistry. 40 (34): 10342â€“9. doi:10.1021/bi0108305. PMIDÂ 11513613.
- Shoeman RL, HÃ¼ttermann C, Hartig R, Traub P (January 2001). "Amino-terminal polypeptides of vimentin are responsible for the changes in nuclear architecture associated with human immunodeficiency virus type 1 protease activity in tissue culture cells". Molecular Biology of the Cell. 12 (1): 143â€“54. doi:10.1091/mbc.12.1.143. PMCÂ 30574. PMIDÂ 11160829.
- Takemura M, Gomi H, Colucci-Guyon E, Itohara S (August 2002). "Protective role of phosphorylation in turnover of glial fibrillary acidic protein in mice". The Journal of Neuroscience. 22 (16): 6972â€“9. doi:10.1523/JNEUROSCI.22-16-06972.2002. PMCÂ 6757867. PMIDÂ 12177195.
- Parry DA, Marekov LN, Steinert PM, Smith TA (2002). "A role for the 1A and L1 rod domain segments in head domain organization and function of intermediate filaments: structural analysis of trichocyte keratin". Journal of Structural Biology. 137 (1â€“2): 97â€“108. doi:10.1006/jsbi.2002.4437. PMIDÂ 12064937.
- Quinlan R, Hutchison C, Lane B (1995). "Intermediate filament proteins". Protein Profile. 2 (8): 795â€“952. PMIDÂ 8771189.
- Helfand BT, Chang L, Goldman RD (January 2004). "Intermediate filaments are dynamic and motile elements of cellular architecture". Journal of Cell Science. 117 (Pt 2): 133â€“41. doi:10.1242/jcs.00936. PMIDÂ 14676269.
- Herrmann H, BÃ¤r H, Kreplak L, Strelkov SV, Aebi U (July 2007). "Intermediate filaments: from cell architecture to nanomechanics". Nature Reviews. Molecular Cell Biology. 8 (7): 562â€“73. doi:10.1038/nrm2197. PMIDÂ 17551517. S2CIDÂ 27115011.Qin Z, Kreplak L, Buehler MJ (October 2009). "Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments". PLOS ONE. 4 (10): e7294. Bibcode:2009PLoSO...4.7294Q. doi:10.1371/journal.pone.0007294. PMCÂ 2752800. PMIDÂ 19806221.Kreplak L, Fudge D (January 2007). "Biomechanical properties of intermediate filaments: from tissues to single filaments and back". BioEssays. 29 (1): 26â€“35. doi:10.1002/bies.20514. PMIDÂ 17187357. S2CIDÂ 6560740.Qin Z, Buehler MJ, Kreplak L (January 2010). "A multi-scale approach to understand the mechanobiology of intermediate filaments". Journal of Biomechanics. 43 (1): 15â€“22. doi:10.1016/j.jbiomech.2009.09.004. PMIDÂ 19811783.Qin Z, Kreplak L, Buehler MJ (October 2009). "Nanomechanical properties of vimentin intermediate filament dimers". Nanotechnology. 20 (42): 425101. Bibcode:2009Nanot..20P5101Q. doi:10.1088/0957-4484/20/42/425101. PMIDÂ 19779230.
- Haimov E, Windoffer R, Leube RE, Urbakh M, Kozlov MM (July 2020). "Model for Bundling of Keratin Intermediate Filaments". Biophysical Journal. 119 (1): 65â€“74. Bibcode:2020BpJ...119...65H. doi:10.1016/j.bpj.2020.05.024. PMCÂ 7335914. PMIDÂ 32533940.
- Brodehl A, Gaertner-Rommel A, Milting H (August 2018). "Molecular insights into cardiomyopathies associated with desmin (DES) mutations". Biophysical Reviews. 10 (4): 983â€“1006. doi:10.1007/s12551-018-0429-0. PMCÂ 6082305. PMIDÂ 29926427.
- "SYNC - Syncoilin - Homo sapiens (Human) - SYNC gene & protein". www.uniprot.org. Retrieved 20 December 2021.
- Bernal A, Arranz L (June 2018). "Nestin-expressing progenitor cells: function, identity and therapeutic implications". Cellular and Molecular Life Sciences. 75 (12): 2177â€“2195. doi:10.1007/s00018-018-2794-z. PMCÂ 5948302. PMIDÂ 29541793.
- Kollmar M (May 2015). "Polyphyly of nuclear lamin genes indicates an early eukaryotic origin of the metazoan-type intermediate filament proteins". Scientific Reports. 5: 10652. Bibcode:2015NatSR...510652K. doi:10.1038/srep10652. PMCÂ 4448529. PMIDÂ 26024016.
- Fischer B, Dittmann S, Brodehl A, Unger A, Stallmeyer B, Paul M, etÂ al. (December 2020). "Functional characterization of novel alpha-helical rod domain desmin (DES) pathogenic variants associated with dilated cardiomyopathy, atrioventricular block and a risk for sudden cardiac death". International Journal of Cardiology. 329: 167â€“174. doi:10.1016/j.ijcard.2020.12.050. PMIDÂ 33373648. S2CIDÂ 229719883.
- BermÃºdez-JimÃ©nez FJ, Carriel V, Brodehl A, Alaminos M, Campos A, Schirmer I, etÂ al. (April 2018). "Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia". Circulation. 137 (15): 1595â€“1610. doi:10.1161/CIRCULATIONAHA.117.028719. PMIDÂ 29212896. S2CIDÂ 4715358.
- Protonotarios A, Brodehl A, Asimaki A, Jager J, Quinn E, Stanasiuk C, etÂ al. (December 2020). "The novel desmin variant p.Leu115Ile is associated with a unique form of biventricular Arrhythmogenic Cardiomyopathy". The Canadian Journal of Cardiology. 37 (6): 857â€“866. doi:10.1016/j.cjca.2020.11.017. PMIDÂ 33290826.
- Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, etÂ al. (December 2010). "De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy". Human Molecular Genetics. 19 (23): 4595â€“607. doi:10.1093/hmg/ddq387. PMIDÂ 20829228.
- Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, etÂ al. (May 2012). "Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants". The Journal of Biological Chemistry. 287 (19): 16047â€“57. doi:10.1074/jbc.M111.313841. PMCÂ 3346104. PMIDÂ 22403400.
- Brodehl A, Pour Hakimi SA, Stanasiuk C, Ratnavadivel S, Hendig D, Gaertner A, etÂ al. (November 2019). "Restrictive Cardiomyopathy is Caused by a Novel Homozygous Desmin (DES) Mutation p.Y122H Leading to a Severe Filament Assembly Defect". Genes. 10 (11): 918. doi:10.3390/genes10110918. PMCÂ 6896098. PMIDÂ 31718026.
- Kley RA, Hellenbroich Y, van der Ven PF, FÃ¼rst DO, Huebner A, Bruchertseifer V, etÂ al. (December 2007). "Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients". BrainÂ : A Journal of Neurology. 130 (Pt 12): 3250â€“64. doi:10.1093/brain/awm271. PMIDÂ 18055494.
- Marakhonov AV, Brodehl A, Myasnikov RP, Sparber PA, Kiseleva AV, Kulikova OV, etÂ al. (June 2019). "Noncompaction cardiomyopathy is caused by a novel in-frame desmin (DES) deletion mutation within the 1A coiled-coil rod segment leading to a severe filament assembly defect". Human Mutation. 40 (6): 734â€“741. doi:10.1002/humu.23747. PMIDÂ 30908796. S2CIDÂ 85515283.
- Schirmer I, Dieding M, Klauke B, Brodehl A, Gaertner-Rommel A, Walhorn V, etÂ al. (March 2018). "A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy". Molecular Genetics & Genomic Medicine. 6 (2): 288â€“293. doi:10.1002/mgg3.358. PMCÂ 5902401. PMIDÂ 29274115.
- Herrmann H, Harris JR, eds. (1998). Intermediate filaments. Springer. ISBNÂ 978-0-306-45854-5.
- Omary MB, Coulombe PA, eds. (2004). Intermediate filament cytoskeleton. Gulf Professional Publishing. ISBNÂ 978-0-12-564173-9.
- Paramio JM, ed. (2006). Intermediate filaments. Springer. ISBNÂ 978-0-387-33780-7.
|Wikimedia Commons has media related to Intermediate filament protein, coiled coil region.|
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.
Intermediate filament protein Provide feedback
No Pfam abstract.
Internal database links
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR039008
Intermediate filaments (IF) [ PUBMED:2183847 , PUBMED:28101862 ] are proteins which are primordial components of the cytoskeleton and the nuclear envelope. They generally form filamentous structures 8 to 14 nm wide. IF proteins are members of a very large multigene family of proteins which has been subdivided in six types:
- Type I: Acidic cytokeratins.
- Type II: Basic cytokeratins.
- Type III: Vimentin, desmin, glial fibrillary acidic protein (GFAP), peripherin, and plasticin.
- Type IV: Neurofilaments L, H and M, alpha-internexin and nestin.
- Type V: Nuclear lamins A, B1, B2 and C.
- Type VI: 'Orphan' IF proteins, which are more distant in terms of their amino acid sequences.
All IF proteins are structurally similar in that they consist of: a central rod domain comprising some 300 to 350 residues which is arranged in coiled- coiled alpha-helices, with at least two short characteristic interruptions; a N-terminal non-helical domain (head) of variable length; and a C-terminal domain (tail) which is also non-helical, and which shows extreme length variation between different IF proteins.
While IF proteins are evolutionary and structurally related, they have limited sequence homologies except in several regions of the rod domain. The IF rod domain is approximately 310 residues long in all cytoplasmic IF proteins and close to 350 residues in the nuclear ones. The IF rod domain exhibits an interrupted alpha-helical conformation and reveals a pronounced seven-residue periodicity in the distribution of apolar residues. The heptad periodicity within the rod domain is interrupted in several places, which generates four consecutive alpha-helical segments: 1A and 1B, which together form the so-called coil 1, and 2A and 2B, which form coil 2. The four alpha-helical segments are interconnected by relatively short, variable linkers L1, L12 and L2 [ PUBMED:12596228 , PUBMED:22869704 ].
IF proteins have a very strong tendency to dimerize via the formation of an alpha-helical coiled coil (CC) by their rod domains [ PUBMED:22869704 ].
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 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.
|Number in seed:||26|
|Number in full:||21973|
|Average length of the domain:||275.50 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||58.00 %|
|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:||24|
|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 Filament domain has been found. There are 84 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.