Editing Intermediate filament

{{Short description|Cytoskeletal structure}}
{{Infobox protein family
| Symbol = IF_tail
| Name = Intermediate filament tail domain
| image = PDB 1ifr EBI.jpg
| width =
| caption = Structure of lamin a/c globular domain
| Pfam = PF00932
| Pfam_clan =
| InterPro = IPR001322
| SMART =
| PROSITE = PDOC00198
| MEROPS =
| SCOP = 1ivt
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
{{Infobox protein family
| Symbol = Filament
| Name = Intermediate filament rod domain
| image = PDB 1gk4 EBI.jpg
| width =
| caption = Human vimentin coil 2b fragment (cys2)
| Pfam = PF00038
| Pfam_clan =
| InterPro = IPR016044
| SMART =
| PROSITE = PDOC00198
| MEROPS =
| SCOP = 1gk7
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
{{Infobox protein family
| Symbol = Filament_head
| Name = Intermediate filament head (DNA binding) region
| image =
| width =
| caption =
| Pfam = PF04732
| Pfam_clan =
| InterPro = IPR006821
| SMART =
| PROSITE =
| MEROPS =
| SCOP = 1gk7
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
{{infobox protein
| Name = Peripherin neuronal intermediate filament protein
| caption =
| image =
| width =
| HGNCid = 9461
| Symbol = PRPH
| AltSymbols =NEF4
| EntrezGene = 5630
| OMIM = 170710
| RefSeq = NM_006262.3
| UniProt = P41219
| PDB =
| ECnumber =
| Chromosome = 12
| Arm = q
| Band = 13.12
| LocusSupplementaryData =
}}
{{infobox protein
| Name = Nestin neuronal stem cell intermediate filament protein
| caption =
| image =
| width =
| HGNCid = 7756
| Symbol = NES
| AltSymbols =
| EntrezGene = 10763
| OMIM = 600915
| RefSeq = NP_006608
| UniProt = P48681
| PDB =
| ECnumber =
| Chromosome = 1
| Arm = q
| Band = 23.1
| LocusSupplementaryData =
}}

'''Intermediate filaments''' ('''IFs''') are [[cytoskeleton|cytoskeletal]] structural components found in the cells of [[vertebrate]]s, and many [[invertebrate]]s.<ref name="pmid17551517">{{cite journal | vauthors = Herrmann H, Bär H, Kreplak L, Strelkov SV, Aebi U | title = Intermediate filaments: from cell architecture to nanomechanics | journal = Nature Reviews. Molecular Cell Biology | volume = 8 | issue = 7 | pages = 562–73 | date = July 2007 | pmid = 17551517 | doi = 10.1038/nrm2197 | s2cid = 27115011 }}</ref><ref name="Chang">{{cite journal | vauthors = Chang L, Goldman RD | title = Intermediate filaments mediate cytoskeletal crosstalk | journal = Nature Reviews. Molecular Cell Biology | volume = 5 | issue = 8 | pages = 601–13 | date = August 2004 | pmid = 15366704 | doi = 10.1038/nrm1438 | s2cid = 31835055 }}</ref><ref>{{citation |author=Traub, P. |year=2012  |title=Intermediate Filaments: A Review |publisher=Springer Berlin Heidelberg  |isbn=978-3-642-70230-3 |url=https://books.google.com/books?id=TVLoCAAAQBAJ |page=33}}</ref> Homologues of the IF protein have been noted in an invertebrate, the [[cephalochordate]] ''[[Branchiostoma]]''.<ref name="pmid9804163">{{cite journal | vauthors = Karabinos A, Riemer D, Erber A, Weber K | title = Homologues of vertebrate type I, II and III intermediate filament (IF) proteins in an invertebrate: the IF multigene family of the cephalochordate Branchiostoma | journal = FEBS Letters | volume = 437 | issue = 1–2 | pages = 15–8 | date = October 1998 | pmid = 9804163 | doi = 10.1016/S0014-5793(98)01190-9 | s2cid = 7886395 | doi-access = free | bibcode = 1998FEBSL.437...15K }}</ref>

Intermediate filaments are composed of a family of related [[protein]]s sharing common structural and sequence features.  Initially designated 'intermediate' because their average diameter (10&nbsp;[[Nanometre|nm]]) is between those of narrower [[microfilament]]s (actin) and wider [[myosin]] filaments found in muscle cells, the diameter of intermediate filaments is now commonly compared to [[actin]] microfilaments (7&nbsp;nm) and [[microtubule]]s (25&nbsp;nm).<ref name="pmid17551517"/><ref name="pmid5664223">{{cite journal | vauthors = Ishikawa H, Bischoff R, Holtzer H | title = Mitosis and intermediate-sized filaments in developing skeletal muscle | journal = The Journal of Cell Biology | volume = 38 | issue = 3 | pages = 538–55 | date = September 1968 | pmid = 5664223 | pmc = 2108373 | doi = 10.1083/jcb.38.3.538 }}</ref> Animal intermediate filaments are subcategorized into six types based on similarities in amino acid sequence and [[protein]] structure.<ref name="interfil">{{cite journal | vauthors = Szeverenyi I, Cassidy AJ, Chung CW, Lee BT, Common JE, Ogg SC, Chen H, Sim SY, Goh WL, Ng KW, Simpson JA, Chee LL, Eng GH, Li B, Lunny DP, Chuon D, Venkatesh A, Khoo KH, McLean WH, Lim YP, Lane EB | display-authors = 6 | title = The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases | journal = Human Mutation | volume = 29 | issue = 3 | pages = 351–360 | date = March 2008 | pmid = 18033728 | doi = 10.1002/humu.20652 | s2cid = 20760837 | doi-access = free }}</ref> Most types are [[cytoplasm]]ic, but one type, Type V is a [[nuclear lamin]]. Unlike microtubules, IF distribution in cells shows no good correlation with the distribution of either [[mitochondria]] or [[endoplasmic reticulum]].<ref name="pmid1363623">{{cite journal | vauthors = Soltys BJ, Gupta RS | title = Interrelationships of endoplasmic reticulum, mitochondria, intermediate filaments, and microtubules--a quadruple fluorescence labeling study | journal = Biochemistry and Cell Biology  | volume = 70 | issue = 10–11 | pages = 1174–86 | date = 1992 | pmid = 1363623 | doi = 10.1139/o92-163 }}</ref>

== Structure ==
[[File:Intermediate filament.svg|thumb|right|300px|Structure of intermediate filament]]
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 [[complementary DNA|cDNAs]].<ref name="pmid6186381">{{cite journal | vauthors = Hanukoglu I, Fuchs E | title = The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins | journal = Cell | volume = 31 | issue = 1 | pages = 243–52 | date = November 1982 | pmid = 6186381 | doi = 10.1016/0092-8674(82)90424-X | url = https://zenodo.org/record/890743 | s2cid = 35796315 }}</ref> 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.<ref name="pmid6191871">{{cite journal | vauthors = Hanukoglu I, Fuchs E | title = The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins | journal = Cell | volume = 33 | issue = 3 | pages = 915–24 | date = July 1983 | pmid = 6191871 | doi = 10.1016/0092-8674(83)90034-X | url = https://zenodo.org/record/890739 | s2cid = 21490380 }}</ref> 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.<ref name="pmid6191871" /><ref name="pmid22705788">{{cite journal | vauthors = Lee CH, Kim MS, Chung BM, Leahy DJ, Coulombe PA | title = Structural basis for heteromeric assembly and perinuclear organization of keratin filaments | journal = Nature Structural & Molecular Biology | volume = 19 | issue = 7 | pages = 707–15 | date = June 2012 | pmid = 22705788 | pmc = 3864793 | doi = 10.1038/nsmb.2330 }}</ref>

The central building block of an intermediate filament is a pair of two intertwined proteins that is called a [[coiled-coil|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 interactions]].<ref name="2014-Hanukoglu">{{cite journal | vauthors = Hanukoglu I, Ezra L | title = Proteopedia entry: coiled-coil structure of keratins | journal = Biochemistry and Molecular Biology Education | volume = 42 | issue = 1 | pages = 93–4 | date = Jan 2014 | pmid = 24265184 | doi = 10.1002/bmb.20746 | s2cid = 30720797 | doi-access = free }}</ref><ref name="Qin2009">{{cite journal | vauthors = Qin Z, Kreplak L, Buehler MJ | title = Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments | journal = PLOS ONE | volume = 4 | issue = 10 | pages = e7294 | date = October 2009 | pmid = 19806221 | pmc = 2752800 | doi = 10.1371/journal.pone.0007294 | bibcode = 2009PLoSO...4.7294Q | doi-access = free }}</ref> The charged residues in the central domain do not have a major role in the binding of the pair in the central domain.<ref name="2014-Hanukoglu" />

Cytoplasmic IFs assemble into non-polar unit-length filaments (ULFs). Identical ULFs associate laterally into staggered, [[Antiparallel (biochemistry)|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.<ref>{{Cite book | vauthors=Lodish H, Berk A, Zipursky SL | url=https://archive.org/details/isbn_9780072930283/page/ | title=Molecular Cell Biology | year=2000 | publisher=W. H. Freeman | location=New York | isbn=978-0-07-243940-3 | page=[https://archive.org/details/isbn_9780072930283/page/ Section 19.6, Intermediate Filaments] | display-authors=etal | url-access=registration }}</ref>
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 12&nbsp;nm.{{cn|date=April 2025}}

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]].<ref name="pmid11513613">{{cite journal | vauthors = Wang Q, Tolstonog GV, Shoeman R, Traub P | title = Sites of nucleic acid binding in type I-IV intermediate filament subunit proteins | journal = Biochemistry | volume = 40 | issue = 34 | pages = 10342–9 | date = August 2001 | pmid = 11513613 | doi = 10.1021/bi0108305 }}</ref> [[Vimentin]] heads are able to alter [[cell nucleus|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]].<ref name="pmid11160829">{{cite journal | vauthors = Shoeman RL, Hüttermann C, Hartig R, Traub P | title = 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 | journal = Molecular Biology of the Cell | volume = 12 | issue = 1 | pages = 143–54 | date = January 2001 | pmid = 11160829 | pmc = 30574 | doi = 10.1091/mbc.12.1.143 }}</ref> [[Phosphorylation]] of the head region can affect filament stability.<ref name="pmid12177195">{{cite journal | vauthors = Takemura M, Gomi H, Colucci-Guyon E, Itohara S | title = Protective role of phosphorylation in turnover of glial fibrillary acidic protein in mice | journal = The Journal of Neuroscience | volume = 22 | issue = 16 | pages = 6972–9 | date = August 2002 | pmid = 12177195 | pmc = 6757867 | doi = 10.1523/JNEUROSCI.22-16-06972.2002 }}</ref> The head has been shown to interact with the rod domain of the same [[protein]].<ref name="pmid12064937">{{cite journal | vauthors = Parry DA, Marekov LN, Steinert PM, Smith TA | title = 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 = Journal of Structural Biology | volume = 137 | issue = 1–2 | pages = 97–108 | year = 2002 | pmid = 12064937 | doi = 10.1006/jsbi.2002.4437 }}</ref>

C-terminal "tail domain" shows extreme length variation between different IF proteins.<ref name="pmid8771189">{{cite journal | vauthors = Quinlan R, Hutchison C, Lane B | title = Intermediate filament proteins | journal = Protein Profile | volume = 2 | issue = 8 | pages = 795–952 | year = 1995 | pmid = 8771189 }}</ref>

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.{{cn|date=April 2025}}

Also, unlike [[actin]] or [[tubulin]], intermediate filaments do not contain a [[binding site]] for a [[nucleoside triphosphate]].

Cytoplasmic IFs do not undergo [[treadmilling]] like microtubules and actin fibers, but are dynamic.<ref name="Helfand">{{cite journal | vauthors = Helfand BT, Chang L, Goldman RD | title = Intermediate filaments are dynamic and motile elements of cellular architecture | journal = Journal of Cell Science | volume = 117 | issue = Pt 2 | pages = 133–41 | date = January 2004 | pmid = 14676269 | doi = 10.1242/jcs.00936 | doi-access = free }}</ref>

== Biomechanical properties ==

IFs are rather deformable proteins that can be stretched several times their initial length.<ref>{{cite journal | vauthors = Herrmann H, Bär H, Kreplak L, Strelkov SV, Aebi U | title = Intermediate filaments: from cell architecture to nanomechanics | journal = Nature Reviews. Molecular Cell Biology | volume = 8 | issue = 7 | pages = 562–73 | date = July 2007 | pmid = 17551517 | doi = 10.1038/nrm2197 | s2cid = 27115011 }}{{cite journal | vauthors = Qin Z, Kreplak L, Buehler MJ | title = Hierarchical structure controls nanomechanical properties of vimentin intermediate filaments | journal = PLOS ONE | volume = 4 | issue = 10 | pages = e7294 | date = October 2009 | pmid = 19806221 | pmc = 2752800 | doi = 10.1371/journal.pone.0007294 | bibcode = 2009PLoSO...4.7294Q | doi-access = free }}{{cite journal | vauthors = Kreplak L, Fudge D | title = Biomechanical properties of intermediate filaments: from tissues to single filaments and back | journal = BioEssays | volume = 29 | issue = 1 | pages = 26–35 | date = January 2007 | pmid = 17187357 | doi = 10.1002/bies.20514 | s2cid = 6560740 }}{{cite journal | vauthors = Qin Z, Buehler MJ, Kreplak L | title = A multi-scale approach to understand the mechanobiology of intermediate filaments | journal = Journal of Biomechanics | volume = 43 | issue = 1 | pages = 15–22 | date = January 2010 | pmid = 19811783 | doi = 10.1016/j.jbiomech.2009.09.004 }}{{cite journal | vauthors = Qin Z, Kreplak L, Buehler MJ | title = Nanomechanical properties of vimentin intermediate filament dimers | journal = Nanotechnology | volume = 20 | issue = 42 | page = 425101 | date = October 2009 | pmid = 19779230 | doi = 10.1088/0957-4484/20/42/425101 | bibcode = 2009Nanot..20P5101Q | s2cid = 6870454 }}</ref> 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.<ref name="Qin2009" /> Initially the coupled alpha-helices of unit-length filaments uncoil as they're strained, then as the strain increases they transition into [[beta-sheet]]s, and finally at increased strain the hydrogen bonds between beta-sheets slip and the ULF monomers slide along each other.<ref name="Qin2009" />

== Types ==
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 9–11&nbsp;nm in diameter when fully assembled.{{cn|date=April 2025}}

Animal IFs are subcategorized into six types based on similarities in amino acid sequence and [[protein]] structure:<ref name="interfil"/>

=== Types I and II – acidic and basic keratins ===
[[File:Epithelial-cells.jpg|thumb|right|[[Keratin]] intermediate filaments (stained red) around [[epithelium|epithelial cells]]]]
{{further|Cytokeratin}}
These proteins are the most diverse among IFs and constitute [[Type I cytokeratin|type I (acidic)]] and [[Type II cytokeratin|type II (basic)]] IF proteins. The many [[isoform]]s are divided in two groups:{{cn|date=April 2025}}
* '''epithelial keratins''' (about 20) in [[epithelial]] cells (image to right)
* '''trichocytic keratins''' (about 13) ([[hair keratin]]s), which make up [[hair]], [[Nail (anatomy)|nails]], [[Horn (anatomy)|horns]] and [[reptile|reptilian]] [[Scale (zoology)|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.<ref name="interfil"/>

[[Cytokeratin]] filaments laterally associate with each other to create a thick bundle of ~50&nbsp;nm radius. The optimal radius of such bundles is determined by the interplay between the long range electrostatic repulsion and short range hydrophobic attraction.<ref>{{cite journal | vauthors = Haimov E, Windoffer R, Leube RE, Urbakh M, Kozlov MM | title = Model for Bundling of Keratin Intermediate Filaments | journal = Biophysical Journal | volume = 119 | issue = 1 | pages = 65–74 | date = July 2020 | pmid = 32533940 | doi = 10.1016/j.bpj.2020.05.024 | pmc = 7335914 | bibcode = 2020BpJ...119...65H | doi-access = free }}</ref> Subsequently, these bundles would intersect through junctions to form a dynamic network, spanning the cytoplasm of epithelial cells.{{cn|date=April 2025}}

=== Type III ===
[[File:Vimentin.jpg|thumb|[[Vimentin]] fibers in [[fibroblast]]s]]
There are four proteins classed as type III intermediate filament proteins, which may form [[homopolymer|homo-]] or [[heteropolymer]]ic proteins.
* '''[[Desmin]]''' IFs are structural components of the [[sarcomere]]s in muscle cells and connect different cell organelles like the desmosomes with the cytoskeleton.<ref>{{cite journal | vauthors = Brodehl A, Gaertner-Rommel A, Milting H | title = Molecular insights into cardiomyopathies associated with desmin (DES) mutations | journal = Biophysical Reviews | volume = 10 | issue = 4 | pages = 983–1006 | date = August 2018 | pmid = 29926427 | pmc = 6082305 | doi = 10.1007/s12551-018-0429-0 }}</ref>
* '''[[Glial fibrillary acidic protein]]''' (GFAP) is found in [[astrocyte]]s and other [[glia]].{{cn|date=April 2025}}
* '''[[Peripherin]]''' found in peripheral neurons.{{cn|date=April 2025}}
* '''[[Vimentin]]''', the most widely distributed of all IF proteins, can be found in [[fibroblast]]s, [[leukocytes]], and blood vessel [[endothelial cell]]s. They support the cellular membranes, keep some [[organelle]]s in a fixed place within the [[cytoplasm]], and transmit membrane receptor signals to the nucleus.<ref name="interfil"/>
* '''[[Syncoilin]]''' is an atypical type III IF protein.<ref name="Uniprot">{{cite web |title=SYNC – Syncoilin – Homo sapiens (Human) – SYNC gene & protein |url=https://www.uniprot.org/uniprot/Q9H7C4 |website=www.uniprot.org |access-date=20 December 2021 |language=en}}</ref>

=== Type IV ===
* '''[[Alpha-internexin]]'''
* '''[[Neurofilament]]s''' – the type IV family of intermediate filaments that is found in high concentrations along the [[axon]]s of vertebrate neurons.{{cn|date=April 2025}}
* '''[[Synemin]]'''
* '''[[Syncoilin]]'''

=== Type V – nuclear lamins ===
* '''[[Lamin]]s'''
Lamins are fibrous proteins having structural function in the cell nucleus.{{cn|date=April 2025}}

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 [[lamin B2|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.{{cn|date=April 2025}}

These proteins localize to two regions of the nuclear compartment, the nuclear lamina—a proteinaceous structure layer subjacent to the inner surface of the [[nuclear envelope]] and throughout the nucleoplasm in the [[Cell nucleus#Nuclear lamina|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.<ref name="interfil"/>

=== Type VI ===
* Beaded filaments: [[BFSP1|Filensin]], [[BFSP2|Phakinin]].<ref name="interfil"/>
* [[Nestin (protein)|Nestin]] (was once proposed for reclassification but due to differences, remains as a type VI IF protein)<ref>{{cite journal | vauthors = Bernal A, Arranz L | title = Nestin-expressing progenitor cells: function, identity and therapeutic implications | journal = Cellular and Molecular Life Sciences | volume = 75 | issue = 12 | pages = 2177–2195 | date = June 2018 | pmid = 29541793 | pmc = 5948302 | doi = 10.1007/s00018-018-2794-z}}</ref>

Vertebrate-only. Related to type I-IV. Used to contain other newly discovered IF proteins not yet assigned to a type.<ref name=Polyphyly/>

== Function ==

=== Cell adhesion ===
At the [[plasma membrane]], some keratins or desmin interact with [[desmosome]]s (cell-cell adhesion) and [[hemidesmosome]]s (cell-matrix adhesion) via adapter proteins.{{cn|date=April 2025}}

=== Associated proteins ===
[[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 [[desmosome]]s (desmosomes connect the cytoskeleton together) through [[plakoglobin]], [[desmoplakin]], [[desmoglein]]s, and [[desmocollin]]s; [[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<ref>{{cite journal | vauthors = Fischer B, Dittmann S, Brodehl A, Unger A, Stallmeyer B, Paul M, Seebohm G, Kayser A, Peischard S, Linke WA, Milting H, Schulze-Bahr E | display-authors = 6 | title = 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 | journal = International Journal of Cardiology | pages = 167–174 | date = December 2020 | volume = 329 | pmid = 33373648 | doi = 10.1016/j.ijcard.2020.12.050 | s2cid = 229719883 }}</ref>
* [[Arrhythmogenic cardiomyopathy]] (ACM), mutations in the ''DES'' gene<ref>{{cite journal | vauthors = Bermúdez-Jiménez FJ, Carriel V, Brodehl A, Alaminos M, Campos A, Schirmer I, Milting H, Abril BÁ, Álvarez M, López-Fernández S, García-Giustiniani D, Monserrat L, Tercedor L, Jiménez-Jáimez J | display-authors = 6 | title = Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia | journal = Circulation | volume = 137 | issue = 15 | pages = 1595–1610 | date = April 2018 | pmid = 29212896 | doi = 10.1161/CIRCULATIONAHA.117.028719 | s2cid = 4715358 | doi-access = free | hdl = 10481/89514 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Protonotarios A, Brodehl A, Asimaki A, Jager J, Quinn E, Stanasiuk C, Ratnavadivel S, Futema M, Akhtar MM, Gossios TD, Ashworth M, Savvatis K, Walhorn V, Anselmetti D, Elliott PM, Syrris P, Milting H, Lopes LR | display-authors = 6 | title = The novel desmin variant p.Leu115Ile is associated with a unique form of biventricular Arrhythmogenic Cardiomyopathy | journal = The Canadian Journal of Cardiology | pages = 857–866 | date = December 2020 | volume = 37 | issue = 6 | pmid = 33290826 | doi = 10.1016/j.cjca.2020.11.017 | s2cid = 228078648 | url = https://discovery.ucl.ac.uk/id/eprint/10117120/ }}</ref><ref name="pmid20829228">{{cite journal | vauthors = Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H | display-authors = 6 | title = De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy | journal = Human Molecular Genetics | volume = 19 | issue = 23 | pages = 4595–607 | date = December 2010 | pmid = 20829228 | doi = 10.1093/hmg/ddq387 | doi-access = free }}</ref><ref name="pmid22403400">{{cite journal | vauthors = Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, Šarić T, Klauke B, Gummert J, Anselmetti D, Heilemann M, Nienhaus GU, Milting H | display-authors = 6 | title = Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants | journal = The Journal of Biological Chemistry | volume = 287 | issue = 19 | pages = 16047–57 | date = May 2012 | pmid = 22403400 | pmc = 3346104 | doi = 10.1074/jbc.M111.313841 | doi-access = free }}</ref>
* Restrictive cardiomyopathy (RCM), mutations in the ''DES'' gene<ref>{{cite journal | vauthors = Brodehl A, Pour Hakimi SA, Stanasiuk C, Ratnavadivel S, Hendig D, Gaertner A, Gerull B, Gummert J, Paluszkiewicz L, Milting H | display-authors = 6 | title = Restrictive Cardiomyopathy is Caused by a Novel Homozygous Desmin (''DES'') Mutation p.Y122H Leading to a Severe Filament Assembly Defect | journal = Genes | volume = 10 | issue = 11 | page = 918 | date = November 2019 | pmid = 31718026 | pmc = 6896098 | doi = 10.3390/genes10110918 | doi-access = free }}</ref>
* Non-compaction cardiomyopathy, mutations in the ''DES'' genes<ref>{{cite journal | vauthors = Kley RA, Hellenbroich Y, van der Ven PF, Fürst DO, Huebner A, Bruchertseifer V, Peters SA, Heyer CM, Kirschner J, Schröder R, Fischer D, Müller K, Tolksdorf K, Eger K, Germing A, Brodherr T, Reum C, Walter MC, Lochmüller H, Ketelsen UP, Vorgerd M | display-authors = 6 | title = Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients | journal =  Brain: A Journal of Neurology| volume = 130 | issue = Pt 12 | pages = 3250–64 | date = December 2007 | pmid = 18055494 | doi = 10.1093/brain/awm271| doi-access = free }}</ref><ref>{{cite journal | vauthors = Marakhonov AV, Brodehl A, Myasnikov RP, Sparber PA, Kiseleva AV, Kulikova OV, Meshkov AN, Zharikova AA, Koretsky SN, Kharlap MS, Stanasiuk C, Mershina EA, Sinitsyn VE, Shevchenko AO, Mozheyko NP, Drapkina OM, Boytsov SA, Milting H, Skoblov MY | display-authors = 6 | title = 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 | journal = Human Mutation | volume = 40 | issue = 6 | pages = 734–741 | date = June 2019 | pmid = 30908796 | doi = 10.1002/humu.23747 | s2cid = 85515283 | doi-access = free }}</ref>
* Cardiomyopathy in combination with skeletal myopathy (''DES'')<ref>{{cite journal | vauthors = Schirmer I, Dieding M, Klauke B, Brodehl A, Gaertner-Rommel A, Walhorn V, Gummert J, Schulz U, Paluszkiewicz L, Anselmetti D, Milting H | display-authors = 6 | title = A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy | journal = Molecular Genetics & Genomic Medicine | volume = 6 | issue = 2 | pages = 288–293 | date = March 2018 | pmid = 29274115 | pmc = 5902401 | doi = 10.1002/mgg3.358 }}</ref>
* [[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|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) are only found 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.<ref name=Polyphyly>{{cite journal | vauthors = Kollmar M | title = Polyphyly of nuclear lamin genes indicates an early eukaryotic origin of the metazoan-type intermediate filament proteins | journal = Scientific Reports | volume = 5 | page = 10652 | date = May 2015 | pmid = 26024016 | pmc = 4448529 | doi = 10.1038/srep10652 | doi-access = free | bibcode = 2015NatSR...510652K }}</ref>

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 descendants, characterized by sequence similarity as well as the exon structure. Functionally-similar proteins out of this clade, like [[crescentin]]s, alveolins, tetrins, and epiplasmins, are therefore only "IF-like". They likely arose through [[convergent evolution]].<ref name=Polyphyly/>

== References ==
{{reflist|2}}

== Further reading ==
{{refbegin}}
* {{cite book | veditors = Herrmann H, Harris JR | title = Intermediate filaments | publisher = Springer | year = 1998 | isbn = 978-0-306-45854-5 | url = https://books.google.com/books?id=DjYdWQl_McQC }}
* {{cite book | veditors = Omary MB, Coulombe PA | title = Intermediate filament cytoskeleton | publisher = Gulf Professional Publishing | year = 2004 | isbn = 978-0-12-564173-9 | url = https://books.google.com/books?id=2vXL7DQgQAUC }}
* {{cite book | veditors = Paramio JM | title = Intermediate filaments | publisher = Springer | year = 2006 | isbn = 978-0-387-33780-7 | url = https://books.google.com/books?id=XpAM-5jQ42oC }}
{{refend}}

== External links ==
{{Commons category|Intermediate filament protein, coiled coil region}}
* {{MeshName|Intermediate+Filament+Proteins}}

{{Cytoskeletal Proteins}}
{{Organelles}}
{{InterPro content|IPR001322}}

{{InterPro content|IPR006821}}

{{DEFAULTSORT:Intermediate Filament}}
[[Category:Protein families]]
[[Category:Cytoskeleton]]