DCTN1: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''Dynactin subunit 1''' is a [[protein]] that in humans is encoded by the '''DCTN1''' [[gene]].<ref name="pmid1828535">{{cite journal | vauthors = Holzbaur EL, Hammarback JA, Paschal BM, Kravit NG, Pfister KK, Vallee RB | title = Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued | journal = Nature | volume = 351 | issue = 6327 | pages = 579–83  | date = Jul 1991 | pmid = 1828535 | pmc =  | doi = 10.1038/351579a0 }}</ref>
'''Dynactin subunit 1''' is a [[protein]] that in humans is encoded by the '''''DCTN1''''' [[gene]].<ref name="pmid1828535" />


== Function ==
== Function ==


This gene encodes the largest [[Protein subunit|subunit]] of [[dynactin]], a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both [[microtubules]] and cytoplasmic [[dynein]]. It is involved in a diverse array of cellular functions, including [[Endoplasmic reticulum|ER]]-to-[[Golgi complex|Golgi]] transport, the centripetal movement of [[lysosome]]s and [[endosome]]s, [[mitotic spindle|spindle formation]], chromosome movement, nuclear positioning, and axonogenesis. This subunit interacts with dynein intermediate chain by its domains directly binding to dynein. Alternative splicing of this gene results in at least 2 functionally distinct isoforms: a ubiquitously expressed one and a brain-specific one. Based on its cytogenetic location, this gene is considered as a candidate gene for limb-girdle muscular dystrophy.<ref name="entrez">{{cite web | title = Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1639| accessdate = }}</ref>
This gene encodes the largest [[Protein subunit|subunit]] of [[dynactin]], a macromolecular complex consisting of 23 subunits (11 individual proteins ranging in size from 22 to 150 kD)<ref name=":0">{{cite journal | vauthors = Urnavicius L, Zhang K, Diamant AG, Motz C, Schlager MA, Yu M, Patel NA, Robinson CV, Carter AP | title = The structure of the dynactin complex and its interaction with dynein | journal = Science | volume = 347 | issue = 6229 | pages = 1441–1446 | date = March 2015 | pmid = 25814576 | pmc = 4413427 | doi = 10.1126/science.aaa4080 }}</ref>. Dynactin binds to cytoplasmic [[dynein]], dynein cargo adaptors, and [[microtubules]]<ref>{{cite journal | vauthors = Cianfrocco MA, DeSantis ME, Leschziner AE, Reck-Peterson SL | title = Mechanism and regulation of cytoplasmic dynein | journal = Annual Review of Cell and Developmental Biology | volume = 31 | pages = 83–108 | date = 2015 | pmid = 26436706 | pmc = 4644480 | doi = 10.1146/annurev-cellbio-100814-125438 }}</ref>. It is involved in a diverse array of cellular functions, including [[Endoplasmic reticulum|ER]]-to-[[Golgi complex|Golgi]] transport, the centripetal movement of [[lysosome]]s and [[endosome]]s, [[mitotic spindle|spindle formation]], chromosome movement, nuclear positioning, and axonogenesis.  
 
This subunit is commonly referred to p150-glued<ref name="pmid1828535">{{cite journal | vauthors = Holzbaur EL, Hammarback JA, Paschal BM, Kravit NG, Pfister KK, Vallee RB | title = Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued | journal = Nature | volume = 351 | issue = 6327 | pages = 579–83 | date = June 1991 | pmid = 1828535 | pmc =  | doi = 10.1038/351579a0 }}</ref>.  It is present in two copies per dynactin complex and forms an ~75nm long flexible arm that extends from the main body of dynactin<ref name=":0" />.  The p150-glued arm contains binding sites for microtubules<ref>{{cite journal | vauthors = Waterman-Storer CM, Karki S, Holzbaur EL | title = The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 5 | pages = 1634–8 | date = February 1995 | pmid = 7878030 | pmc = 42574 }}</ref>, the microtubule plus tip binding protein EB1<ref>{{cite journal | vauthors = Berrueta L, Tirnauer JS, Schuyler SC, Pellman D, Bierer BE | title = The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain | journal = Current Biology | volume = 9 | issue = 8 | pages = 425–8 | date = April 1999 | pmid = 10226031 }}</ref>, and the N-terminus of the dynein intermediate chain<ref>{{cite journal | vauthors = Karki S, Holzbaur EL | title = Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex | journal = The Journal of Biological Chemistry | volume = 270 | issue = 48 | pages = 28806–11 | date = December 1995 | pmid = 7499404 }}</ref><ref>{{cite journal | vauthors = Vaughan KT, Vallee RB | title = Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued | journal = The Journal of Cell Biology | volume = 131 | issue = 6 Pt 1 | pages = 1507–16 | date = December 1995 | pmid = 8522607 | pmc = 2120689 }}</ref>.
 
Alternative splicing of this gene results in at least 2 functionally distinct isoforms: a ubiquitously expressed one and a brain-specific one. Based on its cytogenetic location, this gene is considered as a candidate gene for limb-girdle muscular dystrophy.<ref name="entrez">{{cite web | title = Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1639| access-date = }}</ref>


== Interactions ==
== Interactions ==


DCTN1 has been shown to [[Protein-protein interaction|interact]] with:
DCTN1 has been shown to [[Protein-protein interaction|interact]] with:
* [[BBS4]],<ref name = pmid15107855>{{cite journal | vauthors = Kim JC, Badano JL, Sibold S, Esmail MA, Hill J, Hoskins BE, Leitch CC, Venner K, Ansley SJ, Ross AJ, Leroux MR, Katsanis N, Beales PL | title = The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression | journal = Nat. Genet. | volume = 36 | issue = 5 | pages = 462–70 | date = May 2004 | pmid = 15107855 | doi = 10.1038/ng1352 }}</ref>  
* [[BBS4]],<ref name = pmid15107855>{{cite journal | vauthors = Kim JC, Badano JL, Sibold S, Esmail MA, Hill J, Hoskins BE, Leitch CC, Venner K, Ansley SJ, Ross AJ, Leroux MR, Katsanis N, Beales PL | title = The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression | journal = Nature Genetics | volume = 36 | issue = 5 | pages = 462–70 | date = May 2004 | pmid = 15107855 | doi = 10.1038/ng1352 }}</ref>  
* [[Dystonin]],<ref name = pmid14581450>{{cite journal | vauthors = Liu JJ, Ding J, Kowal AS, Nardine T, Allen E, Delcroix JD, Wu C, Mobley W, Fuchs E, Yang Y | title = BPAG1n4 is essential for retrograde axonal transport in sensory neurons | journal = J. Cell Biol. | volume = 163 | issue = 2 | pages = 223–9 | date = Oct 2003 | pmid = 14581450 | pmc = 2173519 | doi = 10.1083/jcb.200306075 }}</ref>
* [[Dystonin]],<ref name = pmid14581450>{{cite journal | vauthors = Liu JJ, Ding J, Kowal AS, Nardine T, Allen E, Delcroix JD, Wu C, Mobley W, Fuchs E, Yang Y | title = BPAG1n4 is essential for retrograde axonal transport in sensory neurons | journal = The Journal of Cell Biology | volume = 163 | issue = 2 | pages = 223–9 | date = October 2003 | pmid = 14581450 | pmc = 2173519 | doi = 10.1083/jcb.200306075 }}</ref>
* [[Grb2]],<ref name = pmid8955163>{{cite journal | vauthors = Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB | title = Identification of a novel 135-kDa Grb2-binding protein in osteoclasts | journal = J. Biol. Chem. | volume = 271 | issue = 51 | pages = 33141–7 | date = Dec 1996 | pmid = 8955163 | doi = 10.1074/jbc.271.51.33141}}</ref>  and
* [[Grb2]],<ref name = pmid8955163>{{cite journal | vauthors = Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB | title = Identification of a novel 135-kDa Grb2-binding protein in osteoclasts | journal = The Journal of Biological Chemistry | volume = 271 | issue = 51 | pages = 33141–7 | date = December 1996 | pmid = 8955163 | doi = 10.1074/jbc.271.51.33141 }}</ref>  and
* [[RAB6A]].<ref name = pmid12401177>{{cite journal | vauthors = Short B, Preisinger C, Schaletzky J, Kopajtich R, Barr FA | title = The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes | journal = Curr. Biol. | volume = 12 | issue = 20 | pages = 1792–5 | date = Oct 2002 | pmid = 12401177 | doi = 10.1016/s0960-9822(02)01221-6}}</ref>
* [[RAB6A]].<ref name = pmid12401177>{{cite journal | vauthors = Short B, Preisinger C, Schaletzky J, Kopajtich R, Barr FA | title = The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes | journal = Current Biology | volume = 12 | issue = 20 | pages = 1792–5 | date = October 2002 | pmid = 12401177 | doi = 10.1016/s0960-9822(02)01221-6 }}</ref>


== References ==
== References ==
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== Further reading ==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = Waterman-Storer CM, Karki S, Holzbaur EL | title = The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1) | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 92 | issue = 5 | pages = 1634–8 | year = 1995 | pmid = 7878030 | pmc = 42574 | doi = 10.1073/pnas.92.5.1634 }}
* {{cite journal | vauthors = Waterman-Storer CM, Karki S, Holzbaur EL | title = The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 5 | pages = 1634–8 | date = February 1995 | pmid = 7878030 | pmc = 42574 | doi = 10.1073/pnas.92.5.1634 }}
* {{cite journal | vauthors = Paschal BM, Holzbaur EL, Pfister KK, Clark S, Meyer DI, Vallee RB | title = Characterization of a 50-kDa polypeptide in cytoplasmic dynein preparations reveals a complex with p150GLUED and a novel actin | journal = J. Biol. Chem. | volume = 268 | issue = 20 | pages = 15318–23 | year = 1993 | pmid = 8325901 | doi =  }}
* {{cite journal | vauthors = Paschal BM, Holzbaur EL, Pfister KK, Clark S, Meyer DI, Vallee RB | title = Characterization of a 50-kDa polypeptide in cytoplasmic dynein preparations reveals a complex with p150GLUED and a novel actin | journal = The Journal of Biological Chemistry | volume = 268 | issue = 20 | pages = 15318–23 | date = July 1993 | pmid = 8325901 | doi =  }}
* {{cite journal | vauthors = Vaughan KT, Vallee RB | title = Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued | journal = J. Cell Biol. | volume = 131 | issue = 6 Pt 1 | pages = 1507–16 | year = 1995 | pmid = 8522607 | pmc = 2120689 | doi = 10.1083/jcb.131.6.1507 }}
* {{cite journal | vauthors = Vaughan KT, Vallee RB | title = Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued | journal = The Journal of Cell Biology | volume = 131 | issue = 6 Pt 1 | pages = 1507–16 | date = December 1995 | pmid = 8522607 | pmc = 2120689 | doi = 10.1083/jcb.131.6.1507 }}
* {{cite journal | vauthors = Holzbaur EL, Tokito MK | title = Localization of the DCTN1 gene encoding p150Glued to human chromosome 2p13 by fluorescence in situ hybridization | journal = Genomics | volume = 31 | issue = 3 | pages = 398–9 | year = 1996 | pmid = 8838327 | doi = 10.1006/geno.1996.0068 }}
* {{cite journal | vauthors = Holzbaur EL, Tokito MK | title = Localization of the DCTN1 gene encoding p150Glued to human chromosome 2p13 by fluorescence in situ hybridization | journal = Genomics | volume = 31 | issue = 3 | pages = 398–9 | date = February 1996 | pmid = 8838327 | doi = 10.1006/geno.1996.0068 }}
* {{cite journal | vauthors = Tokito MK, Howland DS, Lee VM, Holzbaur EL | title = Functionally distinct isoforms of dynactin are expressed in human neurons | journal = Mol. Biol. Cell | volume = 7 | issue = 8 | pages = 1167–80 | year = 1996 | pmid = 8856662 | pmc = 275970 | doi = 10.1091/mbc.7.8.1167 }}
* {{cite journal | vauthors = Tokito MK, Howland DS, Lee VM, Holzbaur EL | title = Functionally distinct isoforms of dynactin are expressed in human neurons | journal = Molecular Biology of the Cell | volume = 7 | issue = 8 | pages = 1167–80 | date = August 1996 | pmid = 8856662 | pmc = 275970 | doi = 10.1091/mbc.7.8.1167 }}
* {{cite journal | vauthors = Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB | title = Identification of a novel 135-kDa Grb2-binding protein in osteoclasts | journal = J. Biol. Chem. | volume = 271 | issue = 51 | pages = 33141–7 | year = 1996 | pmid = 8955163 | doi = 10.1074/jbc.271.51.33141 }}
* {{cite journal | vauthors = Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB | title = Identification of a novel 135-kDa Grb2-binding protein in osteoclasts | journal = The Journal of Biological Chemistry | volume = 271 | issue = 51 | pages = 33141–7 | date = December 1996 | pmid = 8955163 | doi = 10.1074/jbc.271.51.33141 }}
* {{cite journal | vauthors = Blangy A, Arnaud L, Nigg EA | title = Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor HsEg5 to the dynactin subunit p150 | journal = J. Biol. Chem. | volume = 272 | issue = 31 | pages = 19418–24 | year = 1997 | pmid = 9235942 | doi = 10.1074/jbc.272.31.19418 }}
* {{cite journal | vauthors = Blangy A, Arnaud L, Nigg EA | title = Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor HsEg5 to the dynactin subunit p150 | journal = The Journal of Biological Chemistry | volume = 272 | issue = 31 | pages = 19418–24 | date = August 1997 | pmid = 9235942 | doi = 10.1074/jbc.272.31.19418 }}
* {{cite journal | vauthors = Korthaus D, Wedemeyer N, Lengeling A, Ronsiek M, Jockusch H, Schmitt-John T | title = Integrated radiation hybrid map of human chromosome 2p13: possible involvement of dynactin in neuromuscular diseases | journal = Genomics | volume = 43 | issue = 2 | pages = 242–4 | year = 1997 | pmid = 9244444 | doi = 10.1006/geno.1997.4789 }}
* {{cite journal | vauthors = Korthaus D, Wedemeyer N, Lengeling A, Ronsiek M, Jockusch H, Schmitt-John T | title = Integrated radiation hybrid map of human chromosome 2p13: possible involvement of dynactin in neuromuscular diseases | journal = Genomics | volume = 43 | issue = 2 | pages = 242–4 | date = July 1997 | pmid = 9244444 | doi = 10.1006/geno.1997.4789 }}
* {{cite journal | vauthors = Waterman-Storer CM, Karki SB, Kuznetsov SA, Tabb JS, Weiss DG, Langford GM, Holzbaur EL | title = The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 22 | pages = 12180–5 | year = 1997 | pmid = 9342383 | pmc = 23743 | doi = 10.1073/pnas.94.22.12180 }}
* {{cite journal | vauthors = Waterman-Storer CM, Karki SB, Kuznetsov SA, Tabb JS, Weiss DG, Langford GM, Holzbaur EL | title = The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 22 | pages = 12180–5 | date = October 1997 | pmid = 9342383 | pmc = 23743 | doi = 10.1073/pnas.94.22.12180 }}
* {{cite journal | vauthors = Engelender S, Sharp AH, Colomer V, Tokito MK, Lanahan A, Worley P, Holzbaur EL, Ross CA | title = Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin | journal = Hum. Mol. Genet. | volume = 6 | issue = 13 | pages = 2205–12 | year = 1997 | pmid = 9361024 | doi = 10.1093/hmg/6.13.2205 }}
* {{cite journal | vauthors = Engelender S, Sharp AH, Colomer V, Tokito MK, Lanahan A, Worley P, Holzbaur EL, Ross CA | title = Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin | journal = Human Molecular Genetics | volume = 6 | issue = 13 | pages = 2205–12 | date = December 1997 | pmid = 9361024 | doi = 10.1093/hmg/6.13.2205 }}
* {{cite journal | vauthors = Li SH, Gutekunst CA, Hersch SM, Li XJ | title = Interaction of huntingtin-associated protein with dynactin P150Glued | journal = J. Neurosci. | volume = 18 | issue = 4 | pages = 1261–9 | year = 1998 | pmid = 9454836 | doi =  }}
* {{cite journal | vauthors = Li SH, Gutekunst CA, Hersch SM, Li XJ | title = Interaction of huntingtin-associated protein with dynactin P150Glued | journal = The Journal of Neuroscience | volume = 18 | issue = 4 | pages = 1261–9 | date = February 1998 | pmid = 9454836 | doi =  }}
* {{cite journal | vauthors = Karki S, LaMonte B, Holzbaur EL | title = Characterization of the p22 subunit of dynactin reveals the localization of cytoplasmic dynein and dynactin to the midbody of dividing cells | journal = J. Cell Biol. | volume = 142 | issue = 4 | pages = 1023–34 | year = 1998 | pmid = 9722614 | pmc = 2132867 | doi = 10.1083/jcb.142.4.1023 }}
* {{cite journal | vauthors = Karki S, LaMonte B, Holzbaur EL | title = Characterization of the p22 subunit of dynactin reveals the localization of cytoplasmic dynein and dynactin to the midbody of dividing cells | journal = The Journal of Cell Biology | volume = 142 | issue = 4 | pages = 1023–34 | date = August 1998 | pmid = 9722614 | pmc = 2132867 | doi = 10.1083/jcb.142.4.1023 }}
* {{cite journal | vauthors = Collin GB, Nishina PM, Marshall JD, Naggert JK | title = Human DCTN1: genomic structure and evaluation as a candidate for Alström syndrome | journal = Genomics | volume = 53 | issue = 3 | pages = 359–64 | year = 1998 | pmid = 9799602 | doi = 10.1006/geno.1998.5542 }}
* {{cite journal | vauthors = Collin GB, Nishina PM, Marshall JD, Naggert JK | title = Human DCTN1: genomic structure and evaluation as a candidate for Alström syndrome | journal = Genomics | volume = 53 | issue = 3 | pages = 359–64 | date = November 1998 | pmid = 9799602 | doi = 10.1006/geno.1998.5542 }}
* {{cite journal | vauthors = Tokito MK, Holzbaur EL | title = The genomic structure of DCTN1, a candidate gene for limb-girdle muscular dystrophy (LGMD2B) | journal = Biochim. Biophys. Acta | volume = 1442 | issue = 2-3 | pages = 432–6 | year = 1998 | pmid = 9805007 | doi = 10.1016/S0167-4781(98)00195-X }}
* {{cite journal | vauthors = Tokito MK, Holzbaur EL | title = The genomic structure of DCTN1, a candidate gene for limb-girdle muscular dystrophy (LGMD2B) | journal = Biochimica et Biophysica Acta | volume = 1442 | issue = 2-3 | pages = 432–6 | date = November 1998 | pmid = 9805007 | doi = 10.1016/S0167-4781(98)00195-X }}
* {{cite journal | vauthors = Bingham JB, Schroer TA | title = Self-regulated polymerization of the actin-related protein Arp1 | journal = Curr. Biol. | volume = 9 | issue = 4 | pages = 223–6 | year = 1999 | pmid = 10074429 | doi = 10.1016/S0960-9822(99)80095-5 }}
* {{cite journal | vauthors = Bingham JB, Schroer TA | title = Self-regulated polymerization of the actin-related protein Arp1 | journal = Current Biology | volume = 9 | issue = 4 | pages = 223–6 | date = February 1999 | pmid = 10074429 | doi = 10.1016/S0960-9822(99)80095-5 }}
* {{cite journal | vauthors = Heimann K, Percival JM, Weinberger R, Gunning P, Stow JL | title = Specific isoforms of actin-binding proteins on distinct populations of Golgi-derived vesicles | journal = J. Biol. Chem. | volume = 274 | issue = 16 | pages = 10743–50 | year = 1999 | pmid = 10196146 | doi = 10.1074/jbc.274.16.10743 }}
* {{cite journal | vauthors = Heimann K, Percival JM, Weinberger R, Gunning P, Stow JL | title = Specific isoforms of actin-binding proteins on distinct populations of Golgi-derived vesicles | journal = The Journal of Biological Chemistry | volume = 274 | issue = 16 | pages = 10743–50 | date = April 1999 | pmid = 10196146 | doi = 10.1074/jbc.274.16.10743 }}
* {{cite journal | vauthors = Eckley DM, Gill SR, Melkonian KA, Bingham JB, Goodson HV, Heuser JE, Schroer TA | title = Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end | journal = J. Cell Biol. | volume = 147 | issue = 2 | pages = 307–20 | year = 1999 | pmid = 10525537 | pmc = 2174220 | doi = 10.1083/jcb.147.2.307 }}
* {{cite journal | vauthors = Eckley DM, Gill SR, Melkonian KA, Bingham JB, Goodson HV, Heuser JE, Schroer TA | title = Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end | journal = The Journal of Cell Biology | volume = 147 | issue = 2 | pages = 307–20 | date = October 1999 | pmid = 10525537 | pmc = 2174220 | doi = 10.1083/jcb.147.2.307 }}
* {{cite journal | vauthors = Karki S, Tokito MK, Holzbaur EL | title = A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1 | journal = J. Biol. Chem. | volume = 275 | issue = 7 | pages = 4834–9 | year = 2000 | pmid = 10671518 | doi = 10.1074/jbc.275.7.4834 }}
* {{cite journal | vauthors = Karki S, Tokito MK, Holzbaur EL | title = A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 7 | pages = 4834–9 | date = February 2000 | pmid = 10671518 | doi = 10.1074/jbc.275.7.4834 }}
* {{cite journal | vauthors = Vancoillie G, Lambert J, Haeghen YV, Westbroek W, Mulder A, Koerten HK, Mommaas AM, Van Oostveldt P, Naeyaert JM | title = Colocalization of dynactin subunits P150Glued and P50 with melanosomes in normal human melanocytes | journal = Pigment Cell Res. | volume = 13 | issue = 6 | pages = 449–57 | year = 2000 | pmid = 11153697 | doi = 10.1034/j.1600-0749.2000.130607.x }}
* {{cite journal | vauthors = Vancoillie G, Lambert J, Haeghen YV, Westbroek W, Mulder A, Koerten HK, Mommaas AM, Van Oostveldt P, Naeyaert JM | title = Colocalization of dynactin subunits P150Glued and P50 with melanosomes in normal human melanocytes | journal = Pigment Cell Research | volume = 13 | issue = 6 | pages = 449–57 | date = December 2000 | pmid = 11153697 | doi = 10.1034/j.1600-0749.2000.130607.x }}
{{refend}}
{{refend}}


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{{PDB Gallery|geneid=1639}}
{{PDB Gallery|geneid=1639}}


{{gene-2-stub}}
{{gene-2-stub}}

Latest revision as of 00:53, 28 December 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

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Location (UCSC)n/an/a
PubMed searchn/an/a
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View/Edit Human

Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.[1]

Function

This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 23 subunits (11 individual proteins ranging in size from 22 to 150 kD)[2]. Dynactin binds to cytoplasmic dynein, dynein cargo adaptors, and microtubules[3]. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis.

This subunit is commonly referred to p150-glued[1]. It is present in two copies per dynactin complex and forms an ~75nm long flexible arm that extends from the main body of dynactin[2]. The p150-glued arm contains binding sites for microtubules[4], the microtubule plus tip binding protein EB1[5], and the N-terminus of the dynein intermediate chain[6][7].

Alternative splicing of this gene results in at least 2 functionally distinct isoforms: a ubiquitously expressed one and a brain-specific one. Based on its cytogenetic location, this gene is considered as a candidate gene for limb-girdle muscular dystrophy.[8]

Interactions

DCTN1 has been shown to interact with:

References

  1. 1.0 1.1 Holzbaur EL, Hammarback JA, Paschal BM, Kravit NG, Pfister KK, Vallee RB (June 1991). "Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued". Nature. 351 (6327): 579–83. doi:10.1038/351579a0. PMID 1828535.
  2. 2.0 2.1 Urnavicius L, Zhang K, Diamant AG, Motz C, Schlager MA, Yu M, Patel NA, Robinson CV, Carter AP (March 2015). "The structure of the dynactin complex and its interaction with dynein". Science. 347 (6229): 1441–1446. doi:10.1126/science.aaa4080. PMC 4413427. PMID 25814576.
  3. Cianfrocco MA, DeSantis ME, Leschziner AE, Reck-Peterson SL (2015). "Mechanism and regulation of cytoplasmic dynein". Annual Review of Cell and Developmental Biology. 31: 83–108. doi:10.1146/annurev-cellbio-100814-125438. PMC 4644480. PMID 26436706.
  4. Waterman-Storer CM, Karki S, Holzbaur EL (February 1995). "The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1)". Proceedings of the National Academy of Sciences of the United States of America. 92 (5): 1634–8. PMC 42574. PMID 7878030.
  5. Berrueta L, Tirnauer JS, Schuyler SC, Pellman D, Bierer BE (April 1999). "The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain". Current Biology. 9 (8): 425–8. PMID 10226031.
  6. Karki S, Holzbaur EL (December 1995). "Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex". The Journal of Biological Chemistry. 270 (48): 28806–11. PMID 7499404.
  7. Vaughan KT, Vallee RB (December 1995). "Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued". The Journal of Cell Biology. 131 (6 Pt 1): 1507–16. PMC 2120689. PMID 8522607.
  8. "Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila)".
  9. Kim JC, Badano JL, Sibold S, Esmail MA, Hill J, Hoskins BE, Leitch CC, Venner K, Ansley SJ, Ross AJ, Leroux MR, Katsanis N, Beales PL (May 2004). "The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression". Nature Genetics. 36 (5): 462–70. doi:10.1038/ng1352. PMID 15107855.
  10. Liu JJ, Ding J, Kowal AS, Nardine T, Allen E, Delcroix JD, Wu C, Mobley W, Fuchs E, Yang Y (October 2003). "BPAG1n4 is essential for retrograde axonal transport in sensory neurons". The Journal of Cell Biology. 163 (2): 223–9. doi:10.1083/jcb.200306075. PMC 2173519. PMID 14581450.
  11. Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB (December 1996). "Identification of a novel 135-kDa Grb2-binding protein in osteoclasts". The Journal of Biological Chemistry. 271 (51): 33141–7. doi:10.1074/jbc.271.51.33141. PMID 8955163.
  12. Short B, Preisinger C, Schaletzky J, Kopajtich R, Barr FA (October 2002). "The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes". Current Biology. 12 (20): 1792–5. doi:10.1016/s0960-9822(02)01221-6. PMID 12401177.

Further reading

External links