From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
Dynactin subunit 1 is a
protein that in humans is encoded by the DCTN1
gene .
[5]
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).
[6] Dynactin binds to cytoplasmic
dynein , dynein cargo adaptors, and
microtubules .
[7] 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.
[5] It is present in two copies per dynactin complex and forms an ≈75 nm long flexible arm that extends from the main body of dynactin.
[6] The p150-glued arm contains binding sites for microtubules,
[8] the microtubule plus tip binding protein EB1,
[9] and the N-terminus of the dynein intermediate chain.
[10]
[11]
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.
[12]
Interactions
DCTN1 has been shown to
interact with:
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000204843 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000031865 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
a
b 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.
Bibcode :
1991Natur.351..579H .
doi :
10.1038/351579a0 .
PMID
1828535 .
S2CID
4263574 .
^
a
b 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.
Bibcode :
2015Sci...347.1441U .
doi :
10.1126/science.aaa4080 .
PMC
4413427 .
PMID
25814576 .
^ 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 .
^ 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.
Bibcode :
1995PNAS...92.1634W .
doi :
10.1073/pnas.92.5.1634 .
PMC
42574 .
PMID
7878030 .
^ 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.
Bibcode :
1999CBio....9..425B .
doi :
10.1016/S0960-9822(99)80190-0 .
PMID
10226031 .
S2CID
14191776 .
^ 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.
doi :
10.1074/jbc.270.48.28806 .
PMID
7499404 .
^ 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.
doi :
10.1083/jcb.131.6.1507 .
PMC
2120689 .
PMID
8522607 .
^
"Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila)" .
^ 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 .
^ 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 .
^ 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 .
^ 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.
Bibcode :
2002CBio...12.1792S .
doi :
10.1016/s0960-9822(02)01221-6 .
PMID
12401177 .
S2CID
14031165 .
Further reading
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.
Bibcode :
1995PNAS...92.1634W .
doi :
10.1073/pnas.92.5.1634 .
PMC
42574 .
PMID
7878030 .
Paschal BM, Holzbaur EL, Pfister KK, Clark S, Meyer DI, Vallee RB (July 1993).
"Characterization of a 50-kDa polypeptide in cytoplasmic dynein preparations reveals a complex with p150GLUED and a novel actin" . The Journal of Biological Chemistry . 268 (20): 15318–23.
doi :
10.1016/S0021-9258(18)82472-3 .
PMID
8325901 .
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.
doi :
10.1083/jcb.131.6.1507 .
PMC
2120689 .
PMID
8522607 .
Holzbaur EL, Tokito MK (February 1996).
"Localization of the DCTN1 gene encoding p150Glued to human chromosome 2p13 by fluorescence in situ hybridization" . Genomics . 31 (3): 398–9.
doi :
10.1006/geno.1996.0068 .
PMID
8838327 .
Tokito MK, Howland DS, Lee VM, Holzbaur EL (August 1996).
"Functionally distinct isoforms of dynactin are expressed in human neurons" . Molecular Biology of the Cell . 7 (8): 1167–80.
doi :
10.1091/mbc.7.8.1167 .
PMC
275970 .
PMID
8856662 .
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 .
Blangy A, Arnaud L, Nigg EA (August 1997).
"Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor HsEg5 to the dynactin subunit p150" . The Journal of Biological Chemistry . 272 (31): 19418–24.
doi :
10.1074/jbc.272.31.19418 .
PMID
9235942 .
Korthaus D, Wedemeyer N, Lengeling A, Ronsiek M, Jockusch H, Schmitt-John T (July 1997). "Integrated radiation hybrid map of human chromosome 2p13: possible involvement of dynactin in neuromuscular diseases". Genomics . 43 (2): 242–4.
doi :
10.1006/geno.1997.4789 .
PMID
9244444 .
Waterman-Storer CM, Karki SB, Kuznetsov SA, Tabb JS, Weiss DG, Langford GM, Holzbaur EL (October 1997).
"The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport" . Proceedings of the National Academy of Sciences of the United States of America . 94 (22): 12180–5.
Bibcode :
1997PNAS...9412180W .
doi :
10.1073/pnas.94.22.12180 .
PMC
23743 .
PMID
9342383 .
Engelender S, Sharp AH, Colomer V, Tokito MK, Lanahan A, Worley P, Holzbaur EL, Ross CA (December 1997).
"Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin" . Human Molecular Genetics . 6 (13): 2205–12.
doi :
10.1093/hmg/6.13.2205 .
PMID
9361024 .
Li SH, Gutekunst CA, Hersch SM, Li XJ (February 1998).
"Interaction of huntingtin-associated protein with dynactin P150Glued" . The Journal of Neuroscience . 18 (4): 1261–9.
doi :
10.1523/JNEUROSCI.18-04-01261.1998 .
PMC
6792727 .
PMID
9454836 .
Karki S, LaMonte B, Holzbaur EL (August 1998).
"Characterization of the p22 subunit of dynactin reveals the localization of cytoplasmic dynein and dynactin to the midbody of dividing cells" . The Journal of Cell Biology . 142 (4): 1023–34.
doi :
10.1083/jcb.142.4.1023 .
PMC
2132867 .
PMID
9722614 .
Collin GB, Nishina PM, Marshall JD, Naggert JK (November 1998). "Human DCTN1: genomic structure and evaluation as a candidate for Alström syndrome". Genomics . 53 (3): 359–64.
doi :
10.1006/geno.1998.5542 .
PMID
9799602 .
Tokito MK, Holzbaur EL (November 1998).
"The genomic structure of DCTN1, a candidate gene for limb-girdle muscular dystrophy (LGMD2B)" . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1442 (2–3): 432–6.
doi :
10.1016/S0167-4781(98)00195-X .
PMID
9805007 .
Bingham JB, Schroer TA (February 1999).
"Self-regulated polymerization of the actin-related protein Arp1" . Current Biology . 9 (4): 223–6.
Bibcode :
1999CBio....9..223B .
doi :
10.1016/S0960-9822(99)80095-5 .
PMID
10074429 .
S2CID
208851 .
Heimann K, Percival JM, Weinberger R, Gunning P, Stow JL (April 1999).
"Specific isoforms of actin-binding proteins on distinct populations of Golgi-derived vesicles" . The Journal of Biological Chemistry . 274 (16): 10743–50.
doi :
10.1074/jbc.274.16.10743 .
PMID
10196146 .
Eckley DM, Gill SR, Melkonian KA, Bingham JB, Goodson HV, Heuser JE, Schroer TA (October 1999).
"Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end" . The Journal of Cell Biology . 147 (2): 307–20.
doi :
10.1083/jcb.147.2.307 .
PMC
2174220 .
PMID
10525537 .
Karki S, Tokito MK, Holzbaur EL (February 2000).
"A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1" . The Journal of Biological Chemistry . 275 (7): 4834–9.
doi :
10.1074/jbc.275.7.4834 .
PMID
10671518 .
Vancoillie G, Lambert J, Haeghen YV, Westbroek W, Mulder A, Koerten HK, Mommaas AM, Van Oostveldt P, Naeyaert JM (December 2000).
"Colocalization of dynactin subunits P150Glued and P50 with melanosomes in normal human melanocytes" . Pigment Cell Research . 13 (6): 449–57.
doi :
10.1034/j.1600-0749.2000.130607.x .
PMID
11153697 .
External links
PDB gallery
1txq : Crystal structure of the EB1 C-terminal domain complexed with the CAP-Gly domain of p150Glued
2coy : Solution structure of the CAP-Gly domain in human Dynactin 1
2hkn : Crystal structure of the CAP-Gly domain of human Dynactin-1 (p150-Glued)
2hkq : Crystal structure of the C-terminal domain of human EB1 in complex with the CAP-Gly domain of human Dynactin-1 (p150-Glued)
2hl3 : Crystal structure of the A49M mutant CAP-Gly domain of human Dynactin-1 (p150-Glued) in complex with human EB1 C-terminal hexapeptide
2hl5 : Crystal structure of the C-terminal domain of human EB1 in complex with the A49M mutant CAP-Gly domain of human Dynactin-1 (p150-Glued)