From Wikipedia, the free encyclopedia
Protein and coding gene in humans
Protein diaphanous homolog 1 is a
protein that in humans is encoded by the DIAPH1
gene .
[5]
[6]
[7]
Function
This gene is a
homolog of the
Drosophila diaphanous gene and belongs to the
protein family of the
formins , characterized by the formin homology 2 (FH2)
domain. It has been linked to
autosomal dominant , fully
penetrant , nonsyndromic low-frequency progressive
sensorineural hearing loss .
Actin
polymerization involves proteins known to interact with diaphanous protein in Drosophila and
mouse . It has therefore been speculated that this gene may have a role in the regulation of
actin polymerization in
hair cells of the
inner ear .
Alternatively spliced transcript variants encoding distinct
isoforms have been found for this gene.
[7]
Interactions
DIAPH1 has been shown to
interact with
RHOA .
[8]
Clinical significance
Mutations in this gene have been associated with
macrothrombocytopenia and hearing loss,
[9]
microcephaly , blindness, and early onset seizures
[10]
Its actions on
platelet formation appear to occur at the level of the
megakaryocyte where it is involved in
cytoskeleton formation.
[11]
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000131504 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000024456 –
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 .
^ Lynch ED, Lee MK, Morrow JE, Welcsh PL, León PE, King MC (November 1997). "Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous". Science . 278 (5341): 1315–8.
Bibcode :
1997Sci...278.1315L .
doi :
10.1126/science.278.5341.1315 .
PMID
9360932 .
^ Leon PE, Raventos H, Lynch E, Morrow J, King MC (June 1992).
"The gene for an inherited form of deafness maps to chromosome 5q31" . Proceedings of the National Academy of Sciences of the United States of America . 89 (11): 5181–4.
Bibcode :
1992PNAS...89.5181L .
doi :
10.1073/pnas.89.11.5181 .
PMC
49253 .
PMID
1350680 .
^
a
b
"Entrez Gene: DIAPH1 diaphanous homolog 1 (Drosophila)" .
^ Riento K, Guasch RM, Garg R, Jin B, Ridley AJ (June 2003).
"RhoE binds to ROCK I and inhibits downstream signaling" . Molecular and Cellular Biology . 23 (12): 4219–29.
doi :
10.1128/MCB.23.12.4219-4229.2003 .
PMC
156133 .
PMID
12773565 .
^ Stritt S, Nurden P, Turro E, Greene D, Jansen SB, Westbury SK, et al. (June 2016).
"A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss" . Blood . 127 (23): 2903–14.
doi :
10.1182/blood-2015-10-675629 .
hdl :
1983/57509c95-e756-43c8-96ec-de3a3492481b .
PMID
26912466 .
^ Al-Maawali A, Barry BJ, Rajab A, El-Quessny M, Seman A, Coury SN, et al. (February 2016).
"Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures" . American Journal of Medical Genetics. Part A . 170A (2): 435–40.
doi :
10.1002/ajmg.a.37422 .
PMC
5315085 .
PMID
26463574 .
^ Pan J, Lordier L, Meyran D, Rameau P, Lecluse Y, Kitchen-Goosen S, et al. (2014).
"The formin DIAPH1 (mDia1) regulates megakaryocyte proplatelet formation by remodeling the actin and microtubule cytoskeletons" . Blood . 124 (26): 3967–77.
doi :
10.1182/blood-2013-12-544924 .
PMID
25298036 .
Further reading
Reinhard M, Giehl K, Abel K, Haffner C, Jarchau T, Hoppe V, Jockusch BM, Walter U (April 1995).
"The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins" . The EMBO Journal . 14 (8): 1583–9.
doi :
10.1002/j.1460-2075.1995.tb07146.x .
PMC
398250 .
PMID
7737110 .
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry . 236 (1): 107–13.
doi :
10.1006/abio.1996.0138 .
PMID
8619474 .
Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997).
"Large-scale concatenation cDNA sequencing" . Genome Research . 7 (4): 353–8.
doi :
10.1101/gr.7.4.353 .
PMC
139146 .
PMID
9110174 .
Fujiwara T, Mammoto A, Kim Y, Takai Y (May 2000). "Rho small G-protein-dependent binding of mDia to an Src homology 3 domain-containing IRSp53/BAIAP2". Biochemical and Biophysical Research Communications . 271 (3): 626–9.
doi :
10.1006/bbrc.2000.2671 .
PMID
10814512 .
Kato T, Watanabe N, Morishima Y, Fujita A, Ishizaki T, Narumiya S (February 2001). "Localization of a mammalian homolog of diaphanous, mDia1, to the mitotic spindle in HeLa cells". Journal of Cell Science . 114 (Pt 4): 775–84.
doi :
10.1242/jcs.114.4.775 .
hdl :
2433/150544 .
PMID
11171383 .
Westendorf JJ (December 2001).
"The formin/diaphanous-related protein, FHOS, interacts with Rac1 and activates transcription from the serum response element" . The Journal of Biological Chemistry . 276 (49): 46453–9.
doi :
10.1074/jbc.M105162200 .
PMID
11590143 .
Sahai E, Marshall CJ (June 2002). "ROCK and Dia have opposing effects on adherens junctions downstream of Rho". Nature Cell Biology . 4 (6): 408–15.
doi :
10.1038/ncb796 .
PMID
11992112 .
S2CID
20795071 .
Montagnoli A, Bosotti R, Villa F, Rialland M, Brotherton D, Mercurio C, Berthelsen J, Santocanale C (June 2002).
"Drf1, a novel regulatory subunit for human Cdc7 kinase" . The EMBO Journal . 21 (12): 3171–81.
doi :
10.1093/emboj/cdf290 .
PMC
126049 .
PMID
12065429 .
Tominaga T, Meng W, Togashi K, Urano H, Alberts AS, Tominaga M (December 2002).
"The Rho GTPase effector protein, mDia, inhibits the DNA binding ability of the transcription factor Pax6 and changes the pattern of neurite extension in cerebellar granule cells through its binding to Pax6" . The Journal of Biological Chemistry . 277 (49): 47686–91.
doi :
10.1074/jbc.M207539200 .
PMID
12324464 .
Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology . 21 (5): 566–9.
doi :
10.1038/nbt810 .
PMID
12665801 .
S2CID
23783563 .
Vicente-Manzanares M, Rey M, Pérez-Martínez M, Yáñez-Mó M, Sancho D, Cabrero JR, Barreiro O, de la Fuente H, Itoh K, Sánchez-Madrid F (July 2003).
"The RhoA effector mDia is induced during T cell activation and regulates actin polymerization and cell migration in T lymphocytes" . Journal of Immunology . 171 (2): 1023–34.
doi :
10.4049/jimmunol.171.2.1023 .
PMID
12847276 .
Stüven T, Hartmann E, Görlich D (November 2003).
"Exportin 6: a novel nuclear export receptor that is specific for profilin.actin complexes" . The EMBO Journal . 22 (21): 5928–40.
doi :
10.1093/emboj/cdg565 .
PMC
275422 .
PMID
14592989 .
Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, Ishizaki T, Narumiya S (April 2004). "Cdc42 and mDia3 regulate microtubule attachment to kinetochores". Nature . 428 (6984): 767–71.
Bibcode :
2004Natur.428..767Y .
doi :
10.1038/nature02452 .
PMID
15085137 .
S2CID
4401953 .
Mammoto A, Huang S, Moore K, Oh P, Ingber DE (June 2004).
"Role of RhoA, mDia, and ROCK in cell shape-dependent control of the Skp2-p27kip1 pathway and the G1/S transition" . The Journal of Biological Chemistry . 279 (25): 26323–30.
doi :
10.1074/jbc.M402725200 .
PMID
15096506 .
Rundle DR, Gorbsky G, Tsiokas L (July 2004).
"PKD2 interacts and co-localizes with mDia1 to mitotic spindles of dividing cells: role of mDia1 IN PKD2 localization to mitotic spindles" . The Journal of Biological Chemistry . 279 (28): 29728–39.
doi :
10.1074/jbc.M400544200 .
PMID
15123714 .
Carreira S, Goodall J, Denat L, Rodriguez M, Nuciforo P, Hoek KS, Testori A, Larue L, Goding CR (December 2006).
"Mitf regulation of Dia1 controls melanoma proliferation and invasiveness" . Genes & Development . 20 (24): 3426–39.
doi :
10.1101/gad.406406 .
PMC
1698449 .
PMID
17182868 .
External links
PDB gallery
1v9d : Crystal structure of the core FH2 domain of mouse mDia1
1z2c : Crystal structure of mDIA1 GBD-FH3 in complex with RhoC-GMPPNP
2bap : Crystal structure of the N-terminal mDia1 Armadillo Repeat Region and Dimerisation Domain in complex with the mDia1 autoregulatory domain (DAD)
2bnx : CRYSTAL STRUCTURE OF THE DIMERIC REGULATORY DOMAIN OF MOUSE DIAPHANEOUS-RELATED FORMIN (DRF), MDIA1
2f31 : Crystal structure of the autoinhibitory switch in Formin mDia1; the DID/DAD complex