Mutagenetix > Incidental Mutation

Incidental Mutation 'R0069:Dctn2'

16849

Institutional Source

Beutler Lab

Gene Symbol

Dctn2

Ensembl Gene

ENSMUSG00000025410

Gene Name

dynactin 2

Synonyms

DCTN-50, C130077D06Rik, 2310042E05Rik, RBP50, p50

MMRRC Submission

038360-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0069 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

127102237-127117819 bp(+) (GRCm39)

Type of Mutation

splice site (4471 bp from exon)

DNA Base Change (assembly)

A to T at 127113354 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000112805 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000026476] [ENSMUST00000026479] [ENSMUST00000119078]

AlphaFold

Q99KJ8

Predicted Effect

probably null
Transcript: ENSMUST00000026476

SMART Domains

Protein: ENSMUSP00000026476
Gene: ENSMUSG00000025409

Domain	Start	End	E-Value	Type
Blast:MBD	26	79	8e-10	BLAST
low complexity region	80	94	N/A	INTRINSIC
low complexity region	140	155	N/A	INTRINSIC
low complexity region	183	197	N/A	INTRINSIC
low complexity region	212	229	N/A	INTRINSIC
low complexity region	247	262	N/A	INTRINSIC
low complexity region	269	295	N/A	INTRINSIC
low complexity region	311	342	N/A	INTRINSIC
low complexity region	347	378	N/A	INTRINSIC
low complexity region	383	428	N/A	INTRINSIC
low complexity region	442	455	N/A	INTRINSIC
low complexity region	461	498	N/A	INTRINSIC
low complexity region	500	517	N/A	INTRINSIC
low complexity region	533	563	N/A	INTRINSIC
low complexity region	566	634	N/A	INTRINSIC
low complexity region	636	652	N/A	INTRINSIC
low complexity region	653	674	N/A	INTRINSIC
low complexity region	676	686	N/A	INTRINSIC
low complexity region	733	799	N/A	INTRINSIC
low complexity region	815	849	N/A	INTRINSIC
low complexity region	853	890	N/A	INTRINSIC
low complexity region	949	958	N/A	INTRINSIC
low complexity region	978	1002	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000026479

SMART Domains

Protein: ENSMUSP00000026479
Gene: ENSMUSG00000025410

Domain	Start	End	E-Value	Type
Pfam:Dynamitin	16	400	7.1e-129	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000119078

SMART Domains

Protein: ENSMUSP00000112805
Gene: ENSMUSG00000025409

Domain	Start	End	E-Value	Type
Blast:MBD	26	79	8e-10	BLAST
low complexity region	80	94	N/A	INTRINSIC
low complexity region	140	155	N/A	INTRINSIC
low complexity region	183	197	N/A	INTRINSIC
low complexity region	212	229	N/A	INTRINSIC
low complexity region	247	262	N/A	INTRINSIC
low complexity region	269	295	N/A	INTRINSIC
low complexity region	311	342	N/A	INTRINSIC
low complexity region	347	378	N/A	INTRINSIC
low complexity region	383	428	N/A	INTRINSIC
low complexity region	442	455	N/A	INTRINSIC
low complexity region	461	498	N/A	INTRINSIC
low complexity region	500	517	N/A	INTRINSIC
low complexity region	533	563	N/A	INTRINSIC
low complexity region	566	634	N/A	INTRINSIC
low complexity region	636	652	N/A	INTRINSIC
low complexity region	653	674	N/A	INTRINSIC
low complexity region	676	686	N/A	INTRINSIC
low complexity region	733	798	N/A	INTRINSIC
low complexity region	813	847	N/A	INTRINSIC
low complexity region	851	888	N/A	INTRINSIC
low complexity region	947	956	N/A	INTRINSIC
low complexity region	976	1000	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000126243

SMART Domains

Protein: ENSMUSP00000115238
Gene: ENSMUSG00000025409

Domain	Start	End	E-Value	Type
low complexity region	1	26	N/A	INTRINSIC
low complexity region	31	76	N/A	INTRINSIC
low complexity region	90	103	N/A	INTRINSIC
low complexity region	109	146	N/A	INTRINSIC
low complexity region	148	165	N/A	INTRINSIC
low complexity region	181	211	N/A	INTRINSIC
low complexity region	214	282	N/A	INTRINSIC
low complexity region	284	300	N/A	INTRINSIC
low complexity region	301	322	N/A	INTRINSIC
low complexity region	324	334	N/A	INTRINSIC
low complexity region	381	446	N/A	INTRINSIC
low complexity region	462	496	N/A	INTRINSIC
low complexity region	500	537	N/A	INTRINSIC
low complexity region	596	610	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000136169

SMART Domains

Protein: ENSMUSP00000122504
Gene: ENSMUSG00000025409

Domain	Start	End	E-Value	Type
low complexity region	55	64	N/A	INTRINSIC
low complexity region	84	108	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000218556

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000218752

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000220418

Meta Mutation Damage Score

0.9580

Coding Region Coverage

1x: 86.4%
3x: 80.4%
10x: 57.4%
20x: 26.1%

Validation Efficiency

94% (60/64)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a 50-kD 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 ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 4-5 copies per dynactin molecule. It contains three short alpha-helical coiled-coil domains that may mediate association with self or other dynactin subunits. It may interact directly with the largest subunit (p150) of dynactin and may affix p150 in place. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2012]

Allele List at MGI

All alleles(28) : Targeted(3) Gene trapped(25)

Other mutations in this stock

Total: 25 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2ml1	A	T	6: 128,538,525 (GRCm39)	C632S	probably damaging	Het
Ccnb1ip1	G	A	14: 81,519,382 (GRCm38)	Q322*	probably null	Het
Cd101	A	G	3: 100,915,533 (GRCm39)	V678A	probably benign	Het
Creb1	A	G	1: 64,615,367 (GRCm39)	I240V	possibly damaging	Het
Diablo	A	T	5: 123,656,087 (GRCm39)	S117R	probably damaging	Het
Ebf2	A	T	14: 67,647,499 (GRCm39)	R349S	probably damaging	Het
Gne	A	C	4: 44,060,099 (GRCm39)	V98G	probably damaging	Het
Ints3	A	G	3: 90,307,954 (GRCm39)		probably benign	Het
Itgal	A	G	7: 126,909,503 (GRCm39)	T56A	probably benign	Het
Lzts3	T	A	2: 130,478,460 (GRCm39)	T213S	probably benign	Het
Myo1d	A	G	11: 80,528,779 (GRCm39)	I681T	probably damaging	Het
Pde8a	T	C	7: 80,968,871 (GRCm39)		probably benign	Het
Pole2	A	T	12: 69,256,661 (GRCm39)	V288E	probably damaging	Het
Poteg	T	C	8: 27,937,849 (GRCm39)	S2P	probably benign	Het
Ppp2r5c	A	T	12: 110,534,204 (GRCm39)	M356L	probably benign	Het
Rad54l2	C	A	9: 106,587,564 (GRCm39)	V734L	possibly damaging	Het
Ryr1	A	C	7: 28,809,930 (GRCm39)		probably benign	Het
Slfn10-ps	A	G	11: 82,926,368 (GRCm39)		noncoding transcript	Het
Sult1e1	A	T	5: 87,727,756 (GRCm39)	H175Q	probably damaging	Het
Trgv7	A	G	13: 19,362,592 (GRCm39)	R94G	probably benign	Het
Ube2e3	C	A	2: 78,750,293 (GRCm39)		probably benign	Het
Vps13d	A	G	4: 144,789,133 (GRCm39)	I746T	probably benign	Het
Xpnpep3	T	C	15: 81,314,999 (GRCm39)	V233A	probably benign	Het
Zfp329	A	T	7: 12,544,859 (GRCm39)	S222T	probably damaging	Het
Zswim6	T	C	13: 107,875,098 (GRCm39)		noncoding transcript	Het

Other mutations in Dctn2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00334:Dctn2	APN	10	127,113,559 (GRCm39)	unclassified	probably benign
IGL01749:Dctn2	APN	10	127,117,286 (GRCm39)	missense	possibly damaging	0.47
IGL01797:Dctn2	APN	10	127,113,182 (GRCm39)	missense	possibly damaging	0.94
IGL02021:Dctn2	APN	10	127,110,926 (GRCm39)	critical splice donor site	probably null
IGL02335:Dctn2	APN	10	127,111,690 (GRCm39)	splice site	probably benign
IGL02748:Dctn2	APN	10	127,113,142 (GRCm39)	missense	probably damaging	1.00
IGL03382:Dctn2	APN	10	127,114,057 (GRCm39)	missense	probably damaging	0.99
R0069:Dctn2	UTSW	10	127,113,354 (GRCm39)	splice site	probably null
R0621:Dctn2	UTSW	10	127,113,809 (GRCm39)	critical splice donor site	probably null
R1114:Dctn2	UTSW	10	127,114,011 (GRCm39)	splice site	probably null
R1917:Dctn2	UTSW	10	127,110,918 (GRCm39)	nonsense	probably null
R2238:Dctn2	UTSW	10	127,112,257 (GRCm39)	missense	probably damaging	0.97
R4097:Dctn2	UTSW	10	127,113,362 (GRCm39)	missense	probably damaging	1.00
R4418:Dctn2	UTSW	10	127,114,234 (GRCm39)	missense	probably benign	0.24
R4972:Dctn2	UTSW	10	127,112,572 (GRCm39)	missense	probably damaging	1.00
R6873:Dctn2	UTSW	10	127,112,105 (GRCm39)	splice site	probably null
R7533:Dctn2	UTSW	10	127,103,347 (GRCm39)	missense	possibly damaging	0.87
R7557:Dctn2	UTSW	10	127,114,273 (GRCm39)	missense	probably benign	0.44
R7657:Dctn2	UTSW	10	127,102,383 (GRCm39)	missense	probably damaging	1.00
R8218:Dctn2	UTSW	10	127,112,398 (GRCm39)	missense	probably damaging	0.97
R8557:Dctn2	UTSW	10	127,114,062 (GRCm39)	missense	probably damaging	1.00
R9344:Dctn2	UTSW	10	127,114,084 (GRCm39)	missense	probably damaging	1.00

Protein Function and Prediction

Dctn2 encodes p50/dynamitin, a subunit of the multiprotein dynactin complex. Dynactin associates with dynein to facilitate minus-end-directed movement along microtubules (1). Studies have shown that p50 is required for the stabilization and attachment of the Arp1 rod and the shoulder/sidearm of dynactin (1). Amino acids 1-91 of p50 have been shown to be critical for dynactin function (1). Three coiled-coil motifs [aa 105-136, 219-251, and 281-308 (2)] facilitate the oligomerization of p50 as well as the association of p50 with other dynactin subunits (1;3).

References

1. Jacquot, G., Maidou-Peindara, P., and Benichou, S. (2010) Molecular and Functional Basis for the Scaffolding Role of the p50/dynamitin Subunit of the Microtubule-Associated Dynactin Complex. J Biol Chem. 285, 23019-23031.

2. Echeverri, C. J., Paschal, B. M., Vaughan, K. T., and Vallee, R. B. (1996) Molecular Characterization of the 50-kD Subunit of Dynactin Reveals Function for the Complex in Chromosome Alignment and Spindle Organization during Mitosis. J Cell Biol. 132, 617-633.

3. Maier, K. C., Godfrey, J. E., Echeverri, C. J., Cheong, F. K., and Schroer, T. A. (2008) Dynamitin Mutagenesis Reveals Protein-Protein Interactions Important for Dynactin Structure. Traffic. 9, 481-491.

Posted On

2013-01-20

Science Writer

Anne Murray