Incidental Mutation 'R0042:Mib2'
ID |
15658 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Mib2
|
Ensembl Gene |
ENSMUSG00000029060 |
Gene Name |
mindbomb E3 ubiquitin protein ligase 2 |
Synonyms |
Zzank1, 2210008I11Rik |
MMRRC Submission |
038336-MU
|
Accession Numbers |
|
Essential gene? |
Non essential
(E-score: 0.000)
|
Stock # |
R0042 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
4 |
Chromosomal Location |
155739134-155753655 bp(-) (GRCm39) |
Type of Mutation |
nonsense |
DNA Base Change (assembly) |
A to T
at 155743897 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Cysteine to Stop codon
at position 48
(C48*)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000122269
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000103176]
[ENSMUST00000141108]
|
AlphaFold |
no structure available at present |
Predicted Effect |
probably null
Transcript: ENSMUST00000103176
AA Change: C223*
|
SMART Domains |
Protein: ENSMUSP00000099465 Gene: ENSMUSG00000029060 AA Change: C223*
Domain | Start | End | E-Value | Type |
Pfam:MIB_HERC2
|
12 |
78 |
3.4e-26 |
PFAM |
ZnF_ZZ
|
85 |
130 |
6.44e-9 |
SMART |
Pfam:MIB_HERC2
|
160 |
225 |
4.2e-26 |
PFAM |
Blast:ANK
|
285 |
320 |
2e-13 |
BLAST |
ANK
|
428 |
457 |
8.52e-4 |
SMART |
ANK
|
461 |
490 |
6.71e-2 |
SMART |
ANK
|
494 |
523 |
9.93e-5 |
SMART |
ANK
|
527 |
559 |
1.1e2 |
SMART |
ANK
|
563 |
593 |
9.21e0 |
SMART |
ANK
|
597 |
627 |
3.57e-6 |
SMART |
ANK
|
631 |
660 |
3.31e-1 |
SMART |
ANK
|
664 |
709 |
1.73e3 |
SMART |
Blast:ANK
|
733 |
762 |
9e-10 |
BLAST |
low complexity region
|
763 |
772 |
N/A |
INTRINSIC |
RING
|
798 |
832 |
2.55e-1 |
SMART |
RING
|
877 |
909 |
1.81e-2 |
SMART |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000128204
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000130237
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000139134
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000139788
|
Predicted Effect |
probably null
Transcript: ENSMUST00000141108
AA Change: C48*
|
SMART Domains |
Protein: ENSMUSP00000122269 Gene: ENSMUSG00000029060 AA Change: C48*
Domain | Start | End | E-Value | Type |
Pfam:MIB_HERC2
|
1 |
52 |
7.1e-17 |
PFAM |
internal_repeat_1
|
82 |
150 |
7.77e-12 |
PROSPERO |
internal_repeat_1
|
153 |
220 |
7.77e-12 |
PROSPERO |
ANK
|
289 |
318 |
8.52e-4 |
SMART |
ANK
|
322 |
351 |
6.71e-2 |
SMART |
Pfam:Ank
|
356 |
375 |
2.9e-4 |
PFAM |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000155189
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000151843
|
Meta Mutation Damage Score |
0.9712 |
Coding Region Coverage |
- 1x: 81.9%
- 3x: 73.7%
- 10x: 53.7%
- 20x: 34.5%
|
Validation Efficiency |
94% (58/62) |
MGI Phenotype |
PHENOTYPE: Mice homozygous for a knock-out allele display exencephaly with a variable penetrance that depends on the genetic background. Mice homozygous for a reporter/null allele are viable, fertile and show normal growth, body weight and brain morphology. [provided by MGI curators]
|
Allele List at MGI |
All alleles(16) : Targeted(5) Gene trapped(11)
|
Other mutations in this stock |
Total: 34 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Abca1 |
C |
T |
4: 53,059,245 (GRCm39) |
|
probably benign |
Het |
Adgrf3 |
A |
G |
5: 30,402,426 (GRCm39) |
L534P |
probably damaging |
Het |
Ank2 |
T |
C |
3: 126,730,280 (GRCm39) |
D3568G |
probably damaging |
Het |
Atr |
T |
A |
9: 95,809,409 (GRCm39) |
|
probably benign |
Het |
Ccnb2 |
A |
G |
9: 70,326,335 (GRCm39) |
V34A |
probably benign |
Het |
Dmxl1 |
C |
A |
18: 49,997,102 (GRCm39) |
T466K |
probably benign |
Het |
Eya1 |
T |
C |
1: 14,254,713 (GRCm39) |
D373G |
probably damaging |
Het |
Fam120a |
A |
G |
13: 49,087,490 (GRCm39) |
V290A |
probably damaging |
Het |
Gpr179 |
C |
T |
11: 97,225,757 (GRCm39) |
V2133I |
probably benign |
Het |
Grb10 |
G |
T |
11: 11,886,798 (GRCm39) |
H435Q |
probably damaging |
Het |
Gzmm |
T |
C |
10: 79,530,399 (GRCm39) |
I190T |
probably benign |
Het |
H2-Q3 |
A |
G |
17: 35,578,823 (GRCm39) |
|
noncoding transcript |
Het |
Hspb7 |
A |
G |
4: 141,151,245 (GRCm39) |
E129G |
probably damaging |
Het |
Il17ra |
T |
C |
6: 120,449,086 (GRCm39) |
|
probably benign |
Het |
Itgb3 |
A |
G |
11: 104,557,966 (GRCm39) |
T787A |
possibly damaging |
Het |
Krt4 |
T |
G |
15: 101,831,187 (GRCm39) |
|
probably benign |
Het |
Lgsn |
C |
T |
1: 31,229,534 (GRCm39) |
T85I |
probably benign |
Het |
Metap1 |
C |
T |
3: 138,177,918 (GRCm39) |
V217I |
probably benign |
Het |
Mroh4 |
T |
A |
15: 74,482,154 (GRCm39) |
I768F |
probably damaging |
Het |
Npas3 |
T |
A |
12: 54,095,624 (GRCm39) |
D361E |
probably damaging |
Het |
P4hb |
G |
A |
11: 120,459,092 (GRCm39) |
R134C |
probably damaging |
Het |
Prr35 |
C |
A |
17: 26,166,956 (GRCm39) |
E194* |
probably null |
Het |
Rbl1 |
A |
G |
2: 157,017,624 (GRCm39) |
|
probably benign |
Het |
Rdh10 |
T |
A |
1: 16,178,260 (GRCm39) |
|
probably benign |
Het |
Spata31 |
A |
T |
13: 65,070,377 (GRCm39) |
I842L |
probably benign |
Het |
Stk32b |
A |
C |
5: 37,874,092 (GRCm39) |
D13E |
probably benign |
Het |
Svep1 |
T |
C |
4: 58,123,192 (GRCm39) |
D708G |
possibly damaging |
Het |
Taar6 |
T |
C |
10: 23,861,021 (GRCm39) |
D175G |
probably benign |
Het |
Tmod4 |
T |
C |
3: 95,037,099 (GRCm39) |
D164G |
possibly damaging |
Het |
Ttc23l |
A |
C |
15: 10,551,627 (GRCm39) |
L33W |
probably damaging |
Het |
Ttc39d |
T |
C |
17: 80,523,379 (GRCm39) |
Y13H |
probably benign |
Het |
Utp18 |
G |
T |
11: 93,766,684 (GRCm39) |
T309K |
probably damaging |
Het |
Vps11 |
G |
T |
9: 44,267,588 (GRCm39) |
Y341* |
probably null |
Het |
Vsig8 |
T |
C |
1: 172,387,925 (GRCm39) |
V5A |
possibly damaging |
Het |
|
Other mutations in Mib2 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL01014:Mib2
|
APN |
4 |
155,742,187 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01404:Mib2
|
APN |
4 |
155,739,393 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01819:Mib2
|
APN |
4 |
155,739,715 (GRCm39) |
splice site |
probably null |
|
IGL02147:Mib2
|
APN |
4 |
155,742,144 (GRCm39) |
missense |
probably benign |
|
IGL02260:Mib2
|
APN |
4 |
155,745,628 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02472:Mib2
|
APN |
4 |
155,741,203 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02632:Mib2
|
APN |
4 |
155,740,036 (GRCm39) |
missense |
probably damaging |
0.98 |
IGL03051:Mib2
|
APN |
4 |
155,741,747 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL03077:Mib2
|
APN |
4 |
155,743,900 (GRCm39) |
missense |
probably benign |
0.01 |
R0042:Mib2
|
UTSW |
4 |
155,743,897 (GRCm39) |
nonsense |
probably null |
|
R0115:Mib2
|
UTSW |
4 |
155,740,519 (GRCm39) |
unclassified |
probably benign |
|
R0193:Mib2
|
UTSW |
4 |
155,740,130 (GRCm39) |
missense |
probably benign |
|
R0279:Mib2
|
UTSW |
4 |
155,745,673 (GRCm39) |
missense |
possibly damaging |
0.89 |
R0373:Mib2
|
UTSW |
4 |
155,740,745 (GRCm39) |
missense |
probably damaging |
1.00 |
R0481:Mib2
|
UTSW |
4 |
155,740,519 (GRCm39) |
unclassified |
probably benign |
|
R0563:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R0564:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R0625:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R0714:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R0740:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R0942:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R0987:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R1023:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R1033:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R1037:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R1460:Mib2
|
UTSW |
4 |
155,743,917 (GRCm39) |
missense |
probably damaging |
1.00 |
R1481:Mib2
|
UTSW |
4 |
155,741,456 (GRCm39) |
missense |
probably benign |
0.01 |
R1712:Mib2
|
UTSW |
4 |
155,739,256 (GRCm39) |
missense |
probably damaging |
1.00 |
R2015:Mib2
|
UTSW |
4 |
155,742,337 (GRCm39) |
missense |
probably damaging |
1.00 |
R2072:Mib2
|
UTSW |
4 |
155,744,158 (GRCm39) |
missense |
probably damaging |
0.99 |
R2131:Mib2
|
UTSW |
4 |
155,739,695 (GRCm39) |
splice site |
probably null |
|
R2187:Mib2
|
UTSW |
4 |
155,739,390 (GRCm39) |
missense |
possibly damaging |
0.95 |
R3751:Mib2
|
UTSW |
4 |
155,739,741 (GRCm39) |
missense |
probably damaging |
1.00 |
R3752:Mib2
|
UTSW |
4 |
155,739,741 (GRCm39) |
missense |
probably damaging |
1.00 |
R3753:Mib2
|
UTSW |
4 |
155,739,741 (GRCm39) |
missense |
probably damaging |
1.00 |
R4381:Mib2
|
UTSW |
4 |
155,742,069 (GRCm39) |
missense |
possibly damaging |
0.55 |
R4584:Mib2
|
UTSW |
4 |
155,741,744 (GRCm39) |
missense |
probably damaging |
1.00 |
R4669:Mib2
|
UTSW |
4 |
155,741,872 (GRCm39) |
missense |
possibly damaging |
0.49 |
R4754:Mib2
|
UTSW |
4 |
155,739,822 (GRCm39) |
missense |
possibly damaging |
0.90 |
R4782:Mib2
|
UTSW |
4 |
155,744,229 (GRCm39) |
missense |
probably benign |
0.00 |
R4799:Mib2
|
UTSW |
4 |
155,744,229 (GRCm39) |
missense |
probably benign |
0.00 |
R5036:Mib2
|
UTSW |
4 |
155,740,745 (GRCm39) |
missense |
probably damaging |
1.00 |
R5073:Mib2
|
UTSW |
4 |
155,741,233 (GRCm39) |
missense |
probably damaging |
1.00 |
R5915:Mib2
|
UTSW |
4 |
155,740,508 (GRCm39) |
unclassified |
probably benign |
|
R6695:Mib2
|
UTSW |
4 |
155,745,629 (GRCm39) |
missense |
probably damaging |
1.00 |
R7039:Mib2
|
UTSW |
4 |
155,744,158 (GRCm39) |
missense |
probably damaging |
0.99 |
R7234:Mib2
|
UTSW |
4 |
155,742,350 (GRCm39) |
missense |
probably damaging |
1.00 |
R7582:Mib2
|
UTSW |
4 |
155,739,267 (GRCm39) |
missense |
probably benign |
|
R8133:Mib2
|
UTSW |
4 |
155,741,458 (GRCm39) |
missense |
probably benign |
0.00 |
R8704:Mib2
|
UTSW |
4 |
155,743,620 (GRCm39) |
missense |
possibly damaging |
0.93 |
R8904:Mib2
|
UTSW |
4 |
155,744,173 (GRCm39) |
missense |
probably damaging |
0.99 |
R8987:Mib2
|
UTSW |
4 |
155,745,351 (GRCm39) |
missense |
probably benign |
0.01 |
R8988:Mib2
|
UTSW |
4 |
155,740,729 (GRCm39) |
missense |
possibly damaging |
0.47 |
R9336:Mib2
|
UTSW |
4 |
155,743,394 (GRCm39) |
missense |
probably benign |
|
R9537:Mib2
|
UTSW |
4 |
155,741,952 (GRCm39) |
missense |
probably damaging |
1.00 |
R9640:Mib2
|
UTSW |
4 |
155,745,325 (GRCm39) |
missense |
possibly damaging |
0.77 |
X0012:Mib2
|
UTSW |
4 |
155,739,852 (GRCm39) |
splice site |
probably null |
|
Z1176:Mib2
|
UTSW |
4 |
155,745,598 (GRCm39) |
missense |
probably benign |
0.06 |
Z1177:Mib2
|
UTSW |
4 |
155,739,978 (GRCm39) |
critical splice donor site |
probably null |
|
|
Protein Function and Prediction |
MIB2 is an E3 ligase that is associated with several signaling pathways including Notch and glutamate receptor signaling as well as muscle stability in Drosophila (1-4). MIB2 has also been identified as a component of the activated B-cell CLL/lymphoma 10 (BCL10) complex (5). BCL10 is involved in the activation of NF-κB in both the T-cell receptor (TCR) and B-cell receptor pathways through the promotion of the autoubiquitination and ubiquitination of IKKγ/NEMO, as well as recruitment and activation of TAK1 (5).
|
Expression/Localization |
Northern blot analysis detected a highly expressed transcript in skeletal muscle; lower expression of the transcript was detected in brain, heart, and kidney (6). In another study, Mib2 expression appears to be equal throughout development and in all adult tissues (7). Western blot analysis detected the protein in skeletal muscle, heart, and brain, but not in liver, thymus, or lung (6). Mib2 is localized in cytoplasmic foci near the cell surface (6).
|
Background |
Mib2tm1Art/tm1Art; MGI:3652500
BTNTTFArt.129S6-Mib2tm1Art
Mice homozygous for a knock-out allele display exencephaly with a variable penetrance that depends on the genetic background (7).
Mib2tm1Kong/tm1Kong; MGI:3804450
involves: 129P2/OlaHsd * C57BL/6
Mice homozygous for a reporter/null allele are viable, fertile and show normal growth, body weight and brain morphology (8).
|
References |
3. Jurd, R., Thornton, C., Wang, J., Luong, K., Phamluong, K., Kharazia, V., Gibb, S. L., and Ron, D. (2008) Mind Bomb-2 is an E3 Ligase that Ubiquitinates the N-Methyl-D-Aspartate Receptor NR2B Subunit in a Phosphorylation-Dependent Manner. J Biol Chem. 283, 301-310.
4. Koo, B. K., Yoon, K. J., Yoo, K. W., Lim, H. S., Song, R., So, J. H., Kim, C. H., and Kong, Y. Y. (2005) Mind Bomb-2 is an E3 Ligase for Notch Ligand. J Biol Chem. 280, 22335-22342.
5. Stempin, C. C., Chi, L., Giraldo-Vela, J. P., High, A. A., Hacker, H., and Redecke, V. (2011) The E3 Ubiquitin Ligase Mind Bomb-2 (MIB2) Protein Controls B-Cell CLL/lymphoma 10 (BCL10)-Dependent NF-kappaB Activation. J Biol Chem. 286, 37147-37157.
6. Takeuchi, T., Heng, H. H., Ye, C. J., Liang, S. B., Iwata, J., Sonobe, H., and Ohtsuki, Y. (2003) Down-Regulation of a Novel Actin-Binding Molecule, Skeletrophin, in Malignant Melanoma. Am J Pathol. 163, 1395-1404.
7. Wu, J. I., Rajendra, R., Barsi, J. C., Durfee, L., Benito, E., Gao, G., Kuruvilla, M., Hrdlickova, R., Liss, A. S., and Artzt, K. (2007) Targeted Disruption of Mib2 Causes Exencephaly with a Variable Penetrance. Genesis. 45, 722-727.
8. Koo, B. K., Yoon, M. J., Yoon, K. J., Im, S. K., Kim, Y. Y., Kim, C. H., Suh, P. G., Jan, Y. N., and Kong, Y. Y. (2007) An Obligatory Role of Mind Bomb-1 in Notch Signaling of Mammalian Development. PLoS ONE. 2, e1221.
|
Posted On |
2012-12-21 |
Science Writer |
Anne Murray |