Incidental Mutation '0152:Usp47'
ID 8
Institutional Source Beutler Lab
Gene Symbol Usp47
Ensembl Gene ENSMUSG00000059263
Gene Name ubiquitin specific peptidase 47
Synonyms A630020C16Rik, 4930502N04Rik
Accession Numbers
Essential gene? Probably essential (E-score: 0.839) question?
Stock # 0152 of strain feeble
Quality Score
Status Validated
Chromosome 7
Chromosomal Location 111622692-111710591 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 111655784 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Histidine at position 154 (Y154H)
Ref Sequence ENSEMBL: ENSMUSP00000102264 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000106653] [ENSMUST00000210309] [ENSMUST00000215510]
AlphaFold Q8BY87
Predicted Effect probably damaging
Transcript: ENSMUST00000106653
AA Change: Y154H

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000102264
Gene: ENSMUSG00000059263
AA Change: Y154H

DomainStartEndE-ValueType
Pfam:UCH 167 541 1.2e-50 PFAM
Pfam:UCH_1 168 507 5.1e-31 PFAM
coiled coil region 554 586 N/A INTRINSIC
low complexity region 859 880 N/A INTRINSIC
low complexity region 934 950 N/A INTRINSIC
Pfam:Ubiquitin_2 1026 1095 1.9e-3 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000210309
AA Change: Y174H

PolyPhen 2 Score 0.947 (Sensitivity: 0.79; Specificity: 0.95)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000210591
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211791
Predicted Effect possibly damaging
Transcript: ENSMUST00000215510
AA Change: Y154H

PolyPhen 2 Score 0.952 (Sensitivity: 0.79; Specificity: 0.95)
Meta Mutation Damage Score 0.0926 question?
Coding Region Coverage
  • 1x: 77.9%
  • 3x: 41.0%
Validation Efficiency 83% (65/78)
MGI Phenotype PHENOTYPE: Mouse embryonic fibroblasts from mice homozygous for a gene trap allele exhibit increased sensitivity to UV irradiation. [provided by MGI curators]
Allele List at MGI

All alleles(10) : Gene trapped(10)

Other mutations in this stock
Total: 6 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adck1 A T 12: 88,397,921 (GRCm39) Q185L probably benign Het
Fscn3 A G 6: 28,429,966 (GRCm39) probably benign Homo
Per1 T G 11: 68,994,848 (GRCm39) probably benign Het
Pkhd1 A C 1: 20,593,118 (GRCm39) I1665S possibly damaging Het
Tnrc6a C A 7: 122,779,877 (GRCm39) P1303T probably damaging Het
Zfp952 T A 17: 33,222,195 (GRCm39) probably null Het
Other mutations in Usp47
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00481:Usp47 APN 7 111,673,990 (GRCm39) missense probably benign 0.00
IGL00574:Usp47 APN 7 111,662,542 (GRCm39) missense probably damaging 1.00
IGL00975:Usp47 APN 7 111,692,577 (GRCm39) missense probably damaging 1.00
IGL01289:Usp47 APN 7 111,662,565 (GRCm39) missense probably damaging 1.00
IGL01419:Usp47 APN 7 111,687,118 (GRCm39) missense possibly damaging 0.94
IGL01645:Usp47 APN 7 111,654,069 (GRCm39) missense probably damaging 0.96
IGL01871:Usp47 APN 7 111,676,993 (GRCm39) splice site probably benign
IGL02066:Usp47 APN 7 111,663,604 (GRCm39) missense probably damaging 1.00
IGL02122:Usp47 APN 7 111,706,115 (GRCm39) missense probably damaging 0.97
IGL02153:Usp47 APN 7 111,703,256 (GRCm39) missense probably benign 0.00
IGL02550:Usp47 APN 7 111,703,561 (GRCm39) missense probably damaging 1.00
IGL02710:Usp47 APN 7 111,692,132 (GRCm39) missense probably benign 0.01
IGL02756:Usp47 APN 7 111,692,270 (GRCm39) missense possibly damaging 0.76
IGL03093:Usp47 APN 7 111,688,827 (GRCm39) missense probably damaging 1.00
IGL03398:Usp47 APN 7 111,673,710 (GRCm39) missense probably damaging 1.00
PIT4142001:Usp47 UTSW 7 111,703,548 (GRCm39) splice site probably benign
R0110:Usp47 UTSW 7 111,655,787 (GRCm39) missense possibly damaging 0.88
R0381:Usp47 UTSW 7 111,662,600 (GRCm39) critical splice donor site probably null
R0450:Usp47 UTSW 7 111,655,787 (GRCm39) missense possibly damaging 0.88
R0634:Usp47 UTSW 7 111,707,862 (GRCm39) missense probably damaging 1.00
R0881:Usp47 UTSW 7 111,690,643 (GRCm39) missense possibly damaging 0.51
R1178:Usp47 UTSW 7 111,709,205 (GRCm39) missense possibly damaging 0.68
R1447:Usp47 UTSW 7 111,673,775 (GRCm39) critical splice donor site probably null
R1640:Usp47 UTSW 7 111,682,334 (GRCm39) missense probably damaging 0.99
R1727:Usp47 UTSW 7 111,685,307 (GRCm39) missense probably damaging 0.96
R1866:Usp47 UTSW 7 111,701,077 (GRCm39) missense possibly damaging 0.93
R1876:Usp47 UTSW 7 111,654,127 (GRCm39) missense probably damaging 0.99
R1953:Usp47 UTSW 7 111,692,083 (GRCm39) missense probably benign 0.26
R2117:Usp47 UTSW 7 111,666,443 (GRCm39) critical splice donor site probably null
R2176:Usp47 UTSW 7 111,691,934 (GRCm39) missense probably benign 0.00
R2187:Usp47 UTSW 7 111,666,398 (GRCm39) missense probably damaging 1.00
R2504:Usp47 UTSW 7 111,703,677 (GRCm39) critical splice donor site probably null
R2902:Usp47 UTSW 7 111,692,658 (GRCm39) missense probably damaging 1.00
R2922:Usp47 UTSW 7 111,692,405 (GRCm39) missense probably damaging 1.00
R2939:Usp47 UTSW 7 111,681,743 (GRCm39) missense probably damaging 1.00
R4065:Usp47 UTSW 7 111,652,623 (GRCm39) missense probably benign 0.30
R4179:Usp47 UTSW 7 111,687,091 (GRCm39) missense probably damaging 1.00
R4235:Usp47 UTSW 7 111,709,255 (GRCm39) missense probably damaging 0.99
R4243:Usp47 UTSW 7 111,707,836 (GRCm39) missense probably damaging 1.00
R4281:Usp47 UTSW 7 111,709,200 (GRCm39) missense probably benign 0.03
R4360:Usp47 UTSW 7 111,654,139 (GRCm39) missense probably damaging 1.00
R4604:Usp47 UTSW 7 111,701,038 (GRCm39) missense probably damaging 1.00
R4857:Usp47 UTSW 7 111,681,759 (GRCm39) missense probably damaging 1.00
R5133:Usp47 UTSW 7 111,683,089 (GRCm39) missense probably damaging 1.00
R5179:Usp47 UTSW 7 111,692,639 (GRCm39) missense probably damaging 1.00
R5322:Usp47 UTSW 7 111,652,476 (GRCm39) missense probably damaging 0.99
R5445:Usp47 UTSW 7 111,673,928 (GRCm39) missense probably damaging 1.00
R5465:Usp47 UTSW 7 111,658,209 (GRCm39) missense probably damaging 1.00
R5699:Usp47 UTSW 7 111,709,204 (GRCm39) missense probably benign 0.00
R5961:Usp47 UTSW 7 111,652,523 (GRCm39) missense probably damaging 1.00
R6117:Usp47 UTSW 7 111,687,139 (GRCm39) missense probably damaging 0.98
R6271:Usp47 UTSW 7 111,686,263 (GRCm39) missense probably damaging 1.00
R7155:Usp47 UTSW 7 111,686,220 (GRCm39) missense probably damaging 0.97
R7229:Usp47 UTSW 7 111,692,084 (GRCm39) missense probably benign 0.04
R7246:Usp47 UTSW 7 111,715,116 (GRCm39)
R7285:Usp47 UTSW 7 111,692,315 (GRCm39) missense probably benign 0.02
R7938:Usp47 UTSW 7 111,687,132 (GRCm39) missense probably damaging 0.99
R8079:Usp47 UTSW 7 111,646,177 (GRCm39) missense probably damaging 1.00
R8114:Usp47 UTSW 7 111,692,394 (GRCm39) missense probably damaging 1.00
R8141:Usp47 UTSW 7 111,652,472 (GRCm39) missense possibly damaging 0.60
R8172:Usp47 UTSW 7 111,687,133 (GRCm39) nonsense probably null
R8223:Usp47 UTSW 7 111,703,583 (GRCm39) missense probably damaging 1.00
R8510:Usp47 UTSW 7 111,658,208 (GRCm39) missense probably damaging 1.00
R8701:Usp47 UTSW 7 111,692,402 (GRCm39) missense probably damaging 1.00
R9106:Usp47 UTSW 7 111,681,713 (GRCm39) missense probably damaging 1.00
R9135:Usp47 UTSW 7 111,652,431 (GRCm39) missense probably benign 0.30
R9311:Usp47 UTSW 7 111,703,257 (GRCm39) missense probably benign 0.02
R9417:Usp47 UTSW 7 111,688,801 (GRCm39) missense possibly damaging 0.86
R9487:Usp47 UTSW 7 111,677,063 (GRCm39) missense probably damaging 0.99
R9628:Usp47 UTSW 7 111,705,999 (GRCm39) missense probably benign 0.01
RF010:Usp47 UTSW 7 111,692,145 (GRCm39) missense probably damaging 0.99
X0027:Usp47 UTSW 7 111,687,054 (GRCm39) missense probably damaging 1.00
Nature of Mutation
DNA sequencing using the SOLiD technique identified a T to C transition at position 662 of the Usp47 transcript, in exon 4 of 28 total exons for isoform 2 (Figure 1). In isoform 1, the mutation occurs in exon 5 of 29 total exons. Multiple isoforms of Usp47 are displayed on Ensembl
 
647 TATGTCAGCCAGAACTACTCCTATTCATCAATT
149 -Y--V--S--Q--N--Y--S--Y--S--S--I-
 
The mutated nucleotide is indicated in red lettering, and causes a tyrosine to histidine substitution at amino acid 174 in isoform 1 and amino acid 154 in isoform 2 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 2).
Protein Function and Prediction
The 1376 (isoform 1) amino acid mouse USP47 protein is an uncharacterized ubiquitinyl hydrolase belonging to the peptidase C19 family of proteases. These proteins are also known as ubiquitin-specific processing proteases (UPB). Ubiquitin is a small highly conserved protein that is commonly found conjugated to proteins in eukaryotic cells, where it may act as a marker for rapid degradation, or it may have a chaperone function in protein assembly (1). Ubiquitin is released by cleavage from the bound protein by a protease. Members of the C19 peptidase family are considered to be cysteine peptidases and use the sulphydryl group of a cysteine residue as the nucleophile to form an acyl intermediate. These proteins are characterized by one conserved cysteine (amino acid 197 in USP47), along with two conserved histidines (amino acids 495 and 503). The spacing between the cysteine and the second histidine is thought to be more representative of the cysteine/histidine spacing of a cysteine protease catalytic dyad. UPB proteins are divergent, but exhibit strong homology in the regions surrounding the catalytic Cys and His residues; these are the Cys Box (roughly 19 amino acids) and the His Box (60–90 amino acids). 3D structure of a UPB catalytic domain is depicted in Figure 3 (NCBI cd02659). Ubiquitin binds to a cleft in this domain, which is bordered on opposite sides by the Cys and His Boxes (2)
 
USP47 is phosphorylated on serine 911 (3) and threonine 1016 (4). Other sites predicted to be phosphorylated by homology are serines 832 and 1354, and tyrosine 836.  
 

Isoform 2 of USP47, created by alternative splicing, is missing amino acids 14-33. The Y154/174H alteration occurs just prior to the conserved peptidase C19 domain containing the catalytic cysteine and histidines, and is predicted to be possibly damaging by the PolyPhen program. 

References
Posted On 2009-11-02