USH1G_MOUSE
ID USH1G_MOUSE Reviewed; 461 AA.
AC Q80T11; Q80UG0;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=pre-mRNA splicing regulator USH1G {ECO:0000305};
DE AltName: Full=Jackson shaker protein;
DE AltName: Full=Scaffold protein containing ankyrin repeats and SAM domain;
DE AltName: Full=Usher syndrome type-1G protein homolog;
GN Name=Ush1g; Synonyms=Sans;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND POSSIBLE
RP FUNCTION.
RX PubMed=12588793; DOI=10.1093/hmg/ddg042;
RA Kikkawa Y., Shitara H., Wakana S., Kohara Y., Takada T., Okamoto M.,
RA Taya C., Kamiya K., Yoshikawa Y., Tokano H., Kitamura K., Shimizu K.,
RA Wakabayashi Y., Shiroishi T., Kominami R., Yonekawa H.;
RT "Mutations in a new scaffold protein Sans cause deafness in Jackson shaker
RT mice.";
RL Hum. Mol. Genet. 12:453-461(2003).
RN [2]
RP INTERACTION WITH USH1C, AND POSSIBLE FUNCTION.
RX PubMed=12588794; DOI=10.1093/hmg/ddg051;
RA Weil D., El-Amraoui A., Masmoudi S., Mustapha M., Kikkawa Y., Laine S.,
RA Delmaghani S., Adato A., Nadifi S., Zina Z.B., Hamel C., Gal A., Ayadi H.,
RA Yonekawa H., Petit C.;
RT "Usher syndrome type I G (USH1G) is caused by mutations in the gene
RT encoding SANS, a protein that associates with the USH1C protein,
RT harmonin.";
RL Hum. Mol. Genet. 12:463-471(2003).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH CDH23 AND PCDH15.
RX PubMed=21436032; DOI=10.1073/pnas.1017114108;
RA Caberlotto E., Michel V., Foucher I., Bahloul A., Goodyear R.J.,
RA Pepermans E., Michalski N., Perfettini I., Alegria-Prevot O.,
RA Chardenoux S., Do Cruzeiro M., Hardelin J.P., Richardson G.P., Avan P.,
RA Weil D., Petit C.;
RT "Usher type 1G protein sans is a critical component of the tip-link
RT complex, a structure controlling actin polymerization in stereocilia.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:5825-5830(2011).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=21709241; DOI=10.1073/pnas.1104161108;
RA Grati M., Kachar B.;
RT "Myosin VIIa and sans localization at stereocilia upper tip-link density
RT implicates these Usher syndrome proteins in mechanotransduction.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11476-11481(2011).
RN [5]
RP INTERACTION WITH MAGI2, AND SUBCELLULAR LOCATION.
RX PubMed=24608321; DOI=10.1093/hmg/ddu104;
RA Bauss K., Knapp B., Jores P., Roepman R., Kremer H., Wijk E.V., Maerker T.,
RA Wolfrum U.;
RT "Phosphorylation of the Usher syndrome 1G protein SANS controls Magi2-
RT mediated endocytosis.";
RL Hum. Mol. Genet. 23:3923-3942(2014).
RN [6]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=31637240; DOI=10.3389/fcell.2019.00216;
RA Sorusch N., Yildirim A., Knapp B., Janson J., Fleck W., Scharf C.,
RA Wolfrum U.;
RT "SANS (USH1G) Molecularly Links the Human Usher Syndrome Protein Network to
RT the Intraflagellar Transport Module by Direct Binding to IFT-B Proteins.";
RL Front. Cell Dev. Biol. 7:216-216(2019).
CC -!- FUNCTION: Plays a role in pre-mRNA splicing by regulating the release
CC and transfer of U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-
CC snRNP) complexes from their assembly site in Cajal bodies to nuclear
CC speckles, thereby contributing to the assembly of the pre-catalytic
CC spliceosome on target pre-mRNAs (By similarity). May also participate
CC in recycling of snRNPs back to Cajal bodies during splicing (By
CC similarity). Plays a role in regulating MAGI2-mediated endocytosis (By
CC similarity). Anchoring/scaffolding protein that is a part of the
CC functional network formed by USH1C, USH1G, CDH23 and MYO7A that
CC mediates mechanotransduction in cochlear hair cells. Required for
CC normal development and maintenance of cochlear hair cell bundles.
CC Required for normal hearing. {ECO:0000250|UniProtKB:Q495M9,
CC ECO:0000269|PubMed:21436032, ECO:0000269|PubMed:21709241}.
CC -!- SUBUNIT: Part of a complex composed of USH1C, USH1G and MYO7A (By
CC similarity). Interacts with USH1C (via the first PDZ domain)
CC (PubMed:12588794). Interacts with PDZD7 (By similarity). Interacts with
CC CDH23 and PCDH15; these interactions may recruit USH1G to the plasma
CC membrane (PubMed:21436032). Interacts with intraflagellar transport
CC proteins IFT20, IFT52 AND IFT57 (By similarity). Interacts with
CC splicing factors SF3B1, PRPF6, PRPF31 and SON (By similarity).
CC Interacts with the U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-
CC snRNP) complex in the presence of pre-mRNAs (By similarity). Interacts
CC (via SAM domain) with MAGI2 (via PDZ 6 domain); the interaction is
CC triggered by phosphorylation of USH1G by CK2 and negatively regulates
CC MAGI2-mediated endocytosis (PubMed:24608321).
CC {ECO:0000250|UniProtKB:Q495M9, ECO:0000269|PubMed:12588794,
CC ECO:0000269|PubMed:21436032, ECO:0000269|PubMed:24608321}.
CC -!- INTERACTION:
CC Q80T11; P97479: Myo7a; NbExp=4; IntAct=EBI-7418889, EBI-1149557;
CC Q80T11; Q9ES64-3: Ush1c; NbExp=3; IntAct=EBI-7418889, EBI-7418919;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasm, cytoskeleton. Cell
CC membrane {ECO:0000269|PubMed:21436032}; Peripheral membrane protein
CC {ECO:0000305}. Cell projection, cilium {ECO:0000269|PubMed:24608321,
CC ECO:0000269|PubMed:31637240}. Nucleus speckle
CC {ECO:0000250|UniProtKB:Q495M9}. Nucleus, Cajal body
CC {ECO:0000250|UniProtKB:Q495M9}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:24608321}.
CC Photoreceptor inner segment {ECO:0000269|PubMed:24608321}.
CC Note=Detected at the tip of cochlear hair cell stereocilia. Recruited
CC to the cell membrane via interaction with CDH23 or PCDH15
CC (PubMed:21436032). In photoreceptor cilia, detected predominantly at
CC the cilium base (PubMed:31637240). Expressed in the pericentriolar
CC region of the centrosome (PubMed:24608321).
CC {ECO:0000269|PubMed:21436032, ECO:0000269|PubMed:24608321,
CC ECO:0000269|PubMed:31637240}.
CC -!- TISSUE SPECIFICITY: Detected in stereocilia from cochlear hair cells
CC (at protein level). Detected in retinal photoreceptor cell cilia (at
CC protein level) (PubMed:31637240). Highly expressed in the cochlea,
CC testis, cerebellum and eye, and low levels in brain, thymus and spleen.
CC Significant signals detected in the neurosensory epithelium of inner
CC ear cochlea and saccule, especially in inner and outer hair cells.
CC {ECO:0000269|PubMed:12588793, ECO:0000269|PubMed:21436032,
CC ECO:0000269|PubMed:21709241, ECO:0000269|PubMed:31637240}.
CC -!- DEVELOPMENTAL STAGE: Low-level expression detected in 17.5 dpc embryos
CC but not in embryos earlier than 15.5 dpc.
CC -!- DISEASE: Note=Defects in Ush1g are the cause of the Jackson shaker
CC phenotypes (js). Jackson shaker mice carry recessive mutations
CC predicted to inactivate Ush1g by frameshift resulting in a truncated
CC protein lacking the C-terminal SAM domain. The js phenotype is
CC characterized by deafness, abnormal behavior (circling and/or head-
CC tossing) and degeneration of inner ear neuroepithelia. Defects in the
CC formation of protein complex including Ush1g may disrupt stereocilia
CC bundle in js mice. {ECO:0000269|PubMed:12588793,
CC ECO:0000269|PubMed:12588794, ECO:0000269|PubMed:21436032}.
CC -!- DISRUPTION PHENOTYPE: Mice are deaf, due to defects in hair cell
CC bundles in the cochlea (PubMed:21436032). They develop circling
CC behavior, probably due to balance problems (PubMed:21436032). Reduced
CC expression of Ift20, Ift52 and Ift57 in the ciliary region of
CC photoreceptor cells (PubMed:31637240). {ECO:0000269|PubMed:21436032,
CC ECO:0000269|PubMed:31637240}.
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DR EMBL; AB087502; BAC57430.1; -; mRNA.
DR EMBL; AB087501; BAC57426.1; -; Genomic_DNA.
DR CCDS; CCDS25627.1; -.
DR RefSeq; NP_789817.1; NM_176847.3.
DR AlphaFoldDB; Q80T11; -.
DR SMR; Q80T11; -.
DR BioGRID; 200868; 1.
DR IntAct; Q80T11; 2.
DR MINT; Q80T11; -.
DR STRING; 10090.ENSMUSP00000099326; -.
DR iPTMnet; Q80T11; -.
DR PhosphoSitePlus; Q80T11; -.
DR PaxDb; Q80T11; -.
DR PRIDE; Q80T11; -.
DR Antibodypedia; 19482; 52 antibodies from 17 providers.
DR Ensembl; ENSMUST00000103037; ENSMUSP00000099326; ENSMUSG00000045288.
DR GeneID; 16470; -.
DR KEGG; mmu:16470; -.
DR UCSC; uc007mhc.1; mouse.
DR CTD; 124590; -.
DR MGI; MGI:2450757; Ush1g.
DR VEuPathDB; HostDB:ENSMUSG00000045288; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00390000017548; -.
DR HOGENOM; CLU_028071_0_0_1; -.
DR InParanoid; Q80T11; -.
DR OMA; HSSTCPH; -.
DR PhylomeDB; Q80T11; -.
DR TreeFam; TF324946; -.
DR BioGRID-ORCS; 16470; 4 hits in 72 CRISPR screens.
DR PRO; PR:Q80T11; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q80T11; protein.
DR Bgee; ENSMUSG00000045288; Expressed in olfactory bulb and 20 other tissues.
DR ExpressionAtlas; Q80T11; baseline and differential.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HGNC-UCL.
DR GO; GO:0015030; C:Cajal body; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:MGI.
DR GO; GO:0097546; C:ciliary base; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; ISS:MGI.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0097733; C:photoreceptor cell cilium; ISO:MGI.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:MGI.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0030507; F:spectrin binding; ISO:MGI.
DR GO; GO:0050957; P:equilibrioception; ISO:MGI.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0060113; P:inner ear receptor cell differentiation; IMP:MGI.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IMP:MGI.
DR GO; GO:0045494; P:photoreceptor cell maintenance; ISO:MGI.
DR GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; ISS:UniProtKB.
DR GO; GO:0050953; P:sensory perception of light stimulus; ISO:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR CDD; cd09586; SAM_USH1G; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR037602; USH1G_SAM.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00536; SAM_1; 1.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
PE 1: Evidence at protein level;
KW ANK repeat; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Deafness; Hearing; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..461
FT /note="pre-mRNA splicing regulator USH1G"
FT /id="PRO_0000067078"
FT REPEAT 31..60
FT /note="ANK 1"
FT REPEAT 64..93
FT /note="ANK 2"
FT REPEAT 97..126
FT /note="ANK 3"
FT DOMAIN 385..447
FT /note="SAM"
FT REGION 329..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..366
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q495M9"
FT CONFLICT 176
FT /note="L -> F (in Ref. 1; BAC57426)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 461 AA; 51490 MW; 8C5C4467802F35DB CRC64;
MNDQYHRAAR DGYLELLKEA TRKELNAPDE DGMTPTLWAA YHGNLESLRL IVSRGGDPDK
CDIWGNTPLH LAASNGHLHC LSFLVSFGAN IWCLDNDYHT PLDMAAMKGH MECVRYLDSI
AAKQSSLNPK LVGKLKDKAF REAERRIREC AKMQRKHHER MERRYRRELA ERSDTLSFSS
LTSSTLSRRL QHMTLGSQLP YSQATLHGTA KGKAKIQKKL ERRKQGGEGT FKVSEDGRKS
VRSLSGLQLG SDVMFVRQGT YANPKEWGRA PLRDMFLSDE DSVSRATLAA EPAHSEVSTD
SGHDSLFTRP GLGTMVFRRN YVSSGLHGLG REDGGLDGAG TPRGRLHSSP SLDDDSLGSA
NSLQDRSCGE ELPWDELDLG LDEDLEPETS PLETFLASLH MEDFASLLRH EKIDLEALML
CSDLDLRSIS VPLGPRKKIL GAVRRRRQAL ERPLALEDTE L
