WFS1_MOUSE
ID WFS1_MOUSE Reviewed; 890 AA.
AC P56695; Q9Z276;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Wolframin;
GN Name=Wfs1;
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 [MRNA].
RX PubMed=9817917; DOI=10.1093/hmg/7.13.2021;
RA Strom T.M., Hoertnagel K., Hofmann S., Gekeler F., Scharfe C., Rabl W.,
RA Gerbitz K.-D., Meitinger T.;
RT "Diabetes insipidus, diabetes mellitus, optic atrophy and deafness
RT (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a
RT predicted transmembrane protein.";
RL Hum. Mol. Genet. 7:2021-2028(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Insulinoma;
RX PubMed=9771706; DOI=10.1038/2441;
RA Inoue H., Tanizawa Y., Wasson J., Behn P., Kalidas K., Bernal-Mizrachi E.,
RA Mueckler M., Marshall H., Donis-Keller H., Crock P., Rogers D., Mikuni M.,
RA Kumashiro H., Higashi K., Sobue G., Oka Y., Permutt M.A.;
RT "A gene encoding a transmembrane protein is mutated in patients with
RT diabetes mellitus and optic atrophy (Wolfram Syndrome).";
RL Nat. Genet. 20:143-148(1998).
RN [3]
RP GLYCOSYLATION AT ASN-663 AND ASN-748.
RX PubMed=15522226; DOI=10.1016/j.bbrc.2004.10.017;
RA Yamaguchi S., Ishihara H., Tamura A., Yamada T., Takahashi R., Takei D.,
RA Katagiri H., Oka Y.;
RT "Endoplasmic reticulum stress and N-glycosylation modulate expression of
RT WFS1 protein.";
RL Biochem. Biophys. Res. Commun. 325:250-256(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32 AND SER-158, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=23531866; DOI=10.1038/ejhg.2013.52;
RA Berry V., Gregory-Evans C., Emmett W., Waseem N., Raby J., Prescott D.,
RA Moore A.T., Bhattacharya S.S.;
RT "Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear
RT cataract in humans.";
RL Eur. J. Hum. Genet. 21:1356-1360(2013).
CC -!- FUNCTION: Participates in the regulation of cellular Ca(2+)
CC homeostasis, at least partly, by modulating the filling state of the
CC endoplasmic reticulum Ca(2+) store (By similarity). Negatively
CC regulates the ER stress response and positively regulates the stability
CC of V-ATPase subunits ATP6V1A and ATP1B1 by preventing their degradation
CC through an unknown proteasome-independent mechanism (By similarity).
CC {ECO:0000250|UniProtKB:O76024}.
CC -!- SUBUNIT: Interacts with ATP6V1A. {ECO:0000250|UniProtKB:O76024}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O76024}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:O76024}. Note=Co-localizes with ATP6V1A in the
CC secretory granules in neuroblastoma cell lines.
CC {ECO:0000250|UniProtKB:O76024}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the developing lens.
CC {ECO:0000269|PubMed:23531866}.
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DR EMBL; AJ011971; CAA09892.1; -; mRNA.
DR EMBL; AF084482; AAC64944.1; -; mRNA.
DR CCDS; CCDS19245.1; -.
DR RefSeq; NP_035846.1; NM_011716.2.
DR AlphaFoldDB; P56695; -.
DR SMR; P56695; -.
DR BioGRID; 204558; 10.
DR IntAct; P56695; 1.
DR STRING; 10090.ENSMUSP00000048053; -.
DR GlyConnect; 2828; 5 N-Linked glycans (1 site).
DR GlyGen; P56695; 2 sites, 5 N-linked glycans (1 site).
DR iPTMnet; P56695; -.
DR PhosphoSitePlus; P56695; -.
DR EPD; P56695; -.
DR jPOST; P56695; -.
DR PaxDb; P56695; -.
DR PeptideAtlas; P56695; -.
DR PRIDE; P56695; -.
DR ProteomicsDB; 299674; -.
DR Antibodypedia; 22653; 176 antibodies from 27 providers.
DR Ensembl; ENSMUST00000043964; ENSMUSP00000048053; ENSMUSG00000039474.
DR GeneID; 22393; -.
DR KEGG; mmu:22393; -.
DR UCSC; uc008xff.1; mouse.
DR CTD; 7466; -.
DR MGI; MGI:1328355; Wfs1.
DR VEuPathDB; HostDB:ENSMUSG00000039474; -.
DR eggNOG; ENOG502QSC1; Eukaryota.
DR GeneTree; ENSGT00390000016928; -.
DR HOGENOM; CLU_014606_0_0_1; -.
DR InParanoid; P56695; -.
DR OMA; CHMKMFD; -.
DR OrthoDB; 962936at2759; -.
DR PhylomeDB; P56695; -.
DR TreeFam; TF326849; -.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 22393; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Wfs1; mouse.
DR PRO; PR:P56695; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P56695; protein.
DR Bgee; ENSMUSG00000039474; Expressed in olfactory tubercle and 264 other tissues.
DR ExpressionAtlas; P56695; baseline and differential.
DR Genevisible; P56695; MM.
DR GO; GO:0030425; C:dendrite; ISS:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:BHF-UCL.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0030141; C:secretory granule; ISS:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; IDA:BHF-UCL.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; ISO:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0070628; F:proteasome binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0055074; P:calcium ion homeostasis; ISS:BHF-UCL.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISS:BHF-UCL.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IMP:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; ISS:BHF-UCL.
DR GO; GO:0001822; P:kidney development; ISS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1903892; P:negative regulation of ATF6-mediated unfolded protein response; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:BHF-UCL.
DR GO; GO:0043069; P:negative regulation of programmed cell death; ISS:BHF-UCL.
DR GO; GO:1903573; P:negative regulation of response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; IMP:BHF-UCL.
DR GO; GO:0050877; P:nervous system process; ISS:BHF-UCL.
DR GO; GO:0042048; P:olfactory behavior; IEA:Ensembl.
DR GO; GO:0031016; P:pancreas development; IEA:Ensembl.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISS:BHF-UCL.
DR GO; GO:0045927; P:positive regulation of growth; IMP:BHF-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISS:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:ParkinsonsUK-UCL.
DR GO; GO:0050821; P:protein stabilization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; NAS:BHF-UCL.
DR GO; GO:0003091; P:renal water homeostasis; ISS:BHF-UCL.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:BHF-UCL.
DR GO; GO:0007605; P:sensory perception of sound; ISS:BHF-UCL.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0007601; P:visual perception; ISS:BHF-UCL.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR026208; Wolframin.
DR InterPro; IPR045400; Wolframin_Cys-rich.
DR InterPro; IPR045460; Wolframin_EF-hand.
DR InterPro; IPR026209; Wolframin_fam.
DR InterPro; IPR045461; Wolframin_OB_fold.
DR InterPro; IPR045458; Wolframin_Sel1-like_rpt.
DR PANTHER; PTHR13098; PTHR13098; 1.
DR Pfam; PF20053; WC-rich; 1.
DR Pfam; PF19913; WCOB; 1.
DR Pfam; PF19914; WEF-hand; 1.
DR Pfam; PF20023; WSLR; 2.
DR PRINTS; PR02060; WOLFFAMILY.
DR PRINTS; PR02061; WOLFRAMIN.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasmic vesicle; Endoplasmic reticulum; Glycoprotein;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..890
FT /note="Wolframin"
FT /id="PRO_0000065964"
FT TRANSMEM 314..334
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 340..360
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 402..422
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 427..447
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 465..485
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 496..516
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 529..549
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 563..583
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 589..609
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 632..652
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 653..869
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 870..890
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..323
FT /note="Interaction with ATP6V1A"
FT /evidence="ECO:0000250|UniProtKB:O76024"
FT REGION 1..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..227
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..83
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O76024"
FT MOD_RES 30
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O76024"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 663
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15522226"
FT CARBOHYD 748
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15522226"
FT CONFLICT 215
FT /note="A -> V (in Ref. 2; AAC64944)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 890 AA; 100579 MW; CB6C6CA16171A942 CRC64;
MNSGTPPPSP SGPPPPPAPQ PQARARLNAT ASLEQDKIEP PRAPRPQADP SAGRSAGEAA
APEPRAPQTG SREETDRAGP MKADVEIPFE EVLEKAKAGD PKAQTEVGKH YLRLANDADE
ELNSCSAVAW LILAAKQGRR EAVKLLRRCL ADRKGITSEN EAEVKQLSSE TDLERAVRKA
ALVMYWKLNP KKKKQVAVSE LLENVGQVNE QDGGAQPGPV PKSLQKQRRM LERLVSSESK
NYIALDDFVE LTKKYAKGII PTNLFLQDED EDEDELAGKS PEDLPLRQKV VKYPLHAIME
IKEYLIDVAS KAGMHWLSTI VPTHHINALI FFFIISNLTI DFFAFFIPLV VFYLSFVSMV
ICTLKVFQDS KAWENFRTLT DLLLRFEPNL DVEQAEVNFG WNHLEPYIHF LLSVVFVIFS
FPLASKDCIP CSELAVISTF FTVTSYMSLS SSAEPYTRRA LVTEVAAGLL SLLPTVPVDW
RFLKVLGQTF FTVPVGHFII LNVSLPCLLY VYLFYLFFRM AQLRNFKGTY CYLVPYLVCF
MWCELSVVIL LQSTGLGLVR ASIGYFLFLF ALPILVAGLA LMGTVQFARW FLSLDLTKIM
VTTVICGVPL LFRWWTKANF SVMGMVKSLT KSSMVKLILV WLTAILLFCW FYVYRSEGMK
VYNSTLTWQQ YGFLCGPRAW KETNMARTQI LCSHLEGHRV TWTGRFKYVR VTEIDNSAES
AINMLPFFLG DWMRCLYGEA YPSCSSGNTS TAEEELCRLK QLAKHPCHIK KFDRYKFEIT
VGMPFGTNGN RGHEEDDITK DIVLRASSEF KDVLLNLRQG SLIEFSTILE GRLGSKWPVF
ELKAISCLNC MTQLSPARRH VKIEQDWRST VHGALKFAFD FFFFPFLSAA
