WFS1_DROME
ID WFS1_DROME Reviewed; 853 AA.
AC Q8IMZ9; A0A0B4JDG5; Q8MS19;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Wolframin {ECO:0000305};
GN Name=wfs1 {ECO:0000312|FlyBase:FBgn0039003};
GN ORFNames=CG4917 {ECO:0000312|FlyBase:FBgn0039003};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAM51004.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM51004.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAM51004.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF 592-MET--LYS-853.
RX PubMed=29357349; DOI=10.1371/journal.pgen.1007196;
RA Sakakibara Y., Sekiya M., Fujisaki N., Quan X., Iijima K.M.;
RT "Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous
RT system increases susceptibility to age- and stress-induced neuronal
RT dysfunction and degeneration in Drosophila.";
RL PLoS Genet. 14:E1007196-E1007196(2018).
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). In neurons and
CC glial cells, has a role in maintaining neuronal function and integrity
CC during aging (PubMed:29357349). {ECO:0000250|UniProtKB:O76024,
CC ECO:0000269|PubMed:29357349}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:29357349}. Mitochondrion
CC {ECO:0000269|PubMed:29357349}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A {ECO:0000312|FlyBase:FBgn0039003};
CC IsoId=Q8IMZ9-1; Sequence=Displayed;
CC Name=C {ECO:0000312|FlyBase:FBgn0039003};
CC IsoId=Q8IMZ9-2; Sequence=VSP_059550;
CC -!- TISSUE SPECIFICITY: Detected in adult brain.
CC {ECO:0000269|PubMed:29357349}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in neurons results in
CC age-dependent behavioral deficits and neurodegeneration, which is
CC further enhanced when the knockdown is in both neurons and glial cells;
CC the defects include age-dependent locomotor deficits, increased
CC susceptibility to oxidative stress and glutamate excitotoxicity,
CC increased age-dependent appearance of vacuoles in the central neuropil
CC and optic lobes of the fly brain, and shortened lifespan.
CC {ECO:0000269|PubMed:29357349}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM51004.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE014297; AAN13917.2; -; Genomic_DNA.
DR EMBL; AE014297; ADV37358.1; -; Genomic_DNA.
DR EMBL; AY119144; AAM51004.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001189267.1; NM_001202338.2. [Q8IMZ9-2]
DR RefSeq; NP_651079.2; NM_142822.3. [Q8IMZ9-1]
DR AlphaFoldDB; Q8IMZ9; -.
DR SMR; Q8IMZ9; -.
DR STRING; 7227.FBpp0083728; -.
DR TCDB; 8.A.57.1.2; the wolfram syndrome or wolframin (wolframin) family.
DR GlyGen; Q8IMZ9; 2 sites.
DR PaxDb; Q8IMZ9; -.
DR PRIDE; Q8IMZ9; -.
DR EnsemblMetazoa; FBtr0084334; FBpp0083727; FBgn0039003. [Q8IMZ9-1]
DR EnsemblMetazoa; FBtr0302856; FBpp0291996; FBgn0039003. [Q8IMZ9-2]
DR GeneID; 42679; -.
DR KEGG; dme:Dmel_CG4917; -.
DR UCSC; CG4917-RA; d. melanogaster. [Q8IMZ9-1]
DR CTD; 7466; -.
DR FlyBase; FBgn0039003; wfs1.
DR VEuPathDB; VectorBase:FBgn0039003; -.
DR eggNOG; ENOG502QSC1; Eukaryota.
DR GeneTree; ENSGT00390000016928; -.
DR HOGENOM; CLU_014606_0_0_1; -.
DR OMA; VKLILLC; -.
DR PhylomeDB; Q8IMZ9; -.
DR Reactome; R-DME-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-DME-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 42679; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 42679; -.
DR PRO; PR:Q8IMZ9; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039003; Expressed in testis and 24 other tissues.
DR ExpressionAtlas; Q8IMZ9; baseline and differential.
DR Genevisible; Q8IMZ9; DM.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:FlyBase.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:UniProtKB.
DR GO; GO:0001306; P:age-dependent response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0055074; P:calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0036474; P:cell death in response to hydrogen peroxide; IMP:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IBA:GO_Central.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
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; 1.
DR PRINTS; PR02060; WOLFFAMILY.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein; Membrane;
KW Mitochondrion; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..853
FT /note="Wolframin"
FT /evidence="ECO:0000305"
FT /id="PRO_0000444010"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 259..279
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..305
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..466
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 473..493
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 513..533
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 545..565
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 572..592
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 139..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..169
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 694
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 769
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 55
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_059550"
FT MUTAGEN 592..853
FT /note="Missing: Results in age-dependent locomotor defects
FT and neurodegeneration."
FT /evidence="ECO:0000269|PubMed:29357349"
FT CONFLICT 237
FT /note="R -> H (in Ref. 3; AAM51004)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="T -> A (in Ref. 3; AAM51004)"
FT /evidence="ECO:0000305"
FT CONFLICT 492
FT /note="I -> V (in Ref. 3; AAM51004)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 853 AA; 96789 MW; 9296402B5EDD4886 CRC64;
MATWTQNEPT GVTKRRRWNL EDRASLNKLK HHIAEEGCPQ MQYDLAKELL DNSIVEPNLA
KGNQSQKAVN WLVSAAHNGH EDAVKLLRQC YNDGSGITAE NTDEVRRCLA MTPGERAARK
AARELFACLS NGNEHITPKQ LERKMRRIYN LQRKRRRRDD DRSSSSSEGE QEPECEPLED
VPTIDLANVE RRRLITEAHL VSAASNYSAG QMPSVNDALT LSVPDPRSLD HVPCFYRMIF
HPLIFFTLFY HRLLNLIVSI PNVIPLSVRC SVLVAISWWS SRHMLPLVSY YLSLGIMIWA
TCKMLKTKQQ FVDFRIWSGL FLSYGDQNIE ADIAEHRFLR NNMKPYLYFF CAFICNLIVY
PLVTDAWLPH SELTIISGAL TFITMCVSMY ASSHQLPDWL VIVSFAVNVL AKYPYEMDEV
VSTRWRFLDL RVPTFSSFVI GNGIEFCLNC RTALYLFIPV LLIMMAKRSR WHGVYTFLIP
HCVTLSWLQV CIATSQSSTV FGVMRAALGL AGIVLFLPLF GIVALLVPVF VAIDSLGLAS
EQLRWGSTAL ACGLVVVLSC ILALNRATQK YITMLQLITA ITTACLLVLP YMTSSFKDTP
RFNAMPRAGL HSLSETNTLP WDRFHALCAQ PVHEQPNKIK AQLRCSLLNG MPVIWEGSVT
KVEISRVSNF LEDTIANYLP VWLGRMLRCL HGENISQHFK CDPKLDAQCE EWRSVFKTFN
AQSGSCTLQR WNRYEYELLV KVGTKRSGRL LGRSTTTDVI LRAHHDFGNF TRLLSEGDVV
LFYGILHNSR LLADNVQVKL KTIECVECRS RDLGTASIER VVAASPMDAR LQDLMRGIKY
LLNALLNPLI TFK
