WIF1_DROME
ID WIF1_DROME Reviewed; 456 AA.
AC Q9W3W5; Q961F3;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Protein shifted;
DE AltName: Full=WIF-1-like protein;
DE Flags: Precursor;
GN Name=shf; ORFNames=CG3135;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
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]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP INTERACTION WITH HH, AND MUTAGENESIS OF CYS-363 AND CYS-374.
RX PubMed=15691765; DOI=10.1016/j.devcel.2004.12.018;
RA Gorfinkiel N., Sierra J., Callejo A., Ibanez C., Guerrero I.;
RT "The Drosophila ortholog of the human wnt inhibitor factor shifted controls
RT the diffusion of lipid-modified hedgehog.";
RL Dev. Cell 8:241-253(2005).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP CYS-363 AND CYS-374.
RX PubMed=15691766; DOI=10.1016/j.devcel.2005.01.003;
RA Glise B., Miller C.A., Crozatier M., Halbisen M.A., Wise S., Olson D.J.,
RA Vincent A., Blair S.S.;
RT "Shifted, the Drosophila ortholog of wnt inhibitory factor-1, controls the
RT distribution and movement of hedgehog.";
RL Dev. Cell 8:255-266(2005).
CC -!- FUNCTION: Required for normal accumulation and movement of lipid-
CC modified hedgehog (hh) morphogen. May act by stabilizing the
CC interaction between heparan sulfate proteoglycans (HSPGs) and hh, HSPGs
CC being required for diffusion of hh morphogen. Not involved in wingless
CC (wg) morphogen movement, suggesting that it may provide HSPG
CC specificity for Hh. {ECO:0000269|PubMed:15691765,
CC ECO:0000269|PubMed:15691766}.
CC -!- SUBUNIT: Interacts with hh. {ECO:0000269|PubMed:15691765}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:15691765, ECO:0000269|PubMed:15691766}.
CC Note=Colocalizes with HSPG.
CC -!- TISSUE SPECIFICITY: At the blastoderm stage, it is ubiquitously
CC expressed. As embryogenesis continues, it is expressed in the epidermis
CC and central nervous system, this expression being segmentally
CC modulated. Also highly expressed at the foregut and hindgut throughout
CC embryogenesis. In third instar wing imaginal disks, it is highly
CC expressed in the most anterior and posterior parts of the disk and
CC weakly expressed at the antero/posterior (A/P) compartment border. In
CC the leg disks and the antenna part of the eye-antennal imaginal disk it
CC is also weakly expressed at the A/P compartment border. Weakly
CC expressed in the morphogenetic furrow in the eye primordium.
CC {ECO:0000269|PubMed:15691765, ECO:0000269|PubMed:15691766}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:15691765}.
CC -!- MISCELLANEOUS: In contrast to human WIF1 protein, it does not inhibit
CC wg signaling. When transfected into Drosophila, human WIF1 protein
CC inhibits wg function, indicating a different role for shf and WIF-1.
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DR EMBL; AE014298; AAF46198.2; -; Genomic_DNA.
DR EMBL; AY051622; AAK93046.1; -; mRNA.
DR RefSeq; NP_572349.1; NM_132121.3.
DR AlphaFoldDB; Q9W3W5; -.
DR SMR; Q9W3W5; -.
DR BioGRID; 58102; 6.
DR IntAct; Q9W3W5; 2.
DR STRING; 7227.FBpp0070939; -.
DR GlyGen; Q9W3W5; 6 sites.
DR PaxDb; Q9W3W5; -.
DR PRIDE; Q9W3W5; -.
DR DNASU; 31617; -.
DR EnsemblMetazoa; FBtr0070978; FBpp0070939; FBgn0003390.
DR GeneID; 31617; -.
DR KEGG; dme:Dmel_CG3135; -.
DR UCSC; CG3135-RA; d. melanogaster.
DR CTD; 90525; -.
DR FlyBase; FBgn0003390; shf.
DR VEuPathDB; VectorBase:FBgn0003390; -.
DR eggNOG; KOG1225; Eukaryota.
DR InParanoid; Q9W3W5; -.
DR PhylomeDB; Q9W3W5; -.
DR SignaLink; Q9W3W5; -.
DR BioGRID-ORCS; 31617; 0 hits in 3 CRISPR screens.
DR ChiTaRS; shf; fly.
DR GenomeRNAi; 31617; -.
DR PRO; PR:Q9W3W5; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0003390; Expressed in crop (Drosophila) and 23 other tissues.
DR ExpressionAtlas; Q9W3W5; baseline and differential.
DR Genevisible; Q9W3W5; DM.
DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:FlyBase.
DR GO; GO:0071692; P:protein localization to extracellular region; IMP:FlyBase.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:0008039; P:synaptic target recognition; IMP:FlyBase.
DR Gene3D; 2.60.40.2170; -; 1.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR003306; WIF.
DR InterPro; IPR038677; WIF_sf.
DR Pfam; PF02019; WIF; 1.
DR SMART; SM00181; EGF; 5.
DR SMART; SM00469; WIF; 1.
DR PROSITE; PS00022; EGF_1; 5.
DR PROSITE; PS01186; EGF_2; 4.
DR PROSITE; PS50026; EGF_3; 4.
DR PROSITE; PS50814; WIF; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Disulfide bond; EGF-like domain;
KW Extracellular matrix; Glycoprotein; Reference proteome; Repeat; Secreted;
KW Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..456
FT /note="Protein shifted"
FT /id="PRO_0000007780"
FT DOMAIN 119..261
FT /note="WIF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00222"
FT DOMAIN 279..311
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 315..342
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 343..375
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 376..407
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 412..441
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 34..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 34..65
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 224..261
FT /evidence="ECO:0000250"
FT DISULFID 283..293
FT /evidence="ECO:0000250"
FT DISULFID 287..299
FT /evidence="ECO:0000250"
FT DISULFID 301..310
FT /evidence="ECO:0000250"
FT DISULFID 315..325
FT /evidence="ECO:0000250"
FT DISULFID 319..331
FT /evidence="ECO:0000250"
FT DISULFID 333..342
FT /evidence="ECO:0000250"
FT DISULFID 347..357
FT /evidence="ECO:0000250"
FT DISULFID 351..363
FT /evidence="ECO:0000250"
FT DISULFID 365..374
FT /evidence="ECO:0000250"
FT DISULFID 379..389
FT /evidence="ECO:0000250"
FT DISULFID 383..395
FT /evidence="ECO:0000250"
FT DISULFID 397..406
FT /evidence="ECO:0000250"
FT DISULFID 416..423
FT /evidence="ECO:0000250"
FT DISULFID 418..429
FT /evidence="ECO:0000250"
FT DISULFID 431..440
FT /evidence="ECO:0000250"
FT MUTAGEN 363
FT /note="C->S: In shf919; induces defects in the hh pathway."
FT /evidence="ECO:0000269|PubMed:15691765,
FT ECO:0000269|PubMed:15691766"
FT MUTAGEN 374
FT /note="C->S: In shf2; induces defects in the hh pathway."
FT /evidence="ECO:0000269|PubMed:15691765,
FT ECO:0000269|PubMed:15691766"
SQ SEQUENCE 456 AA; 50741 MW; C87CADB3E220D058 CRC64;
MTHQGIGCLV KWLYLVLIVH TLLCIGQLEC RQQHHNRNNN NNNRRADSSS SEEGHGNTSD
GLDNFADQDA SFVGHGHQPR RGQRKKQQGG GGGGSGGGGG NGGGGGSRHN RNEESGISLW
INEQQLKMLT ALYFPQGYSE RLYAIHNSRV TNDLRDTTLY NFLVIPSEVN YVNFTWKSGR
RKYFYDFDRL QTMDESILKA PTLSIRKSGR IPQEQKNFSI FLPCTGNSSG TASFNVGLKI
QTRHNKPLSG TPIRLNFKKE CAHRGVYDID ASNPTSLTTL QECSLKCGKN GYCNEHHICK
CNVGYTGQYC ETAFCFPQCL NGGNCTAPSV CTCPEGYQGT QCEGGICKDK CLNGGKCIQK
DKCQCSKGYY GLRCEYSKCV IPCKNEGRCI GNNLCRCPNG LRGDHCEIGR KQRSICKCRN
GTCVSHKHCK CHPGFYGRHC NGRKRRHVHR NDDSKF
