WLS_MOUSE
ID WLS_MOUSE Reviewed; 541 AA.
AC Q6DID7; Q8CE42; Q9D2B7;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Protein wntless homolog;
DE AltName: Full=Integral membrane protein GPR177;
DE AltName: Full=Protein evenness interrupted homolog;
DE Short=EVI;
GN Name=Wls; Synonyms=Gpr177;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo, Head, Hippocampus, Ovary, Skin, and Uterus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=20652957; DOI=10.1002/dvdy.22369;
RA Jin J., Morse M., Frey C., Petko J., Levenson R.;
RT "Expression of GPR177 (Wntless/Evi/Sprinter), a highly conserved Wnt-
RT transport protein, in rat tissues, zebrafish embryos, and cultured human
RT cells.";
RL Dev. Dyn. 239:2426-2434(2010).
RN [4]
RP FUNCTION, INDUCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, DEVELOPMENTAL STAGE, AND INTERACTION WITH WNT1; WNT3 AND WNT5A.
RX PubMed=19841259; DOI=10.1073/pnas.0904894106;
RA Fu J., Jiang M., Mirando A.J., Yu H.-M., Hsu W.;
RT "Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for
RT embryonic axis formation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:18598-18603(2009).
RN [5]
RP MUTAGENESIS OF TYR-392 AND TYR-478.
RX PubMed=34587386; DOI=10.1056/nejmoa2033911;
RA Chai G., Szenker-Ravi E., Chung C., Li Z., Wang L., Khatoo M., Marshall T.,
RA Jiang N., Yang X., McEvoy-Venneri J., Stanley V., Anzenberg P., Lang N.,
RA Wazny V., Yu J., Virshup D.M., Nygaard R., Mancia F., Merdzanic R.,
RA Toralles M.B.P., Pitanga P.M.L., Puri R.D., Hernan R., Chung W.K.,
RA Bertoli-Avella A.M., Al-Sannaa N., Zaki M.S., Willert K., Reversade B.,
RA Gleeson J.G.;
RT "A human pleiotropic multiorgan condition caused by deficient Wnt
RT secretion.";
RL N. Engl. J. Med. 385:1292-1301(2021).
CC -!- FUNCTION: Regulates Wnt proteins sorting and secretion in a feedback
CC regulatory mechanism. This reciprocal interaction plays a key role in
CC the regulation of expression, subcellular location, binding and
CC organelle-specific association of Wnt proteins. Also plays an important
CC role in establishment of the anterior-posterior body axis formation
CC during development. {ECO:0000269|PubMed:19841259}.
CC -!- SUBUNIT: Interacts with WNT3A (By similarity). Interacts with WNT1,
CC WNT3 and WNT5. {ECO:0000250, ECO:0000269|PubMed:19841259}.
CC -!- INTERACTION:
CC Q6DID7-1; P04426: Wnt1; NbExp=2; IntAct=EBI-15811068, EBI-1570911;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:19841259}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19841259}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:19841259}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19841259}. Cell membrane
CC {ECO:0000250|UniProtKB:Q5T9L3}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q5T9L3}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q5T9L3};
CC Multi-pass membrane protein {ECO:0000255}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q5T9L3}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6DID7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6DID7-2; Sequence=VSP_022348;
CC -!- TISSUE SPECIFICITY: Expressed in the brain, skeletal muscle, heart
CC muscle, lung, gut, liver, and kidney (at protein level)
CC (PubMed:20652957). In the brain, expressed in the cortex, striatum,
CC hippocampus and to a lesser extent in the cerebellum (at protein level)
CC (PubMed:20652957). Expressed in kidney, lung, skin, intestine, brain,
CC spinal cord, skeleton, eyes, excretion glands, tooth and palatal
CC shelves (PubMed:19841259). In the cerebellum, expressed in Purkinje
CC cells (PubMed:19841259). {ECO:0000269|PubMed:19841259,
CC ECO:0000269|PubMed:20652957}.
CC -!- DEVELOPMENTAL STAGE: Detected at 6.25 dpc in the proximal epiblast at
CC the junction between the embryonic and extraembryonic tissue. Later
CC expression is more restricted to the primitive streak and mesoderm
CC extending to the distal tip of the embryo. Strong expression is found
CC in both posterior visceral endoderm and epiblast at the prestreak, but
CC switched to the mesoderm at late-streak. {ECO:0000269|PubMed:19841259}.
CC -!- INDUCTION: Up-regulated by WNT1. Transcriptionally activated by beta-
CC catenin and by LEF/TCF-dependent transcription.
CC {ECO:0000269|PubMed:19841259}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20652957}.
CC -!- DISRUPTION PHENOTYPE: Mice display embryonic lethality before 10.5 dpc.
CC Embryos show defects in the establishment of the body axis and in the
CC primitive streak and mesoderm formation. {ECO:0000269|PubMed:19841259}.
CC -!- SIMILARITY: Belongs to the wntless family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH18381.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC26266.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC26300.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC32102.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC33950.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK019886; BAB31904.1; -; mRNA.
DR EMBL; AK029053; BAC26266.1; ALT_INIT; mRNA.
DR EMBL; AK029104; BAC26300.1; ALT_INIT; mRNA.
DR EMBL; AK044810; BAC32102.1; ALT_INIT; mRNA.
DR EMBL; AK049842; BAC33950.1; ALT_INIT; mRNA.
DR EMBL; AK077407; BAC36788.1; -; mRNA.
DR EMBL; AK159207; BAE34898.1; -; mRNA.
DR EMBL; BC075615; AAH75615.1; -; mRNA.
DR EMBL; BC018381; AAH18381.1; ALT_INIT; mRNA.
DR CCDS; CCDS38684.1; -. [Q6DID7-1]
DR RefSeq; NP_080858.3; NM_026582.4. [Q6DID7-1]
DR RefSeq; XP_006502027.1; XM_006501964.2.
DR AlphaFoldDB; Q6DID7; -.
DR SMR; Q6DID7; -.
DR BioGRID; 212684; 4.
DR DIP; DIP-49004N; -.
DR IntAct; Q6DID7; 4.
DR STRING; 10090.ENSMUSP00000067898; -.
DR PhosphoSitePlus; Q6DID7; -.
DR EPD; Q6DID7; -.
DR MaxQB; Q6DID7; -.
DR PaxDb; Q6DID7; -.
DR PeptideAtlas; Q6DID7; -.
DR PRIDE; Q6DID7; -.
DR ProteomicsDB; 299790; -. [Q6DID7-1]
DR ProteomicsDB; 299791; -. [Q6DID7-2]
DR Antibodypedia; 33415; 130 antibodies from 27 providers.
DR Ensembl; ENSMUST00000068952; ENSMUSP00000067898; ENSMUSG00000028173. [Q6DID7-1]
DR Ensembl; ENSMUST00000198878; ENSMUSP00000143475; ENSMUSG00000028173. [Q6DID7-1]
DR GeneID; 68151; -.
DR KEGG; mmu:68151; -.
DR UCSC; uc008rwc.1; mouse. [Q6DID7-1]
DR CTD; 79971; -.
DR MGI; MGI:1915401; Wls.
DR VEuPathDB; HostDB:ENSMUSG00000028173; -.
DR eggNOG; ENOG502QSE2; Eukaryota.
DR GeneTree; ENSGT00390000005897; -.
DR HOGENOM; CLU_022911_0_0_1; -.
DR InParanoid; Q6DID7; -.
DR OMA; YWRHLSA; -.
DR OrthoDB; 418201at2759; -.
DR PhylomeDB; Q6DID7; -.
DR TreeFam; TF105975; -.
DR Reactome; R-MMU-3238698; WNT ligand biogenesis and trafficking.
DR BioGRID-ORCS; 68151; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Wls; mouse.
DR PRO; PR:Q6DID7; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q6DID7; protein.
DR Bgee; ENSMUSG00000028173; Expressed in vault of skull and 278 other tissues.
DR ExpressionAtlas; Q6DID7; baseline and differential.
DR Genevisible; Q6DID7; MM.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0032839; C:dendrite cytoplasm; ISO:MGI.
DR GO; GO:0032590; C:dendrite membrane; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISO:MGI.
DR GO; GO:0031301; C:integral component of organelle membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0031852; F:mu-type opioid receptor binding; ISO:MGI.
DR GO; GO:0017147; F:Wnt-protein binding; IDA:UniProtKB.
DR GO; GO:0009948; P:anterior/posterior axis specification; IMP:UniProtKB.
DR GO; GO:0071529; P:cementum mineralization; IGI:MGI.
DR GO; GO:0031017; P:exocrine pancreas development; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030902; P:hindbrain development; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006886; P:intracellular protein transport; ISO:MGI.
DR GO; GO:0001707; P:mesoderm formation; IMP:UniProtKB.
DR GO; GO:0030901; P:midbrain development; IMP:ParkinsonsUK-UCL.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0061357; P:positive regulation of Wnt protein secretion; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:ParkinsonsUK-UCL.
DR GO; GO:0061355; P:Wnt protein secretion; ISO:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IMP:UniProtKB.
DR InterPro; IPR009551; Wntless.
DR PANTHER; PTHR13449; PTHR13449; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasmic vesicle;
KW Developmental protein; Endoplasmic reticulum; Endosome; Glycoprotein;
KW Golgi apparatus; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Wnt signaling pathway.
FT CHAIN 1..541
FT /note="Protein wntless homolog"
FT /id="PRO_0000271779"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q5T9L3"
FT TRANSMEM 16..36
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..232
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q5T9L3"
FT TRANSMEM 233..253
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q5T9L3"
FT TRANSMEM 269..289
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..303
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q5T9L3"
FT TRANSMEM 304..324
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 325..331
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q5T9L3"
FT TRANSMEM 332..352
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 353..380
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q5T9L3"
FT TRANSMEM 381..401
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 402..431
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q5T9L3"
FT TRANSMEM 432..452
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 453..471
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q5T9L3"
FT TRANSMEM 472..492
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 493..541
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q5T9L3"
FT REGION 101..232
FT /note="Interaction with Wnt proteins"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022348"
FT MUTAGEN 392
FT /note="Y->C: Knockin mice have several structural anomalies
FT recapitulating the major defects observed in patients with
FT Zaki syndrome."
FT /evidence="ECO:0000269|PubMed:34587386"
FT MUTAGEN 478
FT /note="Y->C: Knockin mice have several structural anomalies
FT recapitulating the major defects observed in patients with
FT Zaki syndrome."
FT /evidence="ECO:0000269|PubMed:34587386"
FT CONFLICT 113
FT /note="I -> V (in Ref. 1; BAC26266)"
FT /evidence="ECO:0000305"
FT CONFLICT 540
FT /note="Q -> L (in Ref. 1; BAC26266)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 541 AA; 62188 MW; 14BDD97D6050D976 CRC64;
MAGAIIENMS TKKLCIVGGI LLVFQIVAFL VGGLIAPAPT TAVPYTAIKC VDVRKNHHKT
RWLAPWGPNK CDKIRDIEEA IPREIEANDI VFSVHIPLPS MEMSPWFQFM LFILQLDIAF
KLNNQIRENA EISMDVSLGY RDDMFSEWTE MAHERVPRKL KCTFTSPKTP EHEGRYYNCD
VLPFMEIGSV AHKYYLLNIR LPVNEKKKIN VGIGEIKDIR LVGIHQNGGF TKVWFAMKTF
LTPSIFIIMV WYWRRITMMS RPPVLLEKVI FALGISMTFI NIPVEWFSIG FDWTWMLLFG
DIRQGIFYAM LLSFWIIFCG EHMMDQHERN HIAGYWKQVG PIAVGSFCLF IFDMCERGVQ
LTNPFYSIWT TDVGTELAMA FIIVAGICLC LYFLFLCFMV FQVFRNISGK QSSLPAMSKV
RRLHYEGLIF RFKFLMLITL ACAAMTVIFF IVSQVSEGHW KWGGVTVQVS SAFFTGIYGM
WNLYVFALMF LYAPSHKNYG EDQSNGDLGV HSGEELQLTT TITHVDGPTE IYKLTRKEAQ
E
