WDFY2_MOUSE
ID WDFY2_MOUSE Reviewed; 400 AA.
AC Q8BUB4; Q3U9F3;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=WD repeat and FYVE domain-containing protein 2;
DE AltName: Full=Propeller-FYVE protein {ECO:0000303|PubMed:16792529};
DE Short=Prof;
DE AltName: Full=WD40- and FYVE domain-containing protein 2;
GN Name=Wdfy2;
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].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Head;
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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP TISSUE SPECIFICITY, AND INTERACTION WITH AKT1; AKT2; PRKCZ AND PRKCI.
RX PubMed=16792529; DOI=10.1042/bj20060511;
RA Fritzius T., Burkard G., Haas E., Heinrich J., Schweneker M., Bosse M.,
RA Zimmermann S., Frey A.D., Caelers A., Bachmann A.S., Moelling K.;
RT "A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambda.";
RL Biochem. J. 399:9-20(2006).
RN [5]
RP INTERACTION WITH VAMP2, AND COMPLEX FORMATION WITH VAMP2 AND PRKCZ.
RX PubMed=17313651; DOI=10.1111/j.1742-4658.2007.05702.x;
RA Fritzius T., Frey A.D., Schweneker M., Mayer D., Moelling K.;
RT "WD-repeat-propeller-FYVE protein, ProF, binds VAMP2 and protein kinase
RT Czeta.";
RL FEBS J. 274:1552-1566(2007).
RN [6]
RP FUNCTION, INTERACTION WITH FOXO1, COMPLEX FORMATION WITH AKT1 AND FOXO1,
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=18388859; DOI=10.1038/emboj.2008.67;
RA Fritzius T., Moelling K.;
RT "Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis.";
RL EMBO J. 27:1399-1410(2008).
RN [7]
RP FUNCTION, INTERACTION WITH AKT1 AND AKT2, AND SUBCELLULAR LOCATION.
RX PubMed=20189988; DOI=10.1074/jbc.m110.110536;
RA Walz H.A., Shi X., Chouinard M., Bue C.A., Navaroli D.M., Hayakawa A.,
RA Zhou Q.L., Nadler J., Leonard D.M., Corvera S.;
RT "Isoform-specific regulation of Akt signaling by the endosomal protein
RT WDFY2.";
RL J. Biol. Chem. 285:14101-14108(2010).
CC -!- FUNCTION: Acts in an adapter protein-like fashion to mediate the
CC interaction between the kinase PRKCZ and its substrate VAMP2 and
CC increases the PRKCZ-dependent phosphorylation of VAMP2 (By similarity).
CC Positively regulates adipocyte differentiation, by facilitating the
CC phosphorylation and thus inactivation of the anti-adipogenetic
CC transcription factor FOXO1 by the kinase AKT1 (PubMed:18388859). Plays
CC a role in endosomal control of AKT2 signaling; required for insulin-
CC stimulated AKT2 phosphorylation and glucose uptake and insulin-
CC stimulated phosphorylation of AKT2 substrates (PubMed:20189988).
CC Participates in transferrin receptor endocytosis (By similarity).
CC {ECO:0000250|UniProtKB:Q96P53, ECO:0000269|PubMed:18388859,
CC ECO:0000269|PubMed:20189988}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts (via WD repeats 1-3) with
CC AKT1, AKT2, PRKCZ and PRKCI (PubMed:16792529, PubMed:20189988).
CC Interacts with VAMP2 (PubMed:17313651). Forms a complex with VAMP2 and
CC PRKCZ (PubMed:17313651). Interacts with FOXO1 (PubMed:18388859). Forms
CC a complex with AKT1 and FOXO1 (PubMed:18388859).
CC {ECO:0000250|UniProtKB:Q96P53, ECO:0000269|PubMed:16792529,
CC ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:18388859,
CC ECO:0000269|PubMed:20189988}.
CC -!- SUBCELLULAR LOCATION: Endosome {ECO:0000250|UniProtKB:Q96P53}. Early
CC endosome {ECO:0000269|PubMed:20189988}. Cytoplasm
CC {ECO:0000269|PubMed:18388859}. Note=Localizes to intracellular
CC vesicles. Colocalizes with VAMP2 and PRKCZ in intracellular vesicles
CC (By similarity). Colocalizes with AKT2 in early endosomes
CC (PubMed:20189988). {ECO:0000250|UniProtKB:Q96P53,
CC ECO:0000269|PubMed:20189988}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain (at protein level).
CC {ECO:0000269|PubMed:16792529}.
CC -!- INDUCTION: Transiently up-regulated during adipogenesis (at protein
CC level). {ECO:0000269|PubMed:18388859}.
CC -!- DOMAIN: The FYVE-type zinc finger is essential for its vesicular
CC localization. {ECO:0000250|UniProtKB:Q96P53}.
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DR EMBL; AK086275; BAC39640.1; -; mRNA.
DR EMBL; AK131958; BAE20902.1; -; mRNA.
DR EMBL; AK151817; BAE30714.1; -; mRNA.
DR EMBL; CH466535; EDL36078.1; -; Genomic_DNA.
DR EMBL; BC116632; AAI16633.1; -; mRNA.
DR CCDS; CCDS27192.1; -.
DR RefSeq; NP_780755.2; NM_175546.4.
DR AlphaFoldDB; Q8BUB4; -.
DR SMR; Q8BUB4; -.
DR BioGRID; 234549; 1.
DR IntAct; Q8BUB4; 2.
DR MINT; Q8BUB4; -.
DR STRING; 10090.ENSMUSP00000014691; -.
DR PhosphoSitePlus; Q8BUB4; -.
DR EPD; Q8BUB4; -.
DR MaxQB; Q8BUB4; -.
DR PaxDb; Q8BUB4; -.
DR PeptideAtlas; Q8BUB4; -.
DR PRIDE; Q8BUB4; -.
DR ProteomicsDB; 297934; -.
DR Antibodypedia; 24090; 50 antibodies from 13 providers.
DR Ensembl; ENSMUST00000014691; ENSMUSP00000014691; ENSMUSG00000014547.
DR GeneID; 268752; -.
DR KEGG; mmu:268752; -.
DR UCSC; uc007ugy.2; mouse.
DR CTD; 115825; -.
DR MGI; MGI:2442811; Wdfy2.
DR VEuPathDB; HostDB:ENSMUSG00000014547; -.
DR eggNOG; KOG1409; Eukaryota.
DR GeneTree; ENSGT00940000158527; -.
DR HOGENOM; CLU_046919_0_0_1; -.
DR InParanoid; Q8BUB4; -.
DR OMA; NIKAMMD; -.
DR OrthoDB; 555190at2759; -.
DR PhylomeDB; Q8BUB4; -.
DR TreeFam; TF314470; -.
DR BioGRID-ORCS; 268752; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Wdfy2; mouse.
DR PRO; PR:Q8BUB4; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8BUB4; protein.
DR Bgee; ENSMUSG00000014547; Expressed in lacrimal gland and 248 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0031982; C:vesicle; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR042234; WDFY1/WDFY2.
DR InterPro; IPR000306; Znf_FYVE.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR46189; PTHR46189; 1.
DR Pfam; PF01363; FYVE; 1.
DR Pfam; PF00400; WD40; 3.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00064; FYVE; 1.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 3.
DR PROSITE; PS50082; WD_REPEATS_2; 4.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Endosome; Metal-binding; Reference proteome; Repeat; WD repeat;
KW Zinc; Zinc-finger.
FT CHAIN 1..400
FT /note="WD repeat and FYVE domain-containing protein 2"
FT /id="PRO_0000051337"
FT REPEAT 22..61
FT /note="WD 1"
FT REPEAT 66..105
FT /note="WD 2"
FT REPEAT 112..150
FT /note="WD 3"
FT REPEAT 153..192
FT /note="WD 4"
FT REPEAT 197..236
FT /note="WD 5"
FT REPEAT 240..279
FT /note="WD 6"
FT REPEAT 364..399
FT /note="WD 7"
FT ZN_FING 281..352
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 287
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 322
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 325
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 347
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT CONFLICT 298
FT /note="F -> V (in Ref. 1; BAC39640)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 400 AA; 45094 MW; B6CF4F4F0C11E1F9 CRC64;
MAAEIQPQPL TRKPILLQRV EGSQEVVNMA VIVPKEEGVI SVSEDRTVRV WLKRDSGQYW
PSIYHAMPSP CSCMSFNPET RRLSIGLDNG TISEFILSED YNKMTPVKNY QAHQSRVTMV
LFVLELEWVL STGQDKQFAW HCSESGQRLG GYRTSAVASG LQFDVETRHV FIGDHSGQVT
ILKLEQENCT LLTSFRGHTG GVTALCWDPV QRVLFSGSSD HSVIMWDIGG RKGTAIELQG
HNDKVQALSY AQHTRQLISC GGDGGIVVWN MDVERQETPE WLDSDSCQKC DQPFFWNFKQ
MWDSKKIGLR QHHCRKCGKA VCGKCSSKRS SIPLMGFEFE VRVCDSCHEA ITDEERAPTA
TFHDSKHNIV HVHFDATRGW LLTSGTDKVI KLWDMTPVVS
