WDFY2_HUMAN
ID WDFY2_HUMAN Reviewed; 400 AA.
AC Q96P53; B1AL86; Q96CS1;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 148.
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;
DE AltName: Full=Zinc finger FYVE domain-containing protein 22;
GN Name=WDFY2; Synonyms=WDF2, ZFYVE22;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hong W.;
RT "WD40- and FYVE-domain containing protein 2 (WDF2).";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [5]
RP SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH AKT1; AKT2; PRKCZ AND
RP PRKCI, AND DOMAIN FYVE-TYPE.
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 [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16873553; DOI=10.1073/pnas.0508832103;
RA Hayakawa A., Leonard D., Murphy S., Hayes S., Soto M., Fogarty K.,
RA Standley C., Bellve K., Lambright D., Mello C., Corvera S.;
RT "The WD40 and FYVE domain containing protein 2 defines a class of early
RT endosomes necessary for endocytosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11928-11933(2006).
RN [7]
RP FUNCTION, INTERACTION WITH VAMP2, COMPLEX FORMATION WITH VAMP2 AND PRKCZ,
RP AND SUBCELLULAR LOCATION.
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 [8]
RP FUNCTION.
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).
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
CC (PubMed:17313651). Positively regulates adipocyte differentiation, by
CC facilitating the phosphorylation and thus inactivation of the anti-
CC adipogenetic transcription factor FOXO1 by the kinase AKT1
CC (PubMed:18388859). Plays a role in endosomal control of AKT2 signaling;
CC required for insulin-stimulated AKT2 phosphorylation and glucose uptake
CC and insulin-stimulated phosphorylation of AKT2 substrates (By
CC similarity). Participates in transferrin receptor endocytosis
CC (PubMed:16873553). {ECO:0000250|UniProtKB:Q8BUB4,
CC ECO:0000269|PubMed:16873553, ECO:0000269|PubMed:17313651,
CC ECO:0000269|PubMed:18388859}.
CC -!- SUBUNIT: Homodimer (PubMed:16792529). Interacts (via WD repeats 1-3)
CC with AKT1, AKT2, PRKCZ and PRKCI (PubMed:16792529). Interacts with
CC VAMP2 (PubMed:17313651). Forms a complex with VAMP2 and PRKCZ
CC (PubMed:17313651). Interacts with FOXO1 (By similarity). Forms a
CC complex with AKT1 and FOXO1 (By similarity).
CC {ECO:0000250|UniProtKB:Q8BUB4, ECO:0000269|PubMed:16792529,
CC ECO:0000269|PubMed:17313651}.
CC -!- INTERACTION:
CC Q96P53; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-9478589, EBI-714543;
CC Q96P53; Q9NS64: RPRM; NbExp=3; IntAct=EBI-9478589, EBI-1052363;
CC Q96P53; P08247: SYP; NbExp=3; IntAct=EBI-9478589, EBI-9071725;
CC Q96P53; O95070: YIF1A; NbExp=3; IntAct=EBI-9478589, EBI-2799703;
CC -!- SUBCELLULAR LOCATION: Endosome {ECO:0000269|PubMed:16873553}. Early
CC endosome {ECO:0000269|PubMed:16792529}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8BUB4}. Note=Localizes to intracellular
CC vesicles (PubMed:16792529). Colocalizes with VAMP2 and PRKCZ in
CC intracellular vesicles (PubMed:17313651). Colocalizes with AKT2 in
CC early endosomes (By similarity). {ECO:0000250|UniProtKB:Q8BUB4,
CC ECO:0000269|PubMed:16792529, ECO:0000269|PubMed:17313651}.
CC -!- DOMAIN: The FYVE-type zinc finger is essential for its vesicular
CC localization. {ECO:0000269|PubMed:16792529}.
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DR EMBL; AF411978; AAL04162.1; -; mRNA.
DR EMBL; AL136525; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139183; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08883.1; -; Genomic_DNA.
DR EMBL; BC014004; AAH14004.1; -; mRNA.
DR CCDS; CCDS9429.1; -.
DR RefSeq; NP_443182.1; NM_052950.3.
DR AlphaFoldDB; Q96P53; -.
DR SMR; Q96P53; -.
DR BioGRID; 125458; 35.
DR CORUM; Q96P53; -.
DR IntAct; Q96P53; 27.
DR STRING; 9606.ENSP00000298125; -.
DR iPTMnet; Q96P53; -.
DR PhosphoSitePlus; Q96P53; -.
DR BioMuta; WDFY2; -.
DR DMDM; 51316902; -.
DR EPD; Q96P53; -.
DR jPOST; Q96P53; -.
DR MassIVE; Q96P53; -.
DR MaxQB; Q96P53; -.
DR PaxDb; Q96P53; -.
DR PeptideAtlas; Q96P53; -.
DR PRIDE; Q96P53; -.
DR ProteomicsDB; 77632; -.
DR Antibodypedia; 24090; 50 antibodies from 13 providers.
DR DNASU; 115825; -.
DR Ensembl; ENST00000298125.7; ENSP00000298125.4; ENSG00000139668.9.
DR GeneID; 115825; -.
DR KEGG; hsa:115825; -.
DR MANE-Select; ENST00000298125.7; ENSP00000298125.4; NM_052950.4; NP_443182.1.
DR UCSC; uc001vfp.4; human.
DR CTD; 115825; -.
DR DisGeNET; 115825; -.
DR GeneCards; WDFY2; -.
DR HGNC; HGNC:20482; WDFY2.
DR HPA; ENSG00000139668; Low tissue specificity.
DR MIM; 610418; gene.
DR neXtProt; NX_Q96P53; -.
DR OpenTargets; ENSG00000139668; -.
DR PharmGKB; PA134870231; -.
DR VEuPathDB; HostDB:ENSG00000139668; -.
DR eggNOG; KOG1409; Eukaryota.
DR GeneTree; ENSGT00940000158527; -.
DR HOGENOM; CLU_046919_0_0_1; -.
DR InParanoid; Q96P53; -.
DR OMA; NIKAMMD; -.
DR OrthoDB; 555190at2759; -.
DR PhylomeDB; Q96P53; -.
DR TreeFam; TF314470; -.
DR PathwayCommons; Q96P53; -.
DR SignaLink; Q96P53; -.
DR BioGRID-ORCS; 115825; 11 hits in 1079 CRISPR screens.
DR ChiTaRS; WDFY2; human.
DR GenomeRNAi; 115825; -.
DR Pharos; Q96P53; Tbio.
DR PRO; PR:Q96P53; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q96P53; protein.
DR Bgee; ENSG00000139668; Expressed in upper arm skin and 186 other tissues.
DR ExpressionAtlas; Q96P53; baseline and differential.
DR Genevisible; Q96P53; HS.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031982; C:vesicle; IDA: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; IDA: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; IPR011011; Znf_FYVE_PHD.
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 SUPFAM; SSF57903; SSF57903; 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_0000051336"
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 110
FT /note="Y -> C (in Ref. 1; AAL04162)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="G -> E (in Ref. 1; AAL04162)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 400 AA; 45154 MW; 57868799A6C3C7C7 CRC64;
MAAEIQPKPL TRKPILLQRM EGSQEVVNMA VIVPKEEGVI SVSEDRTVRV WLKRDSGQYW
PSVYHAMPSP CSCMSFNPET RRLSIGLDNG TISEFILSED YNKMTPVKNY QAHQSRVTMI
LFVLELEWVL STGQDKQFAW HCSESGQRLG GYRTSAVASG LQFDVETRHV FIGDHSGQVT
ILKLEQENCT LVTTFRGHTG GVTALCWDPV QRVLFSGSSD HSVIMWDIGG RKGTAIELQG
HNDRVQALSY AQHTRQLISC GGDGGIVVWN MDVERQETPE WLDSDSCQKC DQPFFWNFKQ
MWDSKKIGLR QHHCRKCGKA VCGKCSSKRS SIPLMGFEFE VRVCDSCHEA ITDEERAPTA
TFHDSKHNIV HVHFDATRGW LLTSGTDKVI KLWDMTPVVS
