PKHF1_DROME
ID PKHF1_DROME Reviewed; 316 AA.
AC O76902; Q95RM3;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Pleckstrin homology domain-containing family F member 1 homolog {ECO:0000250|UniProtKB:Q96S99};
DE Short=PH domain-containing family F member 1 homolog {ECO:0000250|UniProtKB:Q96S99};
DE AltName: Full=Protein rush hour {ECO:0000303|PubMed:22160599};
GN Name=rush {ECO:0000312|FlyBase:FBgn0025381};
GN Synonyms=EG:80H7.5 {ECO:0000312|FlyBase:FBgn0025381};
GN ORFNames=CG14782 {ECO:0000312|FlyBase:FBgn0025381};
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|EMBL:CAA19842.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=11337470; DOI=10.1101/gr.173801;
RA Benos P.V., Gatt M.K., Murphy L., Harris D., Barrell B., Ferraz C.,
RA Vidal S., Brun C., Demaille J., Cadieu E., Dreano S., Gloux S., Lelaure V.,
RA Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C., Bolshakov S.,
RA Siden-Kiamos I., Papagiannakis G., Spanos L., Louis C., Madueno E.,
RA de Pablos B., Modolell J., Peter A., Schoettler P., Werner M.,
RA Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H., Bucheton A.,
RA Callister D., Campbell L., Henderson N.S., McMillan P.J., Salles C.,
RA Tait E., Valenti P., Saunders R.D., Billaud A., Pachter L., Glover D.M.,
RA Ashburner M.;
RT "From first base: the sequence of the tip of the X chromosome of Drosophila
RT melanogaster, a comparison of two sequencing strategies.";
RL Genome Res. 11:710-730(2001).
RN [2] {ECO:0000312|Proteomes:UP000000803}
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 [3] {ECO:0000312|Proteomes:UP000000803}
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 [4] {ECO:0000312|EMBL:AAO39613.1, ECO:0000312|EMBL:ACL68701.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAO39613.1, ECO:0000312|EMBL:ACL68701.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAO39613.1};
RA Stapleton M., Booth B., Brokstein P., Hong L., Agbayani A., Carlson J.,
RA Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E.,
RA George R., Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G.,
RA Miranda A., Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S.,
RA Patel S., Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M.,
RA Celniker S.;
RL Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000312|EMBL:AAL28825.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-204.
RC STRAIN=Berkeley; TISSUE=Embryo;
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 [6] {ECO:0000305}
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-48 AND ARG-176.
RX PubMed=22160599; DOI=10.1091/mbc.e11-02-0154;
RA Gailite I., Egger-Adam D., Wodarz A.;
RT "The phosphoinositide-associated protein Rush hour regulates endosomal
RT trafficking in Drosophila.";
RL Mol. Biol. Cell 23:433-447(2012).
CC -!- FUNCTION: Functions in the regulation of endosome morphology and late
CC endosome formation. Has a role in controlling trafficking from early to
CC late endosomes and from late endosomes to lysosomes. Important for
CC localization of Gdi to the endosomal membranes. May function in
CC controlling the activity of multiple regulators in the endocytic
CC pathway, perhaps by positively controlling those involved in the early
CC steps of endocytosis such as Rab5 and hrs, and negative regulating
CC those involved in the late stages of endocytosis like car and VhaSFD.
CC {ECO:0000269|PubMed:22160599}.
CC -!- SUBUNIT: Interacts with Gdi (Rab GDP dissociation inhibitor).
CC {ECO:0000269|PubMed:22160599}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:22160599}. Endosome membrane
CC {ECO:0000269|PubMed:22160599}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:22160599}.
CC -!- TISSUE SPECIFICITY: In ovaries, expressed both in the germ line cells
CC and in the overlying somatic follicular epithelium.
CC {ECO:0000269|PubMed:22160599}.
CC -!- DOMAIN: The FYVE-type zinc finger domain is necessary and sufficient
CC for endosome targeting and localization to the plasma membrane.
CC {ECO:0000269|PubMed:22160599}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. No effect on the
CC subcellular localization or expression of Rab7, Rab11 and Avl.
CC {ECO:0000269|PubMed:22160599}.
CC -!- MISCELLANEOUS: The name 'rush hour' derives from the overexpression
CC phenotype which displays a disruption to endosomal trafficking and
CC cargo progression. {ECO:0000303|PubMed:22160599}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL031027; CAA19842.1; -; Genomic_DNA.
DR EMBL; AE014298; AAF45637.1; -; Genomic_DNA.
DR EMBL; AE014298; AHN59255.1; -; Genomic_DNA.
DR EMBL; BT003610; AAO39613.1; -; mRNA.
DR EMBL; BT056254; ACL68701.1; -; mRNA.
DR EMBL; AY061277; AAL28825.1; -; mRNA.
DR PIR; T13601; T13601.
DR RefSeq; NP_001284784.1; NM_001297855.1.
DR RefSeq; NP_569923.2; NM_130567.3.
DR AlphaFoldDB; O76902; -.
DR SMR; O76902; -.
DR DIP; DIP-21949N; -.
DR IntAct; O76902; 2.
DR STRING; 7227.FBpp0070249; -.
DR PaxDb; O76902; -.
DR PRIDE; O76902; -.
DR DNASU; 31105; -.
DR EnsemblMetazoa; FBtr0070259; FBpp0070249; FBgn0025381.
DR EnsemblMetazoa; FBtr0339589; FBpp0308661; FBgn0025381.
DR GeneID; 31105; -.
DR KEGG; dme:Dmel_CG14782; -.
DR UCSC; CG14782-RA; d. melanogaster.
DR CTD; 31105; -.
DR FlyBase; FBgn0025381; rush.
DR VEuPathDB; VectorBase:FBgn0025381; -.
DR eggNOG; KOG1729; Eukaryota.
DR GeneTree; ENSGT00940000156408; -.
DR HOGENOM; CLU_064864_1_0_1; -.
DR InParanoid; O76902; -.
DR OMA; VCMRCKK; -.
DR OrthoDB; 1237900at2759; -.
DR PhylomeDB; O76902; -.
DR BioGRID-ORCS; 31105; 2 hits in 3 CRISPR screens.
DR GenomeRNAi; 31105; -.
DR PRO; PR:O76902; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0025381; Expressed in seminal fluid secreting gland and 12 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IDA:FlyBase.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005770; C:late endosome; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:FlyBase.
DR GO; GO:0006897; P:endocytosis; IGI:FlyBase.
DR GO; GO:0007032; P:endosome organization; IMP:FlyBase.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:FlyBase.
DR CDD; cd01218; PH_Phafin2-like; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR037871; PH_Phafin.
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 Pfam; PF01363; FYVE; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00064; FYVE; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Endocytosis; Endosome; Membrane; Metal-binding;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..316
FT /note="Pleckstrin homology domain-containing family F
FT member 1 homolog"
FT /id="PRO_0000438292"
FT DOMAIN 35..131
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 152..212
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 215..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 161
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 178
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 204
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT MUTAGEN 48
FT /note="K->E: Increase in late endosome size. Loss of
FT binding to various phosphoinositides, but no loss of
FT binding to phosphatidylinositol 3-phosphate (PtdIns3P).
FT Localization to the cell cortex and endosomes is not
FT affected."
FT /evidence="ECO:0000269|PubMed:22160599"
FT MUTAGEN 176
FT /note="R->G: No localization to the endosomes. Present at
FT the plasma membrane and in the cytosol. Loss of binding to
FT PtdIns3P."
FT /evidence="ECO:0000269|PubMed:22160599"
FT CONFLICT 200..204
FT /note="ALRVC -> GVARL (in Ref. 5; AAL28825)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 316 AA; 34219 MW; 9BB23D14D43DDBF1 CRC64;
MVDRLVNSEA NTRRIASVEN CFGSSGVPLA MQGRVLVGEG VLTKMCRKRP KSRQFFLFND
ILVYGNIVIG KKKYNKQHIM PLEEVSLESI ADNQTYRNGW YIRTTTKSFV VFAATSTEKQ
EWMAHINKCV EDLLRKSGKK PVENHAAVWV PDTDASVCMH CKKTQFTFIQ RRHHCRNCGA
VVCAGCSAKK FLLPQQSTKA LRVCDACYER LKHVPSSLGS GEDSAAATGA ASGNKLNTTA
GDSSNDEDSD EETASPGGES HDEPRFYGDN SVLSAVEDSS TITSPSSATT GSLEAPQVTP
SVQSSPAAVA TTGSHC
