PRL1_DROME
ID PRL1_DROME Reviewed; 176 AA.
AC O61722; Q95VY8;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=PRL-1 phosphatase {ECO:0000312|FlyBase:FBgn0024734};
DE EC=3.1.3.48 {ECO:0000250|UniProtKB:Q93096};
DE AltName: Full=Phosphatase of regenerating liver-1 {ECO:0000303|PubMed:31404830};
DE Flags: Precursor;
GN Name=PRL-1 {ECO:0000312|FlyBase:FBgn0024734};
GN Synonyms=BG:DS07473.3 {ECO:0000312|FlyBase:FBgn0024734},
GN PRL {ECO:0000312|FlyBase:FBgn0024734};
GN ORFNames=CG4993 {ECO:0000312|FlyBase:FBgn0024734};
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:AAL26988.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang J., Kirby C.E., Pettiford S.M., Herbst R.;
RT "PTPCAAX protein tyrosine phosphatases: differential expression in tumor
RT cell lines and characterization of their enzymatic activity.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 {ECO:0000312|Proteomes:UP000000803};
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:AAL49127.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL49127.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAL49127.1};
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 [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP 173-CYS--GLN-176.
RX PubMed=23577193; DOI=10.1371/journal.pone.0061084;
RA Pagarigan K.T., Bunn B.W., Goodchild J., Rahe T.K., Weis J.F.,
RA Saucedo L.J.;
RT "Drosophila PRL-1 is a growth inhibitor that counteracts the function of
RT the Src oncogene.";
RL PLoS ONE 8:e61084-e61084(2013).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH UEX, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=31404830; DOI=10.1016/j.isci.2019.07.026;
RA Guo P., Xu X., Wang F., Yuan X., Tu Y., Zhang B., Zheng H., Yu D., Ge W.,
RA Gong Z., Yang X., Xi Y.;
RT "A Novel Neuroprotective Role of Phosphatase of Regenerating Liver-1
RT against CO2 Stimulation in Drosophila.";
RL IScience 19:291-302(2019).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF GLY-144.
RX PubMed=31048465; DOI=10.1126/science.aau9952;
RA Urwyler O., Izadifar A., Vandenbogaerde S., Sachse S., Misbaer A.,
RA Schmucker D.;
RT "Branch-restricted localization of phosphatase Prl-1 specifies axonal
RT synaptogenesis domains.";
RL Science 364:0-0(2019).
CC -!- FUNCTION: Probable phosphatase (Probable). Inhibits growth possibly by
CC negatively regulating Src64B-induced growth (PubMed:23577193).
CC Regulates central nervous system circuit formation and stabilization of
CC synapse-dense terminal arbors (PubMed:31048465). In dorsocentral
CC neurons, regulates synaptogenesis in terminal arbors via modulation of
CC the insulin receptor pathway, likely upstream of Akt1, and via
CC reduction of PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate)
CC levels (PubMed:31048465). In the nervous system, plays a protective
CC role together with uex in response to olfactory carbon dioxide
CC stimulation (PubMed:31404830). {ECO:0000269|PubMed:23577193,
CC ECO:0000269|PubMed:31048465, ECO:0000269|PubMed:31404830,
CC ECO:0000305|PubMed:31048465}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC Evidence={ECO:0000250|UniProtKB:Q93096};
CC -!- SUBUNIT: Homotrimer (By similarity). Interacts with uex, possibly at
CC the plasma membrane (PubMed:31404830). {ECO:0000250|UniProtKB:Q93096,
CC ECO:0000269|PubMed:31404830}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23577193}. Cell
CC membrane {ECO:0000269|PubMed:23577193, ECO:0000269|PubMed:31404830};
CC Lipid-anchor {ECO:0000250|UniProtKB:Q93096}. Apicolateral cell membrane
CC {ECO:0000269|PubMed:23577193}. Cell projection, axon
CC {ECO:0000269|PubMed:31048465}. Note=During embryogenesis localizes to
CC cytoplasmic compartments from 1 to 14 hours after egg laying,
CC thereafter becomes associated with the plasma membrane
CC (PubMed:23577193). Localizes to contralateral axon collaterals of
CC dorsocentral neurons (PubMed:31048465). {ECO:0000269|PubMed:23577193,
CC ECO:0000269|PubMed:31048465}.
CC -!- TISSUE SPECIFICITY: Expressed in the adult head (at protein level)
CC (PubMed:31404830). Expressed in neurons in the antennal lobe and V-
CC glomeruli (at protein level) (PubMed:31404830). Expressed in
CC dorsocentral neurons (at protein level) (PubMed:31048465).
CC {ECO:0000269|PubMed:31048465, ECO:0000269|PubMed:31404830}.
CC -!- DEVELOPMENTAL STAGE: Expressed ubiquitously during embryogenesis and
CC larval development (at protein level) (PubMed:23577193). Expressed in
CC wing disks and developing eyes in both actively dividing cells
CC (anterior to the morphogenetic furrow) and differentiated cells
CC (posterior to the morphogenetic furrow) (at protein level)
CC (PubMed:23577193). {ECO:0000269|PubMed:23577193}.
CC -!- DISRUPTION PHENOTYPE: Viable (PubMed:31404830, PubMed:31048465).
CC Results in delayed hatching, locomotor defects and inability to fly
CC (PubMed:31048465). Results in defects in axonal target areas in several
CC central nervous system circuits (PubMed:31048465). Results in axonal
CC and synapses defects in two distinct brain neuropils in the antennal
CC lobes and mushroom bodies, respectively related to olfaction and
CC olfaction-associated learning (PubMed:31048465). Reduces size of the
CC central nervous system neuropil (a region of densely packed axons,
CC dendrites, and synapses) (PubMed:31048465). When exposed to high
CC concentration of carbon dioxide treatment results in a vertical held-up
CC wing phenotype with calcium hyperactivation of neurons in the antennal
CC lobe (PubMed:31404830, PubMed:31048465). Results in loss of synaptic
CC arborizations from the contralateral mechanosensory neuron axon
CC collateral with no defect in morphology (PubMed:31048465). RNAi-
CC mediated knockdown in mechanosensory neurons eliminates terminal arbors
CC and reduces numbers of synapses in the contralateral projecting axon
CC collateral (PubMed:31048465). {ECO:0000269|PubMed:31048465,
CC ECO:0000269|PubMed:31404830}.
CC -!- MISCELLANEOUS: Compartment-specific localization and function depends
CC on long untranslated sequences (UTR) in the PRL-1 mRNA.
CC {ECO:0000269|PubMed:31048465}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL26988.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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; AF390535; AAL26988.1; ALT_INIT; mRNA.
DR EMBL; AE014134; AAF53506.2; -; Genomic_DNA.
DR EMBL; AE014134; AAN10934.1; -; Genomic_DNA.
DR EMBL; AE014134; AGB93022.1; -; Genomic_DNA.
DR EMBL; AE014134; AGB93023.1; -; Genomic_DNA.
DR EMBL; AY071505; AAL49127.1; -; mRNA.
DR RefSeq; NP_001260487.1; NM_001273558.1.
DR RefSeq; NP_001260488.1; NM_001273559.1.
DR RefSeq; NP_609780.1; NM_135936.3.
DR RefSeq; NP_723956.1; NM_165150.2.
DR AlphaFoldDB; O61722; -.
DR SMR; O61722; -.
DR STRING; 7227.FBpp0080413; -.
DR PaxDb; O61722; -.
DR PRIDE; O61722; -.
DR DNASU; 34952; -.
DR EnsemblMetazoa; FBtr0080856; FBpp0080413; FBgn0024734.
DR EnsemblMetazoa; FBtr0080857; FBpp0080414; FBgn0024734.
DR EnsemblMetazoa; FBtr0332357; FBpp0304634; FBgn0024734.
DR EnsemblMetazoa; FBtr0332358; FBpp0304635; FBgn0024734.
DR GeneID; 34952; -.
DR KEGG; dme:Dmel_CG4993; -.
DR UCSC; CG4993-RA; d. melanogaster.
DR CTD; 34952; -.
DR FlyBase; FBgn0024734; PRL-1.
DR VEuPathDB; VectorBase:FBgn0024734; -.
DR eggNOG; KOG2836; Eukaryota.
DR GeneTree; ENSGT00940000154383; -.
DR HOGENOM; CLU_099263_2_0_1; -.
DR InParanoid; O61722; -.
DR OMA; NGQKNSC; -.
DR PhylomeDB; O61722; -.
DR Reactome; R-DME-8873719; RAB geranylgeranylation.
DR BioGRID-ORCS; 34952; 0 hits in 3 CRISPR screens.
DR ChiTaRS; PRL-1; fly.
DR GenomeRNAi; 34952; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0024734; Expressed in midgut and 18 other tissues.
DR ExpressionAtlas; O61722; baseline.
DR GO; GO:0016327; C:apicolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISS:FlyBase.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro.
DR GO; GO:0071244; P:cellular response to carbon dioxide; IGI:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISS:FlyBase.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00102; Y_phosphatase; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cytoplasm; Hydrolase; Lipoprotein;
KW Membrane; Methylation; Prenylation; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1..176
FT /note="PRL-1 phosphatase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000452474"
FT PROPEP 174..176
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:Q93096"
FT /id="PRO_0000452475"
FT DOMAIN 13..166
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 109
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT MOD_RES 173
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250|UniProtKB:Q93096"
FT LIPID 173
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q93096"
FT MUTAGEN 144
FT /note="G->E: Fails to rescue the loss of terminal
FT arborization in mechanosensory neurons in null flies."
FT /evidence="ECO:0000269|PubMed:31048465"
FT MUTAGEN 173..176
FT /note="Missing: Fails to inhibit growth. Loss of
FT localization to apical membranes. Not necessary to modify
FT src-induced overgrowth."
FT /evidence="ECO:0000269|PubMed:23577193"
SQ SEQUENCE 176 AA; 19973 MW; 836D45EEA604F9FF CRC64;
MSITMRQKDL RPAPALIEYK GMKFLITDRP SDITINHYIM ELKKNNVNTV VRVCEPSYNT
DELETQGITV KDLAFEDGTF PPQQVVDEWF EVLKDKYQQN PEACVAVHCV AGLGRAPVLV
ALALIELGLK YEAAVEMIRD KRRGAINAKQ LSFLEKYKPK ARLKHKNGHK NSCSVQ
