GPRK2_DROME
ID GPRK2_DROME Reviewed; 714 AA.
AC P32866; A9UN94; Q960P0; Q9V9X6;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=G protein-coupled receptor kinase 2 {ECO:0000303|PubMed:9217001};
DE EC=2.7.11.16;
GN Name=Gprk2; Synonyms=Gprk-2; ORFNames=CG17998;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=9217001; DOI=10.1242/dev.124.13.2591;
RA Schneider L.E., Spradling A.C.;
RT "The Drosophila G-protein-coupled receptor kinase homologue Gprk2 is
RT required for egg morphogenesis.";
RL Development 124:2591-2602(1997).
RN [2]
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]
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C.,
RA Celniker S.E.;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 112-714.
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]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 201-714.
RC TISSUE=Retina;
RX PubMed=1662381; DOI=10.1073/pnas.88.24.11067;
RA Cassill J.A., Whitney M., Joazeiro C.A., Becker A., Zuker C.S.;
RT "Isolation of Drosophila genes encoding G protein-coupled receptor
RT kinases.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:11067-11070(1991).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-612 AND THR-613, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: Specifically phosphorylates the activated forms of G protein-
CC coupled receptors (By similarity). Required during oogenesis and
CC embryogenesis; component of a signaling pathway that functions during
CC egg chamber maturation. {ECO:0000250, ECO:0000269|PubMed:9217001}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[G-protein-coupled receptor] + ATP = [G-protein-coupled
CC receptor]-phosphate + ADP + H(+); Xref=Rhea:RHEA:12008, Rhea:RHEA-
CC COMP:11260, Rhea:RHEA-COMP:11261, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.16;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:9217001}.
CC Note=Associated with nurse cell and oocyte plasma membranes during much
CC of oogenesis.
CC -!- TISSUE SPECIFICITY: Expressed in all larval tissues and in adult
CC ovaries. Larval CNS staining is localized to axons projecting to the
CC optic lobes and the mushroom bodies, in the longitudinal connectives,
CC and in cell bodies and nerves of the ring gland corpus allatum. Adult
CC CNS staining is detectable only in cell bodies and processes associated
CC with the ellipsoid body of the central complex and portions of the
CC mushroom bodies. In the wing disk, expression is confined to a stripe
CC that parallels the anterior/posterior boundary of the wing blade and
CC the hinge region, and weak expression in the prospective notum.
CC {ECO:0000269|PubMed:9217001}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:9217001}.
CC -!- DISRUPTION PHENOTYPE: Adult females show severely reduced number of egg
CC chambers and the small germarium in ovarioles. The rare eggs that
CC become fertilized display gross defects in embryogenesis exhibiting
CC fusion of adjacent segments and holes in the dorsal and ventral
CC cuticle. {ECO:0000269|PubMed:9217001}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. GPRK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA28589.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAK93373.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF004674; AAB61467.1; -; mRNA.
DR EMBL; AE014297; AAF57152.1; -; Genomic_DNA.
DR EMBL; BT031258; ABY20499.1; -; mRNA.
DR EMBL; AY051949; AAK93373.1; ALT_INIT; mRNA.
DR EMBL; M80494; AAA28589.1; ALT_FRAME; mRNA.
DR PIR; B41615; B41615.
DR RefSeq; NP_001263143.1; NM_001276214.1.
DR RefSeq; NP_476867.1; NM_057519.4.
DR AlphaFoldDB; P32866; -.
DR SMR; P32866; -.
DR BioGRID; 71932; 16.
DR DIP; DIP-61924N; -.
DR IntAct; P32866; 39.
DR STRING; 7227.FBpp0085149; -.
DR iPTMnet; P32866; -.
DR PaxDb; P32866; -.
DR PRIDE; P32866; -.
DR DNASU; 49045; -.
DR EnsemblMetazoa; FBtr0085788; FBpp0085149; FBgn0261988.
DR EnsemblMetazoa; FBtr0334555; FBpp0306622; FBgn0261988.
DR GeneID; 49045; -.
DR KEGG; dme:Dmel_CG17998; -.
DR CTD; 49045; -.
DR FlyBase; FBgn0261988; Gprk2.
DR VEuPathDB; VectorBase:FBgn0261988; -.
DR eggNOG; KOG0986; Eukaryota.
DR GeneTree; ENSGT00940000167881; -.
DR HOGENOM; CLU_000288_63_41_1; -.
DR InParanoid; P32866; -.
DR OMA; YIVNRIF; -.
DR OrthoDB; 1104340at2759; -.
DR PhylomeDB; P32866; -.
DR BRENDA; 2.7.11.15; 1994.
DR Reactome; R-DME-418555; G alpha (s) signalling events.
DR SignaLink; P32866; -.
DR BioGRID-ORCS; 49045; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Gprk2; fly.
DR GenomeRNAi; 49045; -.
DR PRO; PR:P32866; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0261988; Expressed in brain and 26 other tissues.
DR ExpressionAtlas; P32866; baseline and differential.
DR Genevisible; P32866; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IMP:FlyBase.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:FlyBase.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:FlyBase.
DR GO; GO:0003384; P:apical constriction involved in gastrulation; IMP:FlyBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:FlyBase.
DR GO; GO:0007476; P:imaginal disc-derived wing morphogenesis; IMP:FlyBase.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IGI:FlyBase.
DR GO; GO:0048601; P:oocyte morphogenesis; IMP:FlyBase.
DR GO; GO:0006963; P:positive regulation of antibacterial peptide biosynthetic process; IMP:FlyBase.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; IGI:FlyBase.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IMP:FlyBase.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IDA:FlyBase.
DR GO; GO:0045752; P:positive regulation of Toll signaling pathway; IMP:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IMP:FlyBase.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.167.10; -; 2.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000239; GPCR_kinase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016137; RGS.
DR InterPro; IPR036305; RGS_sf.
DR InterPro; IPR044926; RGS_subdomain_2.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR00717; GPCRKINASE.
DR SMART; SM00315; RGS; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SUPFAM; SSF48097; SSF48097; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS50132; RGS; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Developmental protein; Differentiation; Kinase; Membrane;
KW Nucleotide-binding; Oogenesis; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..714
FT /note="G protein-coupled receptor kinase 2"
FT /id="PRO_0000085966"
FT DOMAIN 53..174
FT /note="RGS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 177..294
FT /note="RGS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 309..574
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 577..642
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..308
FT /note="N-terminal"
FT REGION 141..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 667..714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 141..175
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 197..220
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 697..714
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 435
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 315..323
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 338
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 612
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 613
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 70
FT /note="F -> C (in Ref. 1; AAB61467)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="S -> N (in Ref. 6; AAA28589)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="P -> H (in Ref. 1; AAB61467 and 6; AAA28589)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 714 AA; 80686 MW; 103F853BC74CFD80 CRC64;
MELENIVANT VYLKAREGGS DSNKGKSKKW RKILQFPHIS QCINLKDKLD ISYGYVIDQQ
PIGRELFRLF CENKRPVYFR YITFLDEVVK YEIEYISNRI FIGHDIGRRF LDVEAQLELR
NGSGGDALDA ETQEELLLNS SNANPTETAE TEHCNNTTAN NCNNINNSNN SQHSSDINHK
KLDTRNHNGD DATGNGSSHQ DDGDESVKCQ EGHDDAEKGG GGEGGGGGKC VPVGGYPDEL
VLDVLNDDLI AQVRNKLNSG GKDIFAQCVN AVKAFLAGEP FREFESSMYF HRYLQWKWLE
AQPITYKTFR MYRVLGKGGF GEVCACQVRA TGKMYACKKL EKKRIKKRKG ESMVLIEKQI
LQKINSPFVV NLAYAYETKD ALCLVLTIMN GGDLKFHIYN MGGEPGFELE RARFYAAEVA
CGLQHLHKQG IVYRDCKPEN ILLDDHGHVR ISDLGLAVEI PEGEMVRGRV GTVGYMAPEV
IDNEKYAFSP DWFSFGCLLY EMIEGQAPFR MRKEKVKREE VDRRVKEDPE KYSSKFNDEA
KSMCQQLLAK SIKQRLGCRN GRMGGQDVMA HPFFHSTQLN WRRLEAGMLE PPFVPDPHAV
YAKDVLDIEQ FSTVKGVNID ESDTNFYTKF NTGSVSISWQ NEMMETECFR ELNVFGPEEC
PTPDLQINAA PEPDKAGCFP FRRKKKQPAR TQPIPIPEHL LTTSHSVSST TVES
