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 27-MAR-2024, entry version 188. 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}; 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; 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; 7227-FBpp0085149; -. DR DNASU; 49045; -. DR EnsemblMetazoa; FBtr0085788; FBpp0085149; FBgn0261988. DR EnsemblMetazoa; FBtr0334555; FBpp0306622; FBgn0261988. DR GeneID; 49045; -. DR KEGG; dme:Dmel_CG17998; -. DR AGR; FB:FBgn0261988; -. 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; ISWQTEM; -. DR OrthoDB; 2906348at2759; -. 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 cell types or tissues. DR ExpressionAtlas; P32866; baseline and differential. 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 CDD; cd05605; STKc_GRK4_like; 1. DR Gene3D; 1.10.167.10; Regulator of G-protein Signalling 4, domain 2; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24355:SF28; G PROTEIN-COUPLED RECEPTOR KINASE 2; 1. DR PANTHER; PTHR24355; G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR PRINTS; PR00717; GPCRKINASE. DR SMART; SM00315; RGS; 1. DR SMART; SM00133; S_TK_X; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF48097; Regulator of G-protein signaling, RGS; 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. DR Genevisible; P32866; DM. 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 //