ID   ARBK2_MOUSE             Reviewed;         688 AA.
AC   Q3UYH7; F8VPM8;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   22-FEB-2012, sequence version 2.
DT   24-JAN-2024, entry version 132.
DE   RecName: Full=G protein-coupled receptor kinase 3 {ECO:0000312|MGI:MGI:87941};
DE            EC=2.7.11.15 {ECO:0000250|UniProtKB:P26819};
DE   AltName: Full=Beta-adrenergic receptor kinase 2 {ECO:0000250|UniProtKB:P26819};
DE            Short=Beta-ARK-2 {ECO:0000250|UniProtKB:P26819};
GN   Name=Grk3 {ECO:0000312|MGI:MGI:87941};
GN   Synonyms=Adrbk2 {ECO:0000250|UniProtKB:P35626};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Specifically phosphorylates the agonist-occupied form of the
CC       beta-adrenergic and closely related receptors.
CC       {ECO:0000250|UniProtKB:P26819}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[beta-adrenergic receptor] + ATP = [beta-adrenergic receptor]-
CC         phosphate + ADP + H(+); Xref=Rhea:RHEA:19429, Rhea:RHEA-COMP:11222,
CC         Rhea:RHEA-COMP:11223, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43176, ChEBI:CHEBI:68546, ChEBI:CHEBI:456216;
CC         EC=2.7.11.15; Evidence={ECO:0000250|UniProtKB:P26819};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19430;
CC         Evidence={ECO:0000250|UniProtKB:P26819};
CC   -!- SUBUNIT: Interacts with GIT1. {ECO:0000250|UniProtKB:P26819}.
CC   -!- SUBCELLULAR LOCATION: Postsynapse {ECO:0000250|UniProtKB:P26819}.
CC       Presynapse {ECO:0000250|UniProtKB:P26819}.
CC   -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:P35626}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC       protein kinase family. GPRK subfamily. {ECO:0000305}.
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DR   EMBL; AK134672; BAE22235.1; -; mRNA.
DR   EMBL; AC107631; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS19545.1; -.
DR   RefSeq; NP_001272735.1; NM_001285806.1.
DR   RefSeq; NP_796052.2; NM_177078.4.
DR   AlphaFoldDB; Q3UYH7; -.
DR   SMR; Q3UYH7; -.
DR   BioGRID; 235781; 2.
DR   IntAct; Q3UYH7; 2.
DR   STRING; 10090.ENSMUSP00000070445; -.
DR   GlyGen; Q3UYH7; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q3UYH7; -.
DR   PhosphoSitePlus; Q3UYH7; -.
DR   MaxQB; Q3UYH7; -.
DR   PaxDb; 10090-ENSMUSP00000070445; -.
DR   PeptideAtlas; Q3UYH7; -.
DR   ProteomicsDB; 281902; -.
DR   Antibodypedia; 234; 480 antibodies from 34 providers.
DR   DNASU; 320129; -.
DR   Ensembl; ENSMUST00000065167.9; ENSMUSP00000070445.5; ENSMUSG00000042249.12.
DR   GeneID; 320129; -.
DR   KEGG; mmu:320129; -.
DR   UCSC; uc008ytt.2; mouse.
DR   AGR; MGI:87941; -.
DR   CTD; 157; -.
DR   MGI; MGI:87941; Grk3.
DR   VEuPathDB; HostDB:ENSMUSG00000042249; -.
DR   eggNOG; KOG0986; Eukaryota.
DR   GeneTree; ENSGT00940000157699; -.
DR   InParanoid; Q3UYH7; -.
DR   OMA; KHFSLTI; -.
DR   OrthoDB; 3415459at2759; -.
DR   PhylomeDB; Q3UYH7; -.
DR   TreeFam; TF313940; -.
DR   BRENDA; 2.7.11.15; 3474.
DR   Reactome; R-MMU-418555; G alpha (s) signalling events.
DR   Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   BioGRID-ORCS; 320129; 7 hits in 81 CRISPR screens.
DR   ChiTaRS; Adrbk2; mouse.
DR   PRO; PR:Q3UYH7; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; Q3UYH7; Protein.
DR   Bgee; ENSMUSG00000042249; Expressed in rostral migratory stream and 238 other cell types or tissues.
DR   ExpressionAtlas; Q3UYH7; baseline and differential.
DR   GO; GO:0030424; C:axon; ISO:MGI.
DR   GO; GO:0044292; C:dendrite terminus; ISO:MGI.
DR   GO; GO:0043198; C:dendritic shaft; ISO:MGI.
DR   GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR   GO; GO:0098793; C:presynapse; ISO:MGI.
DR   GO; GO:0097225; C:sperm midpiece; ISO:MGI.
DR   GO; GO:0030018; C:Z disc; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0047696; F:beta-adrenergic receptor kinase activity; ISO:MGI.
DR   GO; GO:0031748; F:D1 dopamine receptor binding; ISO:MGI.
DR   GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR   GO; GO:0004703; F:G protein-coupled receptor kinase activity; IDA:MGI.
DR   GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; ISO:MGI.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0043647; P:inositol phosphate metabolic process; ISO:MGI.
DR   GO; GO:0006886; P:intracellular protein transport; ISO:MGI.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR   GO; GO:0031623; P:receptor internalization; ISO:MGI.
DR   GO; GO:0046154; P:rhodopsin metabolic process; ISO:MGI.
DR   CDD; cd01240; PH_GRK2_subgroup; 1.
DR   CDD; cd08747; RGS_GRK2_GRK3; 1.
DR   Gene3D; 1.10.287.1270; -; 3.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
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; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR016137; RGS.
DR   InterPro; IPR036305; RGS_sf.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24355:SF17; BETA-ADRENERGIC RECEPTOR KINASE 2; 1.
DR   PANTHER; PTHR24355; G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE; 1.
DR   Pfam; PF00169; PH; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF00615; RGS; 1.
DR   PRINTS; PR00717; GPCRKINASE.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00315; RGS; 1.
DR   SMART; SM00133; S_TK_X; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF50729; PH domain-like; 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; PS50003; PH_DOMAIN; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   PROSITE; PS50132; RGS; 1.
DR   Genevisible; Q3UYH7; MM.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell projection; Kinase; Nucleotide-binding;
KW   Reference proteome; Serine/threonine-protein kinase; Synapse; Transferase;
KW   Ubl conjugation.
FT   CHAIN           1..688
FT                   /note="G protein-coupled receptor kinase 3"
FT                   /id="PRO_0000260828"
FT   DOMAIN          54..175
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   DOMAIN          191..453
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          454..521
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT   DOMAIN          558..652
FT                   /note="PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT   REGION          1..190
FT                   /note="N-terminal"
FT   ACT_SITE        317
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         197..205
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         220
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   CONFLICT        319
FT                   /note="K -> N (in Ref. 1; BAE22235)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   688 AA;  79657 MW;  9E587AE1BBA41EAD CRC64;
     MADLEAVLAD VSYLMAMEKS KTAPAARASK KVVLPEPSIR SVMQRYLAER NEITFDKIFN
     QKIGFLLFKD FCLNEIGEAV PQVKFYEEIK EYEKLDNEED RLRRSRQMYD AYIMRELLSS
     THQFSKQAVE HVQSHLSKKQ VTATLFQPYI EEICESLRGD IFQKFMESDK FTRFCQWKNV
     ELNIHLSMND FSVHRIIGRG GFGEVYGCRK ADTGKMYAMK CLDKKRVKMK QGETLALNER
     IMLSLVSTGD CPFIVCMTYA FHTPDKLCFI LDLMNGGDMH YHLSQHGVFS EKEMRFYASE
     IILGLEHMHT CFVVYRDLKP ANILLDEYGH VRISDLGLAC DFSKKKPHAS VGTHGYMAPE
     VLQKGTCYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH EIDRMTLTVN VQLPDAFSPE
     LRSLLEGLLQ RDVSQRLGCG GGGARELKEH IFFKGIDWQH VYLRKYPPPL IPPRGEVNAA
     DAFDIGSFDE EDTKGIKLLD CDQDLYKNFP LVISERWQQE VVETIYDAVN ADTDKIEARR
     KAKNKQLGQE EDYAMGKDCI MHGYMLKLGN PFLTQWQRRY FYLFPNRLEW RGEGESRQSL
     LTMEQIMSVE ETQIKDRKCI LLRIKGGKQF VLQCESDPEF AQWLKELTCT FNEAQRLLRR
     APKFLNKPRA AILEFSKPPL CHRNSSGL
//