G protein-coupled receptor kinase 5 (EC 2.7.11.16) (G protein-coupled receptor kinase GRK5)
1_MELEN 6_ IVANT 11_ VLLKA 16_ REGGG 21_ GKRKG 26_ KSKKW 31_ KEILK 36_ FPHIS 41_ QCEDL 46_ RRTID 51_ RDYCS 56_ LCDKQ 61_ PIGRL 66_ LFRQF 71_ CETRP 76_ GLECY 81_ IQFLD 86_ SVAEY 91_ EVTPD 96_ EKLGE 101_ KGKEI 106_ MTKYL 111_ TPKSP 116_ VFIAQ 121_ VGQDL 126_ VSQTE 131_ EKLLQ 136_ KPCKE 141_ LFSAC 146_ AQSVH 151_ EYLRG 156_ EPFHE 161_ YLDSM 166_ FFDRF 171_ LQWKW 176_ LERQP 181_ VTKNT 186_ FRQYR 191_ VLGKG 196_ GFGEV 201_ CACQV 206_ RATGK 211_ MYACK 216_ RLEKK 221_ RIKKR 226_ KGESM 231_ ALNEK 236_ QILEK 241_ VNSQF 246_ VVNLA 251_ YAYET 256_ KDALC 261_ LVLTI 266_ MNGGD 271_ LKFHI 276_ YNMGN 281_ PGFEE 286_ ERALF 291_ YAAEI 296_ LCGLE 301_ DLHRE 306_ NTVYR 311_ DLKPE 316_ NILLD 321_ DYGHI 326_ RISDL 331_ GLAVK 336_ IPEGD 341_ LIRGR 346_ VGTVG 351_ YMAPE 356_ VLNNQ 361_ RYGLS 366_ PDYWG 371_ LGCLI 376_ YEMIE 381_ GQSPF 386_ RGRKE 391_ KVKRE 396_ EVDRR 401_ VLETE 406_ EVYSH 411_ KFSEE 416_ AKSIC 421_ KMLLT 426_ KDAKQ 431_ RLGCQ 436_ EEGAA 441_ EVKRH 446_ PFFRN 451_ MNFKR 456_ LEAGM 461_ LDPPF 466_ VPDPR 471_ AVYCK 476_ DVLDI 481_ EQFST 486_ VKGVN 491_ LDHTD 496_ DDFYS 501_ KFSTG 506_ SVSIP 511_ WQNEM 516_ IETEC 521_ FKELN 526_ VFGPN 531_ GTLPP 536_ DLNRN 541_ HPPEP 546_ PKKGL 551_ LQRLF 556_ KRQHQ 561_ NNSKS 566_ SPSSK 571_ TSFNH 576_ HINSN 581_HVSSN
1: Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro)