ID GRK1_HUMAN Reviewed; 563 AA. AC Q15835; Q53X14; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 211. DE RecName: Full=Rhodopsin kinase GRK1; DE Short=RK; DE EC=2.7.11.14 {ECO:0000269|PubMed:15946941}; DE AltName: Full=G protein-coupled receptor kinase 1 {ECO:0000312|HGNC:HGNC:10013}; DE Flags: Precursor; GN Name=GRK1 {ECO:0000312|HGNC:HGNC:10013}; Synonyms=RHOK; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Retina; RX PubMed=9147475; DOI=10.1017/s0952523800011366; RA Zhao X., Haeseleer F., Fariss R.N., Huang J., Baehr W., Milam A.H., RA Palczewski K.; RT "Molecular cloning and localization of rhodopsin kinase in the mammalian RT pineal."; RL Vis. Neurosci. 14:225-232(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=8812493; DOI=10.1006/geno.1996.0399; RA Khani S.C., Abitbol M., Yamamoto S., Maravic-Magovcevic I., Dryja T.P.; RT "Characterization and chromosomal localization of the gene for human RT rhodopsin kinase."; RL Genomics 35:571-576(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Corpus callosum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [5] RP TISSUE SPECIFICITY. RX PubMed=11717351; DOI=10.1523/jneurosci.21-23-09175.2001; RA Weiss E.R., Ducceschi M.H., Horner T.J., Li A., Craft C.M., Osawa S.; RT "Species-specific differences in expression of G-protein-coupled receptor RT kinase (GRK) 7 and GRK1 in mammalian cone photoreceptor cells: implications RT for cone cell phototransduction."; RL J. Neurosci. 21:9175-9184(2001). RN [6] RP BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, FUNCTION IN RP PHOSPHORYLATION OF RHO, PHOSPHORYLATION AT SER-21, ACTIVITY REGULATION, RP AUTOPHOSPHORYLATION, AND MUTAGENESIS OF SER-21 AND LYS-219. RX PubMed=15946941; DOI=10.1074/jbc.m505117200; RA Horner T.J., Osawa S., Schaller M.D., Weiss E.R.; RT "Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase RT attenuates their enzymatic activities."; RL J. Biol. Chem. 280:28241-28250(2005). RN [7] {ECO:0007744|PDB:5AFP} RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-25 IN COMPLEX WITH NCS1. RX PubMed=25979333; DOI=10.1074/jbc.m114.627059; RA Pandalaneni S., Karuppiah V., Saleem M., Haynes L.P., Burgoyne R.D., RA Mayans O., Derrick J.P., Lian L.Y.; RT "Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein- RT coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of RT Interactions."; RL J. Biol. Chem. 290:18744-18756(2015). RN [8] RP VARIANTS GLN-136; MET-298; SER-330; HIS-438; SER-514; THR-522 AND LEU-536. RX PubMed=9268593; DOI=10.1006/exer.1997.9998; RA Yamamoto S., Khani S.C., Berson E.L., Dryja T.P.; RT "Evaluation of the rhodopsin kinase gene in patients with retinitis RT pigmentosa."; RL Exp. Eye Res. 65:249-253(1997). RN [9] RP VARIANT CSNBO2 ASP-380. RX PubMed=9020843; DOI=10.1038/ng0297-175; RA Yamamoto S., Sippel K.C., Berson E.L., Dryja T.P.; RT "Defects in the rhodopsin kinase gene in the Oguchi form of stationary RT night blindness."; RL Nat. Genet. 15:175-178(1997). RN [10] RP VARIANT CSNBO2 HIS-391. RX PubMed=17070587; DOI=10.1016/j.ophtha.2006.05.069; RA Hayashi T., Gekka T., Takeuchi T., Goto-Omoto S., Kitahara K.; RT "A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease RT with markedly reduced cone responses."; RL Ophthalmology 114:134-141(2007). CC -!- FUNCTION: Retina-specific kinase involved in the signal turnoff via CC phosphorylation of rhodopsin (RHO), the G protein- coupled receptor CC that initiates the phototransduction cascade (PubMed:15946941). This CC rapid desensitization is essential for scotopic vision and permits CC rapid adaptation to changes in illumination (By similarity). May play a CC role in the maintenance of the outer nuclear layer in the retina (By CC similarity). {ECO:0000250|UniProtKB:Q9WVL4, CC ECO:0000269|PubMed:15946941}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[rhodopsin] = ADP + H(+) + O-phospho-L- CC threonyl-[rhodopsin]; Xref=Rhea:RHEA:56552, Rhea:RHEA-COMP:14596, CC Rhea:RHEA-COMP:14597, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.14; Evidence={ECO:0000269|PubMed:15946941}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[rhodopsin] = ADP + H(+) + O-phospho-L-seryl- CC [rhodopsin]; Xref=Rhea:RHEA:23356, Rhea:RHEA-COMP:14594, Rhea:RHEA- CC COMP:14595, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.14; CC Evidence={ECO:0000269|PubMed:15946941}; CC -!- ACTIVITY REGULATION: Inhibited by RCVRN, which prevents the interaction CC between GRK1 and RHO (By similarity). Inhibition is calcium-dependent CC (By similarity). Inhibited by phosphorylation of Ser-21. CC {ECO:0000250|UniProtKB:P28327, ECO:0000269|PubMed:15946941}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=3.5 uM for rhodopsin {ECO:0000269|PubMed:15946941}; CC KM=10.6 uM for ATP {ECO:0000269|PubMed:15946941}; CC Vmax=1132 nmol/min/mg enzyme {ECO:0000269|PubMed:15946941}; CC -!- SUBUNIT: Interacts (via N-terminus) with RCVRN (via C-terminus); the CC interaction is Ca(2+)-dependent (By similarity). Interacts (when CC prenylated) with PDE6D; this promotes release from membranes (By CC similarity). May form a complex composed of RHO, GRK1 and RCVRN in a CC Ca(2+)-dependent manner; RCVRN prevents the interaction between GRK1 CC and RHO (By similarity). {ECO:0000250|UniProtKB:P28327}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P28327}; Lipid- CC anchor {ECO:0000250|UniProtKB:P28327}. Cell projection, cilium, CC photoreceptor outer segment {ECO:0000250|UniProtKB:Q9WVL4}. CC Note=Subcellular location is not affected by light or dark conditions. CC {ECO:0000250|UniProtKB:Q9WVL4}. CC -!- TISSUE SPECIFICITY: Retinal-specific. Expressed in rods and cones CC cells. {ECO:0000269|PubMed:11717351}. CC -!- PTM: Autophosphorylated, Ser-21 is a minor site of autophosphorylation CC compared to Ser-491 and Thr-492 (By similarity). Phosphorylation at CC Ser-21 is regulated by light and activated by cAMP. {ECO:0000250, CC ECO:0000269|PubMed:15946941}. CC -!- PTM: Farnesylation is required for full activity. CC {ECO:0000250|UniProtKB:P28327}. CC -!- DISEASE: Night blindness, congenital stationary, Oguchi type 2 (CSNBO2) CC [MIM:613411]: A non-progressive retinal disorder characterized by CC impaired night vision, often associated with nystagmus and myopia. CC Congenital stationary night blindness Oguchi type is associated with CC fundus discoloration and abnormally slow dark adaptation. CC {ECO:0000269|PubMed:17070587, ECO:0000269|PubMed:9020843}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. GPRK subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Mutations of the RHOK gene; Note=Retina CC International's Scientific Newsletter; CC URL="https://www.retina-international.org/files/sci-news/rkmut.htm"; 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; U63973; AAB05929.1; -; mRNA. DR EMBL; L77503; AAG50439.1; -; mRNA. DR EMBL; L77502; AAT00534.2; -; Genomic_DNA. DR EMBL; L77496; AAT00534.2; JOINED; Genomic_DNA. DR EMBL; L77497; AAT00534.2; JOINED; Genomic_DNA. DR EMBL; L77498; AAT00534.2; JOINED; Genomic_DNA. DR EMBL; L77499; AAT00534.2; JOINED; Genomic_DNA. DR EMBL; L77500; AAT00534.2; JOINED; Genomic_DNA. DR EMBL; L77501; AAT00534.2; JOINED; Genomic_DNA. DR EMBL; AC187648; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK289912; BAF82601.1; -; mRNA. DR CCDS; CCDS81785.1; -. DR RefSeq; NP_002920.1; NM_002929.2. DR PDB; 5AFP; X-ray; 2.30 A; C/D=1-25. DR PDBsum; 5AFP; -. DR AlphaFoldDB; Q15835; -. DR SMR; Q15835; -. DR BioGRID; 111943; 11. DR IntAct; Q15835; 1. DR STRING; 9606.ENSP00000334876; -. DR BindingDB; Q15835; -. DR ChEMBL; CHEMBL5607; -. DR DrugCentral; Q15835; -. DR GuidetoPHARMACOLOGY; 1465; -. DR iPTMnet; Q15835; -. DR PhosphoSitePlus; Q15835; -. DR BioMuta; GRK1; -. DR DMDM; 2833269; -. DR MassIVE; Q15835; -. DR MaxQB; Q15835; -. DR PaxDb; 9606-ENSP00000334876; -. DR PeptideAtlas; Q15835; -. DR ProteomicsDB; 60785; -. DR Antibodypedia; 25983; 399 antibodies from 34 providers. DR DNASU; 6011; -. DR Ensembl; ENST00000335678.7; ENSP00000334876.5; ENSG00000185974.7. DR Ensembl; ENST00000672946.1; ENSP00000499886.1; ENSG00000288263.1. DR GeneID; 6011; -. DR KEGG; hsa:6011; -. DR MANE-Select; ENST00000335678.7; ENSP00000334876.5; NM_002929.3; NP_002920.1. DR UCSC; uc010tkf.3; human. DR AGR; HGNC:10013; -. DR CTD; 6011; -. DR DisGeNET; 6011; -. DR GeneCards; GRK1; -. DR HGNC; HGNC:10013; GRK1. DR HPA; ENSG00000185974; Tissue enriched (retina). DR MalaCards; GRK1; -. DR MIM; 180381; gene. DR MIM; 613411; phenotype. DR neXtProt; NX_Q15835; -. DR OpenTargets; ENSG00000185974; -. DR Orphanet; 215; Congenital stationary night blindness. DR Orphanet; 75382; Oguchi disease. DR PharmGKB; PA34391; -. DR VEuPathDB; HostDB:ENSG00000185974; -. DR eggNOG; KOG0986; Eukaryota. DR GeneTree; ENSGT00940000159927; -. DR HOGENOM; CLU_000288_63_41_1; -. DR InParanoid; Q15835; -. DR OMA; PASKSGM; -. DR OrthoDB; 2906348at2759; -. DR PhylomeDB; Q15835; -. DR TreeFam; TF313940; -. DR BRENDA; 2.7.11.14; 2681. DR PathwayCommons; Q15835; -. DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade. DR SABIO-RK; Q15835; -. DR SignaLink; Q15835; -. DR SIGNOR; Q15835; -. DR BioGRID-ORCS; 6011; 10 hits in 314 CRISPR screens. DR ChiTaRS; GRK1; human. DR GenomeRNAi; 6011; -. DR Pharos; Q15835; Tchem. DR PRO; PR:Q15835; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q15835; Protein. DR Bgee; ENSG00000185974; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 40 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0097381; C:photoreceptor disc membrane; TAS:Reactome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0050254; F:rhodopsin kinase activity; IDA:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB. DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; TAS:ProtInc. DR GO; GO:0022400; P:regulation of rhodopsin mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central. DR GO; GO:0016056; P:rhodopsin mediated signaling pathway; TAS:ProtInc. DR GO; GO:0007601; P:visual perception; TAS:ProtInc. DR CDD; cd05608; STKc_GRK1; 1. DR Gene3D; 1.10.167.10; Regulator of G-protein Signalling 4, domain 2; 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; IPR037716; GRK1_dom. 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 InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24355; G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE; 1. DR PANTHER; PTHR24355:SF11; RHODOPSIN KINASE GRK1; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00615; RGS; 1. DR PRINTS; PR00717; GPCRKINASE. DR SMART; SM00315; RGS; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 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; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50132; RGS; 1. DR Genevisible; Q15835; HS. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell projection; KW Congenital stationary night blindness; Disease variant; Kinase; KW Lipoprotein; Membrane; Methylation; Nucleotide-binding; Phosphoprotein; KW Prenylation; Reference proteome; Sensory transduction; KW Serine/threonine-protein kinase; Transferase; Vision. FT CHAIN 1..560 FT /note="Rhodopsin kinase GRK1" FT /id="PRO_0000024375" FT PROPEP 561..563 FT /note="Removed in mature form" FT /evidence="ECO:0000250" FT /id="PRO_0000024376" FT DOMAIN 58..175 FT /note="RGS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171" FT DOMAIN 190..455 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 456..521 FT /note="AGC-kinase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618" FT REGION 1..189 FT /note="N-terminal" FT REGION 1..15 FT /note="Interaction with RCVRN" FT /evidence="ECO:0000250|UniProtKB:P28327" FT REGION 456..563 FT /note="C-terminal" FT REGION 539..563 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 546..563 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 317 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 196..204 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 219 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 5 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28327" FT MOD_RES 8 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P28327" FT MOD_RES 21 FT /note="Phosphoserine; by PKA and autocatalysis" FT /evidence="ECO:0000269|PubMed:15946941" FT MOD_RES 491 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P28327" FT MOD_RES 492 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P28327" FT MOD_RES 560 FT /note="Cysteine methyl ester" FT /evidence="ECO:0000250|UniProtKB:P28327" FT LIPID 560 FT /note="S-farnesyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P28327" FT VARIANT 136 FT /note="E -> Q (in dbSNP:rs542688076)" FT /evidence="ECO:0000269|PubMed:9268593" FT /id="VAR_008283" FT VARIANT 298 FT /note="T -> M (in dbSNP:rs572803634)" FT /evidence="ECO:0000269|PubMed:9268593" FT /id="VAR_008284" FT VARIANT 330 FT /note="N -> S (in dbSNP:rs375409897)" FT /evidence="ECO:0000269|PubMed:9268593" FT /id="VAR_008285" FT VARIANT 380 FT /note="V -> D (in CSNBO2; dbSNP:rs777094000)" FT /evidence="ECO:0000269|PubMed:9020843" FT /id="VAR_006215" FT VARIANT 391 FT /note="P -> H (in CSNBO2; dbSNP:rs570621429)" FT /evidence="ECO:0000269|PubMed:17070587" FT /id="VAR_037904" FT VARIANT 438 FT /note="R -> H (in dbSNP:rs750619057)" FT /evidence="ECO:0000269|PubMed:9268593" FT /id="VAR_008286" FT VARIANT 514 FT /note="C -> S (in dbSNP:rs771561763)" FT /evidence="ECO:0000269|PubMed:9268593" FT /id="VAR_008287" FT VARIANT 522 FT /note="M -> T (in dbSNP:rs779749742)" FT /evidence="ECO:0000269|PubMed:9268593" FT /id="VAR_008288" FT VARIANT 536 FT /note="S -> L (in dbSNP:rs553969577)" FT /evidence="ECO:0000269|PubMed:9268593" FT /id="VAR_008289" FT MUTAGEN 21 FT /note="S->E: Not phosphorylated by PKA." FT /evidence="ECO:0000269|PubMed:15946941" FT MUTAGEN 219 FT /note="K->A: Loss of autophosphorylation and RHO FT phosphorylation." FT /evidence="ECO:0000269|PubMed:15946941" FT HELIX 7..14 FT /evidence="ECO:0007829|PDB:5AFP" SQ SEQUENCE 563 AA; 63526 MW; 1244DCB97D40F53D CRC64; MDFGSLETVV ANSAFIAARG SFDGSSSQPS RDKKYLAKLK LPPLSKCESL RDSLSLEFES VCLEQPIGKK LFQQFLQSAE KHLPALELWK DIEDYDTADN DLQPQKAQTI LAQYLDPQAK LFCSFLDEGI VAKFKEGPVE IQDGLFQPLL QATLAHLGQA PFQEYLGSLY FLRFLQWKWL EAQPMGEDWF LDFRVLGKGG FGEVSACQMK ATGKLYACKK LNKKRLKKRK GYQGAMVEKK ILMKVHSRFI VSLAYAFETK ADLCLVMTIM NGGDIRYHIY NVNEENPGFP EPRALFYTAQ IICGLEHLHQ RRIVYRDLKP ENVLLDNDGN VRISDLGLAV ELLDGQSKTK GYAGTPGFMA PELLQGEEYD FSVDYFALGV TLYEMIAARG PFRARGEKVE NKELKHRIIS EPVKYPDKFS QASKDFCEAL LEKDPEKRLG FRDETCDKLR AHPLFKDLNW RQLEAGMLMP PFIPDSKTVY AKDIQDVGAF STVKGVAFDK TDTEFFQEFA TGNCPIPWQE EMIETGIFGE LNVWRSDGQM PDDMKGISGG SSSSSKSGMC LVS //