MRCKG_MOUSE
ID MRCKG_MOUSE Reviewed; 1551 AA.
AC Q80UW5;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Serine/threonine-protein kinase MRCK gamma;
DE EC=2.7.11.1;
DE AltName: Full=CDC42-binding protein kinase gamma;
DE AltName: Full=DMPK-like gamma;
DE AltName: Full=Myotonic dystrophy kinase-related CDC42-binding kinase gamma;
DE Short=MRCK gamma;
DE Short=Myotonic dystrophy protein kinase-like gamma;
DE AltName: Full=Myotonic dystrophy protein kinase-like alpha;
GN Name=Cdc42bpg {ECO:0000312|MGI:MGI:2652845};
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 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 [2] {ECO:0000305, ECO:0000312|EMBL:AAH46418.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 699-1551.
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH46418.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH46418.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Pancreas;
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: May act as a downstream effector of CDC42 in cytoskeletal
CC reorganization. Contributes to the actomyosin contractility required
CC for cell invasion, through the regulation of MYPT1 and thus MLC2
CC phosphorylation (By similarity). {ECO:0000250|UniProtKB:Q5VT25}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q6DT37};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q6DT37};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q6DT37};
CC -!- ACTIVITY REGULATION: Maintained in an inactive, closed conformation by
CC an interaction between the kinase domain and the negative
CC autoregulatory C-terminal coiled-coil region. Agonist binding to the
CC phorbol ester binding site disrupts this, releasing the kinase domain
CC to allow N-terminus-mediated dimerization and kinase activation by
CC transautophosphorylation (By similarity).
CC {ECO:0000250|UniProtKB:Q5VT25}.
CC -!- SUBUNIT: Homodimer and homotetramer via the coiled coil regions.
CC Interacts tightly with GTP-bound but not GDP-bound CDC42 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Note=Concentrates at the
CC leading edge of cells. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. DMPK subfamily. {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; AC127556; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC046418; AAH46418.1; -; mRNA.
DR CCDS; CCDS50365.1; -.
DR RefSeq; NP_001028514.1; NM_001033342.1.
DR AlphaFoldDB; Q80UW5; -.
DR SMR; Q80UW5; -.
DR BioGRID; 232205; 2.
DR IntAct; Q80UW5; 1.
DR STRING; 10090.ENSMUSP00000025681; -.
DR iPTMnet; Q80UW5; -.
DR PhosphoSitePlus; Q80UW5; -.
DR EPD; Q80UW5; -.
DR MaxQB; Q80UW5; -.
DR PaxDb; Q80UW5; -.
DR PeptideAtlas; Q80UW5; -.
DR PRIDE; Q80UW5; -.
DR ProteomicsDB; 295654; -.
DR Antibodypedia; 15651; 35 antibodies from 15 providers.
DR DNASU; 240505; -.
DR Ensembl; ENSMUST00000025681; ENSMUSP00000025681; ENSMUSG00000024769.
DR GeneID; 240505; -.
DR KEGG; mmu:240505; -.
DR UCSC; uc008gia.2; mouse.
DR CTD; 55561; -.
DR MGI; MGI:2652845; Cdc42bpg.
DR VEuPathDB; HostDB:ENSMUSG00000024769; -.
DR eggNOG; KOG0612; Eukaryota.
DR GeneTree; ENSGT01030000234517; -.
DR HOGENOM; CLU_000288_140_1_1; -.
DR InParanoid; Q80UW5; -.
DR OMA; PWQHRIR; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; Q80UW5; -.
DR TreeFam; TF313551; -.
DR BioGRID-ORCS; 240505; 6 hits in 77 CRISPR screens.
DR ChiTaRS; Cdc42bpg; mouse.
DR PRO; PR:Q80UW5; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q80UW5; protein.
DR Bgee; ENSMUSG00000024769; Expressed in lip and 60 other tissues.
DR Genevisible; Q80UW5; MM.
DR GO; GO:0031252; C:cell leading edge; ISS:UniProtKB.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0031032; P:actomyosin structure organization; IBA:GO_Central.
DR GO; GO:0051179; P:localization; IEA:UniProt.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR CDD; cd00029; C1; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR001180; CNH_dom.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033235; MRCK_gamma.
DR InterPro; IPR014930; Myotonic_dystrophy_kinase_coil.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR22988:SF22; PTHR22988:SF22; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00780; CNH; 1.
DR Pfam; PF08826; DMPK_coil; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00036; CNH; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50219; CNH; 1.
DR PROSITE; PS50108; CRIB; 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; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Coiled coil; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1551
FT /note="Serine/threonine-protein kinase MRCK gamma"
FT /id="PRO_0000086398"
FT DOMAIN 71..337
FT /note="Protein kinase"
FT /evidence="ECO:0000250|UniProtKB:Q6DT37,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 338..408
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 946..1065
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1091..1365
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT DOMAIN 1436..1449
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT ZN_FING 877..926
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 578..605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 820..886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1441..1551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 442..675
FT /evidence="ECO:0000255"
FT COILED 729..801
FT /evidence="ECO:0000255"
FT COMPBIAS 1508..1533
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 195
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P54265,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 77..85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P54265,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q6DT37,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 216
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 228
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 234
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1481
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6DT37"
FT CONFLICT 1065
FT /note="R -> Q (in Ref. 2; AAH46418)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1551 AA; 172147 MW; 74458CA5FEF6F8A7 CRC64;
MEQRLRALEQ LVRGEAGGSP GLDGLLDLLL GVHQELSSAP LRRERNVAQF LSWASPFVTK
VKELRLQRDD FEILKVIGRG AFGEVAVVRQ RGSGQIFAMK MLHKWEMLKR AETACFREER
DVLVKGDSRW VTALHYAFQD EEYLYLVMDY YAGGDLLTLL SRFEDRLPPE LAQFYLAEMV
LAIHSLHQLG YVHRDVKPDN ILLDMNGHIR LADFGSCLRL NNNGMVDSSV AVGTPDYISP
EILQAMEEGK GHYGPQCDWW SLGVCAYELL FGETPFYAES LVETYGKIMN HEDHLQFPAD
VTDVPASAQD LIRQLLCRQE ERLGRGGLDD FRKHPFFEGV DWERLATSTA PYIPELRGPM
DTSNFDVDDD TLNRPETLPP SSHGAFSGHH LPFVGFTYTS GSPFDVQSSE LMAAPEGTPH
CVEQVKVELS HKCQEPLHGP LQPQELVRLQ KEVQVLQEKL AETLRDSKAS LSQTDGLHAR
SPAPNIQLQQ EKDRLQQELT EAQAALRVQD AELCQAQNRQ EEFLQRLWEA QEREAAAASQ
IQALNSQLEE AWVVRRELEG QVTTLSQEVT RLQGQCKQES SQAKTVHAAP ETNGIGSPEG
QSQEAQLRKE VAALREQLEH ACSQGISVGK EEVLCRLQEE NQRLSREQER LAGELELELQ
SKQRLEGERR ETESNWEAQI ADILSWVNDE KVSRGYLQAL ATKMAEELES LRNVGTQTLP
TRPLDHQWKA RRLQKMEASA RLELQSALEA EIRAKQSLQE QLTQVQEAQR QAERRLQEAE
KQSQALQQEV AELREELQAR GPGDARPSTS LIPLLSFWNT EKDSAKDPGN SGEGPRSGAE
AELRPEGRRS LRMGSVFPRV PAATTTPAEG PPAKPGSHTL RPRSFPSPTK CLRCTSLMLG
LGRQGLGCDT CGYFCHSACA SQAPPCPVPP ELLRTALGVH PETGTGTAYE GFLSVPRPSG
VRRGWQRVYA ALSDSRLLLF DAPDPRGSLA SGVLLQALDL RDPQFSATPV LAPDVIHAQS
KDLPRIFRVT ASQLTVPPTT CTVLLLAENE GERERWLQVL GELQRLLLDA RPRPRPVYTL
KEAYDNGLPL LPHALCAAVI DQERLALGTE EGLFVIHLHS NDIFQVGDCR RVQRLAVSSA
AGLLAVLCGR GPSVRLFALD ELESAEVAGA KIPESRGCQA LVAGRILQAR TPVLCVAVKR
QVLCYQLGPG PGPWQRRIRE LQAPAPVQSL GLLGDRLCVG AAGTFALYPL LNEAAPLALG
TGLVAEELPA SRGGLGEALG AVELSLSELL LLFATAGVYV DSAGRKSRSH ELLWPAAPTG
WGYTAPYLTV FSENALDVFD VRRAEWVQTV PLKKVRPLNP EGSLFLYGTE KVRLTYLRNP
LAEKDEFDIP DLTDNSRRQL FRTKSKRRFF FRVSDELRQQ QRREMLKDPF VRSKFISPPT
NFNHLVHVGP TEGRPNTRDG TRAQEQKSRG ARSSGPQRPH SFSEAFRRPV STGSDGLPGE
TDPLVKRKPW TSLSSESVSC PQGSLSPAAS LIQVSERPRS LPPDPESESS P
