MRCKG_HUMAN
ID MRCKG_HUMAN Reviewed; 1551 AA.
AC Q6DT37; O00565;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 163.
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=MRCKG;
DE Short=Myotonic dystrophy protein kinase-like gamma;
DE AltName: Full=Myotonic dystrophy protein kinase-like alpha;
GN Name=CDC42BPG {ECO:0000312|HGNC:HGNC:29829}; Synonyms=DMPK2;
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] {ECO:0000305, ECO:0000312|EMBL:AAT67172.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Colon {ECO:0000269|PubMed:15194684};
RX PubMed=15194684; DOI=10.1074/jbc.m405252200;
RA Ng Y., Tan I., Lim L., Leung T.;
RT "Expression of the human myotonic dystrophy kinase-related Cdc42-binding
RT kinase gamma is regulated by promoter DNA methylation and Sp1 binding.";
RL J. Biol. Chem. 279:34156-34164(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3] {ECO:0000305, ECO:0000312|EMBL:CAA73006.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 113-401.
RX PubMed=9341881; DOI=10.1007/s004390050562;
RA Kedra D., Seroussi E., Fransson I., Trifunovic J., Clark M.,
RA Lagercrantz J., Blennow E., Mehlin H., Dumanski J.;
RT "The germinal centre kinase gene and a novel CDC25-like gene are located in
RT the vicinity of the PYGM gene on 11q13.";
RL Hum. Genet. 100:611-619(1997).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1482, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [5]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-168; PHE-280; PRO-362 AND ASP-537.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
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 ECO:0000269|PubMed:15194684}.
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:0000269|PubMed:15194684};
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:0000269|PubMed:15194684};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15194684};
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 -!- INTERACTION:
CC Q6DT37; Q9UHD2: TBK1; NbExp=3; IntAct=EBI-689124, EBI-356402;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15194684}.
CC Note=Concentrates at the leading edge of cells.
CC -!- TISSUE SPECIFICITY: Expressed in heart and skeletal muscle.
CC {ECO:0000269|PubMed:15194684}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. DMPK subfamily. {ECO:0000305}.
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DR EMBL; AY648038; AAT67172.1; -; mRNA.
DR EMBL; AP001187; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y12337; CAA73006.1; -; mRNA.
DR CCDS; CCDS31601.1; -.
DR RefSeq; NP_059995.2; NM_017525.2.
DR AlphaFoldDB; Q6DT37; -.
DR SMR; Q6DT37; -.
DR BioGRID; 120719; 50.
DR IntAct; Q6DT37; 7.
DR MINT; Q6DT37; -.
DR STRING; 9606.ENSP00000345133; -.
DR BindingDB; Q6DT37; -.
DR ChEMBL; CHEMBL5615; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q6DT37; -.
DR iPTMnet; Q6DT37; -.
DR PhosphoSitePlus; Q6DT37; -.
DR BioMuta; CDC42BPG; -.
DR DMDM; 290457650; -.
DR EPD; Q6DT37; -.
DR jPOST; Q6DT37; -.
DR MassIVE; Q6DT37; -.
DR MaxQB; Q6DT37; -.
DR PaxDb; Q6DT37; -.
DR PeptideAtlas; Q6DT37; -.
DR PRIDE; Q6DT37; -.
DR ProteomicsDB; 66255; -.
DR Antibodypedia; 15651; 35 antibodies from 15 providers.
DR DNASU; 55561; -.
DR Ensembl; ENST00000342711.6; ENSP00000345133.5; ENSG00000171219.9.
DR GeneID; 55561; -.
DR KEGG; hsa:55561; -.
DR MANE-Select; ENST00000342711.6; ENSP00000345133.5; NM_017525.3; NP_059995.2.
DR UCSC; uc001obs.5; human.
DR CTD; 55561; -.
DR DisGeNET; 55561; -.
DR GeneCards; CDC42BPG; -.
DR HGNC; HGNC:29829; CDC42BPG.
DR HPA; ENSG00000171219; Tissue enhanced (esophagus, skin).
DR MIM; 613991; gene.
DR neXtProt; NX_Q6DT37; -.
DR OpenTargets; ENSG00000171219; -.
DR PharmGKB; PA134901493; -.
DR VEuPathDB; HostDB:ENSG00000171219; -.
DR eggNOG; KOG0612; Eukaryota.
DR GeneTree; ENSGT01030000234517; -.
DR HOGENOM; CLU_000288_140_3_1; -.
DR InParanoid; Q6DT37; -.
DR OMA; PWQHRIR; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; Q6DT37; -.
DR TreeFam; TF313551; -.
DR PathwayCommons; Q6DT37; -.
DR SignaLink; Q6DT37; -.
DR BioGRID-ORCS; 55561; 11 hits in 1104 CRISPR screens.
DR ChiTaRS; CDC42BPG; human.
DR GenomeRNAi; 55561; -.
DR Pharos; Q6DT37; Tchem.
DR PRO; PR:Q6DT37; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6DT37; protein.
DR Bgee; ENSG00000171219; Expressed in skin of abdomen and 96 other tissues.
DR Genevisible; Q6DT37; HS.
DR GO; GO:0031252; C:cell leading edge; IDA:UniProtKB.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA: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:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA: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; 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 SMART; SM00109; C1; 1.
DR SMART; SM00036; CNH; 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;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1551
FT /note="Serine/threonine-protein kinase MRCK gamma"
FT /id="PRO_0000086397"
FT DOMAIN 71..337
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:15194684"
FT DOMAIN 338..408
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 947..1066
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1092..1366
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT DOMAIN 1437..1450
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT ZN_FING 878..927
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 467..486
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 655..675
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 801..849
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 863..886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1442..1551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 406..678
FT /evidence="ECO:0000255"
FT COILED 730..802
FT /evidence="ECO:0000255"
FT COMPBIAS 1460..1474
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1510..1537
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:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:15194684"
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 1482
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 168
FT /note="P -> L (in dbSNP:rs34454471)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040840"
FT VARIANT 280
FT /note="S -> F (in a glioblastoma multiforme sample; somatic
FT mutation; dbSNP:rs770462360)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040841"
FT VARIANT 362
FT /note="T -> P (in dbSNP:rs55688429)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040842"
FT VARIANT 537
FT /note="A -> D (in dbSNP:rs34241745)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040843"
FT VARIANT 1135
FT /note="Q -> R (in dbSNP:rs3741395)"
FT /id="VAR_057105"
FT CONFLICT 628
FT /note="P -> R (in Ref. 1; AAT67172)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1551 AA; 172459 MW; A6D042D5D11318D7 CRC64;
MERRLRALEQ LARGEAGGCP GLDGLLDLLL ALHHELSSGP LRRERSVAQF LSWASPFVSK
VKELRLQRDD FEILKVIGRG AFGEVTVVRQ RDTGQIFAMK MLHKWEMLKR AETACFREER
DVLVKGDSRW VTTLHYAFQD EEYLYLVMDY YAGGDLLTLL SRFEDRLPPE LAQFYLAEMV
LAIHSLHQLG YVHRDVKPDN VLLDVNGHIR LADFGSCLRL NTNGMVDSSV AVGTPDYISP
EILQAMEEGK GHYGPQCDWW SLGVCAYELL FGETPFYAES LVETYGKIMN HEDHLQFPPD
VPDVPASAQD LIRQLLCRQE ERLGRGGLDD FRNHPFFEGV DWERLASSTA PYIPELRGPM
DTSNFDVDDD TLNHPGTLPP PSHGAFSGHH LPFVGFTYTS GSHSPESSSE AWAALERKLQ
CLEQEKVELS RKHQEALHAP TDHRELEQLR KEVQTLRDRL PEMLRDKASL SQTDGPPAGS
PGQDSDLRQE LDRLHRELAE GRAGLQAQEQ ELCRAQGQQE ELLQRLQEAQ EREAATASQT
RALSSQLEEA RAAQRELEAQ VSSLSRQVTQ LQGQWEQRLE ESSQAKTIHT ASETNGMGPP
EGGPQEAQLR KEVAALREQL EQAHSHRPSG KEEALCQLQE ENRRLSREQE RLEAELAQEQ
ESKQRLEGER RETESNWEAQ LADILSWVND EKVSRGYLQA LATKMAEELE SLRNVGTQTL
PARPLDHQWK ARRLQKMEAS ARLELQSALE AEIRAKQGLQ ERLTQVQEAQ LQAERRLQEA
EKQSQALQQE LAMLREELRA RGPVDTKPSN SLIPFLSFRS SEKDSAKDPG ISGEATRHGG
EPDLRPEGRR SLRMGAVFPR APTANTASTE GLPAKPGSHT LRPRSFPSPT KCLRCTSLML
GLGRQGLGCD ACGYFCHTTC APQAPPCPVP PDLLRTALGV HPETGTGTAY EGFLSVPRPS
GVRRGWQRVF AALSDSRLLL FDAPDLRLSP PSGALLQVLD LRDPQFSATP VLASDVIHAQ
SRDLPRIFRV TTSQLAVPPT TCTVLLLAES EGERERWLQV LGELQRLLLD ARPRPRPVYT
LKEAYDNGLP LLPHTLCAAI LDQDRLALGT EEGLFVIHLR SNDIFQVGEC RRVQQLTLSP
SAGLLVVLCG RGPSVRLFAL AELENIEVAG AKIPESRGCQ VLAAGSILQA RTPVLCVAVK
RQVLCYQLGP GPGPWQRRIR ELQAPATVQS LGLLGDRLCV GAAGGFALYP LLNEAAPLAL
GAGLVPEELP PSRGGLGEAL GAVELSLSEF LLLFTTAGIY VDGAGRKSRG HELLWPAAPM
GWGYAAPYLT VFSENSIDVF DVRRAEWVQT VPLKKVRPLN PEGSLFLYGT EKVRLTYLRN
QLAEKDEFDI PDLTDNSRRQ LFRTKSKRRF FFRVSEEQQK QQRREMLKDP FVRSKLISPP
TNFNHLVHVG PANGRPGARD KSPAPEEKGR VARGSGPQRP HSFSEALRRP ASMGSEGLGG
DADPMKRKPW TSLSSESVSC PQGSLSPATS LMQVSERPRS LPLSPELESS P
