ID MRCKB_RAT Reviewed; 1713 AA.
AC Q7TT49; O54875;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-APR-2013, entry version 95.
DE RecName: Full=Serine/threonine-protein kinase MRCK beta;
DE EC=2.7.11.1;
DE AltName: Full=CDC42-binding protein kinase beta;
DE AltName: Full=DMPK-like beta;
DE AltName: Full=Myotonic dystrophy kinase-related CDC42-binding kinase beta;
DE Short=MRCK beta;
DE Short=Myotonic dystrophy protein kinase-like beta;
GN Name=Cdc42bpb;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9418861;
RA Leung T., Chen X.-Q., Tan I., Manser E., Lim L.;
RT "Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a
RT Cdc42 effector in promoting cytoskeletal reorganization.";
RL Mol. Cell. Biol. 18:130-140(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Huang C.Q., Wu S.L., Cheng Z.;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND INTERACTION WITH LURAP1 AND MYO18A.
RX PubMed=18854160; DOI=10.1016/j.cell.2008.09.018;
RA Tan I., Yong J., Dong J.M., Lim L., Leung T.;
RT "A tripartite complex containing MRCK modulates lamellar actomyosin
RT retrograde flow.";
RL Cell 135:123-136(2008).
RN [4]
RP FUNCTION, INTERACTION WITH TJP1, MUTAGENESIS OF PHE-952; TYR-954;
RP LEU-964 AND PHE-966, AND SUBCELLULAR LOCATION.
RX PubMed=21240187; DOI=10.1038/emboj.2010.353;
RA Huo L., Wen W., Wang R., Kam C., Xia J., Feng W., Zhang M.;
RT "Cdc42-dependent formation of the ZO-1/MRCKbeta complex at the leading
RT edge controls cell migration.";
RL EMBO J. 30:665-678(2011).
RN [5]
RP FUNCTION IN PHOSPHORYLATION OF PPP1R12A AND MYL9/MLC2, AND ENZYME
RP REGULATION.
RX PubMed=21457715; DOI=10.1016/j.febslet.2011.03.054;
RA Tan I., Lai J., Yong J., Li S.F., Leung T.;
RT "Chelerythrine perturbs lamellar actomyosin filaments by selective
RT inhibition of myotonic dystrophy kinase-related Cdc42-binding
RT kinase.";
RL FEBS Lett. 585:1260-1268(2011).
CC -!- FUNCTION: Serine/threonine-protein kinase which is an important
CC downstream effector of CDC42 and plays a role in the regulation of
CC cytoskeleton reorganization and cell migration. Regulates actin
CC cytoskeletal reorganization via phosphorylation of PPP1R12C and
CC MYL9/MLC2. In concert with MYO18A and LURAP1, is involved in
CC modulating lamellar actomyosin retrograde flow that is crucial to
CC cell protrusion and migration. Phosphorylates PPP1R12A.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium (By similarity).
CC -!- ENZYME REGULATION: Maintained in an inactive, closed conformation
CC by an interaction between the kinase domain and the negative
CC autoregulatory C-terminal coiled-coil region. Agonist binding to
CC the phorbol ester binding site disrupts this, releasing the kinase
CC domain to allow N-terminus-mediated dimerization and kinase
CC activation by transautophosphorylation (By similarity). Inhibited
CC by chelerythrine chloride.
CC -!- SUBUNIT: Homodimer and homotetramer via the coiled coil regions.
CC Interacts tightly with GTP-bound but not GDP-bound CDC42 (By
CC similarity). Interacts with TJP1; this interaction requires the
CC presence of catalytically active CDC42. Forms a tripartite complex
CC with MYO18A and LURAP1 with the latter acting as an adapter
CC connecting CDC42BPB and MYO18A. LURAP1 binding results in
CC activation of CDC42BPB by abolition of its negative
CC autoregulation.
CC -!- INTERACTION:
CC D4A8G3:Lurap1; NbExp=4; IntAct=EBI-692673, EBI-2015467;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cell junction.
CC Note=Displays a dispersed punctate distribution and concentrates
CC along the cell periphery, especially at the leading edge and cell-
CC cell junction. This concentration is PH-domain dependent (By
CC similarity). Detected at the leading edge of migrating and wounded
CC cells; this localization requires the presence of catalytically
CC active CDC42.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined with highest
CC levels in lung and kidney.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. DMPK subfamily.
CC -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
CC -!- SIMILARITY: Contains 1 CNH domain.
CC -!- SIMILARITY: Contains 1 CRIB domain.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC02942.1; Type=Frameshift; Positions=1613, 1633, 1680;
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DR EMBL; AF021936; AAC02942.1; ALT_FRAME; mRNA.
DR EMBL; AY277590; AAP34403.1; -; mRNA.
DR IPI; IPI00392875; -.
DR PIR; T14050; T14050.
DR RefSeq; NP_446072.2; NM_053620.3.
DR UniGene; Rn.105815; -.
DR ProteinModelPortal; Q7TT49; -.
DR SMR; Q7TT49; 11-414.
DR IntAct; Q7TT49; 3.
DR PhosphoSite; Q7TT49; -.
DR PaxDb; Q7TT49; -.
DR PRIDE; Q7TT49; -.
DR Ensembl; ENSRNOT00000039059; ENSRNOP00000036487; ENSRNOG00000009675.
DR GeneID; 113960; -.
DR KEGG; rno:113960; -.
DR UCSC; RGD:621753; rat.
DR CTD; 9578; -.
DR RGD; 621753; Cdc42bpb.
DR eggNOG; COG0515; -.
DR GeneTree; ENSGT00690000101983; -.
DR HOGENOM; HOG000294133; -.
DR HOVERGEN; HBG055933; -.
DR InParanoid; Q7TT49; -.
DR KO; K16307; -.
DR OMA; TTESCFS; -.
DR OrthoDB; EOG4640B1; -.
DR NextBio; 618097; -.
DR Genevestigator; Q7TT49; -.
DR GermOnline; ENSRNOG00000009675; Rattus norvegicus.
DR GO; GO:0042641; C:actomyosin; IDA:UniProtKB.
DR GO; GO:0031252; C:cell leading edge; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0017048; F:Rho GTPase binding; IDA:RGD.
DR GO; GO:0005083; F:small GTPase regulator activity; IEA:InterPro.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0031032; P:actomyosin structure organization; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR001180; Citron.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR014930; Myotonic_dystrophy_kinase_coil.
DR InterPro; IPR000095; PAK_box_Rho-bd.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR001849; Pleckstrin_homology.
DR InterPro; IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
DR InterPro; IPR000719; Prot_kinase_cat_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR026611; Ser/Thr_kinase_MRCK.
DR PANTHER; PTHR22988:SF2; PTHR22988:SF2; 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 PRINTS; PR00008; DAGPEDOMAIN.
DR ProDom; PD011252; Myotonic_dystrophy_kinase_coil; 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; Kinase_like; 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; Cell junction; Cell membrane; Coiled coil;
KW Complete proteome; Cytoplasm; Kinase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1 1713 Serine/threonine-protein kinase MRCK
FT beta.
FT /FTId=PRO_0000086396.
FT DOMAIN 76 342 Protein kinase.
FT DOMAIN 343 413 AGC-kinase C-terminal.
FT DOMAIN 1096 1215 PH.
FT DOMAIN 1241 1515 CNH.
FT DOMAIN 1585 1598 CRIB.
FT NP_BIND 82 90 ATP (By similarity).
FT ZN_FING 1026 1076 Phorbol-ester/DAG-type.
FT COILED 434 649 Potential.
FT COILED 681 815 Potential.
FT COILED 882 939 Potential.
FT ACT_SITE 200 200 Proton acceptor (By similarity).
FT BINDING 105 105 ATP (By similarity).
FT MOD_RES 221 221 Phosphoserine; by autocatalysis (By
FT similarity).
FT MOD_RES 233 233 Phosphoserine; by autocatalysis (By
FT similarity).
FT MOD_RES 239 239 Phosphothreonine; by autocatalysis (By
FT similarity).
FT MOD_RES 954 954 Phosphotyrosine (By similarity).
FT MOD_RES 1692 1692 Phosphoserine (By similarity).
FT MOD_RES 1695 1695 Phosphoserine (By similarity).
FT MUTAGEN 952 952 F->Q: Abolishes interaction with TJP1;
FT when associated with Q-954.
FT MUTAGEN 954 954 Y->Q: Abolishes interaction with TJP1;
FT when associated with Q-952.
FT MUTAGEN 964 964 L->Q: Abolishes interaction with TJP1;
FT when associated with Q-966.
FT MUTAGEN 966 966 F->Q: Abolishes interaction with TJP1;
FT when associated with Q-964.
FT CONFLICT 706 706 A -> R (in Ref. 1; AAC02942).
FT CONFLICT 1523 1523 R -> C (in Ref. 1; AAC02942).
SQ SEQUENCE 1713 AA; 194888 MW; 80C999262C96DAA6 CRC64;
MSAKVRLKKL EQLLLDGPWR NESSLSVETL LDVLVCLYTE CSHSALRRDK YVAEFLEWAK
PFTQLVKDMQ LHREDFEIIK VIGRGAFGEV AVVKMKNTER IYAMKILNKW EMLKRAETAC
FREERDVLVN GDCQWITALH YAFQDENYLY LVMDYYVGGD LLTLLSKFED KLPEDMARFY
IGEMVLAIDS IHQLHYVHRD IKPDNVLLDV NGHIRLADFG SCLKMNDDGT VQSSVAVGTP
DYISPEILQA MEDGMGKYGP ECDWWSLGVC MYEMLYGETP FYAESLVETY GKIMNHEERF
QFPSHVTDVS EEAKDLIQRL ICSRERRLGQ NGIEDFKKHA FFEGLNWENI RNLEAPYIPD
VSSPSDTSNF DVDDDVLRNI EILPPGSHTG FSGLHLPFIG FTFTTESCFS DRGSLKSMIQ
SNTLTKDEDV QRDLENSLQI EAYERRIRRL EQEKLELSRK LQESTQTVQS LHGSTRALGN
SNRDKEIKRL NEELERMKSK MADSNRLERQ LEDTVTLRQE HEDSTQRLKG LEKQYRLARQ
EKEELHKQLV EASERLKSQT KELKDAHQQR KRALQEFSEL NERMAELRSQ KQKVSRQLRD
KEEEMEVAMQ KIDSMRQDIR KSEKSRKELE ARLEDAVAEA SKERKLREHS ESFSKQMERE
LETLKVKQGG RGPGATLEHQ QEISKIRSEL EKKVLFYEEE LVRREASHVL EVKNVKKEVH
ESESHQLALQ KEVLMLKDKL EKSKRERHSE MEEAIGAMKD KYERERAMLF DENKKLTAEN
EKLCSFVDKL TAQNRQLEDE LQDLASKKES VAHWEAQIAE IIQWVSDEKD ARGYLQALAS
KMTEELETLR SSSLGSRTLD PLWKVRRSQK LDMSARLELQ SALEAEIRAK QLVHEELRKV
KDTSLAFESK LKESEAKNRE LLEEMQSLKK RMEEKFRADT GLKLPDFQDP IFEYFNTAPL
AHDLTFRTSS ASDQETQASK LDLSPSVSVA TSTEQQEDAA RSQQRPSTVP LPNTQALAMA
GPKPKAHQFS IKSFPSPTQC SHCTSLMVGL IRQGYACEVC AFSCHVSCKD SAPQVCPIPP
EQSKRPLGVD VQRGIGTAYK GYVKVPKPTG VKKGWQRAYA VVCDCKLFLY DLPEGKSTQP
GVIASQVLDL RDDEFAVSSV LASDVIHATR RDIPCIFRVT ASLLGSPSKT SSLLILTENE
NEKRKWVGIL EGLQAILHKN RLRSQVVHVA QEAYDSSLPL IKTVLAAAIV DGDRIAVGLE
EGLYVIELTR DVIVRAADCK KVYQIELAPK EKLILLLCGR NHHVHLYPWT SFDGAEASNF
DIKLPETKGC QLIATGTLRK SSSTCLFVAV KRLVLCYEIQ RTKPFHRKFN EIVAPGHVQW
MAMFKDRLCV GYPSGFSLLS IQGDGQPLDL VNPADPSLAF LSQQSFDALC AVELKSEEYL
LCFSHMGLYV DPQGRRSRTQ ELMWPAAPVA CSCSSSHVTV YSEYGVDVFD VRTMEWVQTI
GLRRIRPLNS DGSLNLLGCE PPRLIYFKNK FSGTVLNVPD TSDNSKKQML RTRSKRRFVF
KVPEEERLQQ RREMLRDPEL RSKMISNPTN FNHVAHMGPG DGMQVLMDLP LSAAPTAQEE
KQGPAPTGLP RQLPSRNKPY VSWPSSGGSE PGVPVPLRSM SDPDQDFDKE PDSDSTKHST
PSNSSNPSGP PSPNSPHRSQ LPLEGLDQPA CDA
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