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Database: UniProt
Entry: Q7TT49
LinkDB: Q7TT49
Original site: Q7TT49 
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   01-OCT-2014, entry version 106.
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 {ECO:0000312|EMBL:AAP34403.1};
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] {ECO:0000305, ECO:0000312|EMBL:AAC02942.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Brain {ECO:0000312|EMBL:AAC02942.1};
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] {ECO:0000312|EMBL:AAP34403.1}
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       {ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21240187,
CC       ECO:0000269|PubMed:21457715}.
CC   -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC       {ECO:0000250|UniProtKB:Q5VT25}.
CC   -!- COFACTOR: Magnesium. {ECO:0000250|UniProtKB:Q5VT25}.
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. {ECO:0000250,
CC       ECO:0000269|PubMed:21457715}.
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. {ECO:0000250, ECO:0000269|PubMed:18854160,
CC       ECO:0000269|PubMed:21240187}.
CC   -!- INTERACTION:
CC       D4A8G3:Lurap1; NbExp=4; IntAct=EBI-692673, EBI-2015467;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC       {ECO:0000269|PubMed:21240187}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:21240187}; Cytoplasmic side
CC       {ECO:0000269|PubMed:21240187}. Cell junction
CC       {ECO:0000269|PubMed:21240187}. Note=Displays a dispersed punctate
CC       distribution and concentrates along the cell periphery, especially
CC       at the leading edge and cell-cell junction. This concentration is
CC       PH-domain dependent (By similarity). Detected at the leading edge
CC       of migrating and wounded cells; this localization requires the
CC       presence of catalytically active CDC42. {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues examined with highest
CC       levels in lung and kidney. {ECO:0000269|PubMed:9418861}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC       protein kinase family. DMPK subfamily. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 CNH domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00795}.
CC   -!- SIMILARITY: Contains 1 CRIB domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00057}.
CC   -!- SIMILARITY: Contains 1 PH domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00145}.
CC   -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger.
CC       {ECO:0000255|PROSITE-ProRule:PRU00226}.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC02942.1; Type=Frameshift; Positions=1613, 1633, 1680; Evidence={ECO:0000305};
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DR   EMBL; AF021936; AAC02942.1; ALT_FRAME; mRNA.
DR   EMBL; AY277590; AAP34403.1; -; mRNA.
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; 6.
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; ENSGT00750000117511; -.
DR   HOGENOM; HOG000294133; -.
DR   HOVERGEN; HBG055933; -.
DR   InParanoid; Q7TT49; -.
DR   KO; K16307; -.
DR   OMA; SCFSDRG; -.
DR   OrthoDB; EOG7F511X; -.
DR   PhylomeDB; Q7TT49; -.
DR   TreeFam; TF313551; -.
DR   NextBio; 618097; -.
DR   PRO; PR:Q7TT49; -.
DR   Genevestigator; Q7TT49; -.
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:0005515; F:protein binding; IPI:IntAct.
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:0030036; P:actin cytoskeleton organization; IMP:RGD.
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   GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR   InterPro; IPR000961; AGC-kinase_C.
DR   InterPro; IPR001180; Citron.
DR   InterPro; IPR000095; CRIB_dom.
DR   InterPro; IPR020454; DAG/PE-bd.
DR   InterPro; IPR011009; Kinase-like_dom.
DR   InterPro; IPR014930; Myotonic_dystrophy_kinase_coil.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
DR   InterPro; IPR000719; Prot_kinase_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   Pfam; PF00130; C1_1; 1.
DR   Pfam; PF00780; CNH; 1.
DR   Pfam; PF08826; DMPK_coil; 1.
DR   Pfam; PF00069; Pkinase; 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; SSF56112; 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                                {ECO:0000250|UniProtKB:Q5VT25,
FT                                ECO:0000255|PROSITE-ProRule:PRU00159}.
FT   DOMAIN      343    413       AGC-kinase C-terminal.
FT   DOMAIN     1096   1215       PH. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00145}.
FT   DOMAIN     1241   1515       CNH. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00795}.
FT   DOMAIN     1585   1598       CRIB. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00057}.
FT   NP_BIND      82     90       ATP. {ECO:0000250|UniProtKB:P54265,
FT                                ECO:0000255|PROSITE-ProRule:PRU00159}.
FT   ZN_FING    1026   1076       Phorbol-ester/DAG-type.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00226}.
FT   COILED      434    649       {ECO:0000255}.
FT   COILED      681    815       {ECO:0000255}.
FT   COILED      882    939       {ECO:0000255}.
FT   ACT_SITE    200    200       Proton acceptor.
FT                                {ECO:0000250|UniProtKB:P54265,
FT                                ECO:0000255|PROSITE-ProRule:PRU00159,
FT                                ECO:0000255|PROSITE-ProRule:PRU10027}.
FT   BINDING     105    105       ATP. {ECO:0000250|UniProtKB:Q5VT25,
FT                                ECO:0000255|PROSITE-ProRule:PRU00159}.
FT   MOD_RES     221    221       Phosphoserine; by autocatalysis.
FT                                {ECO:0000250}.
FT   MOD_RES     233    233       Phosphoserine; by autocatalysis.
FT                                {ECO:0000250}.
FT   MOD_RES     239    239       Phosphothreonine; by autocatalysis.
FT                                {ECO:0000250}.
FT   MOD_RES     954    954       Phosphotyrosine. {ECO:0000250}.
FT   MOD_RES    1692   1692       Phosphoserine. {ECO:0000250}.
FT   MOD_RES    1695   1695       Phosphoserine. {ECO:0000250}.
FT   MUTAGEN     952    952       F->Q: Abolishes interaction with TJP1;
FT                                when associated with Q-954.
FT                                {ECO:0000269|PubMed:21240187}.
FT   MUTAGEN     954    954       Y->Q: Abolishes interaction with TJP1;
FT                                when associated with Q-952.
FT                                {ECO:0000269|PubMed:21240187}.
FT   MUTAGEN     964    964       L->Q: Abolishes interaction with TJP1;
FT                                when associated with Q-966.
FT                                {ECO:0000269|PubMed:21240187}.
FT   MUTAGEN     966    966       F->Q: Abolishes interaction with TJP1;
FT                                when associated with Q-964.
FT                                {ECO:0000269|PubMed:21240187}.
FT   CONFLICT    706    706       A -> R (in Ref. 1; AAC02942).
FT                                {ECO:0000305}.
FT   CONFLICT   1523   1523       R -> C (in Ref. 1; AAC02942).
FT                                {ECO:0000305}.
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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