MRCKB_HUMAN
ID MRCKB_HUMAN Reviewed; 1711 AA.
AC Q9Y5S2; A9JR72; Q2L7A5; Q86TJ1; Q9ULU5;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Serine/threonine-protein kinase MRCK beta;
DE EC=2.7.11.1;
DE AltName: Full=CDC42-binding protein kinase beta;
DE Short=CDC42BP-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:AAD37506.1};
GN Synonyms=KIAA1124 {ECO:0000312|EMBL:BAA86438.2};
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:AAD37506.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain {ECO:0000312|EMBL:AAD37506.1};
RX PubMed=10198171; DOI=10.1006/geno.1999.5769;
RA Moncrieff C.L., Bailey M.E., Morrison N., Johnson K.J.;
RT "Cloning and chromosomal localization of human Cdc42-binding protein kinase
RT beta.";
RL Genomics 57:297-300(1999).
RN [2] {ECO:0000312|EMBL:BAA86438.2}
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LYS-1203.
RC TISSUE=Brain {ECO:0000312|EMBL:BAA86438.2};
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis from
RT size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [3] {ECO:0000305}
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-1077.
RG NIEHS SNPs program;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAH47871.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-1203.
RC TISSUE=PNS {ECO:0000312|EMBL:AAH47871.1};
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1690, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH LURAP1
RP 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1690, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1690, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP 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 edge
RT controls cell migration.";
RL EMBO J. 30:665-678(2011).
RN [14]
RP FUNCTION IN PHOSPHORYLATION OF PPP1R12A AND MYL9/MLC2, AND ACTIVITY
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 kinase.";
RL FEBS Lett. 585:1260-1268(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1690 AND SER-1693, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1690, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-423; SER-1680; SER-1682 AND
RP SER-1686, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-671, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [19]
RP INTERACTION WITH STRP1; STRN3 AND SIKE1.
RX PubMed=25743393; DOI=10.1038/ncomms7449;
RA Lant B., Yu B., Goudreault M., Holmyard D., Knight J.D., Xu P., Zhao L.,
RA Chin K., Wallace E., Zhen M., Gingras A.C., Derry W.B.;
RT "CCM-3/STRIPAK promotes seamless tube extension through endocytic
RT recycling.";
RL Nat. Commun. 6:6449-6449(2015).
RN [20]
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=29162624; DOI=10.1083/jcb.201703044;
RA Gagliardi P.A., Somale D., Puliafito A., Chiaverina G., di Blasio L.,
RA Oneto M., Bianchini P., Bussolino F., Primo L.;
RT "MRCKalpha is activated by caspase cleavage to assemble an apical actin
RT ring for epithelial cell extrusion.";
RL J. Cell Biol. 217:231-249(2018).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 2-417 IN COMPLEXES WITH FASUDIL
RP AND TPCA-1, FUNCTION, SUBUNIT, AND CATALYTIC ACTIVITY.
RX PubMed=21949762; DOI=10.1371/journal.pone.0024825;
RA Heikkila T., Wheatley E., Crighton D., Schroder E., Boakes A., Kaye S.J.,
RA Mezna M., Pang L., Rushbrooke M., Turnbull A., Olson M.F.;
RT "Co-crystal structures of inhibitors with MRCKbeta, a key regulator of
RT tumor cell invasion.";
RL PLoS ONE 6:E24825-E24825(2011).
RN [22]
RP VARIANTS [LARGE SCALE ANALYSIS] GLU-500; GLN-555; GLN-671; TRP-876;
RP LYS-1315 AND TYR-1633.
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: 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 (PubMed:21457715, PubMed:21949762). In concert with MYO18A
CC and LURAP1, is involved in modulating lamellar actomyosin retrograde
CC flow that is crucial to cell protrusion and migration
CC (PubMed:18854160). Phosphorylates PPP1R12A (PubMed:21457715). In
CC concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the
CC lamellipodium resulting in its activation and subsequent
CC phosphorylation of CFL1 which is important for lamellipodial F-actin
CC regulation (By similarity). {ECO:0000250|UniProtKB:Q7TT50,
CC ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21457715,
CC ECO:0000269|PubMed:21949762}.
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:Q5VT25, ECO:0000269|PubMed:21949762};
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:Q5VT25,
CC ECO:0000269|PubMed:21949762};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q5VT25};
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). Inhibited by chelerythrine
CC chloride. {ECO:0000250, ECO:0000269|PubMed:21457715}.
CC -!- SUBUNIT: Homodimer and homotetramer via the coiled coil regions
CC (PubMed:21949762). Interacts tightly with GTP-bound but not GDP-bound
CC CDC42. Interacts with TJP1, when in the presence of catalytically
CC active CDC42 (By similarity). Forms a tripartite complex with MYO18A
CC and LURAP1 with the latter acting as an adapter connecting CDC42BPB and
CC MYO18A. LURAP1 binding results in activation of CDC42BPB by abolition
CC of its negative autoregulation (PubMed:18854160). Interacts with
CC STRIP1, STRN3 and SIKE1 (PubMed:25743393). Interacts with CPNE4 (via
CC VWFA domain). Interacts with LURAP1. Interacts (via AGC-kinase C-
CC terminal domain) with FAM89B/LRAP25 (via LRR repeat). Forms a
CC tripartite complex with FAM89B/LRAP25 and LIMK1 (By similarity).
CC {ECO:0000250|UniProtKB:Q7TT49, ECO:0000250|UniProtKB:Q7TT50,
CC ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21949762,
CC ECO:0000269|PubMed:25743393}.
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}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q3UU96}. Note=Displays a dispersed punctate
CC distribution and concentrates along the cell periphery, especially at
CC the leading edge and cell-cell junction. This concentration is PH-
CC domain dependent (By similarity). Detected at the leading edge of
CC migrating cells. Localization at the leading edge of migrating cells
CC requires interaction with catalytically active CDC42 (PubMed:21240187).
CC Localizes in the lamellipodium in a FAM89B/LRAP25-dependent manner (By
CC similarity). {ECO:0000250|UniProtKB:O54874,
CC ECO:0000250|UniProtKB:Q3UU96, ECO:0000269|PubMed:21240187}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined, with high levels
CC in heart, brain, placenta and lung. {ECO:0000269|PubMed:10198171}.
CC -!- PTM: Proteolytically cleaved by caspases upon apoptosis induction.
CC {ECO:0000269|PubMed:29162624}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. DMPK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH47871.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAA86438.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdc42bpb/";
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DR EMBL; AF128625; AAD37506.1; -; mRNA.
DR EMBL; AB032950; BAA86438.2; ALT_INIT; mRNA.
DR EMBL; DQ355971; ABC67469.1; -; Genomic_DNA.
DR EMBL; BC047871; AAH47871.1; ALT_SEQ; mRNA.
DR EMBL; BC155541; AAI55542.1; -; mRNA.
DR CCDS; CCDS9978.1; -.
DR RefSeq; NP_006026.3; NM_006035.3.
DR PDB; 3QFV; X-ray; 2.65 A; A/B=1-415.
DR PDB; 3TKU; X-ray; 2.15 A; A/B=2-417.
DR PDB; 4UAK; X-ray; 1.73 A; A=2-417.
DR PDB; 4UAL; X-ray; 1.71 A; A=2-417.
DR PDB; 5OTE; X-ray; 1.68 A; A=2-417.
DR PDB; 5OTF; X-ray; 2.00 A; A=2-417.
DR PDBsum; 3QFV; -.
DR PDBsum; 3TKU; -.
DR PDBsum; 4UAK; -.
DR PDBsum; 4UAL; -.
DR PDBsum; 5OTE; -.
DR PDBsum; 5OTF; -.
DR AlphaFoldDB; Q9Y5S2; -.
DR SMR; Q9Y5S2; -.
DR BioGRID; 114947; 90.
DR IntAct; Q9Y5S2; 27.
DR MINT; Q9Y5S2; -.
DR STRING; 9606.ENSP00000355237; -.
DR BindingDB; Q9Y5S2; -.
DR ChEMBL; CHEMBL5052; -.
DR DrugCentral; Q9Y5S2; -.
DR iPTMnet; Q9Y5S2; -.
DR MetOSite; Q9Y5S2; -.
DR PhosphoSitePlus; Q9Y5S2; -.
DR BioMuta; CDC42BPB; -.
DR DMDM; 92090617; -.
DR EPD; Q9Y5S2; -.
DR jPOST; Q9Y5S2; -.
DR MassIVE; Q9Y5S2; -.
DR MaxQB; Q9Y5S2; -.
DR PaxDb; Q9Y5S2; -.
DR PeptideAtlas; Q9Y5S2; -.
DR PRIDE; Q9Y5S2; -.
DR ProteomicsDB; 86490; -.
DR Antibodypedia; 14692; 178 antibodies from 28 providers.
DR DNASU; 9578; -.
DR Ensembl; ENST00000361246.7; ENSP00000355237.2; ENSG00000198752.11.
DR GeneID; 9578; -.
DR KEGG; hsa:9578; -.
DR MANE-Select; ENST00000361246.7; ENSP00000355237.2; NM_006035.4; NP_006026.3.
DR UCSC; uc001ymi.2; human.
DR CTD; 9578; -.
DR DisGeNET; 9578; -.
DR GeneCards; CDC42BPB; -.
DR HGNC; HGNC:1738; CDC42BPB.
DR HPA; ENSG00000198752; Low tissue specificity.
DR MIM; 614062; gene.
DR neXtProt; NX_Q9Y5S2; -.
DR OpenTargets; ENSG00000198752; -.
DR PharmGKB; PA26268; -.
DR VEuPathDB; HostDB:ENSG00000198752; -.
DR eggNOG; KOG0612; Eukaryota.
DR GeneTree; ENSGT01030000234517; -.
DR HOGENOM; CLU_000288_140_3_1; -.
DR InParanoid; Q9Y5S2; -.
DR OMA; CGRSHHV; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; Q9Y5S2; -.
DR TreeFam; TF313551; -.
DR PathwayCommons; Q9Y5S2; -.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR SignaLink; Q9Y5S2; -.
DR SIGNOR; Q9Y5S2; -.
DR BioGRID-ORCS; 9578; 12 hits in 1111 CRISPR screens.
DR ChiTaRS; CDC42BPB; human.
DR GenomeRNAi; 9578; -.
DR Pharos; Q9Y5S2; Tchem.
DR PRO; PR:Q9Y5S2; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9Y5S2; protein.
DR Bgee; ENSG00000198752; Expressed in stromal cell of endometrium and 184 other tissues.
DR ExpressionAtlas; Q9Y5S2; baseline and differential.
DR Genevisible; Q9Y5S2; HS.
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; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
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:0004672; F:protein kinase activity; IDA: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:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
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:0007010; P:cytoskeleton organization; TAS:ProtInc.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; TAS:ProtInc.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd00029; C1; 1.
DR CDD; cd05624; STKc_MRCK_beta; 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; IPR020454; DAG/PE-bd.
DR InterPro; IPR031597; KELK.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033232; MRCK_beta.
DR InterPro; IPR042718; MRCKB_STKc.
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:SF34; PTHR22988:SF34; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00780; CNH; 1.
DR Pfam; PF08826; DMPK_coil; 1.
DR Pfam; PF15796; KELK; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
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 3D-structure; ATP-binding; Cell junction; Cell membrane; Cell projection;
KW Coiled coil; Cytoplasm; Kinase; Magnesium; Membrane; Metal-binding;
KW Methylation; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1711
FT /note="Serine/threonine-protein kinase MRCK beta"
FT /id="PRO_0000086394"
FT DOMAIN 76..342
FT /note="Protein kinase"
FT /evidence="ECO:0000250|UniProtKB:Q5VT25,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 343..413
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 1095..1214
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1240..1513
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT DOMAIN 1583..1596
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT ZN_FING 1025..1075
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 461..484
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 969..1009
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1611..1711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 431..815
FT /evidence="ECO:0000255"
FT COILED 878..939
FT /evidence="ECO:0000255"
FT COMPBIAS 461..478
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 969..993
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1628..1657
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1660..1674
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 200
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P54265,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 82..90
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P54265,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q5VT25,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 221
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 233
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 239
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 423
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 671
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 954
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q7TT50"
FT MOD_RES 1680
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1682
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1686
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1690
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 1693
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VARIANT 500
FT /note="K -> E (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation; dbSNP:rs1158962067)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040834"
FT VARIANT 555
FT /note="R -> Q (in dbSNP:rs36001612)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040835"
FT VARIANT 671
FT /note="R -> Q (in dbSNP:rs55948035)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040836"
FT VARIANT 876
FT /note="R -> W (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs1595472741)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040837"
FT VARIANT 1077
FT /note="I -> V (in dbSNP:rs34822377)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_025847"
FT VARIANT 1203
FT /note="R -> K (in dbSNP:rs146298297)"
FT /evidence="ECO:0000269|PubMed:10574461,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_070886"
FT VARIANT 1315
FT /note="E -> K (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040838"
FT VARIANT 1633
FT /note="S -> Y (in dbSNP:rs56412851)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040839"
FT CONFLICT 1017
FT /note="A -> V (in Ref. 1; AAD37506)"
FT /evidence="ECO:0000305"
FT CONFLICT 1123
FT /note="D -> E (in Ref. 1; AAD37506)"
FT /evidence="ECO:0000305"
FT HELIX 3..20
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:3QFV"
FT HELIX 27..41
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 50..69
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 76..84
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 86..95
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 101..108
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 109..114
FT /evidence="ECO:0007829|PDB:5OTE"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 121..130
FT /evidence="ECO:0007829|PDB:5OTE"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 139..144
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 146..153
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 161..167
FT /evidence="ECO:0007829|PDB:5OTE"
FT TURN 168..170
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 174..193
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:5OTF"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:3QFV"
FT STRAND 231..235
FT /evidence="ECO:0007829|PDB:3TKU"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 245..250
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 255..258
FT /evidence="ECO:0007829|PDB:3TKU"
FT HELIX 261..276
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 286..294
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 296..299
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 311..318
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 330..333
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 334..337
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:5OTE"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:5OTE"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:4UAK"
FT HELIX 396..398
FT /evidence="ECO:0007829|PDB:5OTE"
FT STRAND 403..406
FT /evidence="ECO:0007829|PDB:3QFV"
FT STRAND 408..412
FT /evidence="ECO:0007829|PDB:3QFV"
SQ SEQUENCE 1711 AA; 194315 MW; 041A009E0273ABE0 CRC64;
MSAKVRLKKL EQLLLDGPWR NESALSVETL LDVLVCLYTE CSHSALRRDK YVAEFLEWAK
PFTQLVKEMQ LHREDFEIIK VIGRGAFGEV AVVKMKNTER IYAMKILNKW EMLKRAETAC
FREERDVLVN GDCQWITALH YAFQDENHLY LVMDYYVGGD LLTLLSKFED KLPEDMARFY
IGEMVLAIDS IHQLHYVHRD IKPDNVLLDV NGHIRLADFG SCLKMNDDGT VQSSVAVGTP
DYISPEILQA MEDGMGKYGP ECDWWSLGVC MYEMLYGETP FYAESLVETY GKIMNHEERF
QFPSHVTDVS EEAKDLIQRL ICSRERRLGQ NGIEDFKKHA FFEGLNWENI RNLEAPYIPD
VSSPSDTSNF DVDDDVLRNT EILPPGSHTG FSGLHLPFIG FTFTTESCFS DRGSLKSIMQ
SNTLTKDEDV QRDLEHSLQM EAYERRIRRL EQEKLELSRK LQESTQTVQS LHGSSRALSN
SNRDKEIKKL NEEIERLKNK IADSNRLERQ LEDTVALRQE REDSTQRLRG LEKQHRVVRQ
EKEELHKQLV EASERLKSQA KELKDAHQQR KLALQEFSEL NERMAELRAQ KQKVSRQLRD
KEEEMEVATQ KVDAMRQEMR RAEKLRKELE AQLDDAVAEA SKERKLREHS ENFCKQMESE
LEALKVKQGG RGAGATLEHQ QEISKIKSEL EKKVLFYEEE LVRREASHVL EVKNVKKEVH
DSESHQLALQ KEILMLKDKL EKSKRERHNE MEEAVGTIKD KYERERAMLF DENKKLTAEN
EKLCSFVDKL TAQNRQLEDE LQDLAAKKES VAHWEAQIAE IIQWVSDEKD ARGYLQALAS
KMTEELEALR SSSLGSRTLD PLWKVRRSQK LDMSARLELQ SALEAEIRAK QLVQEELRKV
KDANLTLESK LKDSEAKNRE LLEEMEILKK KMEEKFRADT GLKLPDFQDS IFEYFNTAPL
AHDLTFRTSS ASEQETQAPK PEASPSMSVA ASEQQEDMAR PPQRPSAVPL PTTQALALAG
PKPKAHQFSI KSFSSPTQCS HCTSLMVGLI RQGYACEVCS FACHVSCKDG APQVCPIPPE
QSKRPLGVDV QRGIGTAYKG HVKVPKPTGV KKGWQRAYAV VCDCKLFLYD LPEGKSTQPG
VIASQVLDLR DDEFSVSSVL ASDVIHATRR DIPCIFRVTA SLLGAPSKTS SLLILTENEN
EKRKWVGILE GLQSILHKNR LRNQVVHVPL EAYDSSLPLI KAILTAAIVD ADRIAVGLEE
GLYVIEVTRD VIVRAADCKK VHQIELAPRE KIVILLCGRN HHVHLYPWSS LDGAEGSFDI
KLPETKGCQL MATATLKRNS GTCLFVAVKR LILCYEIQRT KPFHRKFNEI VAPGSVQCLA
VLRDRLCVGY PSGFCLLSIQ GDGQPLNLVN PNDPSLAFLS QQSFDALCAV ELESEEYLLC
FSHMGLYVDP QGRRARAQEL MWPAAPVACS CSPTHVTVYS EYGVDVFDVR TMEWVQTIGL
RRIRPLNSEG TLNLLNCEPP RLIYFKSKFS GAVLNVPDTS DNSKKQMLRT RSKRRFVFKV
PEEERLQQRR EMLRDPELRS KMISNPTNFN HVAHMGPGDG MQVLMDLPLS AVPPSQEERP
GPAPTNLARQ PPSRNKPYIS WPSSGGSEPS VTVPLRSMSD PDQDFDKEPD SDSTKHSTPS
NSSNPSGPPS PNSPHRSQLP LEGLEQPACD T
