ID MRCKA_HUMAN Reviewed; 1732 AA.
AC Q5VT25; O75039; Q59GZ1; Q5H9N9; Q5T797; Q5VT26; Q5VT27; Q86XX2; Q86XX3;
AC Q99646;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 27-MAR-2024, entry version 177.
DE RecName: Full=Serine/threonine-protein kinase MRCK alpha;
DE EC=2.7.11.1 {ECO:0000269|PubMed:29162624};
DE AltName: Full=CDC42-binding protein kinase alpha;
DE AltName: Full=DMPK-like alpha;
DE AltName: Full=Myotonic dystrophy kinase-related CDC42-binding kinase alpha;
DE Short=MRCK alpha;
DE Short=Myotonic dystrophy protein kinase-like alpha;
GN Name=CDC42BPA {ECO:0000312|EMBL:CAH71336.1}; Synonyms=KIAA0451;
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:CAD57746.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5), AND FUNCTION.
RC TISSUE=Colon {ECO:0000312|EMBL:CAD57746.1};
RX PubMed=15723050; DOI=10.1038/ncb1230;
RA Wilkinson S., Paterson H.F., Marshall C.J.;
RT "Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and
RT cell invasion.";
RL Nat. Cell Biol. 7:255-261(2005).
RN [2] {ECO:0000305, ECO:0000312|EMBL:CAD57745.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT VAL-1712.
RC TISSUE=Brain {ECO:0000312|EMBL:CAD57745.1};
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS ILE-1317
RP AND VAL-1712.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAB37126.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-496, FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Mammary gland {ECO:0000269|PubMed:9092543};
RX PubMed=9092543; DOI=10.1074/jbc.272.15.10013;
RA Zhao Y., Loyer P., Li H., Valentine V., Kidd V., Kraft A.S.;
RT "Cloning and chromosomal location of a novel member of the myotonic
RT dystrophy family of protein kinases.";
RL J. Biol. Chem. 272:10013-10020(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 799-1732 (ISOFORM 6), AND VARIANT
RP VAL-1712.
RC TISSUE=Brain;
RX PubMed=9455484; DOI=10.1093/dnares/4.5.345;
RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D.,
RA Nomura N., Ohara O.;
RT "Characterization of cDNA clones in size-fractionated cDNA libraries from
RT human brain.";
RL DNA Res. 4:345-349(1997).
RN [7] {ECO:0000305, ECO:0000312|EMBL:CAD57745.1}
RP SEQUENCE REVISION.
RA Ohara O.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [8] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1521-1644, FUNCTION, INTERACTION WITH CDC42,
RP AND MUTAGENESIS OF HIS-1579 AND HIS-1582.
RC TISSUE=Brain {ECO:0000269|PubMed:9418861};
RX PubMed=9418861; DOI=10.1128/mcb.18.1.130;
RA Leung T., Chen X.-Q., Tan I., Manser E., Lim L.;
RT "Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42
RT effector in promoting cytoskeletal reorganization.";
RL Mol. Cell. Biol. 18:130-140(1998).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF PPP1R12C.
RX PubMed=11399775; DOI=10.1074/jbc.m102615200;
RA Tan I., Ng C.H., Lim L., Leung T.;
RT "Phosphorylation of a novel myosin binding subunit of protein phosphatase 1
RT reveals a conserved mechanism in the regulation of actin cytoskeleton.";
RL J. Biol. Chem. 276:21209-21216(2001).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF LIMK1 AND LIMK2.
RX PubMed=11340065; DOI=10.1074/jbc.c100196200;
RA Sumi T., Matsumoto K., Shibuya A., Nakamura T.;
RT "Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-
RT binding kinase alpha.";
RL J. Biol. Chem. 276:23092-23096(2001).
RN [11] {ECO:0000305}
RP ACTIVITY REGULATION, OLIGOMERIZATION, PHOSPHORYLATION AT SER-222; SER-234
RP AND THR-240, AND MUTAGENESIS OF LYS-106; SER-222; SER-234; THR-240 AND
RP THR-403.
RX PubMed=11283256; DOI=10.1128/mcb.21.8.2767-2778.2001;
RA Tan I., Seow K.T., Lim L., Leung T.;
RT "Intermolecular and intramolecular interactions regulate catalytic activity
RT of myotonic dystrophy kinase-related Cdc42-binding kinase alpha.";
RL Mol. Cell. Biol. 21:2767-2778(2001).
RN [12]
RP ALTERNATIVE SPLICING.
RX PubMed=12568720; DOI=10.1016/s0378-1119(02)01185-x;
RA Tan I., Cheong A., Lim L., Leung T.;
RT "Genomic organization of human myotonic dystrophy kinase-related Cdc42-
RT binding kinase alpha reveals multiple alternative splicing and functional
RT diversity.";
RL Gene 304:107-115(2003).
RN [13]
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1545; SER-1719 AND SER-1721,
RP AND 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 [15]
RP FUNCTION, AND INDUCTION.
RX PubMed=20188707; DOI=10.1016/j.bbrc.2010.02.148;
RA Cmejla R., Ptackova P., Petrak J., Savvulidi F., Cerny J., Sebesta O.,
RA Vyoral D.;
RT "Human MRCKalpha is regulated by cellular iron levels and interferes with
RT transferrin iron uptake.";
RL Biochem. Biophys. Res. Commun. 395:163-167(2010).
RN [16]
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 [17]
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1651, AND IDENTIFICATION BY
RP 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1611; SER-1613; SER-1629;
RP SER-1651; SER-1664 AND SER-1721, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1669 AND SER-1693, AND
RP 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 [21]
RP FUNCTION, CATALYTIC ACTIVITY, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF
RP ASP-478 AND ASP-984.
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 [22]
RP VARIANTS [LARGE SCALE ANALYSIS] LYS-50; MET-231; THR-537; MET-780; CYS-790;
RP THR-1148; HIS-1211; ILE-1317; LYS-1418; VAL-1469 AND ALA-1618.
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 (PubMed:15723050,
CC PubMed:9418861, PubMed:9092543). Regulates actin cytoskeletal
CC reorganization via phosphorylation of PPP1R12C and MYL9/MLC2
CC (PubMed:21457715). In concert with MYO18A and LURAP1, is involved in
CC modulating lamellar actomyosin retrograde flow that is crucial to cell
CC protrusion and migration (PubMed:18854160). Phosphorylates: PPP1R12A,
CC LIMK1 and LIMK2 (PubMed:11340065, PubMed:11399775). May play a role in
CC TFRC-mediated iron uptake (PubMed:20188707). In concert with
CC FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium
CC resulting in its activation and subsequent phosphorylation of CFL1
CC which is important for lamellipodial F-actin regulation (By
CC similarity). Triggers the formation of an extrusion apical actin ring
CC required for epithelial extrusion of apoptotic cells (PubMed:29162624).
CC {ECO:0000250|UniProtKB:Q3UU96, ECO:0000269|PubMed:11340065,
CC ECO:0000269|PubMed:11399775, ECO:0000269|PubMed:15723050,
CC ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:20188707,
CC ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:29162624,
CC ECO:0000269|PubMed:9092543, ECO:0000269|PubMed:9418861}.
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:9092543};
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:29162624,
CC ECO:0000269|PubMed:9092543};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:9092543};
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. Inhibited by chelerythrine chloride.
CC {ECO:0000269|PubMed:11283256, ECO:0000269|PubMed:21457715}.
CC -!- SUBUNIT: Homodimer and homotetramer via the coiled coil regions
CC (PubMed:11283256). Interacts tightly with GTP-bound but not GDP-bound
CC CDC42 (PubMed:9418861). Forms a tripartite complex with MYO18A and
CC LURAP1 with the latter acting as an adapter connecting CDC42BPA and
CC MYO18A. LURAP1 binding results in activation of CDC42BPA by abolition
CC of its negative autoregulation (PubMed:18854160). Interacts with
CC LURAP1. Interacts (via AGC-kinase C-terminal domain) with FAM89B/LRAP25
CC (via LRR repeat). Forms a tripartite complex with FAM89B/LRAP25 and
CC LIMK1 (By similarity). {ECO:0000250|UniProtKB:Q3UU96,
CC ECO:0000269|PubMed:11283256, ECO:0000269|PubMed:18854160,
CC ECO:0000269|PubMed:9418861}.
CC -!- INTERACTION:
CC Q5VT25; P60953: CDC42; NbExp=5; IntAct=EBI-689171, EBI-81752;
CC Q5VT25; Q5VT25: CDC42BPA; NbExp=9; IntAct=EBI-689171, EBI-689171;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O54874}. Cell
CC projection, lamellipodium {ECO:0000250|UniProtKB:Q3UU96}. Note=Displays
CC a dispersed punctate distribution and concentrates along the cell
CC periphery, especially at the leading edge and cell-cell junction. This
CC concentration is PH-domain dependent. Localizes in the lamellipodium in
CC a FAM89B/LRAP25-dependent manner. {ECO:0000250|UniProtKB:O54874,
CC ECO:0000250|UniProtKB:Q3UU96}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=Additional isoforms seem to exist. They arise due to a two
CC alternate splice sites, the first site involves splicing of exons
CC 21-24 while the second site involves exons 36-40.;
CC Name=1 {ECO:0000305};
CC IsoId=Q5VT25-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=Q5VT25-2; Sequence=VSP_051861, VSP_051863;
CC Name=3 {ECO:0000269|PubMed:15723050};
CC IsoId=Q5VT25-3; Sequence=VSP_051859, VSP_051860;
CC Name=4 {ECO:0000269|PubMed:16710414};
CC IsoId=Q5VT25-4; Sequence=VSP_051862;
CC Name=5 {ECO:0000269|PubMed:15723050};
CC IsoId=Q5VT25-5; Sequence=VSP_051860;
CC Name=6;
CC IsoId=Q5VT25-6; Sequence=VSP_051860, VSP_035286;
CC -!- TISSUE SPECIFICITY: Abundant in the heart, brain, skeletal muscle,
CC kidney, and pancreas, with little or no expression in the lung and
CC liver. {ECO:0000269|PubMed:9092543}.
CC -!- INDUCTION: Regulated by cellular iron levels.
CC {ECO:0000269|PubMed:20188707}.
CC -!- PTM: Proteolytically cleaved by caspases upon apoptosis induction. The
CC cleavage at Asp-478 by CASP3 increases its kinase activity (in vitro).
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=BAD92205.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ518975; CAD57745.1; -; mRNA.
DR EMBL; AJ518976; CAD57746.1; -; mRNA.
DR EMBL; AB208968; BAD92205.1; ALT_INIT; mRNA.
DR EMBL; CR933723; CAI46252.1; -; mRNA.
DR EMBL; AL353689; CAI19113.1; -; Genomic_DNA.
DR EMBL; AL451047; CAH71184.1; -; Genomic_DNA.
DR EMBL; AL353689; CAH71184.1; JOINED; Genomic_DNA.
DR EMBL; AL627308; CAH71184.1; JOINED; Genomic_DNA.
DR EMBL; AL451047; CAH71185.1; -; Genomic_DNA.
DR EMBL; AL627308; CAH71185.1; JOINED; Genomic_DNA.
DR EMBL; AL353689; CAH71185.1; JOINED; Genomic_DNA.
DR EMBL; AL627308; CAH71336.1; -; Genomic_DNA.
DR EMBL; AL353689; CAH71336.1; JOINED; Genomic_DNA.
DR EMBL; AL451047; CAH71336.1; JOINED; Genomic_DNA.
DR EMBL; AL627308; CAH71337.1; -; Genomic_DNA.
DR EMBL; AL353689; CAH71337.1; JOINED; Genomic_DNA.
DR EMBL; AL451047; CAH71337.1; JOINED; Genomic_DNA.
DR EMBL; AL353689; CAI19108.1; -; Genomic_DNA.
DR EMBL; AL451047; CAI19108.1; JOINED; Genomic_DNA.
DR EMBL; AL627308; CAI19108.1; JOINED; Genomic_DNA.
DR EMBL; AL451047; CAH71183.1; -; Genomic_DNA.
DR EMBL; AL353689; CAH71183.1; JOINED; Genomic_DNA.
DR EMBL; AL627308; CAH71183.1; JOINED; Genomic_DNA.
DR EMBL; AL627308; CAH71338.1; -; Genomic_DNA.
DR EMBL; AL353689; CAH71338.1; JOINED; Genomic_DNA.
DR EMBL; AL451047; CAH71338.1; JOINED; Genomic_DNA.
DR EMBL; AL353689; CAI19109.1; -; Genomic_DNA.
DR EMBL; AL627308; CAI19109.1; JOINED; Genomic_DNA.
DR EMBL; AL451047; CAI19109.1; JOINED; Genomic_DNA.
DR EMBL; AL353689; CAI19110.1; -; Genomic_DNA.
DR EMBL; AL451047; CAI19110.1; JOINED; Genomic_DNA.
DR EMBL; AL627308; CAI19110.1; JOINED; Genomic_DNA.
DR EMBL; AB007920; BAA32296.2; -; mRNA.
DR EMBL; U59305; AAB37126.1; -; mRNA.
DR CCDS; CCDS1558.1; -. [Q5VT25-5]
DR CCDS; CCDS1559.1; -. [Q5VT25-3]
DR CCDS; CCDS91169.1; -. [Q5VT25-2]
DR CCDS; CCDS91170.1; -. [Q5VT25-1]
DR RefSeq; NP_003598.2; NM_003607.3. [Q5VT25-5]
DR RefSeq; NP_055641.3; NM_014826.4. [Q5VT25-3]
DR RefSeq; XP_005273378.1; XM_005273321.3. [Q5VT25-6]
DR RefSeq; XP_005273379.1; XM_005273322.3.
DR RefSeq; XP_005273381.1; XM_005273324.3.
DR AlphaFoldDB; Q5VT25; -.
DR SMR; Q5VT25; -.
DR BioGRID; 114051; 161.
DR IntAct; Q5VT25; 51.
DR MINT; Q5VT25; -.
DR STRING; 9606.ENSP00000355731; -.
DR BindingDB; Q5VT25; -.
DR ChEMBL; CHEMBL4516; -.
DR DrugCentral; Q5VT25; -.
DR GuidetoPHARMACOLOGY; 1507; -.
DR GlyCosmos; Q5VT25; 1 site, 1 glycan.
DR GlyGen; Q5VT25; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5VT25; -.
DR PhosphoSitePlus; Q5VT25; -.
DR SwissPalm; Q5VT25; -.
DR BioMuta; CDC42BPA; -.
DR DMDM; 74746874; -.
DR CPTAC; non-CPTAC-5684; -.
DR EPD; Q5VT25; -.
DR jPOST; Q5VT25; -.
DR MassIVE; Q5VT25; -.
DR MaxQB; Q5VT25; -.
DR PaxDb; 9606-ENSP00000355731; -.
DR PeptideAtlas; Q5VT25; -.
DR ProteomicsDB; 65291; -. [Q5VT25-1]
DR ProteomicsDB; 65292; -. [Q5VT25-2]
DR ProteomicsDB; 65293; -. [Q5VT25-3]
DR ProteomicsDB; 65294; -. [Q5VT25-4]
DR ProteomicsDB; 65295; -. [Q5VT25-5]
DR ProteomicsDB; 65296; -. [Q5VT25-6]
DR Pumba; Q5VT25; -.
DR Antibodypedia; 34655; 293 antibodies from 36 providers.
DR DNASU; 8476; -.
DR Ensembl; ENST00000334218.9; ENSP00000335341.6; ENSG00000143776.20. [Q5VT25-1]
DR Ensembl; ENST00000366766.8; ENSP00000355728.5; ENSG00000143776.20. [Q5VT25-2]
DR Ensembl; ENST00000366767.7; ENSP00000355729.3; ENSG00000143776.20. [Q5VT25-3]
DR Ensembl; ENST00000366769.7; ENSP00000355731.3; ENSG00000143776.20. [Q5VT25-5]
DR GeneID; 8476; -.
DR KEGG; hsa:8476; -.
DR MANE-Select; ENST00000366766.8; ENSP00000355728.5; NM_001394014.1; NP_001380943.1. [Q5VT25-2]
DR UCSC; uc001hqr.4; human. [Q5VT25-1]
DR AGR; HGNC:1737; -.
DR CTD; 8476; -.
DR DisGeNET; 8476; -.
DR GeneCards; CDC42BPA; -.
DR HGNC; HGNC:1737; CDC42BPA.
DR HPA; ENSG00000143776; Low tissue specificity.
DR MIM; 603412; gene.
DR neXtProt; NX_Q5VT25; -.
DR OpenTargets; ENSG00000143776; -.
DR PharmGKB; PA26267; -.
DR VEuPathDB; HostDB:ENSG00000143776; -.
DR eggNOG; KOG0612; Eukaryota.
DR GeneTree; ENSGT01030000234517; -.
DR HOGENOM; CLU_000288_140_3_1; -.
DR InParanoid; Q5VT25; -.
DR OMA; SYCEGYL; -.
DR OrthoDB; 988261at2759; -.
DR PhylomeDB; Q5VT25; -.
DR TreeFam; TF313551; -.
DR PathwayCommons; Q5VT25; -.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR SignaLink; Q5VT25; -.
DR SIGNOR; Q5VT25; -.
DR BioGRID-ORCS; 8476; 7 hits in 1193 CRISPR screens.
DR ChiTaRS; CDC42BPA; human.
DR GeneWiki; CDC42BPA; -.
DR GenomeRNAi; 8476; -.
DR Pharos; Q5VT25; Tchem.
DR PRO; PR:Q5VT25; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5VT25; Protein.
DR Bgee; ENSG00000143776; Expressed in medial globus pallidus and 211 other cell types or tissues.
DR ExpressionAtlas; Q5VT25; baseline and differential.
DR Genevisible; Q5VT25; 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:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:0030036; P:actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0031032; P:actomyosin structure organization; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR CDD; cd20864; C1_MRCKalpha; 1.
DR CDD; cd00132; CRIB; 1.
DR CDD; cd01243; PH_MRCK; 1.
DR CDD; cd05623; STKc_MRCK_alpha; 1.
DR Gene3D; 1.20.5.340; -; 1.
DR Gene3D; 3.30.60.20; -; 1.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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; IPR031597; KELK.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR026611; MRCK_alpha_cat.
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; MYOTONIC DYSTROPHY S/T KINASE-RELATED; 1.
DR PANTHER; PTHR22988:SF31; SERINE_THREONINE-PROTEIN KINASE MRCK ALPHA; 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 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; SSF57889; Cysteine-rich domain; 1.
DR SUPFAM; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR SUPFAM; SSF69322; Tricorn protease domain 2; 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 Alternative splicing; ATP-binding; Cell projection; Coiled coil; Cytoplasm;
KW Kinase; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..1732
FT /note="Serine/threonine-protein kinase MRCK alpha"
FT /id="PRO_0000086392"
FT DOMAIN 77..343
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:9092543"
FT DOMAIN 344..414
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 1082..1201
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1227..1499
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT DOMAIN 1571..1584
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT ZN_FING 1012..1062
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 968..1003
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1591..1732
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 437..820
FT /evidence="ECO:0000255"
FT COILED 880..943
FT /evidence="ECO:0000255"
FT COMPBIAS 968..992
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1602..1649
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1657..1676
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1695..1732
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 201
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P54265,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 83..91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P54265,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 106
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:11283256"
FT SITE 478..479
FT /note="Cleavage; by CASP3 in vitro"
FT /evidence="ECO:0000269|PubMed:29162624"
FT SITE 984..985
FT /note="Cleavage; by CASP3 in vitro"
FT /evidence="ECO:0000269|PubMed:29162624"
FT MOD_RES 222
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11283256"
FT MOD_RES 234
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11283256"
FT MOD_RES 240
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11283256"
FT MOD_RES 1127
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54874"
FT MOD_RES 1545
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1611
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1629
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1651
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1664
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1669
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1693
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1719
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1721
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 550..630
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15723050"
FT /id="VSP_051859"
FT VAR_SEQ 969..1009
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16710414, ECO:0000303|Ref.2"
FT /id="VSP_051862"
FT VAR_SEQ 969..981
FT /note="Missing (in isoform 3, isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15723050,
FT ECO:0000303|PubMed:9455484"
FT /id="VSP_051860"
FT VAR_SEQ 969
FT /note="R -> TDPVENTYVWNPSVKFHIQSRST (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_051861"
FT VAR_SEQ 973..981
FT /note="CTPASKGRR -> TSSEAEPVK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_051863"
FT VAR_SEQ 1597
FT /note="M -> MPGFPYPSPHHHSGLISSPINFEHIYHMTVNSAEKFLSPDSINPEYS
FT PSLRSVPGTPSFMTLR (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:9455484"
FT /id="VSP_035286"
FT VARIANT 50
FT /note="E -> K (in a lung neuroendocrine carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040830"
FT VARIANT 231
FT /note="T -> M (in dbSNP:rs34614709)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040831"
FT VARIANT 537
FT /note="I -> T (in dbSNP:rs56364976)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040832"
FT VARIANT 780
FT /note="T -> M (in dbSNP:rs56119119)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045583"
FT VARIANT 790
FT /note="Y -> C (in dbSNP:rs34943764)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045584"
FT VARIANT 1148
FT /note="A -> T (in dbSNP:rs56219089)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045585"
FT VARIANT 1211
FT /note="R -> H (in dbSNP:rs961490)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045586"
FT VARIANT 1317
FT /note="V -> I (in dbSNP:rs1929860)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_045587"
FT VARIANT 1418
FT /note="I -> K"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040833"
FT VARIANT 1469
FT /note="A -> V (in dbSNP:rs55687355)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045588"
FT VARIANT 1618
FT /note="T -> A (in dbSNP:rs2297417)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045589"
FT VARIANT 1699
FT /note="A -> V (in dbSNP:rs2802269)"
FT /id="VAR_045590"
FT VARIANT 1712
FT /note="A -> V (in dbSNP:rs2802269)"
FT /evidence="ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:9455484, ECO:0000269|Ref.2"
FT /id="VAR_057104"
FT MUTAGEN 106
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:11283256"
FT MUTAGEN 222
FT /note="S->L: Increase in autophosphorylation but not kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:11283256"
FT MUTAGEN 234
FT /note="S->A: Loss of autophosphorylation and kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:11283256"
FT MUTAGEN 240
FT /note="T->A: Loss of autophosphorylation and kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:11283256"
FT MUTAGEN 403
FT /note="T->A: Loss of autophosphorylation and kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:11283256"
FT MUTAGEN 478
FT /note="D->A: Prevents cleavage by CASP3, impairs the
FT increase of its kinase activity and impairs extrusion
FT apical actin ring assembly."
FT /evidence="ECO:0000269|PubMed:29162624"
FT MUTAGEN 984
FT /note="D->A: Prevents cleavage by CASP3."
FT /evidence="ECO:0000269|PubMed:29162624"
FT MUTAGEN 1579
FT /note="H->A: Loss of CDC42 binding; when associated with A-
FT 1582."
FT /evidence="ECO:0000269|PubMed:9418861"
FT MUTAGEN 1582
FT /note="H->A: Loss of CDC42 binding; when associated with A-
FT 1579."
FT /evidence="ECO:0000269|PubMed:9418861"
FT CONFLICT 25
FT /note="C -> Y (in Ref. 5; AAB37126)"
FT /evidence="ECO:0000305"
FT CONFLICT 809
FT /note="D -> N (in Ref. 3; CAI46252)"
FT /evidence="ECO:0000305"
FT CONFLICT 1521
FT /note="L -> V (in Ref. 8)"
FT /evidence="ECO:0000305"
FT CONFLICT 1688
FT /note="G -> K (in Ref. 6; BAA32296)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1732 AA; 197307 MW; 48B10F81B5405A0A CRC64;
MSGEVRLRQL EQFILDGPAQ TNGQCFSVET LLDILICLYD ECNNSPLRRE KNILEYLEWA
KPFTSKVKQM RLHREDFEIL KVIGRGAFGE VAVVKLKNAD KVFAMKILNK WEMLKRAETA
CFREERDVLV NGDNKWITTL HYAFQDDNNL YLVMDYYVGG DLLTLLSKFE DRLPEDMARF
YLAEMVIAID SVHQLHYVHR DIKPDNILMD MNGHIRLADF GSCLKLMEDG TVQSSVAVGT
PDYISPEILQ AMEDGKGRYG PECDWWSLGV CMYEMLYGET PFYAESLVET YGKIMNHKER
FQFPAQVTDV SENAKDLIRR LICSREHRLG QNGIEDFKKH PFFSGIDWDN IRNCEAPYIP
EVSSPTDTSN FDVDDDCLKN SETMPPPTHT AFSGHHLPFV GFTYTSSCVL SDRSCLRVTA
GPTSLDLDVN VQRTLDNNLA TEAYERRIKR LEQEKLELSR KLQESTQTVQ ALQYSTVDGP
LTASKDLEIK NLKEEIEKLR KQVTESSHLE QQLEEANAVR QELDDAFRQI KAYEKQIKTL
QQEREDLNKE LVQASERLKN QSKELKDAHC QRKLAMQEFM EINERLTELH TQKQKLARHV
RDKEEEVDLV MQKVESLRQE LRRTERAKKE LEVHTEALAA EASKDRKLRE QSEHYSKQLE
NELEGLKQKQ ISYSPGVCSI EHQQEITKLK TDLEKKSIFY EEELSKREGI HANEIKNLKK
ELHDSEGQQL ALNKEIMILK DKLEKTRRES QSEREEFESE FKQQYEREKV LLTEENKKLT
SELDKLTTLY ENLSIHNQQL EEEVKDLADK KESVAHWEAQ ITEIIQWVSD EKDARGYLQA
LASKMTEELE ALRNSSLGTR ATDMPWKMRR FAKLDMSARL ELQSALDAEI RAKQAIQEEL
NKVKASNIIT ECKLKDSEKK NLELLSEIEQ LIKDTEELRS EKGIEHQDSQ HSFLAFLNTP
TDALDQFERS PSCTPASKGR RTVDSTPLSV HTPTLRKKGC PGSTGFPPKR KTHQFFVKSF
TTPTKCHQCT SLMVGLIRQG CSCEVCGFSC HITCVNKAPT TCPVPPEQTK GPLGIDPQKG
IGTAYEGHVR IPKPAGVKKG WQRALAIVCD FKLFLYDIAE GKASQPSVVI SQVIDMRDEE
FSVSSVLASD VIHASRKDIP CIFRVTASQL SASNNKCSIL MLADTENEKN KWVGVLSELH
KILKKNKFRD RSVYVPKEAY DSTLPLIKTT QAAAIIDHER IALGNEEGLF VVHVTKDEII
RVGDNKKIHQ IELIPNDQLV AVISGRNRHV RLFPMSALDG RETDFYKLSE TKGCQTVTSG
KVRHGALTCL CVAMKRQVLC YELFQSKTRH RKFKEIQVPY NVQWMAIFSE QLCVGFQSGF
LRYPLNGEGN PYSMLHSNDH TLSFIAHQPM DAICAVEISS KEYLLCFNSI GIYTDCQGRR
SRQQELMWPA NPSSCCYNAP YLSVYSENAV DIFDVNSMEW IQTLPLKKVR PLNNEGSLNL
LGLETIRLIY FKNKMAEGDE LVVPETSDNS RKQMVRNINN KRRYSFRVPE EERMQQRREM
LRDPEMRNKL ISNPTNFNHI AHMGPGDGIQ ILKDLPMNPR PQESRTVFSG SVSIPSITKS
RPEPGRSMSA SSGLSARSSA QNGSALKREF SGGSYSAKRQ PMPSPSEGSL SSGGMDQGSD
APARDFDGED SDSPRHSTAS NSSNLSSPPS PASPRKTKSL SLESTDRGSW DP
//
