MARK1_HUMAN
ID MARK1_HUMAN Reviewed; 795 AA.
AC Q9P0L2; D3DTB0; D3DTB1; Q2HIY1; Q5VTF9; Q5VTG0; Q96SW9; Q9P251;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Serine/threonine-protein kinase MARK1;
DE EC=2.7.11.1;
DE EC=2.7.11.26;
DE AltName: Full=MAP/microtubule affinity-regulating kinase 1;
DE AltName: Full=PAR1 homolog c;
DE Short=Par-1c;
DE Short=Par1c;
GN Name=MARK1 {ECO:0000312|HGNC:HGNC:6896};
GN Synonyms=KIAA1477 {ECO:0000312|EMBL:BAA96001.1},
GN MARK {ECO:0000312|EMBL:AAF72103.1};
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}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ACTIVITY REGULATION,
RP PHOSPHORYLATION AT THR-215, AND MUTAGENESIS OF THR-215.
RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110;
RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J.,
RA Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily,
RT including MARK/PAR-1.";
RL EMBO J. 23:833-843(2004).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF72103.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Zhou H.J., Huang X.W., Zhou Y., Hu S.L., Yuan J.G., Qiang B.Q.;
RT "Cloning and isolating human MARK.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAA96001.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain {ECO:0000269|PubMed:10819331};
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [4] {ECO:0000305, ECO:0000312|EMBL:BAB55152.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
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 [6] {ECO:0000305, ECO:0000312|EMBL:AAF72103.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 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 [8] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=9108484; DOI=10.1016/s0092-8674(00)80208-1;
RA Drewes G., Ebneth A., Preuss U., Mandelkow E.-M., Mandelkow E.;
RT "MARK - a novel family of protein kinases that phosphorylate microtubule-
RT associated proteins and trigger microtubule disruption.";
RL Cell 89:297-308(1997).
RN [9]
RP NEUROFIBRILLARY TANGLES IN ALZHEIMER BRAIN.
RX PubMed=11089574; DOI=10.1093/jnen/59.11.966;
RA Chin J.Y., Knowles R.B., Schneider A., Drewes G., Mandelkow E.M.,
RA Hyman B.T.;
RT "Microtubule-affinity regulating kinase (MARK) is tightly associated with
RT neurofibrillary tangles in Alzheimer brain: a fluorescence resonance energy
RT transfer study.";
RL J. Neuropathol. Exp. Neurol. 59:966-971(2000).
RN [10]
RP FUNCTION.
RX PubMed=11433294; DOI=10.1038/35083016;
RA Sun T.-Q., Lu B., Feng J.-J., Reinhard C., Jan Y.N., Fantl W.J.,
RA Williams L.T.;
RT "PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt
RT signalling.";
RL Nat. Cell Biol. 3:628-636(2001).
RN [11]
RP PHOSPHORYLATION AT THR-208, ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=17573348; DOI=10.1074/jbc.m700590200;
RA Kojima Y., Miyoshi H., Clevers H.C., Oshima M., Aoki M., Taketo M.M.;
RT "Suppression of tubulin polymerization by the LKB1-microtubule-associated
RT protein/microtubule affinity-regulating kinase signaling.";
RL J. Biol. Chem. 282:23532-23540(2007).
RN [12]
RP POSSIBLE INVOLVEMENT IN AUTISM.
RX PubMed=18492799; DOI=10.1093/hmg/ddn154;
RA Maussion G., Carayol J., Lepagnol-Bestel A.M., Tores F., Loe-Mie Y.,
RA Milbreta U., Rousseau F., Fontaine K., Renaud J., Moalic J.M., Philippi A.,
RA Chedotal A., Gorwood P., Ramoz N., Hager J., Simonneau M.;
RT "Convergent evidence identifying MAP/microtubule affinity-regulating kinase
RT 1 (MARK1) as a susceptibility gene for autism.";
RL Hum. Mol. Genet. 17:2541-2551(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5 AND SER-403, AND
RP IDENTIFICATION BY 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, AND IDENTIFICATION BY
RP 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 [16]
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 [17]
RP REVIEW.
RX PubMed=19559622; DOI=10.1016/j.tibs.2009.03.008;
RA Matenia D., Mandelkow E.M.;
RT "The tau of MARK: a polarized view of the cytoskeleton.";
RL Trends Biochem. Sci. 34:332-342(2009).
RN [18]
RP REVIEW.
RX PubMed=20071654; DOI=10.1096/fj.09-148064;
RA Marx A., Nugoor C., Panneerselvam S., Mandelkow E.;
RT "Structure and function of polarity-inducing kinase family MARK/Par-1
RT within the branch of AMPK/Snf1-related kinases.";
RL FASEB J. 24:1637-1648(2010).
RN [19]
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 [20]
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 [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [22]
RP FUNCTION, INTERACTION WITH MAPT, AND SUBCELLULAR LOCATION.
RX PubMed=23666762; DOI=10.1007/s12017-013-8232-3;
RA Gu G.J., Lund H., Wu D., Blokzijl A., Classon C., von Euler G.,
RA Landegren U., Sunnemark D., Kamali-Moghaddam M.;
RT "Role of individual MARK isoforms in phosphorylation of tau at Ser262 in
RT Alzheimer's disease.";
RL NeuroMolecular Med. 15:458-469(2013).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 45-371.
RX PubMed=16803889; DOI=10.1074/jbc.m604865200;
RA Marx A., Nugoor C., Muller J., Panneerselvam S., Timm T., Bilang M.,
RA Mylonas E., Svergun D.I., Mandelkow E.M., Mandelkow E.;
RT "Structural variations in the catalytic and ubiquitin-associated domains of
RT microtubule-associated protein/microtubule affinity regulating kinase
RT (MARK) 1 and MARK2.";
RL J. Biol. Chem. 281:27586-27599(2006).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 683-795, DOMAIN KA1, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF ARG-698; ARG-701; 771-ARG--LYS-773 AND
RP 773-LYS-ARG-774.
RX PubMed=21145462; DOI=10.1016/j.cell.2010.11.028;
RA Moravcevic K., Mendrola J.M., Schmitz K.R., Wang Y.H., Slochower D.,
RA Janmey P.A., Lemmon M.A.;
RT "Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by
RT binding acidic phospholipids.";
RL Cell 143:966-977(2010).
RN [25]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-233; THR-355; MET-530; LEU-578 AND
RP GLY-691.
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 (PubMed:23666762). Involved
CC in cell polarity and microtubule dynamics regulation. Phosphorylates
CC DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein
CC MAPT/TAU (PubMed:23666762). Involved in cell polarity by
CC phosphorylating the microtubule-associated proteins MAP2, MAP4 and
CC MAPT/TAU at KXGS motifs, causing detachment from microtubules, and
CC their disassembly. Involved in the regulation of neuronal migration
CC through its dual activities in regulating cellular polarity and
CC microtubule dynamics, possibly by phosphorylating and regulating DCX.
CC Also acts as a positive regulator of the Wnt signaling pathway,
CC probably by mediating phosphorylation of dishevelled proteins (DVL1,
CC DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294,
CC ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}.
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:14976552};
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:14976552};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by phosphorylation at Ser-219 (By
CC similarity). Activated by phosphorylation on Thr-215. {ECO:0000250,
CC ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:17573348}.
CC -!- SUBUNIT: Interacts with MAPT/TAU. {ECO:0000269|PubMed:23666762}.
CC -!- INTERACTION:
CC Q9P0L2; P05067: APP; NbExp=3; IntAct=EBI-968587, EBI-77613;
CC Q9P0L2; P63172: DYNLT1; NbExp=3; IntAct=EBI-968587, EBI-1176455;
CC Q9P0L2; Q0VD86: INCA1; NbExp=3; IntAct=EBI-968587, EBI-6509505;
CC Q9P0L2; O95988: TCL1B; NbExp=5; IntAct=EBI-968587, EBI-727338;
CC Q9P0L2; Q8IY57-5: YAF2; NbExp=3; IntAct=EBI-968587, EBI-12111538;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21145462};
CC Peripheral membrane protein {ECO:0000269|PubMed:21145462}. Cytoplasm,
CC cytoskeleton {ECO:0000250}. Cytoplasm {ECO:0000269|PubMed:23666762}.
CC Cell projection, dendrite {ECO:0000269|PubMed:23666762}. Note=Appears
CC to localize to an intracellular network. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9P0L2-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=Q9P0L2-2; Sequence=VSP_051702, VSP_051704;
CC Name=3 {ECO:0000305};
CC IsoId=Q9P0L2-3; Sequence=VSP_051703, VSP_051704;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, brain,
CC fetal brain and fetal kidney. {ECO:0000269|PubMed:9108484}.
CC -!- DOMAIN: The UBA domain does not seem to bind ubiquitin and ubiquitin-
CC like and might play a role in regulating the enzyme conformation and
CC localization. Activation of the kinase activity following
CC phosphorylation at Thr-208 is accompanied by a conformational change
CC that alters the orientation of the UBA domain with respect to the
CC catalytic domain (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The KA1 domain mediates binding to phospholipids and targeting
CC to membranes. Binds phosphatidic acid (PA), phosphatidylserine (PtdSer)
CC and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).
CC {ECO:0000269|PubMed:21145462}.
CC -!- PTM: Phosphorylation at Thr-613 by PRKCZ/aPKC in polarized epithelial
CC cells inhibits the kinase activity (By similarity). Phosphorylated at
CC Thr-215 by STK11/LKB1 in complex with STE20-related adapter-alpha
CC (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-215 by TAOK1
CC activates the kinase activity, leading to phosphorylation and
CC detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-219 by
CC GSK3-beta (GSK3B) inhibits the kinase activity. {ECO:0000250,
CC ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:17573348}.
CC -!- DISEASE: Note=Genetic variations in MARK1 may be associated with
CC susceptibility to autism. MARK1 is overexpressed in the prefrontal
CC cortex of patients with autism and causes changes in the function of
CC cortical dendrites.
CC -!- MISCELLANEOUS: Phosphorylation of MAPT/tau by MARK1 could play a role
CC in early steps of Alzheimer disease. Pathological aggregation of
CC MAPT/tau to neurofibrillary tangles, filamentous structures consisting
CC of paired helical filaments (PHFs), is one of the hallmarks of
CC Alzheimer disease. Hyperphosphorylation by MARK1 could be the initial
CC step for this abnormal aggregation of tau in Alzheimer disease and
CC animal models of tauopathy (PubMed:11089574).
CC {ECO:0000305|PubMed:11089574}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA96001.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB55152.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF154845; AAF72103.1; -; mRNA.
DR EMBL; AB040910; BAA96001.1; ALT_INIT; mRNA.
DR EMBL; AK027493; BAB55152.1; ALT_FRAME; mRNA.
DR EMBL; AC096640; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL592406; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93299.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93300.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93302.1; -; Genomic_DNA.
DR EMBL; BC113869; AAI13870.1; -; mRNA.
DR EMBL; BC114478; AAI14479.1; -; mRNA.
DR CCDS; CCDS31029.2; -. [Q9P0L2-1]
DR CCDS; CCDS65789.1; -. [Q9P0L2-3]
DR RefSeq; NP_001273057.1; NM_001286128.1. [Q9P0L2-3]
DR RefSeq; NP_061120.3; NM_018650.4. [Q9P0L2-1]
DR PDB; 2HAK; X-ray; 2.60 A; A/B/C/D/E/F/G/H=45-371.
DR PDB; 3OSE; X-ray; 1.70 A; A=683-795.
DR PDB; 6C9D; X-ray; 2.50 A; A/B=45-795.
DR PDBsum; 2HAK; -.
DR PDBsum; 3OSE; -.
DR PDBsum; 6C9D; -.
DR AlphaFoldDB; Q9P0L2; -.
DR SASBDB; Q9P0L2; -.
DR SMR; Q9P0L2; -.
DR BioGRID; 110309; 51.
DR DIP; DIP-39777N; -.
DR IntAct; Q9P0L2; 38.
DR MINT; Q9P0L2; -.
DR STRING; 9606.ENSP00000483424; -.
DR BindingDB; Q9P0L2; -.
DR ChEMBL; CHEMBL5940; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9P0L2; -.
DR GuidetoPHARMACOLOGY; 2097; -.
DR CarbonylDB; Q9P0L2; -.
DR iPTMnet; Q9P0L2; -.
DR PhosphoSitePlus; Q9P0L2; -.
DR BioMuta; MARK1; -.
DR DMDM; 124056494; -.
DR EPD; Q9P0L2; -.
DR jPOST; Q9P0L2; -.
DR MassIVE; Q9P0L2; -.
DR MaxQB; Q9P0L2; -.
DR PaxDb; Q9P0L2; -.
DR PeptideAtlas; Q9P0L2; -.
DR PRIDE; Q9P0L2; -.
DR ProteomicsDB; 83571; -. [Q9P0L2-1]
DR ProteomicsDB; 83572; -. [Q9P0L2-2]
DR ProteomicsDB; 83573; -. [Q9P0L2-3]
DR Antibodypedia; 2072; 458 antibodies from 32 providers.
DR DNASU; 4139; -.
DR Ensembl; ENST00000366917.6; ENSP00000355884.5; ENSG00000116141.17. [Q9P0L2-1]
DR Ensembl; ENST00000366918.8; ENSP00000355885.4; ENSG00000116141.17. [Q9P0L2-3]
DR GeneID; 4139; -.
DR KEGG; hsa:4139; -.
DR MANE-Select; ENST00000366917.6; ENSP00000355884.5; NM_018650.5; NP_061120.3.
DR UCSC; uc001hmm.6; human. [Q9P0L2-1]
DR CTD; 4139; -.
DR DisGeNET; 4139; -.
DR GeneCards; MARK1; -.
DR HGNC; HGNC:6896; MARK1.
DR HPA; ENSG00000116141; Low tissue specificity.
DR MIM; 606511; gene.
DR neXtProt; NX_Q9P0L2; -.
DR OpenTargets; ENSG00000116141; -.
DR PharmGKB; PA30639; -.
DR VEuPathDB; HostDB:ENSG00000116141; -.
DR eggNOG; KOG0586; Eukaryota.
DR GeneTree; ENSGT00940000157560; -.
DR InParanoid; Q9P0L2; -.
DR OMA; DWVIFED; -.
DR PhylomeDB; Q9P0L2; -.
DR TreeFam; TF315213; -.
DR PathwayCommons; Q9P0L2; -.
DR SignaLink; Q9P0L2; -.
DR SIGNOR; Q9P0L2; -.
DR BioGRID-ORCS; 4139; 14 hits in 1111 CRISPR screens.
DR ChiTaRS; MARK1; human.
DR EvolutionaryTrace; Q9P0L2; -.
DR GeneWiki; MARK1; -.
DR GenomeRNAi; 4139; -.
DR Pharos; Q9P0L2; Tchem.
DR PRO; PR:Q9P0L2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9P0L2; protein.
DR Bgee; ENSG00000116141; Expressed in cortical plate and 177 other tissues.
DR ExpressionAtlas; Q9P0L2; baseline and differential.
DR Genevisible; Q9P0L2; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine 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:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; IMP:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0051654; P:establishment of mitochondrion localization; ISS:ARUK-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISS:ARUK-UCL.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IDA:ARUK-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; NAS:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050773; P:regulation of dendrite development; ISS:ARUK-UCL.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:ARUK-UCL.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033627; MARK1.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015940; UBA.
DR PANTHER; PTHR24346:SF21; PTHR24346:SF21; 1.
DR Pfam; PF02149; KA1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00627; UBA; 1.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF103243; SSF103243; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50032; KA1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50030; UBA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Autism;
KW Autism spectrum disorder; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Kinase; Lipid-binding; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Wnt signaling pathway.
FT CHAIN 1..795
FT /note="Serine/threonine-protein kinase MARK1"
FT /id="PRO_0000086298"
FT DOMAIN 60..311
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 325..370
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 746..795
FT /note="KA1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 377..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 539..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..40
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..423
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..459
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..563
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 583..614
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 679..700
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 182
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 66..74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O08678,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 5
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 208
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17573348"
FT MOD_RES 215
FT /note="Phosphothreonine; by LKB1 and TAOK1"
FT /evidence="ECO:0000269|PubMed:14976552"
FT MOD_RES 219
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:O08678"
FT MOD_RES 382
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 390
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08678"
FT MOD_RES 475
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 613
FT /note="Phosphothreonine; by PKC/PRKCZ"
FT /evidence="ECO:0000250"
FT MOD_RES 666
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT VAR_SEQ 1..135
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_051702"
FT VAR_SEQ 120..141
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10819331"
FT /id="VSP_051703"
FT VAR_SEQ 663..677
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10819331,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_051704"
FT VARIANT 233
FT /note="Y -> C (in a gastric adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040760"
FT VARIANT 355
FT /note="N -> T (in an ovarian serous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040761"
FT VARIANT 530
FT /note="V -> M (in dbSNP:rs56212551)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040762"
FT VARIANT 578
FT /note="P -> L (in dbSNP:rs55691439)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040763"
FT VARIANT 645
FT /note="R -> G (in dbSNP:rs12123778)"
FT /id="VAR_030018"
FT VARIANT 691
FT /note="E -> G (in dbSNP:rs55688276)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040764"
FT MUTAGEN 215
FT /note="T->A: Prevents phosphorylation and activation by
FT STK11/LKB1 complex."
FT /evidence="ECO:0000269|PubMed:14976552"
FT MUTAGEN 215
FT /note="T->E: Constitutively active."
FT /evidence="ECO:0000269|PubMed:14976552"
FT MUTAGEN 698
FT /note="R->S: Impairs phospholipid-binding, targeting to
FT membrane and vesicle-binding; when associated with S-701."
FT /evidence="ECO:0000269|PubMed:21145462"
FT MUTAGEN 701
FT /note="R->S: Impairs phospholipid-binding, targeting to
FT membrane and vesicle-binding; when associated with S-698."
FT /evidence="ECO:0000269|PubMed:21145462"
FT MUTAGEN 771..773
FT /note="RFK->AFA: Impairs phospholipid-binding."
FT /evidence="ECO:0000269|PubMed:21145462"
FT CONFLICT 16
FT /note="E -> V (in Ref. 2; AAF72103)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="S -> T (in Ref. 2; AAF72103)"
FT /evidence="ECO:0000305"
FT CONFLICT 522
FT /note="D -> N (in Ref. 4; BAB55152)"
FT /evidence="ECO:0000305"
FT CONFLICT 544
FT /note="V -> A (in Ref. 4; BAB55152)"
FT /evidence="ECO:0000305"
FT CONFLICT 763
FT /note="P -> A (in Ref. 4; BAB55152)"
FT /evidence="ECO:0000305"
FT CONFLICT 794
FT /note="K -> M (in Ref. 3; BAA96001)"
FT /evidence="ECO:0000305"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:6C9D"
FT STRAND 60..68
FT /evidence="ECO:0007829|PDB:6C9D"
FT STRAND 70..79
FT /evidence="ECO:0007829|PDB:6C9D"
FT TURN 80..82
FT /evidence="ECO:0007829|PDB:6C9D"
FT STRAND 85..92
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 98..111
FT /evidence="ECO:0007829|PDB:6C9D"
FT STRAND 122..127
FT /evidence="ECO:0007829|PDB:6C9D"
FT STRAND 129..136
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 146..151
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 156..175
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:6C9D"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:6C9D"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 225..228
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 236..252
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 282..291
FT /evidence="ECO:0007829|PDB:6C9D"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 302..305
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:6C9D"
FT STRAND 316..318
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 333..341
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 346..355
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 360..368
FT /evidence="ECO:0007829|PDB:6C9D"
FT TURN 706..708
FT /evidence="ECO:0007829|PDB:6C9D"
FT HELIX 714..727
FT /evidence="ECO:0007829|PDB:3OSE"
FT STRAND 731..736
FT /evidence="ECO:0007829|PDB:3OSE"
FT STRAND 739..745
FT /evidence="ECO:0007829|PDB:3OSE"
FT TURN 747..750
FT /evidence="ECO:0007829|PDB:3OSE"
FT STRAND 753..762
FT /evidence="ECO:0007829|PDB:3OSE"
FT HELIX 763..765
FT /evidence="ECO:0007829|PDB:3OSE"
FT STRAND 767..777
FT /evidence="ECO:0007829|PDB:3OSE"
FT HELIX 779..792
FT /evidence="ECO:0007829|PDB:3OSE"
SQ SEQUENCE 795 AA; 89003 MW; 71BF6EB76912631B CRC64;
MSARTPLPTV NERDTENHTS VDGYTEPHIQ PTKSSSRQNI PRCRNSITSA TDEQPHIGNY
RLQKTIGKGN FAKVKLARHV LTGREVAVKI IDKTQLNPTS LQKLFREVRI MKILNHPNIV
KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR AKFRQIVSAV QYCHQKYIVH
RDLKAENLLL DGDMNIKIAD FGFSNEFTVG NKLDTFCGSP PYAAPELFQG KKYDGPEVDV
WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM STDCENLLKK LLVLNPIKRG
SLEQIMKDRW MNVGHEEEEL KPYTEPDPDF NDTKRIDIMV TMGFARDEIN DALINQKYDE
VMATYILLGR KPPEFEGGES LSSGNLCQRS RPSSDLNNST LQSPAHLKVQ RSISANQKQR
RFSDHAGPSI PPAVSYTKRP QANSVESEQK EEWDKDVARK LGSTTVGSKS EMTASPLVGP
ERKKSSTIPS NNVYSGGSMA RRNTYVCERT TDRYVALQNG KDSSLTEMSV SSISSAGSSV
ASAVPSARPR HQKSMSTSGH PIKVTLPTIK DGSEAYRPGT TQRVPAASPS AHSISTATPD
RTRFPRGSSS RSTFHGEQLR ERRSVAYNGP PASPSHETGA FAHARRGTST GIISKITSKF
VRRDPSEGEA SGRTDTSRST SGEPKERDKE EGKDSKPRSL RFTWSMKTTS SMDPNDMMRE
IRKVLDANNC DYEQKERFLL FCVHGDARQD SLVQWEMEVC KLPRLSLNGV RFKRISGTSI
AFKNIASKIA NELKL
