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 27-MAR-2024, entry version 197. 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}, MARK GN {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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 73. DR DIP; DIP-39777N; -. DR IntAct; Q9P0L2; 37. 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; 9606-ENSP00000483424; -. DR PeptideAtlas; Q9P0L2; -. DR ProteomicsDB; 83571; -. [Q9P0L2-1] DR ProteomicsDB; 83572; -. [Q9P0L2-2] DR ProteomicsDB; 83573; -. [Q9P0L2-3] DR Pumba; Q9P0L2; -. DR Antibodypedia; 2072; 508 antibodies from 33 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 AGR; HGNC:6896; -. 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 OrthoDB; 5475340at2759; -. DR PhylomeDB; Q9P0L2; -. DR TreeFam; TF315213; -. DR PathwayCommons; Q9P0L2; -. DR SignaLink; Q9P0L2; -. DR SIGNOR; Q9P0L2; -. DR BioGRID-ORCS; 4139; 14 hits in 1190 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 178 other cell types or tissues. DR ExpressionAtlas; Q9P0L2; baseline and differential. 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 CDD; cd12196; MARK1-3_C; 1. DR CDD; cd14072; STKc_MARK; 1. DR CDD; cd14405; UBA_MARK1; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1. DR Gene3D; 3.30.310.80; Kinase associated domain 1, KA1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR028375; KA1/Ssp2_C. DR InterPro; IPR001772; KA1_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR049508; MARK1-4_cat. 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; MAP/MICROTUBULE AFFINITY-REGULATING KINASE; 1. DR PANTHER; PTHR24346:SF21; SERINE_THREONINE-PROTEIN KINASE MARK1; 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; KA1-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q9P0L2; HS. 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 //