MYPT1_HUMAN
ID MYPT1_HUMAN Reviewed; 1030 AA.
AC O14974; B4DZ09; F8VWB4; Q2NKL4; Q569H0; Q86WU3; Q8NFR6; Q9BYH0;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Protein phosphatase 1 regulatory subunit 12A;
DE AltName: Full=Myosin phosphatase-targeting subunit 1;
DE Short=Myosin phosphatase target subunit 1;
DE AltName: Full=Protein phosphatase myosin-binding subunit;
GN Name=PPP1R12A {ECO:0000312|HGNC:HGNC:7618};
GN Synonyms=MBS, MYPT1 {ECO:0000305};
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Liver;
RX PubMed=9286714; DOI=10.1006/geno.1997.4859;
RA Takahashi N., Ito M., Tanaka J., Nakano T., Kaibuchi K., Odai H.,
RA Takemura K.;
RT "Localization of the gene coding for myosin phosphatase, target subunit 1
RT (MYPT1) to human chromosome 12q15-q21.";
RL Genomics 44:150-152(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RA Guo J.H., Chen X.Y., Yu L.;
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Xia D., Kamm K., Stull J.T.;
RT "Molecular cloning and functional analysis of a new isoform of human
RT MYPT1.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Testis;
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=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-722 (ISOFORM 4).
RC TISSUE=Blood, and Brain;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-79.
RX PubMed=11342221; DOI=10.1016/s0167-4781(00)00285-2;
RA Machida H., Ito M., Okamoto R., Shiraki K., Isaka N., Hartshorne D.J.,
RA Nakano T.;
RT "Molecular cloning and analysis of the 5'-flanking region of human MYPT1
RT gene.";
RL Biochim. Biophys. Acta 1517:424-429(2001).
RN [8]
RP PROTEIN SEQUENCE OF 63-76; 95-105 AND 217-228, FUNCTION, AND HYDROXYLATION
RP AT ASN-67; ASN-100 AND ASN-226 BY HIF1AN.
RX PubMed=19245366; DOI=10.1042/bj20081905;
RA Webb J.D., Muranyi A., Pugh C.W., Ratcliffe P.J., Coleman M.L.;
RT "MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a
RT substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-
RT inducible factor (FIH).";
RL Biochem. J. 420:327-333(2009).
RN [9]
RP INTERACTION WITH PRKG1, PHOSPHORYLATION BY PRKG1, AND SUBUNIT.
RX PubMed=10567269; DOI=10.1126/science.286.5444.1583;
RA Surks H.K., Mochizuki N., Kasai Y., Georgescu S.P., Tang K.M., Ito M.,
RA Lincoln T.M., Mendelsohn M.E.;
RT "Regulation of myosin phosphatase by a specific interaction with cGMP-
RT dependent protein kinase Ialpha.";
RL Science 286:1583-1587(1999).
RN [10]
RP PHOSPHORYLATION BY DMPK.
RX PubMed=11287000; DOI=10.1016/s0014-5793(01)02283-9;
RA Muranyi A., Zhang R., Liu F., Hirano K., Ito M., Epstein H.F.,
RA Hartshorne D.J.;
RT "Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase
RT targeting subunit and inhibits myosin phosphatase activity.";
RL FEBS Lett. 493:80-84(2001).
RN [11]
RP INTERACTION WITH PPP1R12B.
RX PubMed=11067852; DOI=10.1074/jbc.m008566200;
RA Arimura T., Suematsu N., Zhou Y.-B., Nishimura J., Satoh S., Takeshita A.,
RA Kanaide H., Kimura A.;
RT "Identification, characterization, and functional analysis of heart-
RT specific myosin light chain phosphatase small subunit.";
RL J. Biol. Chem. 276:6073-6082(2001).
RN [12]
RP PHOSPHORYLATION AT SER-852.
RX PubMed=11331307; DOI=10.1083/jcb.153.3.569;
RA Katoh K., Kano Y., Amano M., Onishi H., Kaibuchi K., Fujiwara K.;
RT "Rho-kinase--mediated contraction of isolated stress fibers.";
RL J. Cell Biol. 153:569-584(2001).
RN [13]
RP INTERACTION WITH ROCK1, AND PHOSPHORYLATION.
RX PubMed=11283607; DOI=10.1038/35070019;
RA Sebbagh M., Renvoize C., Hamelin J., Riche N., Bertoglio J., Breard J.;
RT "Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and
RT apoptotic membrane blebbing.";
RL Nat. Cell Biol. 3:346-352(2001).
RN [14]
RP PHOSPHORYLATION AT THR-696 BY RAF1, AND INTERACTION WITH RAF1.
RX PubMed=11719507; DOI=10.1074/jbc.m106343200;
RA Broustas C.G., Grammatikakis N., Eto M., Dent P., Brautigan D.L., Kasid U.;
RT "Phosphorylation of the myosin-binding subunit of myosin phosphatase by
RT Raf-1 and inhibition of phosphatase activity.";
RL J. Biol. Chem. 277:3053-3059(2002).
RN [15]
RP SUBUNIT, MUTAGENESIS OF LEU-1007; LEU-1014; LEU-1021 AND LEU-1028, AND
RP INTERACTION WITH PRKG1.
RX PubMed=12873707; DOI=10.1016/s0898-6568(03)00057-3;
RA Surks H.K., Mendelsohn M.E.;
RT "Dimerization of cGMP-dependent protein kinase 1alpha and the myosin-
RT binding subunit of myosin phosphatase: role of leucine zipper domains.";
RL Cell. Signal. 15:937-944(2003).
RN [16]
RP INTERACTION WITH IL16, AND SUBCELLULAR LOCATION.
RX PubMed=12923170; DOI=10.1074/jbc.m306669200;
RA Bannert N., Vollhardt K., Asomuddinov B., Haag M., Koenig H., Norley S.,
RA Kurth R.;
RT "PDZ domain-mediated interaction of interleukin-16 precursor proteins with
RT myosin phosphatase targeting subunits.";
RL J. Biol. Chem. 278:42190-42199(2003).
RN [17]
RP INTERACTION WITH ROCK1, AND PHOSPHORYLATION.
RX PubMed=12773565; DOI=10.1128/mcb.23.12.4219-4229.2003;
RA Riento K., Guasch R.M., Garg R., Jin B., Ridley A.J.;
RT "RhoE binds to ROCK I and inhibits downstream signaling.";
RL Mol. Cell. Biol. 23:4219-4229(2003).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [19]
RP PHOSPHORYLATION AT SER-692; SER-695; THR-696 AND SER-852 BY PRKG1.
RX PubMed=15194681; DOI=10.1074/jbc.m405957200;
RA Wooldridge A.A., MacDonald J.A., Erdodi F., Ma C., Borman M.A.,
RA Hartshorne D.J., Haystead T.A.J.;
RT "Smooth muscle phosphatase is regulated in vivo by exclusion of
RT phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695
RT in response to cyclic nucleotides.";
RL J. Biol. Chem. 279:34496-34504(2004).
RN [20]
RP PHOSPHORYLATION AT THR-696.
RC TISSUE=Colon;
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 [21]
RP PHOSPHORYLATION BY ZIPK/DAPK3, AND INTERACTION WITH ZIPK/DAPK3.
RX PubMed=17126281; DOI=10.1016/j.abb.2006.09.026;
RA Takamoto N., Komatsu S., Komaba S., Niiro N., Ikebe M.;
RT "Novel ZIP kinase isoform lacks leucine zipper.";
RL Arch. Biochem. Biophys. 456:194-203(2006).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [23]
RP INTERACTION WITH NCKAP1L.
RX PubMed=16417406; DOI=10.1371/journal.pbio.0040038;
RA Weiner O.D., Rentel M.C., Ott A., Brown G.E., Jedrychowski M., Yaffe M.B.,
RA Gygi S.P., Cantley L.C., Bourne H.R., Kirschner M.W.;
RT "Hem-1 complexes are essential for Rac activation, actin polymerization,
RT and myosin regulation during neutrophil chemotaxis.";
RL PLoS Biol. 4:E38-E38(2006).
RN [24]
RP INTERACTION WITH PRKG1.
RX PubMed=17904578; DOI=10.1016/j.jmb.2007.08.049;
RA Lee E., Hayes D.B., Langsetmo K., Sundberg E.J., Tao T.C.;
RT "Interactions between the leucine-zipper motif of cGMP-dependent protein
RT kinase and the C-terminal region of the targeting subunit of myosin light
RT chain phosphatase.";
RL J. Mol. Biol. 373:1198-1212(2007).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-432; SER-473 AND
RP SER-601, PHOSPHORYLATION BY PLK1, AND MUTAGENESIS OF SER-473.
RX PubMed=18477460; DOI=10.1016/j.devcel.2008.02.013;
RA Yamashiro S., Yamakita Y., Totsukawa G., Goto H., Kaibuchi K., Ito M.,
RA Hartshorne D.J., Matsumura F.;
RT "Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing
RT polo-like kinase 1.";
RL Dev. Cell 14:787-797(2008).
RN [26]
RP INTERACTION WITH PRKG1, AND SUBUNIT.
RX PubMed=18782776; DOI=10.1074/jbc.m804916200;
RA Sharma A.K., Zhou G.-P., Kupferman J., Surks H.K., Christensen E.N.,
RA Chou J.J., Mendelsohn M.E., Rigby A.C.;
RT "Probing the interaction between the coiled coil leucine zipper of cGMP-
RT dependent protein kinase Ialpha and the C terminus of the myosin binding
RT subunit of the myosin light chain phosphatase.";
RL J. Biol. Chem. 283:32860-32869(2008).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299; SER-422; SER-445;
RP SER-477; SER-507; THR-696; SER-862 AND SER-871, AND IDENTIFICATION BY MASS
RP 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 [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [31]
RP PHOSPHORYLATION, AND INTERACTION WITH ROCK1 AND ROCK2.
RX PubMed=19131646; DOI=10.1161/circresaha.108.188524;
RA Wang Y., Zheng X.R., Riddick N., Bryden M., Baur W., Zhang X., Surks H.K.;
RT "ROCK isoform regulation of myosin phosphatase and contractility in
RT vascular smooth muscle cells.";
RL Circ. Res. 104:531-540(2009).
RN [32]
RP PHOSPHORYLATION AT THR-696.
RX PubMed=19997641; DOI=10.1371/journal.pone.0008190;
RA Lock F.E., Hotchin N.A.;
RT "Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte
RT differentiation.";
RL PLoS ONE 4:E8190-E8190(2009).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-871, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [34]
RP FUNCTION, INTERACTION WITH PPP1CB AND 14-3-3, DOMAIN KVKF MOTIF, AND
RP PHOSPHORYLATION AT SER-445; SER-472 AND SER-910.
RX PubMed=20354225; DOI=10.1126/scisignal.2000616;
RA Zagorska A., Deak M., Campbell D.G., Banerjee S., Hirano M., Aizawa S.,
RA Prescott A.R., Alessi D.R.;
RT "New roles for the LKB1-NUAK pathway in controlling myosin phosphatase
RT complexes and cell adhesion.";
RL Sci. Signal. 3:RA25-RA25(2010).
RN [35]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=20634291; DOI=10.1074/jbc.m110.143966;
RA Lontay B., Bodoor K., Weitzel D.H., Loiselle D., Fortner C., Lengyel S.,
RA Zheng D., Devente J., Hickner R., Haystead T.A.;
RT "Smoothelin-like 1 protein regulates myosin phosphatase-targeting subunit 1
RT expression during sexual development and pregnancy.";
RL J. Biol. Chem. 285:29357-29366(2010).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299; SER-422 AND SER-871, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [37]
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 [38]
RP PHOSPHORYLATION BY CDC42BP AND DMPK.
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 [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299; SER-422 AND SER-507, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299; SER-422; THR-443;
RP SER-445; TYR-446; SER-473; SER-507; SER-509; SER-618; THR-696; SER-903;
RP SER-908; SER-910 AND SER-995, 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 [42]
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 [43]
RP VARIANTS GUBS 472-SER--LYS-1030 DEL; 504-ARG--LYS-1030 DEL;
RP 678-SER--LYS-1030 DEL; 858-TRP--LYS-1030 DEL AND 900-ARG--LYS-1030 DEL, AND
RP INVOLVEMENT IN GUBS.
RX PubMed=31883643; DOI=10.1016/j.ajhg.2019.12.004;
RA Hughes J.J., Alkhunaizi E., Kruszka P., Pyle L.C., Grange D.K.,
RA Berger S.I., Payne K.K., Masser-Frye D., Hu T., Christie M.R., Clegg N.J.,
RA Everson J.L., Martinez A.F., Walsh L.E., Bedoukian E., Jones M.C.,
RA Harris C.J., Riedhammer K.M., Choukair D., Fechner P.Y., Rutter M.M.,
RA Hufnagel S.B., Roifman M., Kletter G.B., Delot E., Vilain E.,
RA Lipinski R.J., Vezina C.M., Muenke M., Chitayat D.;
RT "Loss-of-function variants in PPP1R12A: from isolated sex reversal to
RT holoprosencephaly spectrum and urogenital malformations.";
RL Am. J. Hum. Genet. 106:121-128(2020).
RN [44]
RP STRUCTURE BY NMR OF 658-714, AND PHOSPHORYLATION AT THR-696.
RX PubMed=19701943; DOI=10.1002/prot.22529;
RA Mori S., Iwaoka R., Eto M., Ohki S.-Y.;
RT "Solution structure of the inhibitory phosphorylation domain of myosin
RT phosphatase targeting subunit 1.";
RL Proteins 77:732-735(2009).
CC -!- FUNCTION: Key regulator of protein phosphatase 1C (PPP1C). Mediates
CC binding to myosin. As part of the PPP1C complex, involved in
CC dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent
CC suppression of HIF1A activity. {ECO:0000269|PubMed:18477460,
CC ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:20354225}.
CC -!- SUBUNIT: PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC,
CC and one or several targeting or regulatory subunits. PPP1R12A mediates
CC binding to myosin. Interacts with ARHA and CIT (By similarity). Binds
CC PPP1R12B, ROCK1 and IL16. Interacts directly with PRKG1. Non-covalent
CC dimer of 2 dimers; PRKG1-PRKG1 and PPP1R12A-PPP1R12A. Interacts with
CC SMTNL1 (By similarity). Interacts with PPP1CB; the interaction is
CC direct. Interacts (when phosphorylated at Ser-445, Ser-472 and Ser-910)
CC with 14-3-3. Interacts with ROCK1 and ROCK2. Interacts with isoform 1
CC and isoform 2 of ZIPK/DAPK3. Interacts with RAF1. Interacts with
CC HIF1AN. Interacts with NCKAP1L (PubMed:16417406).
CC {ECO:0000250|UniProtKB:Q9DBR7, ECO:0000269|PubMed:10567269,
CC ECO:0000269|PubMed:11067852, ECO:0000269|PubMed:11283607,
CC ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:12773565,
CC ECO:0000269|PubMed:12873707, ECO:0000269|PubMed:12923170,
CC ECO:0000269|PubMed:16417406, ECO:0000269|PubMed:17126281,
CC ECO:0000269|PubMed:17904578, ECO:0000269|PubMed:18782776,
CC ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:20354225}.
CC -!- INTERACTION:
CC O14974; Q9UBB4: ATXN10; NbExp=3; IntAct=EBI-351726, EBI-702390;
CC O14974; O43293: DAPK3; NbExp=5; IntAct=EBI-351726, EBI-77293;
CC O14974; P01100: FOS; NbExp=2; IntAct=EBI-351726, EBI-852851;
CC O14974; O18734: CPI17; Xeno; NbExp=2; IntAct=EBI-351726, EBI-15674919;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12923170,
CC ECO:0000269|PubMed:18477460}. Cytoplasm, cytoskeleton, stress fiber
CC {ECO:0000269|PubMed:12923170}. Note=Also along actomyosin filaments.
CC {ECO:0000269|PubMed:12923170}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=O14974-1; Sequence=Displayed;
CC Name=2; Synonyms=Myosin phosphatase target subunit 1 variant;
CC IsoId=O14974-2; Sequence=VSP_009253;
CC Name=3; Synonyms=Myosin phosphatase target subunit 1 variant 2;
CC IsoId=O14974-3; Sequence=VSP_009251;
CC Name=4;
CC IsoId=O14974-4; Sequence=VSP_009252;
CC Name=5;
CC IsoId=O14974-5; Sequence=VSP_045079;
CC -!- TISSUE SPECIFICITY: Expressed in striated muscles, specifically in type
CC 2a fibers (at protein level). {ECO:0000269|PubMed:20634291}.
CC -!- DEVELOPMENTAL STAGE: Induced by 2-fold during pregnancy, including in
CC abdominus rectus muscle. {ECO:0000269|PubMed:20634291}.
CC -!- DOMAIN: Heterotetramerization is mediated by the interaction between a
CC coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS,
CC the myosin-binding subunit of the myosin phosphatase. {ECO:0000250}.
CC -!- DOMAIN: The KVKF motif mediates interaction with PPP1CB.
CC {ECO:0000269|PubMed:20354225}.
CC -!- PTM: Phosphorylated by CIT (Rho-associated kinase) (By similarity).
CC Phosphorylated cooperatively by ROCK1 and CDC42BP on Thr-696.
CC Phosphorylated on upon DNA damage, probably by ATM or ATR. In vitro,
CC phosphorylation of Ser-695 by PKA and PKG appears to prevent
CC phosphorylation of the inhibitory site Thr-696, probably mediated by
CC PRKG1. Phosphorylation at Ser-445, Ser-472 and Ser-910 by NUAK1
CC promotes interaction with 14-3-3, leading to inhibit interaction with
CC myosin light chain MLC2, preventing dephosphorylation of MLC2. May be
CC phosphorylated at Thr-696 by DMPK; may inhibit the myosin phosphatase
CC activity. Phosphorylated at Ser-473 by CDK1 during mitosis, creating
CC docking sites for the POLO box domains of PLK1. Subsequently, PLK1
CC binds and phosphorylates PPP1R12A. {ECO:0000250,
CC ECO:0000269|PubMed:10567269, ECO:0000269|PubMed:11283607,
CC ECO:0000269|PubMed:11287000, ECO:0000269|PubMed:11331307,
CC ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:12773565,
CC ECO:0000269|PubMed:15194681, ECO:0000269|PubMed:15723050,
CC ECO:0000269|PubMed:17126281, ECO:0000269|PubMed:18477460,
CC ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19701943,
CC ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:20354225,
CC ECO:0000269|PubMed:21457715}.
CC -!- DISEASE: Genitourinary and/or brain malformation syndrome (GUBS)
CC [MIM:618820]: An autosomal dominant syndrome characterized by multiple
CC congenital anomalies including urogenital malformations and brain
CC abnormalities ranging from agenesis of the corpus callosum to
CC anencephaly. {ECO:0000269|PubMed:31883643}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH47898.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH92481.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; D87930; BAA22378.1; -; mRNA.
DR EMBL; AY380574; AAQ88438.1; -; mRNA.
DR EMBL; AF458589; AAM49717.1; -; mRNA.
DR EMBL; AK302692; BAG63921.1; -; mRNA.
DR EMBL; AC018476; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073569; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC074270; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047898; AAH47898.1; ALT_SEQ; mRNA.
DR EMBL; BC092481; AAH92481.1; ALT_SEQ; mRNA.
DR EMBL; BC111752; AAI11753.1; -; mRNA.
DR EMBL; AB042196; BAB39107.1; -; Genomic_DNA.
DR CCDS; CCDS44947.1; -. [O14974-1]
DR CCDS; CCDS44948.1; -. [O14974-5]
DR CCDS; CCDS58259.1; -. [O14974-3]
DR CCDS; CCDS58260.1; -. [O14974-2]
DR RefSeq; NP_001137357.1; NM_001143885.1. [O14974-1]
DR RefSeq; NP_001137358.1; NM_001143886.1. [O14974-5]
DR RefSeq; NP_001231919.1; NM_001244990.1. [O14974-2]
DR RefSeq; NP_001231921.1; NM_001244992.1. [O14974-3]
DR RefSeq; NP_002471.1; NM_002480.2. [O14974-1]
DR RefSeq; XP_011536685.1; XM_011538383.2.
DR PDB; 2KJY; NMR; -; A=658-714.
DR PDB; 5HUZ; NMR; -; A/B=931-978.
DR PDBsum; 2KJY; -.
DR PDBsum; 5HUZ; -.
DR AlphaFoldDB; O14974; -.
DR BMRB; O14974; -.
DR SMR; O14974; -.
DR BioGRID; 110742; 243.
DR CORUM; O14974; -.
DR DIP; DIP-33186N; -.
DR ELM; O14974; -.
DR IntAct; O14974; 104.
DR MINT; O14974; -.
DR STRING; 9606.ENSP00000389168; -.
DR GlyGen; O14974; 51 sites, 2 O-linked glycans (51 sites).
DR iPTMnet; O14974; -.
DR MetOSite; O14974; -.
DR PhosphoSitePlus; O14974; -.
DR BioMuta; PPP1R12A; -.
DR OGP; O14974; -.
DR EPD; O14974; -.
DR jPOST; O14974; -.
DR MassIVE; O14974; -.
DR MaxQB; O14974; -.
DR PaxDb; O14974; -.
DR PeptideAtlas; O14974; -.
DR PRIDE; O14974; -.
DR ProteomicsDB; 28963; -.
DR ProteomicsDB; 48344; -. [O14974-1]
DR ProteomicsDB; 48345; -. [O14974-2]
DR ProteomicsDB; 48346; -. [O14974-3]
DR ProteomicsDB; 48347; -. [O14974-4]
DR Antibodypedia; 29770; 637 antibodies from 38 providers.
DR DNASU; 4659; -.
DR Ensembl; ENST00000261207.9; ENSP00000261207.5; ENSG00000058272.19. [O14974-1]
DR Ensembl; ENST00000437004.6; ENSP00000416769.2; ENSG00000058272.19. [O14974-2]
DR Ensembl; ENST00000450142.7; ENSP00000389168.2; ENSG00000058272.19. [O14974-1]
DR Ensembl; ENST00000546369.5; ENSP00000449514.1; ENSG00000058272.19. [O14974-5]
DR Ensembl; ENST00000550107.5; ENSP00000446855.1; ENSG00000058272.19. [O14974-3]
DR GeneID; 4659; -.
DR KEGG; hsa:4659; -.
DR MANE-Select; ENST00000450142.7; ENSP00000389168.2; NM_002480.3; NP_002471.1.
DR UCSC; uc001syz.4; human. [O14974-1]
DR CTD; 4659; -.
DR DisGeNET; 4659; -.
DR GeneCards; PPP1R12A; -.
DR GeneReviews; PPP1R12A; -.
DR HGNC; HGNC:7618; PPP1R12A.
DR HPA; ENSG00000058272; Low tissue specificity.
DR MalaCards; PPP1R12A; -.
DR MIM; 602021; gene.
DR MIM; 618820; phenotype.
DR neXtProt; NX_O14974; -.
DR OpenTargets; ENSG00000058272; -.
DR PharmGKB; PA33617; -.
DR VEuPathDB; HostDB:ENSG00000058272; -.
DR eggNOG; KOG0505; Eukaryota.
DR GeneTree; ENSGT00940000156120; -.
DR InParanoid; O14974; -.
DR OMA; RKYETNA; -.
DR OrthoDB; 477969at2759; -.
DR PhylomeDB; O14974; -.
DR TreeFam; TF105543; -.
DR BRENDA; 3.1.3.53; 2681.
DR PathwayCommons; O14974; -.
DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-HSA-5625740; RHO GTPases activate PKNs.
DR Reactome; R-HSA-5625900; RHO GTPases activate CIT.
DR Reactome; R-HSA-5627117; RHO GTPases Activate ROCKs.
DR Reactome; R-HSA-5627123; RHO GTPases activate PAKs.
DR SignaLink; O14974; -.
DR SIGNOR; O14974; -.
DR BioGRID-ORCS; 4659; 689 hits in 1086 CRISPR screens.
DR ChiTaRS; PPP1R12A; human.
DR EvolutionaryTrace; O14974; -.
DR GeneWiki; PPP1R12A; -.
DR GenomeRNAi; 4659; -.
DR Pharos; O14974; Tbio.
DR PRO; PR:O14974; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O14974; protein.
DR Bgee; ENSG00000058272; Expressed in calcaneal tendon and 216 other tissues.
DR ExpressionAtlas; O14974; baseline and differential.
DR Genevisible; O14974; HS.
DR GO; GO:0031672; C:A band; ISS:UniProtKB.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0043292; C:contractile fiber; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0072357; C:PTW/PP1 phosphatase complex; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; ISS:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; IDA:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:UniProtKB.
DR GO; GO:0019208; F:phosphatase regulator activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0035508; P:positive regulation of myosin-light-chain-phosphatase activity; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IMP:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IDA:UniProtKB.
DR GO; GO:0035507; P:regulation of myosin-light-chain-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0046822; P:regulation of nucleocytoplasmic transport; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR DisProt; DP01163; -.
DR Gene3D; 1.25.40.20; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR017401; MYPT1/MYPT2/Mbs85.
DR InterPro; IPR031775; PRKG1_interact.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF15898; PRKG1_interact; 1.
DR PIRSF; PIRSF038141; PP1_12ABC_vert; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 6.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Disease variant; Hydroxylation; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1030
FT /note="Protein phosphatase 1 regulatory subunit 12A"
FT /id="PRO_0000067025"
FT REPEAT 39..68
FT /note="ANK 1"
FT REPEAT 72..101
FT /note="ANK 2"
FT REPEAT 105..134
FT /note="ANK 3"
FT REPEAT 138..164
FT /note="ANK 4"
FT REPEAT 198..227
FT /note="ANK 5"
FT REPEAT 231..260
FT /note="ANK 6"
FT REGION 290..628
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 643..928
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 682..864
FT /note="Interaction with ROCK2"
FT /evidence="ECO:0000269|PubMed:19131646"
FT MOTIF 35..38
FT /note="KVKF motif"
FT COMPBIAS 303..320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 321..355
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 374..416
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..436
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..614
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 643..659
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..686
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 708..764
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 766..813
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 814..842
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 872..886
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 887..901
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 67
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000269|PubMed:19245366"
FT MOD_RES 100
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000269|PubMed:19245366"
FT MOD_RES 226
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000269|PubMed:19245366"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18477460"
FT MOD_RES 443
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 445
FT /note="Phosphoserine; by NUAK1"
FT /evidence="ECO:0000269|PubMed:20354225,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 446
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 472
FT /note="Phosphoserine; by NUAK1"
FT /evidence="ECO:0000269|PubMed:20354225"
FT MOD_RES 473
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:18477460,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 601
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18477460"
FT MOD_RES 618
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 692
FT /note="Phosphoserine; by PKA and PKG; in vitro"
FT /evidence="ECO:0000269|PubMed:15194681"
FT MOD_RES 695
FT /note="Phosphoserine; by PKA and PKG; in vitro"
FT /evidence="ECO:0000269|PubMed:15194681"
FT MOD_RES 696
FT /note="Phosphothreonine; by ROCK1, ROCK2, CDC42BP,
FT ZIPK/DAPK3 and RAF1"
FT /evidence="ECO:0000269|PubMed:11719507,
FT ECO:0000269|PubMed:15194681, ECO:0000269|PubMed:15723050,
FT ECO:0000269|PubMed:19701943, ECO:0000269|PubMed:19997641,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 802
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR7"
FT MOD_RES 852
FT /note="Phosphoserine; by ROCK2"
FT /evidence="ECO:0000269|PubMed:11331307,
FT ECO:0000269|PubMed:15194681"
FT MOD_RES 862
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 871
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 903
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 908
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 910
FT /note="Phosphoserine; by NUAK1"
FT /evidence="ECO:0000269|PubMed:20354225,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 995
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..87
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045079"
FT VAR_SEQ 552..607
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_009251"
FT VAR_SEQ 608..666
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009252"
FT VAR_SEQ 935..969
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_009253"
FT VARIANT 116
FT /note="C -> W (in dbSNP:rs12582646)"
FT /id="VAR_038949"
FT VARIANT 305
FT /note="T -> P (in dbSNP:rs2596781)"
FT /id="VAR_038950"
FT VARIANT 472..1030
FT /note="Missing (in GUBS)"
FT /evidence="ECO:0000269|PubMed:31883643"
FT /id="VAR_083871"
FT VARIANT 504..1030
FT /note="Missing (in GUBS)"
FT /evidence="ECO:0000269|PubMed:31883643"
FT /id="VAR_083872"
FT VARIANT 678..1030
FT /note="Missing (in GUBS)"
FT /evidence="ECO:0000269|PubMed:31883643"
FT /id="VAR_083873"
FT VARIANT 734
FT /note="K -> N (in dbSNP:rs12820960)"
FT /id="VAR_038951"
FT VARIANT 858..1030
FT /note="Missing (in GUBS)"
FT /evidence="ECO:0000269|PubMed:31883643"
FT /id="VAR_083874"
FT VARIANT 900..1030
FT /note="Missing (in GUBS)"
FT /evidence="ECO:0000269|PubMed:31883643"
FT /id="VAR_083875"
FT MUTAGEN 445
FT /note="S->A: Abolishes phosphorylation by NUAK1 and
FT interaction with 14-3-3; when associated with A-472 and A-
FT 910."
FT MUTAGEN 472
FT /note="S->A: Abolishes phosphorylation by NUAK1 and
FT interaction with 14-3-3; when associated with A-445 and A-
FT 910."
FT MUTAGEN 473
FT /note="S->A: Abolishes binding to the POLO box domains of
FT PLK1."
FT /evidence="ECO:0000269|PubMed:18477460"
FT MUTAGEN 910
FT /note="S->A: Abolishes phosphorylation by NUAK1 and
FT interaction with 14-3-3; when associated with A-445 and A-
FT 472."
FT MUTAGEN 1007
FT /note="L->A: Loss of binding to PRKG1; when associated with
FT A-1014."
FT /evidence="ECO:0000269|PubMed:12873707"
FT MUTAGEN 1014
FT /note="L->A: Loss of binding to PRKG1; when associated with
FT A-1007."
FT /evidence="ECO:0000269|PubMed:12873707"
FT MUTAGEN 1021
FT /note="L->A: Loss of binding to PRKG1; when associated with
FT A-1028."
FT /evidence="ECO:0000269|PubMed:12873707"
FT MUTAGEN 1028
FT /note="L->A: Loss of binding to PRKG1; when associated with
FT A-1021."
FT /evidence="ECO:0000269|PubMed:12873707"
FT CONFLICT 2
FT /note="K -> Q (in Ref. 6; AAI11753)"
FT /evidence="ECO:0000305"
FT CONFLICT 322
FT /note="T -> A (in Ref. 6; AAH92481)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="K -> R (in Ref. 4; BAG63921)"
FT /evidence="ECO:0000305"
FT CONFLICT 653
FT /note="A -> V (in Ref. 6; AAH92481)"
FT /evidence="ECO:0000305"
FT CONFLICT 690
FT /note="R -> G (in Ref. 2; AAQ88438)"
FT /evidence="ECO:0000305"
FT CONFLICT 783
FT /note="S -> P (in Ref. 2; AAQ88438)"
FT /evidence="ECO:0000305"
FT CONFLICT 930
FT /note="T -> P (in Ref. 2; AAQ88438)"
FT /evidence="ECO:0000305"
FT CONFLICT 959
FT /note="D -> G (in Ref. 2; AAQ88438)"
FT /evidence="ECO:0000305"
FT CONFLICT 1027
FT /note="K -> Q (in Ref. 2; AAQ88438)"
FT /evidence="ECO:0000305"
FT HELIX 659..668
FT /evidence="ECO:0007829|PDB:2KJY"
FT HELIX 674..696
FT /evidence="ECO:0007829|PDB:2KJY"
FT TURN 699..701
FT /evidence="ECO:0007829|PDB:2KJY"
FT HELIX 702..710
FT /evidence="ECO:0007829|PDB:2KJY"
FT HELIX 932..965
FT /evidence="ECO:0007829|PDB:5HUZ"
SQ SEQUENCE 1030 AA; 115281 MW; EA43E9BFF5DA08FF CRC64;
MKMADAKQKR NEQLKRWIGS ETDLEPPVVK RQKTKVKFDD GAVFLAACSS GDTDEVLKLL
HRGADINYAN VDGLTALHQA CIDDNVDMVK FLVENGANIN QPDNEGWIPL HAAASCGYLD
IAEFLIGQGA HVGAVNSEGD TPLDIAEEEA MEELLQNEVN RQGVDIEAAR KEEERIMLRD
ARQWLNSGHI NDVRHAKSGG TALHVAAAKG YTEVLKLLIQ AGYDVNIKDY DGWTPLHAAA
HWGKEEACRI LVDNLCDMEM VNKVGQTAFD VADEDILGYL EELQKKQNLL HSEKRDKKSP
LIESTANMDN NQSQKTFKNK ETLIIEPEKN ASRIESLEQE KVDEEEEGKK DESSCSSEED
EEDDSESEAE TDKTKPLASV TNANTSSTQA APVAVTTPTV SSGQATPTSP IKKFPTTATK
ISPKEEERKD ESPATWRLGL RKTGSYGALA EITASKEGQK EKDTAGVTRS ASSPRLSSSL
DNKEKEKDSK GTRLAYVAPT IPRRLASTSD IEEKENRDSS SLRTSSSYTR RKWEDDLKKN
SSVNEGSTYH KSCSFGRRQD DLISSSVPST TSTPTVTSAA GLQKSLLSST STTTKITTGS
SSAGTQSSTS NRLWAEDSTE KEKDSVPTAV TIPVAPTVVN AAASTTTLTT TTAGTVSSTT
EVRERRRSYL TPVRDEESES QRKARSRQAR QSRRSTQGVT LTDLQEAEKT IGRSRSTRTR
EQENEEKEKE EKEKQDKEKQ EEKKESETSR EDEYKQKYSR TYDETYQRYR PVSTSSSTTP
SSSLSTMSSS LYASSQLNRP NSLVGITSAY SRGITKENER EGEKREEEKE GEDKSQPKSI
RERRRPREKR RSTGVSFWTQ DSDENEQEQQ SDTEEGSNKK ETQTDSISRY ETSSTSAGDR
YDSLLGRSGS YSYLEERKPY SSRLEKDDST DFKKLYEQIL AENEKLKAQL HDTNMELTDL
KLQLEKATQR QERFADRSLL EMEKRERRAL ERRISEMEEE LKMLPDLKAD NQRLKDENGA
LIRVISKLSK
