ID PPM1K_HUMAN Reviewed; 372 AA. AC Q8N3J5; B2RAZ1; Q05CT5; Q49AB5; Q4W5E6; Q56AN8; Q8IUZ7; Q8IXG7; Q8ND70; AC Q96NT4; DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 17-JUN-2020, entry version 147. DE RecName: Full=Protein phosphatase 1K, mitochondrial; DE EC=3.1.3.16; DE AltName: Full=PP2C domain-containing protein phosphatase 1K; DE AltName: Full=PP2C-like mitochondrial protein; DE AltName: Full=PP2C-type mitochondrial phosphoprotein phosphatase; DE Short=PTMP; DE AltName: Full=Protein phosphatase 2C isoform kappa; DE Short=PP2C-kappa; DE Flags: Precursor; GN Name=PPM1K; Synonyms=PP2CM; 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), FUNCTION, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF ASP-298. RX PubMed=17374715; DOI=10.1101/gad.1499107; RA Lu G., Ren S., Korge P., Choi J., Dong Y., Weiss J., Koehler C., RA Chen J.-N., Wang Y.; RT "A novel mitochondrial matrix serine/threonine protein phosphatase RT regulates the mitochondria permeability transition pore and is essential RT for cellular survival and development."; RL Genes Dev. 21:784-796(2007). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RA Mao Y., Xie Y., Dai J.; RT "Cloning and characterization of a novel human PP2C gene from fetal RT brain."; RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=17336929; DOI=10.1016/j.bbrc.2007.02.108; RA Joshi M.A., Jeoung N.H., Popov K.M., Harris R.A.; RT "Identification of a novel PP2C-type mitochondrial phosphatase."; RL Biochem. Biophys. Res. Commun. 356:38-44(2007). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Xu J., Stagliano N., Deponte J. III, Rodrigue-Way A., Golden S., Katz S., RA Jeyaseelan R., Donoghue M., Meyers R., Gottfried S., Wysong D., RA McGovern K., Pollman M., Breitbart R.E., Acton S.; RT "Protein phosphatase 2C kappa is upregulated in heart failure and RT attenuates agonist-induced cardiomyocyte hypertrophy."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cerebellum, and 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Amygdala, and Lymph node; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [8] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT RP LYS-94. RC TISSUE=Pancreas, and Testis; 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 [10] RP INVOLVEMENT IN MSUDMV. RX PubMed=23086801; DOI=10.1002/humu.22242; RA Oyarzabal A., Martinez-Pardo M., Merinero B., Navarrete R., Desviat L.R., RA Ugarte M., Rodriguez-Pombo P.; RT "A novel regulatory defect in the branched-chain alpha-keto acid RT dehydrogenase complex due to a mutation in the PPM1K gene causes a mild RT variant phenotype of maple syrup urine disease."; RL Hum. Mutat. 34:355-362(2013). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 89-351, AND MAGNESIUM-BINDING. RX PubMed=18058037; DOI=10.1007/s10969-007-9036-1; RA Almo S.C., Bonanno J.B., Sauder J.M., Emtage S., Dilorenzo T.P., RA Malashkevich V., Wasserman S.R., Swaminathan S., Eswaramoorthy S., RA Agarwal R., Kumaran D., Madegowda M., Ragumani S., Patskovsky Y., RA Alvarado J., Ramagopal U.A., Faber-Barata J., Chance M.R., Sali A., RA Fiser A., Zhang Z.Y., Lawrence D.S., Burley S.K.; RT "Structural genomics of protein phosphatases."; RL J. Struct. Funct. Genomics 8:121-140(2007). RN [12] RP VARIANT HIS-26. RX PubMed=23200863; DOI=10.1016/j.ajhg.2012.10.024; RA Charlesworth G., Plagnol V., Holmstroem K.M., Bras J., Sheerin U.M., RA Preza E., Rubio-Agusti I., Ryten M., Schneider S.A., Stamelou M., RA Trabzuni D., Abramov A.Y., Bhatia K.P., Wood N.W.; RT "Mutations in ANO3 cause dominant craniocervical dystonia: ion channel RT implicated in pathogenesis."; RL Am. J. Hum. Genet. 91:1041-1050(2012). CC -!- FUNCTION: Regulates the mitochondrial permeability transition pore and CC is essential for cellular survival and development. CC {ECO:0000269|PubMed:17374715}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83421; EC=3.1.3.16; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:61977; EC=3.1.3.16; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=10.7 mM for p-nitrophenylphosphate {ECO:0000269|PubMed:17336929}; CC Vmax=3.6 umol/min/mg enzyme toward p-nitrophenylphosphate (at 30 CC degrees Celsius) {ECO:0000269|PubMed:17336929}; CC Vmax=4 nmol/min/mg enzyme toward branched-chain alpha-ketoacid CC dehydrogenase complex (at 37 degrees Celsius) CC {ECO:0000269|PubMed:17336929}; CC Note=Half maximal activity toward p-nitrophenylphosphate achieved CC with 3.7 mM of manganese ions.; CC -!- INTERACTION: CC Q8N3J5; Q13490: BIRC2; NbExp=6; IntAct=EBI-3923368, EBI-514538; CC Q8N3J5; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-3923368, EBI-14103818; CC Q8N3J5; O75031: HSF2BP; NbExp=3; IntAct=EBI-3923368, EBI-7116203; CC Q8N3J5; P43364: MAGEA11; NbExp=3; IntAct=EBI-3923368, EBI-739552; CC Q8N3J5; Q5T124-6: UBXN11; NbExp=3; IntAct=EBI-3923368, EBI-11524408; CC Q8N3J5; Q96HA8: WDYHV1; NbExp=3; IntAct=EBI-3923368, EBI-741158; CC Q8N3J5; P98170: XIAP; NbExp=3; IntAct=EBI-3923368, EBI-517127; CC Q8N3J5; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-3923368, EBI-11741890; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:17336929, ECO:0000269|PubMed:17374715}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8N3J5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N3J5-2; Sequence=VSP_023158, VSP_023159; CC Name=3; CC IsoId=Q8N3J5-3; Sequence=VSP_023156, VSP_023157; CC -!- DISEASE: Maple syrup urine disease, mild variant (MSUDMV) [MIM:615135]: CC A mild form of maple syrup urine disease, a metabolic disorder due to CC an enzyme defect in the catabolic pathway of the branched-chain amino CC acids leucine, isoleucine, and valine. Accumulation of these 3 amino CC acids and their corresponding keto acids leads to encephalopathy and CC progressive neurodegeneration. Clinical features include mental and CC physical retardation, feeding problems, and a maple syrup odor to the CC urine. The keto acids of the branched-chain amino acids are present in CC the urine. If untreated, maple syrup urine disease can lead to CC seizures, coma, and death. The disease is often classified by its CC pattern of signs and symptoms. The most common and severe form of the CC disease is the classic type, which becomes apparent soon after birth. CC Variant forms of the disorder become apparent later in infancy or CC childhood and are typically milder, but they still involve CC developmental delay and other medical problems if not treated. MSUDMV CC is characterized by increased plasma levels of branched-chain amino CC acids (BCAA) apparent at birth. Treatment with a low-protein diet free CC of BCAA can result in normal psychomotor development and lack of CC metabolic episodes. {ECO:0000269|PubMed:23086801}. Note=The gene CC represented in this entry is involved in disease pathogenesis. CC -!- SIMILARITY: Belongs to the PP2C family. {ECO:0000305}. CC -!- CAUTION: PubMed:18058037 has crystallized PPM1K in the presence of CC magnesium ions. However, PubMed:17336929 reported that no activity CC toward p-nitrophenylphosphate was seen in the absence of manganese ions CC and magnesium could not substitute for manganese. {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; AY157615; AAO17296.1; -; mRNA. DR EMBL; AF351614; AAN76514.1; -; mRNA. DR EMBL; AY994097; AAX77016.1; -; mRNA. DR EMBL; AY435431; AAR06213.1; -; mRNA. DR EMBL; AK054678; BAB70790.1; -; mRNA. DR EMBL; AK314417; BAG37038.1; -; mRNA. DR EMBL; AL834167; CAD38869.2; -; mRNA. DR EMBL; AL834271; CAD38946.1; -; mRNA. DR EMBL; AC107067; AAY41021.1; -; Genomic_DNA. DR EMBL; AC108213; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471057; EAX06016.1; -; Genomic_DNA. DR EMBL; BC020850; AAH20850.1; ALT_TERM; mRNA. DR EMBL; BC037552; AAH37552.1; -; mRNA. DR EMBL; BC041350; AAH41350.1; -; mRNA. DR CCDS; CCDS3629.1; -. [Q8N3J5-1] DR RefSeq; NP_689755.3; NM_152542.4. [Q8N3J5-1] DR RefSeq; XP_006714174.1; XM_006714111.3. [Q8N3J5-1] DR RefSeq; XP_016863292.1; XM_017007803.1. [Q8N3J5-1] DR PDB; 2IQ1; X-ray; 2.25 A; A=89-351. DR PDB; 4DA1; X-ray; 2.38 A; A=84-360. DR PDB; 6AK7; X-ray; 2.60 A; A=90-349. DR PDBsum; 2IQ1; -. DR PDBsum; 4DA1; -. DR PDBsum; 6AK7; -. DR SMR; Q8N3J5; -. DR BioGRID; 127472; 26. DR IntAct; Q8N3J5; 35. DR MINT; Q8N3J5; -. DR STRING; 9606.ENSP00000477341; -. DR DEPOD; Q8N3J5; -. DR iPTMnet; Q8N3J5; -. DR PhosphoSitePlus; Q8N3J5; -. DR BioMuta; PPM1K; -. DR DMDM; 74750962; -. DR EPD; Q8N3J5; -. DR jPOST; Q8N3J5; -. DR MassIVE; Q8N3J5; -. DR PaxDb; Q8N3J5; -. DR PeptideAtlas; Q8N3J5; -. DR PRIDE; Q8N3J5; -. DR ProteomicsDB; 71811; -. [Q8N3J5-1] DR ProteomicsDB; 71812; -. [Q8N3J5-2] DR ProteomicsDB; 71813; -. [Q8N3J5-3] DR Antibodypedia; 14616; 148 antibodies. DR DNASU; 152926; -. DR Ensembl; ENST00000608933; ENSP00000477341; ENSG00000163644. [Q8N3J5-1] DR GeneID; 152926; -. DR KEGG; hsa:152926; -. DR UCSC; uc003hrm.6; human. [Q8N3J5-1] DR CTD; 152926; -. DR DisGeNET; 152926; -. DR EuPathDB; HostDB:ENSG00000163644.14; -. DR GeneCards; PPM1K; -. DR HGNC; HGNC:25415; PPM1K. DR HPA; ENSG00000163644; Tissue enhanced (heart). DR MalaCards; PPM1K; -. DR MIM; 611065; gene. DR MIM; 615135; phenotype. DR neXtProt; NX_Q8N3J5; -. DR OpenTargets; ENSG00000163644; -. DR Orphanet; 268162; Intermediate maple syrup urine disease. DR PharmGKB; PA134912083; -. DR eggNOG; KOG0698; Eukaryota. DR eggNOG; COG0631; LUCA. DR GeneTree; ENSGT00940000156633; -. DR HOGENOM; CLU_013173_1_3_1; -. DR InParanoid; Q8N3J5; -. DR KO; K17505; -. DR OMA; SNTRFDP; -. DR OrthoDB; 1044139at2759; -. DR PhylomeDB; Q8N3J5; -. DR TreeFam; TF354344; -. DR BRENDA; 3.1.3.16; 2681. DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism. DR SIGNOR; Q8N3J5; -. DR BioGRID-ORCS; 152926; 1 hit in 787 CRISPR screens. DR ChiTaRS; PPM1K; human. DR EvolutionaryTrace; Q8N3J5; -. DR GeneWiki; PPM1K; -. DR GenomeRNAi; 152926; -. DR Pharos; Q8N3J5; Tbio. DR PRO; PR:Q8N3J5; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q8N3J5; protein. DR Bgee; ENSG00000163644; Expressed in left ventricle myocardium and 205 other tissues. DR ExpressionAtlas; Q8N3J5; baseline and differential. DR Genevisible; Q8N3J5; HS. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0004724; F:magnesium-dependent protein serine/threonine phosphatase activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IBA:GO_Central. DR GO; GO:0009083; P:branched-chain amino acid catabolic process; TAS:Reactome. DR CDD; cd00143; PP2Cc; 1. DR Gene3D; 3.60.40.10; -; 1. DR InterPro; IPR015655; PP2C. DR InterPro; IPR000222; PP2C_BS. DR InterPro; IPR036457; PPM-type_dom_sf. DR InterPro; IPR001932; PPM-type_phosphatase_dom. DR PANTHER; PTHR13832; PTHR13832; 1. DR Pfam; PF00481; PP2C; 1. DR SMART; SM00331; PP2C_SIG; 1. DR SMART; SM00332; PP2Cc; 1. DR SUPFAM; SSF81606; SSF81606; 1. DR PROSITE; PS01032; PPM_1; 1. DR PROSITE; PS51746; PPM_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Hydrolase; Magnesium; Manganese; KW Metal-binding; Mitochondrion; Phosphoprotein; Polymorphism; KW Protein phosphatase; Reference proteome; Transit peptide. FT TRANSIT 1..29 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 30..372 FT /note="Protein phosphatase 1K, mitochondrial" FT /id="PRO_0000278208" FT DOMAIN 94..346 FT /note="PPM-type phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082" FT METAL 127 FT /note="Magnesium" FT METAL 128 FT /note="Magnesium; via carbonyl oxygen" FT METAL 337 FT /note="Magnesium" FT MOD_RES 248 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BXN7" FT VAR_SEQ 148..150 FT /note="DLL -> YVQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023156" FT VAR_SEQ 151..372 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023157" FT VAR_SEQ 181..233 FT /note="ATLLTSGTTATVALLRDGIELVVASVGDSRAILCRKGKPMKLTIDHTPERKD FT E -> ENCAWSAALDLEPVDTICGASVEREICLILSQVKESSGSYPGLREGSHISLSH FT (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_023158" FT VAR_SEQ 234..372 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_023159" FT VARIANT 26 FT /note="R -> H (in dbSNP:rs369916009)" FT /evidence="ECO:0000269|PubMed:23200863" FT /id="VAR_069736" FT VARIANT 94 FT /note="N -> K (in dbSNP:rs17853762)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_030691" FT VARIANT 321 FT /note="E -> K (in dbSNP:rs35523553)" FT /id="VAR_050621" FT MUTAGEN 298 FT /note="D->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:17374715" FT CONFLICT 17 FT /note="V -> A (in Ref. 3; AAX77016)" FT /evidence="ECO:0000305" FT CONFLICT 194 FT /note="L -> I (in Ref. 3; AAX77016)" FT /evidence="ECO:0000305" FT CONFLICT 211 FT /note="A -> V (in Ref. 9; AAH20850)" FT /evidence="ECO:0000305" FT CONFLICT 264 FT /note="I -> V (in Ref. 5; BAB70790)" FT /evidence="ECO:0000305" FT HELIX 92..94 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 96..100 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 103..106 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 109..115 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 117..131 FT /evidence="ECO:0000244|PDB:2IQ1" FT HELIX 133..149 FT /evidence="ECO:0000244|PDB:2IQ1" FT TURN 150..152 FT /evidence="ECO:0000244|PDB:2IQ1" FT HELIX 156..176 FT /evidence="ECO:0000244|PDB:2IQ1" FT HELIX 183..185 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 190..196 FT /evidence="ECO:0000244|PDB:2IQ1" FT TURN 197..199 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 200..208 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 210..215 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 218..221 FT /evidence="ECO:0000244|PDB:2IQ1" FT HELIX 231..239 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 244..246 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 252..254 FT /evidence="ECO:0000244|PDB:2IQ1" FT TURN 255..257 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 258..262 FT /evidence="ECO:0000244|PDB:6AK7" FT HELIX 267..269 FT /evidence="ECO:0000244|PDB:2IQ1" FT TURN 270..273 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 279..284 FT /evidence="ECO:0000244|PDB:2IQ1" FT TURN 287..289 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 290..296 FT /evidence="ECO:0000244|PDB:2IQ1" FT HELIX 298..301 FT /evidence="ECO:0000244|PDB:2IQ1" FT HELIX 306..314 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 316..318 FT /evidence="ECO:0000244|PDB:2IQ1" FT HELIX 319..332 FT /evidence="ECO:0000244|PDB:2IQ1" FT STRAND 339..345 FT /evidence="ECO:0000244|PDB:2IQ1" SQ SEQUENCE 372 AA; 40997 MW; 9DD37EEC0EAD3313 CRC64; MSTAALITLV RSGGNQVRRR VLLSSRLLQD DRRVTPTCHS STSEPRCSRF DPDGSGSPAT WDNFGIWDNR IDEPILLPPS IKYGKPIPKI SLENVGCASQ IGKRKENEDR FDFAQLTDEV LYFAVYDGHG GPAAADFCHT HMEKCIMDLL PKEKNLETLL TLAFLEIDKA FSSHARLSAD ATLLTSGTTA TVALLRDGIE LVVASVGDSR AILCRKGKPM KLTIDHTPER KDEKERIKKC GGFVAWNSLG QPHVNGRLAM TRSIGDLDLK TSGVIAEPET KRIKLHHADD SFLVLTTDGI NFMVNSQEIC DFVNQCHDPN EAAHAVTEQA IQYGTEDNST AVVVPFGAWG KYKNSEINFS FSRSFASSGR WA //