ID   PDK4_HUMAN              Reviewed;         411 AA.
AC   Q16654;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 202.
DE   RecName: Full=[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial;
DE            EC=2.7.11.2;
DE   AltName: Full=Pyruvate dehydrogenase kinase isoform 4;
DE   Flags: Precursor;
GN   Name=PDK4; Synonyms=PDHK4;
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 [GENOMIC DNA / MRNA].
RX   PubMed=8798399; DOI=10.1074/jbc.271.37.22376;
RA   Rowles J., Scherer S.W., Xi T., Majer M., Nickle D.C., Rommens J.M.,
RA   Popov K.M., Harris R.A., Riebow N.L., Xia J., Tsui L.-C., Bogardus C.,
RA   Prochazka M.;
RT   "Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate
RT   dehydrogenase kinase isoenzyme in human.";
RL   J. Biol. Chem. 271:22376-22382(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Cervix;
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   [4]
RP   TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=14966024; DOI=10.1152/japplphysiol.01318.2003;
RA   Spriet L.L., Tunstall R.J., Watt M.J., Mehan K.A., Hargreaves M.,
RA   Cameron-Smith D.;
RT   "Pyruvate dehydrogenase activation and kinase expression in human skeletal
RT   muscle during fasting.";
RL   J. Appl. Physiol. 96:2082-2087(2004).
RN   [5]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=15955060; DOI=10.1111/j.1742-4658.2005.04713.x;
RA   Abbot E.L., McCormack J.G., Reynet C., Hassall D.G., Buchan K.W.,
RA   Yeaman S.J.;
RT   "Diverging regulation of pyruvate dehydrogenase kinase isoform gene
RT   expression in cultured human muscle cells.";
RL   FEBS J. 272:3004-3014(2005).
RN   [6]
RP   INDUCTION BY PPARD.
RX   PubMed=17669420; DOI=10.1016/j.jmb.2007.06.091;
RA   Degenhardt T., Saramaki A., Malinen M., Rieck M., Vaisanen S., Huotari A.,
RA   Herzig K.H., Muller R., Carlberg C.;
RT   "Three members of the human pyruvate dehydrogenase kinase gene family are
RT   direct targets of the peroxisome proliferator-activated receptor
RT   beta/delta.";
RL   J. Mol. Biol. 372:341-355(2007).
RN   [7]
RP   FUNCTION.
RX   PubMed=21852536; DOI=10.1101/gad.16771811;
RA   Grassian A.R., Metallo C.M., Coloff J.L., Stephanopoulos G., Brugge J.S.;
RT   "Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell
RT   proliferation.";
RL   Genes Dev. 25:1716-1733(2011).
RN   [8]
RP   INDUCTION.
RX   PubMed=20715114; DOI=10.1002/ijc.25599;
RA   Blouin J.M., Penot G., Collinet M., Nacfer M., Forest C., Laurent-Puig P.,
RA   Coumoul X., Barouki R., Benelli C., Bortoli S.;
RT   "Butyrate elicits a metabolic switch in human colon cancer cells by
RT   targeting the pyruvate dehydrogenase complex.";
RL   Int. J. Cancer 128:2591-2601(2011).
RN   [9]
RP   FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX   PubMed=21816445; DOI=10.1016/j.metabol.2011.06.014;
RA   Kulkarni S.S., Salehzadeh F., Fritz T., Zierath J.R., Krook A., Osler M.E.;
RT   "Mitochondrial regulators of fatty acid metabolism reflect metabolic
RT   dysfunction in type 2 diabetes mellitus.";
RL   Metabolism 61:175-185(2012).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 20-411 IN COMPLEX WITH ATP,
RP   FUNCTION, ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF TYR-157;
RP   ARG-161; ASP-394 AND TRP-395.
RX   PubMed=18658136; DOI=10.1074/jbc.m802249200;
RA   Wynn R.M., Kato M., Chuang J.L., Tso S.C., Li J., Chuang D.T.;
RT   "Pyruvate dehydrogenase kinase-4 structures reveal a metastable open
RT   conformation fostering robust core-free basal activity.";
RL   J. Biol. Chem. 283:25305-25315(2008).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 20-411 IN COMPLEX WITH ATP
RP   ANALOG, CATALYTIC ACTIVITY, AND SUBUNIT.
RX   PubMed=21904029; DOI=10.1107/s090744491102405x;
RA   Kukimoto-Niino M., Tokmakov A., Terada T., Ohbayashi N., Fujimoto T.,
RA   Gomi S., Shiromizu I., Kawamoto M., Matsusue T., Shirouzu M., Yokoyama S.;
RT   "Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4.";
RL   Acta Crystallogr. D 67:763-773(2011).
RN   [12]
RP   VARIANTS [LARGE SCALE ANALYSIS] VAL-17; MET-19 AND GLY-109.
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: Kinase that plays a key role in regulation of glucose and
CC       fatty acid metabolism and homeostasis via phosphorylation of the
CC       pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate
CC       dehydrogenase activity, and thereby regulates metabolite flux through
CC       the tricarboxylic acid cycle, down-regulates aerobic respiration and
CC       inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition
CC       of pyruvate dehydrogenase decreases glucose utilization and increases
CC       fat metabolism in response to prolonged fasting and starvation. Plays
CC       an important role in maintaining normal blood glucose levels under
CC       starvation, and is involved in the insulin signaling cascade. Via its
CC       regulation of pyruvate dehydrogenase activity, plays an important role
CC       in maintaining normal blood pH and in preventing the accumulation of
CC       ketone bodies under starvation. In the fed state, mediates cellular
CC       responses to glucose levels and to a high-fat diet. Regulates both
CC       fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role
CC       in the generation of reactive oxygen species. Protects detached
CC       epithelial cells against anoikis. Plays a role in cell proliferation
CC       via its role in regulating carbohydrate and fatty acid metabolism.
CC       {ECO:0000269|PubMed:15955060, ECO:0000269|PubMed:18658136,
CC       ECO:0000269|PubMed:21816445, ECO:0000269|PubMed:21852536}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[pyruvate dehydrogenase E1 alpha subunit] = ADP
CC         + H(+) + O-phospho-L-seryl-[pyruvate dehydrogenase E1 alpha subunit];
CC         Xref=Rhea:RHEA:23052, Rhea:RHEA-COMP:13689, Rhea:RHEA-COMP:13690,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.2;
CC         Evidence={ECO:0000269|PubMed:21904029};
CC   -!- SUBUNIT: Homodimer. Interacts with the pyruvate dehydrogenase complex
CC       subunit DLAT, and is part of the multimeric pyruvate dehydrogenase
CC       complex that contains multiple copies of pyruvate dehydrogenase (E1),
CC       dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide
CC       dehydrogenase (DLD, E3). {ECO:0000269|PubMed:18658136,
CC       ECO:0000269|PubMed:21904029}.
CC   -!- INTERACTION:
CC       Q16654; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-2861674, EBI-742388;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC   -!- TISSUE SPECIFICITY: Ubiquitous; highest levels of expression in heart
CC       and skeletal muscle. {ECO:0000269|PubMed:14966024,
CC       ECO:0000269|PubMed:21816445}.
CC   -!- INDUCTION: Up-regulated by prolonged fasting, in glucose-deprived cells
CC       and in response to a high-fat diet. Down-regulated by insulin. Up-
CC       regulated by PPARD. {ECO:0000269|PubMed:14966024,
CC       ECO:0000269|PubMed:15955060, ECO:0000269|PubMed:17669420,
CC       ECO:0000269|PubMed:20715114, ECO:0000269|PubMed:21816445}.
CC   -!- SIMILARITY: Belongs to the PDK/BCKDK protein kinase family.
CC       {ECO:0000305}.
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DR   EMBL; U54628; AAC50670.1; -; Genomic_DNA.
DR   EMBL; U54618; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54619; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54620; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54621; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54622; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54623; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54624; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54625; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54626; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54627; AAC50670.1; JOINED; Genomic_DNA.
DR   EMBL; U54617; AAC50669.1; -; mRNA.
DR   EMBL; AC002451; AAB67048.1; -; Genomic_DNA.
DR   EMBL; BC040239; AAH40239.1; -; mRNA.
DR   CCDS; CCDS5643.1; -.
DR   RefSeq; NP_002603.1; NM_002612.3.
DR   PDB; 2E0A; X-ray; 1.86 A; A/B=20-411.
DR   PDB; 2ZDX; X-ray; 2.54 A; A/B=20-411.
DR   PDB; 2ZDY; X-ray; 2.40 A; A/B=20-411.
DR   PDB; 2ZKJ; X-ray; 2.00 A; A/B=20-411.
DR   PDB; 3D2R; X-ray; 2.03 A; A/B=20-411.
DR   PDB; 7EAT; X-ray; 2.10 A; A/B=10-411.
DR   PDB; 7EBB; X-ray; 1.90 A; A/B=10-411.
DR   PDB; 7EBG; X-ray; 1.95 A; A/B=10-411.
DR   PDBsum; 2E0A; -.
DR   PDBsum; 2ZDX; -.
DR   PDBsum; 2ZDY; -.
DR   PDBsum; 2ZKJ; -.
DR   PDBsum; 3D2R; -.
DR   PDBsum; 7EAT; -.
DR   PDBsum; 7EBB; -.
DR   PDBsum; 7EBG; -.
DR   AlphaFoldDB; Q16654; -.
DR   SMR; Q16654; -.
DR   BioGRID; 111192; 55.
DR   IntAct; Q16654; 48.
DR   STRING; 9606.ENSP00000005178; -.
DR   BindingDB; Q16654; -.
DR   ChEMBL; CHEMBL4141; -.
DR   DrugBank; DB08356; 4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol.
DR   DrugBank; DB00755; Tretinoin.
DR   DrugCentral; Q16654; -.
DR   GuidetoPHARMACOLOGY; 2144; -.
DR   iPTMnet; Q16654; -.
DR   PhosphoSitePlus; Q16654; -.
DR   BioMuta; PDK4; -.
DR   DMDM; 3183120; -.
DR   EPD; Q16654; -.
DR   jPOST; Q16654; -.
DR   MassIVE; Q16654; -.
DR   PaxDb; 9606-ENSP00000005178; -.
DR   PeptideAtlas; Q16654; -.
DR   ProteomicsDB; 61013; -.
DR   Pumba; Q16654; -.
DR   Antibodypedia; 15901; 678 antibodies from 36 providers.
DR   DNASU; 5166; -.
DR   Ensembl; ENST00000005178.6; ENSP00000005178.5; ENSG00000004799.8.
DR   GeneID; 5166; -.
DR   KEGG; hsa:5166; -.
DR   MANE-Select; ENST00000005178.6; ENSP00000005178.5; NM_002612.4; NP_002603.1.
DR   UCSC; uc003uoa.4; human.
DR   AGR; HGNC:8812; -.
DR   CTD; 5166; -.
DR   DisGeNET; 5166; -.
DR   GeneCards; PDK4; -.
DR   HGNC; HGNC:8812; PDK4.
DR   HPA; ENSG00000004799; Tissue enhanced (skeletal muscle, tongue).
DR   MIM; 602527; gene.
DR   neXtProt; NX_Q16654; -.
DR   OpenTargets; ENSG00000004799; -.
DR   PharmGKB; PA33157; -.
DR   VEuPathDB; HostDB:ENSG00000004799; -.
DR   eggNOG; KOG0787; Eukaryota.
DR   GeneTree; ENSGT01030000234646; -.
DR   HOGENOM; CLU_023861_1_1_1; -.
DR   InParanoid; Q16654; -.
DR   OMA; HQENCPS; -.
DR   OrthoDB; 3058550at2759; -.
DR   PhylomeDB; Q16654; -.
DR   TreeFam; TF314918; -.
DR   BRENDA; 2.7.11.2; 2681.
DR   PathwayCommons; Q16654; -.
DR   Reactome; R-HSA-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR   Reactome; R-HSA-5362517; Signaling by Retinoic Acid.
DR   SignaLink; Q16654; -.
DR   SIGNOR; Q16654; -.
DR   BioGRID-ORCS; 5166; 8 hits in 1195 CRISPR screens.
DR   ChiTaRS; PDK4; human.
DR   EvolutionaryTrace; Q16654; -.
DR   GeneWiki; PDK4; -.
DR   GenomeRNAi; 5166; -.
DR   Pharos; Q16654; Tchem.
DR   PRO; PR:Q16654; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q16654; Protein.
DR   Bgee; ENSG00000004799; Expressed in seminal vesicle and 188 other cell types or tissues.
DR   ExpressionAtlas; Q16654; baseline and differential.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR   GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR   GO; GO:0004740; F:pyruvate dehydrogenase (acetyl-transferring) kinase activity; EXP:Reactome.
DR   GO; GO:0071398; P:cellular response to fatty acid; IMP:UniProtKB.
DR   GO; GO:0009267; P:cellular response to starvation; IDA:UniProtKB.
DR   GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR   GO; GO:0008286; P:insulin receptor signaling pathway; IMP:UniProtKB.
DR   GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:UniProtKB.
DR   GO; GO:0010510; P:regulation of acetyl-CoA biosynthetic process from pyruvate; IMP:UniProtKB.
DR   GO; GO:0045124; P:regulation of bone resorption; IEA:Ensembl.
DR   GO; GO:0010565; P:regulation of cellular ketone metabolic process; ISS:UniProtKB.
DR   GO; GO:0042304; P:regulation of fatty acid biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0046320; P:regulation of fatty acid oxidation; ISS:UniProtKB.
DR   GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB.
DR   GO; GO:0006885; P:regulation of pH; ISS:UniProtKB.
DR   GO; GO:0042594; P:response to starvation; ISS:UniProtKB.
DR   CDD; cd16929; HATPase_PDK-like; 1.
DR   Gene3D; 1.20.140.20; Alpha-ketoacid/pyruvate dehydrogenase kinase, N-terminal domain; 1.
DR   Gene3D; 3.30.565.10; Histidine kinase-like ATPase, C-terminal domain; 1.
DR   InterPro; IPR036784; AK/P_DHK_N_sf.
DR   InterPro; IPR018955; BCDHK/PDK_N.
DR   InterPro; IPR039028; BCKD/PDK.
DR   InterPro; IPR003594; HATPase_C.
DR   InterPro; IPR036890; HATPase_C_sf.
DR   InterPro; IPR005467; His_kinase_dom.
DR   PANTHER; PTHR11947:SF22; [PYRUVATE DEHYDROGENASE (ACETYL-TRANSFERRING)] KINASE ISOZYME 4, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR11947; PYRUVATE DEHYDROGENASE KINASE; 1.
DR   Pfam; PF10436; BCDHK_Adom3; 1.
DR   Pfam; PF02518; HATPase_c; 1.
DR   SMART; SM00387; HATPase_c; 1.
DR   SUPFAM; SSF69012; alpha-ketoacid dehydrogenase kinase, N-terminal domain; 1.
DR   SUPFAM; SSF55874; ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase; 1.
DR   PROSITE; PS50109; HIS_KIN; 1.
DR   Genevisible; Q16654; HS.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Kinase; Mitochondrion; Nucleotide-binding;
KW   Reference proteome; Transferase; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..411
FT                   /note="[Pyruvate dehydrogenase (acetyl-transferring)]
FT                   kinase isozyme 4, mitochondrial"
FT                   /id="PRO_0000023445"
FT   DOMAIN          138..368
FT                   /note="Histidine kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT   BINDING         254..261
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:18658136"
FT   BINDING         293
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:18658136"
FT   BINDING         312..313
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:18658136"
FT   BINDING         329..334
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:18658136"
FT   SITE            157
FT                   /note="Interaction with the other subunit in the homodimer"
FT   SITE            161
FT                   /note="Interaction with the other subunit in the homodimer"
FT   SITE            395
FT                   /note="Interaction with the other subunit in the homodimer"
FT   VARIANT         17
FT                   /note="A -> V (in dbSNP:rs56391840)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042298"
FT   VARIANT         19
FT                   /note="L -> M (in dbSNP:rs55761955)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042299"
FT   VARIANT         109
FT                   /note="D -> G (in dbSNP:rs34898343)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042300"
FT   MUTAGEN         157
FT                   /note="Y->F: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:18658136"
FT   MUTAGEN         161
FT                   /note="R->A: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:18658136"
FT   MUTAGEN         394
FT                   /note="D->A: Loss of activity; when associated with A-395."
FT                   /evidence="ECO:0000269|PubMed:18658136"
FT   MUTAGEN         395
FT                   /note="W->A: Loss of activity; when associated with A-394."
FT                   /evidence="ECO:0000269|PubMed:18658136"
FT   HELIX           22..27
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           37..42
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   TURN            45..47
FT                   /evidence="ECO:0007829|PDB:7EBB"
FT   HELIX           50..72
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           77..80
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           83..100
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          103..105
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           110..127
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           130..142
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   TURN            149..151
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           153..180
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          194..199
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           200..219
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          225..234
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          240..243
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           245..266
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   TURN            267..269
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          270..272
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          276..282
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          284..293
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           300..302
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           303..306
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          328..330
FT                   /evidence="ECO:0007829|PDB:7EBG"
FT   HELIX           333..343
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          347..353
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   TURN            354..356
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   STRAND          357..367
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   TURN            368..370
FT                   /evidence="ECO:0007829|PDB:2E0A"
FT   HELIX           380..385
FT                   /evidence="ECO:0007829|PDB:2E0A"
SQ   SEQUENCE   411 AA;  46469 MW;  C17B78B6057000E9 CRC64;
     MKAARFVLRS AGSLNGAGLV PREVEHFSRY SPSPLSMKQL LDFGSENACE RTSFAFLRQE
     LPVRLANILK EIDILPTQLV NTSSVQLVKS WYIQSLMDLV EFHEKSPDDQ KALSDFVDTL
     IKVRNRHHNV VPTMAQGIIE YKDACTVDPV TNQNLQYFLD RFYMNRISTR MLMNQHILIF
     SDSQTGNPSH IGSIDPNCDV VAVVQDAFEC SRMLCDQYYL SSPELKLTQV NGKFPDQPIH
     IVYVPSHLHH MLFELFKNAM RATVEHQENQ PSLTPIEVIV VLGKEDLTIK ISDRGGGVPL
     RIIDRLFSYT YSTAPTPVMD NSRNAPLAGF GYGLPISRLY AKYFQGDLNL YSLSGYGTDA
     IIYLKALSSE SIEKLPVFNK SAFKHYQMSS EADDWCIPSR EPKNLAKEVA M
//