IDHC_HUMAN
ID IDHC_HUMAN Reviewed; 414 AA.
AC O75874; Q567U4; Q6FHQ6; Q7Z3V0; Q93090; Q9NTJ9; Q9UKW8;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2002, sequence version 2.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Isocitrate dehydrogenase [NADP] cytoplasmic;
DE Short=IDH;
DE Short=IDH1 {ECO:0000303|PubMed:19935646};
DE EC=1.1.1.42 {ECO:0000269|PubMed:10521434, ECO:0000269|PubMed:19935646};
DE AltName: Full=Cytosolic NADP-isocitrate dehydrogenase;
DE AltName: Full=IDPc;
DE AltName: Full=NADP(+)-specific ICDH;
DE AltName: Full=Oxalosuccinate decarboxylase;
GN Name=IDH1; Synonyms=PICD;
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].
RX PubMed=9866202; DOI=10.1093/oxfordjournals.molbev.a025894;
RA Nekrutenko A., Hillis D.M., Patton J.C., Bradley R.D., Baker R.J.;
RT "Cytosolic isocitrate dehydrogenase in humans, mice, and voles and
RT phylogenetic analysis of the enzyme family.";
RL Mol. Biol. Evol. 15:1674-1684(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, FUNCTION, CATALYTIC
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10521434; DOI=10.1074/jbc.274.43.30527;
RA Geisbrecht B.V., Gould S.J.;
RT "The human PICD gene encodes a cytoplasmic and peroxisomal NADP(+)-
RT dependent isocitrate dehydrogenase.";
RL J. Biol. Chem. 274:30527-30533(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Endometrium;
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Placenta;
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 [9]
RP PROTEIN SEQUENCE OF 5-20; 30-49; 101-109; 120-132; 141-212; 223-233;
RP 250-270; 322-338 AND 389-400, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 100-253.
RA Kullmann F., Vogt T., Welsh J., McClelland M.;
RT "Differential gene expression in epithelial cells induced by bile salts:
RT identification by RNA arbitrarily primed PCR.";
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-321, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-42, AND IDENTIFICATION BY
RP 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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [16] {ECO:0007744|PDB:1T09, ECO:0007744|PDB:1T0L}
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEXES WITH NADP; ISOCITRATE
RP AND CALCIUM IONS, AND SUBUNIT.
RX PubMed=15173171; DOI=10.1074/jbc.m404298200;
RA Xu X., Zhao J., Xu Z., Peng B., Huang Q., Arnold E., Ding J.;
RT "Structures of human cytosolic NADP-dependent isocitrate dehydrogenase
RT reveal a novel self-regulatory mechanism of activity.";
RL J. Biol. Chem. 279:33946-33957(2004).
RN [17] {ECO:0007744|PDB:3INM}
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF VARIANT HIS-132 IN COMPLEX WITH
RP NADP AND ALPHA-KETOGLUTARATE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF VARIANTS
RP CYS-132; HIS-132; LEU-132 AND SER-132, INVOLVEMENT IN DISEASE, AND
RP INVOLVEMENT IN GLM.
RX PubMed=19935646; DOI=10.1038/nature08617;
RA Dang L., White D.W., Gross S., Bennett B.D., Bittinger M.A., Driggers E.M.,
RA Fantin V.R., Jang H.G., Jin S., Keenan M.C., Marks K.M., Prins R.M.,
RA Ward P.S., Yen K.E., Liau L.M., Rabinowitz J.D., Cantley L.C.,
RA Thompson C.B., Vander Heiden M.G., Su S.M.;
RT "Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.";
RL Nature 462:739-744(2009).
RN [18]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-132.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [19]
RP VARIANTS HIS-132 AND SER-132.
RX PubMed=18772396; DOI=10.1126/science.1164382;
RA Parsons D.W., Jones S., Zhang X., Lin J.C.-H., Leary R.J., Angenendt P.,
RA Mankoo P., Carter H., Siu I.-M., Gallia G.L., Olivi A., McLendon R.,
RA Rasheed B.A., Keir S., Nikolskaya T., Nikolsky Y., Busam D.A., Tekleab H.,
RA Diaz L.A. Jr., Hartigan J., Smith D.R., Strausberg R.L., Marie S.K.N.,
RA Shinjo S.M.O., Yan H., Riggins G.J., Bigner D.D., Karchin R.,
RA Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E.,
RA Kinzler K.W.;
RT "An integrated genomic analysis of human glioblastoma multiforme.";
RL Science 321:1807-1812(2008).
RN [20]
RP VARIANTS CYS-132; GLY-132 AND LEU-132, AND INVOLVEMENT IN GLM.
RX PubMed=19117336; DOI=10.1002/humu.20937;
RA Bleeker F.E., Lamba S., Leenstra S., Troost D., Hulsebos T.,
RA Vandertop W.P., Frattini M., Molinari F., Knowles M., Cerrato A.,
RA Rodolfo M., Scarpa A., Felicioni L., Buttitta F., Malatesta S.,
RA Marchetti A., Bardelli A.;
RT "IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-
RT grade gliomas but not in other solid tumors.";
RL Hum. Mutat. 30:7-11(2009).
RN [21]
RP VARIANTS CYS-132; GLY-132 AND HIS-132, INVOLVEMENT IN DISEASE, AND
RP CHARACTERIZATION OF VARIANT CYS-132.
RX PubMed=26161668; DOI=10.1371/journal.pone.0131998;
RA Jin Y., Elalaf H., Watanabe M., Tamaki S., Hineno S., Matsunaga K.,
RA Woltjen K., Kobayashi Y., Nagata S., Ikeya M., Kato T. Jr., Okamoto T.,
RA Matsuda S., Toguchida J.;
RT "Mutant IDH1 Dysregulates the Differentiation of Mesenchymal Stem Cells in
RT Association with Gene-Specific Histone Modifications to Cartilage- and
RT Bone-Related Genes.";
RL PLoS ONE 10:E0131998-E0131998(2015).
CC -!- FUNCTION: Catalyzes the NADP(+)-dependent oxidative decarboxylation of
CC isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate),
CC which is required by other enzymes such as the phytanoyl-CoA
CC dioxygenase (PubMed:10521434, PubMed:19935646). Plays a critical role
CC in the generation of NADPH, an important cofactor in many biosynthesis
CC pathways (PubMed:10521434). May act as a corneal epithelial crystallin
CC and may be involved in maintaining corneal epithelial transparency (By
CC similarity). {ECO:0000250|UniProtKB:Q9XSG3,
CC ECO:0000269|PubMed:10521434, ECO:0000269|PubMed:19935646,
CC ECO:0000303|PubMed:10521434}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH;
CC Xref=Rhea:RHEA:19629, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.42;
CC Evidence={ECO:0000269|PubMed:10521434, ECO:0000269|PubMed:19935646};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19630;
CC Evidence={ECO:0000269|PubMed:19935646};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19935646};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:19935646};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.
CC {ECO:0000269|PubMed:19935646};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=112 uM for NADP(+) {ECO:0000269|PubMed:10521434};
CC KM=49 uM for NADP(+) {ECO:0000269|PubMed:19935646};
CC KM=29 uM for magnesium chloride {ECO:0000269|PubMed:19935646};
CC KM=76 uM for isocitrate {ECO:0000269|PubMed:10521434};
CC KM=65 uM for isocitrate {ECO:0000269|PubMed:19935646};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15173171,
CC ECO:0000269|PubMed:19935646}.
CC -!- INTERACTION:
CC O75874; P0DP23: CALM1; NbExp=7; IntAct=EBI-715695, EBI-25817233;
CC O75874; P27797: CALR; NbExp=3; IntAct=EBI-715695, EBI-1049597;
CC O75874; P36957: DLST; NbExp=3; IntAct=EBI-715695, EBI-351007;
CC O75874; O75874: IDH1; NbExp=4; IntAct=EBI-715695, EBI-715695;
CC O75874; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-715695, EBI-1055945;
CC O75874; P16284: PECAM1; NbExp=3; IntAct=EBI-715695, EBI-716404;
CC O75874; P17612: PRKACA; NbExp=3; IntAct=EBI-715695, EBI-476586;
CC O75874; P50454: SERPINH1; NbExp=3; IntAct=EBI-715695, EBI-350723;
CC O75874; P37173: TGFBR2; NbExp=3; IntAct=EBI-715695, EBI-296151;
CC O75874; Q05086-3: UBE3A; NbExp=3; IntAct=EBI-715695, EBI-11026619;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10521434}.
CC Peroxisome {ECO:0000269|PubMed:10521434}.
CC -!- PTM: Acetylation at Lys-374 dramatically reduces catalytic activity.
CC {ECO:0000250}.
CC -!- DISEASE: Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant
CC central nervous system neoplasms derived from glial cells. They
CC comprise astrocytomas and glioblastoma multiforme that are derived from
CC astrocytes, oligodendrogliomas derived from oligodendrocytes and
CC ependymomas derived from ependymocytes. {ECO:0000269|PubMed:19117336,
CC ECO:0000269|PubMed:19935646}. Note=The gene represented in this entry
CC is involved in disease pathogenesis. Mutations affecting Arg-132 are
CC tissue-specific, and suggest that this residue plays a unique role in
CC the development of high-grade gliomas. Mutations of Arg-132 to Cys,
CC His, Leu or Ser abolish magnesium binding and abolish the conversion of
CC isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is
CC converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-
CC hydroxyglutarate are correlated with an elevated risk of malignant
CC brain tumors. {ECO:0000269|PubMed:19935646}.
CC -!- DISEASE: Note=Genetic variations are associated with cartilaginous
CC tumors such as enchondroma or chondrosarcoma. Mutations of Arg-132 to
CC Cys, Gly or His abolish the conversion of isocitrate to alpha-
CC ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-
CC hydroxyglutarate. {ECO:0000269|PubMed:26161668}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Isocitrate dehydrogenase entry;
CC URL="https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase";
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DR EMBL; AF020038; AAD02918.1; -; mRNA.
DR EMBL; AF113917; AAD29284.1; -; mRNA.
DR EMBL; AL136702; CAB66637.1; -; mRNA.
DR EMBL; CR541695; CAG46496.1; -; mRNA.
DR EMBL; BX537411; CAD97653.1; -; mRNA.
DR EMBL; AC016697; AAX93221.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70439.1; -; Genomic_DNA.
DR EMBL; BC012846; AAH12846.1; -; mRNA.
DR EMBL; BC093020; AAH93020.1; -; mRNA.
DR EMBL; U62389; AAB17375.1; -; mRNA.
DR CCDS; CCDS2381.1; -.
DR PIR; T46280; T46280.
DR RefSeq; NP_001269315.1; NM_001282386.1.
DR RefSeq; NP_001269316.1; NM_001282387.1.
DR RefSeq; NP_005887.2; NM_005896.3.
DR PDB; 1T09; X-ray; 2.70 A; A/B=1-414.
DR PDB; 1T0L; X-ray; 2.41 A; A/B/C/D=1-414.
DR PDB; 3INM; X-ray; 2.10 A; A/B/C=1-414.
DR PDB; 3MAP; X-ray; 2.80 A; A/B=1-414.
DR PDB; 3MAR; X-ray; 3.41 A; A/B=1-414.
DR PDB; 3MAS; X-ray; 3.20 A; A/B=1-414.
DR PDB; 4I3K; X-ray; 3.31 A; A/B=1-414.
DR PDB; 4I3L; X-ray; 3.29 A; A/B=1-414.
DR PDB; 4KZO; X-ray; 2.20 A; A/B/C=1-414.
DR PDB; 4L03; X-ray; 2.10 A; A/B/C=1-414.
DR PDB; 4L04; X-ray; 2.87 A; A/B/C/D/E/F=1-414.
DR PDB; 4L06; X-ray; 2.28 A; A/B/C/D/E/F=1-414.
DR PDB; 4UMX; X-ray; 1.88 A; A/B=1-414.
DR PDB; 4UMY; X-ray; 2.07 A; A/B=1-414.
DR PDB; 4XRX; X-ray; 3.20 A; A/B=1-414.
DR PDB; 4XS3; X-ray; 3.29 A; A/B=1-414.
DR PDB; 5DE1; X-ray; 2.25 A; A/B=2-414.
DR PDB; 5GIR; X-ray; 1.93 A; C/D=126-137.
DR PDB; 5K10; EM; 3.80 A; A/B=3-413.
DR PDB; 5K11; EM; 3.80 A; A/B=3-413.
DR PDB; 5L57; X-ray; 2.69 A; A=1-414.
DR PDB; 5L58; X-ray; 3.04 A; A=1-414.
DR PDB; 5LGE; X-ray; 2.70 A; A/B/C/D=1-414.
DR PDB; 5SUN; X-ray; 2.48 A; A/B=1-414.
DR PDB; 5SVF; X-ray; 2.34 A; A/B/C/D=1-414.
DR PDB; 5TQH; X-ray; 2.20 A; A/B/C/D=1-414.
DR PDB; 5YFM; X-ray; 2.40 A; A/B/C=1-414.
DR PDB; 5YFN; X-ray; 2.50 A; A/B=1-414.
DR PDB; 6ADG; X-ray; 3.00 A; A/B/C=1-414.
DR PDB; 6B0Z; X-ray; 2.33 A; A/B/C/D=1-414.
DR PDB; 6BKX; X-ray; 1.65 A; A/B/C=1-414.
DR PDB; 6BKY; X-ray; 2.17 A; A/B/C/D/E/F=1-414.
DR PDB; 6BKZ; X-ray; 2.01 A; A/B=1-414.
DR PDB; 6BL0; X-ray; 2.17 A; A/B/C=1-414.
DR PDB; 6BL1; X-ray; 2.02 A; A/B/C=1-414.
DR PDB; 6BL2; X-ray; 1.92 A; A/B/C=1-414.
DR PDB; 6IO0; X-ray; 2.20 A; A/B=1-414.
DR PDB; 6O2Y; X-ray; 2.80 A; A/B/C=1-414.
DR PDB; 6O2Z; X-ray; 2.50 A; A/B=1-414.
DR PDB; 6PAY; X-ray; 2.20 A; A/B/C/D=1-414.
DR PDB; 6Q6F; X-ray; 3.30 A; A/B=1-414.
DR PDB; 6U4J; X-ray; 2.11 A; A/B=1-414.
DR PDB; 6VEI; X-ray; 2.10 A; A/B=1-414.
DR PDB; 6VG0; X-ray; 2.66 A; A/B/C=1-414.
DR PDBsum; 1T09; -.
DR PDBsum; 1T0L; -.
DR PDBsum; 3INM; -.
DR PDBsum; 3MAP; -.
DR PDBsum; 3MAR; -.
DR PDBsum; 3MAS; -.
DR PDBsum; 4I3K; -.
DR PDBsum; 4I3L; -.
DR PDBsum; 4KZO; -.
DR PDBsum; 4L03; -.
DR PDBsum; 4L04; -.
DR PDBsum; 4L06; -.
DR PDBsum; 4UMX; -.
DR PDBsum; 4UMY; -.
DR PDBsum; 4XRX; -.
DR PDBsum; 4XS3; -.
DR PDBsum; 5DE1; -.
DR PDBsum; 5GIR; -.
DR PDBsum; 5K10; -.
DR PDBsum; 5K11; -.
DR PDBsum; 5L57; -.
DR PDBsum; 5L58; -.
DR PDBsum; 5LGE; -.
DR PDBsum; 5SUN; -.
DR PDBsum; 5SVF; -.
DR PDBsum; 5TQH; -.
DR PDBsum; 5YFM; -.
DR PDBsum; 5YFN; -.
DR PDBsum; 6ADG; -.
DR PDBsum; 6B0Z; -.
DR PDBsum; 6BKX; -.
DR PDBsum; 6BKY; -.
DR PDBsum; 6BKZ; -.
DR PDBsum; 6BL0; -.
DR PDBsum; 6BL1; -.
DR PDBsum; 6BL2; -.
DR PDBsum; 6IO0; -.
DR PDBsum; 6O2Y; -.
DR PDBsum; 6O2Z; -.
DR PDBsum; 6PAY; -.
DR PDBsum; 6Q6F; -.
DR PDBsum; 6U4J; -.
DR PDBsum; 6VEI; -.
DR PDBsum; 6VG0; -.
DR AlphaFoldDB; O75874; -.
DR SMR; O75874; -.
DR BioGRID; 109643; 95.
DR CORUM; O75874; -.
DR DIP; DIP-59311N; -.
DR IntAct; O75874; 31.
DR MINT; O75874; -.
DR STRING; 9606.ENSP00000390265; -.
DR BindingDB; O75874; -.
DR ChEMBL; CHEMBL2007625; -.
DR DrugBank; DB09374; Indocyanine green acid form.
DR DrugBank; DB01727; Isocitric Acid.
DR DrugBank; DB14568; Ivosidenib.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugCentral; O75874; -.
DR GuidetoPHARMACOLOGY; 2884; -.
DR GlyGen; O75874; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75874; -.
DR MetOSite; O75874; -.
DR PhosphoSitePlus; O75874; -.
DR SwissPalm; O75874; -.
DR BioMuta; IDH1; -.
DR OGP; O75874; -.
DR REPRODUCTION-2DPAGE; IPI00027223; -.
DR UCD-2DPAGE; O75874; -.
DR EPD; O75874; -.
DR jPOST; O75874; -.
DR MassIVE; O75874; -.
DR PaxDb; O75874; -.
DR PeptideAtlas; O75874; -.
DR PRIDE; O75874; -.
DR ProteomicsDB; 50234; -.
DR ABCD; O75874; 4 sequenced antibodies.
DR Antibodypedia; 34198; 988 antibodies from 47 providers.
DR DNASU; 3417; -.
DR Ensembl; ENST00000345146.7; ENSP00000260985.2; ENSG00000138413.14.
DR Ensembl; ENST00000415913.5; ENSP00000390265.1; ENSG00000138413.14.
DR Ensembl; ENST00000446179.5; ENSP00000410513.1; ENSG00000138413.14.
DR GeneID; 3417; -.
DR KEGG; hsa:3417; -.
DR MANE-Select; ENST00000345146.7; ENSP00000260985.2; NM_005896.4; NP_005887.2.
DR CTD; 3417; -.
DR DisGeNET; 3417; -.
DR GeneCards; IDH1; -.
DR HGNC; HGNC:5382; IDH1.
DR HPA; ENSG00000138413; Tissue enhanced (liver).
DR MalaCards; IDH1; -.
DR MIM; 137800; phenotype.
DR MIM; 147700; gene.
DR neXtProt; NX_O75874; -.
DR OpenTargets; ENSG00000138413; -.
DR Orphanet; 251579; Giant cell glioblastoma.
DR Orphanet; 251576; Gliosarcoma.
DR Orphanet; 163634; Maffucci syndrome.
DR Orphanet; 99646; Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria.
DR Orphanet; 296; Ollier disease.
DR PharmGKB; PA29630; -.
DR VEuPathDB; HostDB:ENSG00000138413; -.
DR eggNOG; KOG1526; Eukaryota.
DR GeneTree; ENSGT00390000012547; -.
DR HOGENOM; CLU_023296_1_1_1; -.
DR InParanoid; O75874; -.
DR OMA; HGTVQRH; -.
DR OrthoDB; 511880at2759; -.
DR PhylomeDB; O75874; -.
DR TreeFam; TF300428; -.
DR BioCyc; MetaCyc:HS06502-MON; -.
DR BRENDA; 1.1.1.42; 2681.
DR PathwayCommons; O75874; -.
DR Reactome; R-HSA-2978092; Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate.
DR Reactome; R-HSA-389542; NADPH regeneration.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2.
DR SABIO-RK; O75874; -.
DR SignaLink; O75874; -.
DR SIGNOR; O75874; -.
DR BioGRID-ORCS; 3417; 19 hits in 1070 CRISPR screens.
DR ChiTaRS; IDH1; human.
DR EvolutionaryTrace; O75874; -.
DR GeneWiki; IDH1; -.
DR GenomeRNAi; 3417; -.
DR Pharos; O75874; Tclin.
DR PRO; PR:O75874; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O75874; protein.
DR Bgee; ENSG00000138413; Expressed in corpus epididymis and 210 other tissues.
DR ExpressionAtlas; O75874; baseline and differential.
DR Genevisible; O75874; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0050661; F:NADP binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0006103; P:2-oxoglutarate metabolic process; IDA:UniProtKB.
DR GO; GO:0008585; P:female gonad development; IEA:Ensembl.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:Ensembl.
DR GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
DR GO; GO:0006102; P:isocitrate metabolic process; IDA:UniProtKB.
DR GO; GO:0006739; P:NADP metabolic process; IBA:GO_Central.
DR GO; GO:0071071; P:regulation of phospholipid biosynthetic process; IEA:Ensembl.
DR GO; GO:0060696; P:regulation of phospholipid catabolic process; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0048545; P:response to steroid hormone; IEA:Ensembl.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR004790; Isocitrate_DH_NADP.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR PANTHER; PTHR11822; PTHR11822; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR PIRSF; PIRSF000108; IDH_NADP; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00127; nadp_idh_euk; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW Glyoxylate bypass; Magnesium; Manganese; Metal-binding; NADP;
KW Oxidoreductase; Peroxisome; Phosphoprotein; Reference proteome;
KW Tricarboxylic acid cycle.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..414
FT /note="Isocitrate dehydrogenase [NADP] cytoplasmic"
FT /id="PRO_0000083575"
FT BINDING 75..77
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0000269|PubMed:19935646, ECO:0007744|PDB:1T09,
FT ECO:0007744|PDB:1T0L, ECO:0007744|PDB:3INM,
FT ECO:0007744|PDB:3MAP, ECO:0007744|PDB:3MAR,
FT ECO:0007744|PDB:3MAS, ECO:0007744|PDB:4I3K,
FT ECO:0007744|PDB:4I3L, ECO:0007744|PDB:4KZO,
FT ECO:0007744|PDB:4L03, ECO:0007744|PDB:4L04,
FT ECO:0007744|PDB:4L06, ECO:0007744|PDB:4UMX,
FT ECO:0007744|PDB:4UMY, ECO:0007744|PDB:4XRX,
FT ECO:0007744|PDB:4XS3, ECO:0007744|PDB:5DE1,
FT ECO:0007744|PDB:5L57, ECO:0007744|PDB:5L58,
FT ECO:0007744|PDB:5LGE, ECO:0007744|PDB:5SUN,
FT ECO:0007744|PDB:5SVF, ECO:0007744|PDB:5TQH"
FT BINDING 77
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0007744|PDB:1T0L"
FT BINDING 82
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0000269|PubMed:19935646, ECO:0007744|PDB:1T09,
FT ECO:0007744|PDB:1T0L, ECO:0007744|PDB:3INM,
FT ECO:0007744|PDB:3MAP, ECO:0007744|PDB:3MAR,
FT ECO:0007744|PDB:3MAS, ECO:0007744|PDB:4I3K,
FT ECO:0007744|PDB:4I3L, ECO:0007744|PDB:4KZO,
FT ECO:0007744|PDB:4L03, ECO:0007744|PDB:4L04,
FT ECO:0007744|PDB:4L06, ECO:0007744|PDB:4UMX,
FT ECO:0007744|PDB:4UMY, ECO:0007744|PDB:4XRX,
FT ECO:0007744|PDB:4XS3, ECO:0007744|PDB:5DE1,
FT ECO:0007744|PDB:5L57, ECO:0007744|PDB:5LGE,
FT ECO:0007744|PDB:5SUN, ECO:0007744|PDB:5SVF,
FT ECO:0007744|PDB:5TQH"
FT BINDING 94..100
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0007744|PDB:1T0L"
FT BINDING 109
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0007744|PDB:1T0L"
FT BINDING 132
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0007744|PDB:1T0L"
FT BINDING 212
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0007744|PDB:1T0L"
FT BINDING 252
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000305|PubMed:15173171,
FT ECO:0000305|PubMed:19935646, ECO:0007744|PDB:1T0L,
FT ECO:0007744|PDB:3INM"
FT BINDING 260
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0000269|PubMed:19935646, ECO:0007744|PDB:1T0L,
FT ECO:0007744|PDB:3INM"
FT BINDING 275
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:15173171,
FT ECO:0000305|PubMed:19935646, ECO:0007744|PDB:1T0L,
FT ECO:0007744|PDB:3INM"
FT BINDING 279
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:15173171,
FT ECO:0000305|PubMed:19935646, ECO:0007744|PDB:1T0L,
FT ECO:0007744|PDB:3INM"
FT BINDING 310..315
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0000269|PubMed:19935646, ECO:0007744|PDB:1T09,
FT ECO:0007744|PDB:1T0L, ECO:0007744|PDB:3INM,
FT ECO:0007744|PDB:3MAP, ECO:0007744|PDB:3MAR,
FT ECO:0007744|PDB:3MAS, ECO:0007744|PDB:4I3K,
FT ECO:0007744|PDB:4I3L, ECO:0007744|PDB:4KZO,
FT ECO:0007744|PDB:4L03, ECO:0007744|PDB:4L04,
FT ECO:0007744|PDB:4L06, ECO:0007744|PDB:4UMX,
FT ECO:0007744|PDB:4UMY, ECO:0007744|PDB:4XRX,
FT ECO:0007744|PDB:4XS3, ECO:0007744|PDB:5DE1,
FT ECO:0007744|PDB:5L57, ECO:0007744|PDB:5L58,
FT ECO:0007744|PDB:5LGE, ECO:0007744|PDB:5SUN,
FT ECO:0007744|PDB:5SVF, ECO:0007744|PDB:5TQH"
FT BINDING 328
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15173171,
FT ECO:0000269|PubMed:19935646, ECO:0007744|PDB:1T09,
FT ECO:0007744|PDB:1T0L, ECO:0007744|PDB:3INM,
FT ECO:0007744|PDB:3MAP, ECO:0007744|PDB:3MAR,
FT ECO:0007744|PDB:3MAS, ECO:0007744|PDB:4I3K,
FT ECO:0007744|PDB:4I3L, ECO:0007744|PDB:4KZO,
FT ECO:0007744|PDB:4L03, ECO:0007744|PDB:4L04,
FT ECO:0007744|PDB:4L06, ECO:0007744|PDB:4UMX,
FT ECO:0007744|PDB:4UMY, ECO:0007744|PDB:4XRX,
FT ECO:0007744|PDB:4XS3, ECO:0007744|PDB:5DE1,
FT ECO:0007744|PDB:5L57, ECO:0007744|PDB:5L58,
FT ECO:0007744|PDB:5LGE, ECO:0007744|PDB:5SUN,
FT ECO:0007744|PDB:5SVF, ECO:0007744|PDB:5TQH"
FT SITE 139
FT /note="Critical for catalysis"
FT SITE 212
FT /note="Critical for catalysis"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 42
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 81
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 126
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 224
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 233
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 243
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 321
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 400
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT VARIANT 132
FT /note="R -> C (in colorectal cancer and glioma samples;
FT glioblastoma multiforme; somatic mutation; found in
FT patients with cartilaginous tumors; abolishes magnesium
FT binding and alters enzyme activity so that isocitrate is no
FT longer converted to alpha-ketoglutarate but instead alpha-
FT ketoglutarate is converted to R(-)-2-hydroxyglutarate;
FT induces histone methylation; enhances expression of
FT chondrocyte-related genes; disturbs the formation of
FT cartilaginous matrix; inhibits osteogenic differentiation;
FT dbSNP:rs121913499)"
FT /evidence="ECO:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:19117336, ECO:0000269|PubMed:19935646,
FT ECO:0000269|PubMed:26161668"
FT /id="VAR_036013"
FT VARIANT 132
FT /note="R -> G (in a glioma sample; glioblastoma multiforme;
FT somatic mutation; found in patients with cartilaginous
FT tumors; dbSNP:rs121913499)"
FT /evidence="ECO:0000269|PubMed:19117336,
FT ECO:0000269|PubMed:26161668"
FT /id="VAR_055454"
FT VARIANT 132
FT /note="R -> H (in a glioma sample; glioblastoma multiforme;
FT somatic mutation; found in patients with cartilaginous
FT tumors; abolishes magnesium binding and alters enzyme
FT activity so that isocitrate is no longer converted to
FT alpha-ketoglutarate but instead alpha-ketoglutarate is
FT converted to R(-)-2-hydroxyglutarate; dbSNP:rs121913500)"
FT /evidence="ECO:0000269|PubMed:18772396,
FT ECO:0000269|PubMed:19935646, ECO:0000269|PubMed:26161668"
FT /id="VAR_055455"
FT VARIANT 132
FT /note="R -> L (in a glioma sample; glioblastoma multiforme;
FT somatic mutation; abolishes magnesium binding and alters
FT enzyme activity so that isocitrate is no longer converted
FT to alpha-ketoglutarate but instead alpha-ketoglutarate is
FT converted to R(-)-2-hydroxyglutarate; dbSNP:rs121913500)"
FT /evidence="ECO:0000269|PubMed:19117336,
FT ECO:0000269|PubMed:19935646"
FT /id="VAR_055456"
FT VARIANT 132
FT /note="R -> S (in a glioma sample; glioblastoma multiforme;
FT somatic mutation; abolishes magnesium binding and alters
FT enzyme activity so that isocitrate is no longer converted
FT to alpha-ketoglutarate but instead alpha-ketoglutarate is
FT converted to R(-)-2-hydroxyglutarate; dbSNP:rs121913499)"
FT /evidence="ECO:0000269|PubMed:18772396,
FT ECO:0000269|PubMed:19935646"
FT /id="VAR_055457"
FT VARIANT 178
FT /note="V -> I (in dbSNP:rs34218846)"
FT /id="VAR_049780"
FT CONFLICT 32
FT /note="F -> I (in Ref. 3; CAB66637)"
FT /evidence="ECO:0000305"
FT CONFLICT 126
FT /note="K -> E (in Ref. 3; CAB66637)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="F -> S (in Ref. 5; CAD97653)"
FT /evidence="ECO:0000305"
FT CONFLICT 174
FT /note="E -> G (in Ref. 5; CAD97653)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="K -> I (in Ref. 1; AAD02918)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="A -> S (in Ref. 6; AAH93020)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="P -> L (in Ref. 1; AAD02918)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="K -> R (in Ref. 1; AAD02918)"
FT /evidence="ECO:0000305"
FT STRAND 5..14
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 17..30
FT /evidence="ECO:0007829|PDB:6BKX"
FT TURN 31..34
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 35..43
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 46..51
FT /evidence="ECO:0007829|PDB:6BKX"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 55..67
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 80..86
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 95..103
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:6ADG"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:6PAY"
FT STRAND 128..133
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 142..146
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 148..156
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 165..172
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:6ADG"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:3MAR"
FT HELIX 186..203
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 207..211
FT /evidence="ECO:0007829|PDB:6BKX"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:6Q6F"
FT HELIX 219..234
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 236..241
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 251..260
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 265..269
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 271..285
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:4UMX"
FT STRAND 291..296
FT /evidence="ECO:0007829|PDB:6BKX"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 313..320
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 330..347
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 350..368
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 374..381
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 383..385
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:6BKX"
FT HELIX 394..414
FT /evidence="ECO:0007829|PDB:6BKX"
SQ SEQUENCE 414 AA; 46659 MW; 60428B0B6E5851DC CRC64;
MSKKISGGSV VEMQGDEMTR IIWELIKEKL IFPYVELDLH SYDLGIENRD ATNDQVTKDA
AEAIKKHNVG VKCATITPDE KRVEEFKLKQ MWKSPNGTIR NILGGTVFRE AIICKNIPRL
VSGWVKPIII GRHAYGDQYR ATDFVVPGPG KVEITYTPSD GTQKVTYLVH NFEEGGGVAM
GMYNQDKSIE DFAHSSFQMA LSKGWPLYLS TKNTILKKYD GRFKDIFQEI YDKQYKSQFE
AQKIWYEHRL IDDMVAQAMK SEGGFIWACK NYDGDVQSDS VAQGYGSLGM MTSVLVCPDG
KTVEAEAAHG TVTRHYRMYQ KGQETSTNPI ASIFAWTRGL AHRAKLDNNK ELAFFANALE
EVSIETIEAG FMTKDLAACI KGLPNVQRSD YLNTFEFMDK LGENLKIKLA QAKL
