ID CLPX_HUMAN Reviewed; 633 AA. AC O76031; A1L428; A8K8F1; B9EGI8; Q9H4D9; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 11-JUL-2001, sequence version 2. DT 27-MAR-2024, entry version 196. DE RecName: Full=ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial; DE Flags: Precursor; GN Name=CLPX; 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], SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Skeletal muscle; RX PubMed=11003706; DOI=10.1007/s003350010173; RA Corydon T.J., Wilsbech M., Jespersgaard C., Andresen B.S., Borglum A.D., RA Pedersen S., Bolund L., Gregersen N., Bross P.; RT "Human and mouse mitochondrial orthologs of bacterial ClpX."; RL Mamm. Genome 11:899-905(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, 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 [5] RP FUNCTION, AND SUBUNIT. RX PubMed=11923310; DOI=10.1074/jbc.m201642200; RA Kang S.G., Ortega J., Singh S.K., Wang N., Huang N.N., Steven A.C., RA Maurizi M.R.; RT "Functional proteolytic complexes of the human mitochondrial ATP-dependent RT protease, hClpXP."; RL J. Biol. Chem. 277:21095-21102(2002). RN [6] RP SUBUNIT, AND INTERACTION WITH CLPP. RX PubMed=15522782; DOI=10.1016/j.jsb.2004.07.004; RA Kang S.G., Maurizi M.R., Thompson M., Mueser T., Ahvazi B.; RT "Crystallography and mutagenesis point to an essential role for the N- RT terminus of human mitochondrial ClpP."; RL J. Struct. Biol. 148:338-352(2004). RN [7] RP SUBUNIT, AND IDENTIFICATION IN A COMPLEX WITH CLPP. RX PubMed=16115876; DOI=10.1074/jbc.m507240200; RA Kang S.G., Dimitrova M.N., Ortega J., Ginsburg A., Maurizi M.R.; RT "Human mitochondrial ClpP is a stable heptamer that assembles into a RT tetradecamer in the presence of ClpX."; RL J. Biol. Chem. 280:35424-35432(2005). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617, 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 [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-437, 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 [11] 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 [12] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TFAM. RX PubMed=22841477; DOI=10.1016/j.yexcr.2012.07.012; RA Kasashima K., Sumitani M., Endo H.; RT "Maintenance of mitochondrial genome distribution by mitochondrial AAA+ RT protein ClpX."; RL Exp. Cell Res. 318:2335-2343(2012). RN [13] RP FUNCTION, MUTAGENESIS OF GLU-359, SUBUNIT, AND INTERACTION WITH CLPP. RX PubMed=22710082; DOI=10.1016/j.jsb.2012.06.001; RA Lowth B.R., Kirstein-Miles J., Saiyed T., Broetz-Oesterhelt H., RA Morimoto R.I., Truscott K.N., Dougan D.A.; RT "Substrate recognition and processing by a Walker B mutant of the human RT mitochondrial AAA+ protein CLPX."; RL J. Struct. Biol. 179:193-201(2012). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [15] 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 [16] RP FUNCTION. RX PubMed=25957689; DOI=10.1016/j.cell.2015.04.017; RA Kardon J.R., Yien Y.Y., Huston N.C., Branco D.S., Hildick-Smith G.J., RA Rhee K.Y., Paw B.H., Baker T.A.; RT "Mitochondrial ClpX activates a key enzyme for heme biosynthesis and RT erythropoiesis."; RL Cell 161:858-867(2015). RN [17] 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 [18] RP INVOLVEMENT IN EPP2, FUNCTION, VARIANT EPP2 ASP-298, AND CHARACTERIZATION RP OF VARIANT EPP2 ASP-298. RX PubMed=28874591; DOI=10.1073/pnas.1700632114; RA Yien Y.Y., Ducamp S., van der Vorm L.N., Kardon J.R., Manceau H., RA Kannengiesser C., Bergonia H.A., Kafina M.D., Karim Z., Gouya L., RA Baker T.A., Puy H., Phillips J.D., Nicolas G., Paw B.H.; RT "Mutation in human CLPX elevates levels of delta-aminolevulinate synthase RT and protoporphyrin IX to promote erythropoietic protoporphyria."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E8045-E8052(2017). CC -!- FUNCTION: ATP-dependent specificity component of the Clp protease CC complex. Hydrolyzes ATP (PubMed:28874591). Targets specific substrates CC for degradation by the Clp complex (PubMed:11923310, PubMed:22710082). CC Can perform chaperone functions in the absence of CLPP. Enhances the CC DNA-binding activity of TFAM and is required for maintaining a normal CC mitochondrial nucleoid structure (PubMed:22841477). ATP-dependent CC unfoldase that stimulates the incorporation of the pyridoxal phosphate CC cofactor into 5-aminolevulinate synthase, thereby activating 5- CC aminolevulinate (ALA) synthesis, the first step in heme biosynthesis CC (PubMed:28874591). Important for efficient erythropoiesis through up- CC regulation of heme biosynthesis (PubMed:25957689, PubMed:28874591). CC {ECO:0000269|PubMed:11923310, ECO:0000269|PubMed:22710082, CC ECO:0000269|PubMed:22841477, ECO:0000269|PubMed:25957689, CC ECO:0000269|PubMed:28874591}. CC -!- SUBUNIT: Homohexamer that forms a ring structure; this hexamerization CC requires ATP binding. Component of the Clp complex formed by the CC assembly of two CLPP heptameric rings with two CLPX hexameric rings, CC giving rise to a symmetrical structure with two central CLPP rings CC flanked by a CLPX ring at either end of the complex. Interacts with CC TFAM. {ECO:0000269|PubMed:11923310, ECO:0000269|PubMed:15522782, CC ECO:0000269|PubMed:16115876, ECO:0000269|PubMed:22710082, CC ECO:0000269|PubMed:22841477}. CC -!- INTERACTION: CC O76031; PRO_0000005516 [Q16740]: CLPP; NbExp=2; IntAct=EBI-1052667, EBI-25815820; CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion matrix, CC mitochondrion nucleoid. CC -!- TISSUE SPECIFICITY: Higher expression in skeletal muscle and heart and CC to a lesser extent in liver, brain, placenta, lung, kidney and CC pancreas. {ECO:0000269|PubMed:11003706}. CC -!- DISEASE: Protoporphyria, erythropoietic, 2 (EPP2) [MIM:618015]: An CC autosomal dominant form of porphyria with onset in infancy. Porphyrias CC are inherited defects in the biosynthesis of heme, resulting in the CC accumulation and increased excretion of porphyrins or porphyrin CC precursors. They are classified as erythropoietic or hepatic, depending CC on whether the enzyme deficiency occurs in red blood cells or in the CC liver. Erythropoietic protoporphyria is marked by excessive CC protoporphyrin in erythrocytes, plasma, liver and feces, and by widely CC varying photosensitive skin changes ranging from a burning or pruritic CC sensation to erythema, edema and wheals. {ECO:0000269|PubMed:28874591}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the ClpX chaperone family. {ECO:0000255|PROSITE- CC ProRule:PRU01250}. 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; AJ006267; CAA06933.2; -; mRNA. DR EMBL; AJ276980; CAC01291.1; -; Genomic_DNA. DR EMBL; AJ276981; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276966; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276967; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276968; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276969; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276970; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276971; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276972; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276973; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276974; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276975; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276976; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AJ276977; CAC01291.1; JOINED; Genomic_DNA. DR EMBL; AK292316; BAF85005.1; -; mRNA. DR EMBL; CH471082; EAW77715.1; -; Genomic_DNA. DR EMBL; BC130373; AAI30374.1; -; mRNA. DR EMBL; BC136487; AAI36488.1; -; mRNA. DR CCDS; CCDS10202.1; -. DR RefSeq; NP_006651.2; NM_006660.4. DR AlphaFoldDB; O76031; -. DR SMR; O76031; -. DR BioGRID; 116056; 213. DR ComplexPortal; CPX-6177; Mitochondrial endopeptidase ClpXP complex. DR CORUM; O76031; -. DR DIP; DIP-50293N; -. DR IntAct; O76031; 82. DR MINT; O76031; -. DR STRING; 9606.ENSP00000300107; -. DR BindingDB; O76031; -. DR ChEMBL; CHEMBL3797014; -. DR GlyGen; O76031; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O76031; -. DR PhosphoSitePlus; O76031; -. DR SwissPalm; O76031; -. DR BioMuta; CLPX; -. DR EPD; O76031; -. DR jPOST; O76031; -. DR MassIVE; O76031; -. DR MaxQB; O76031; -. DR PaxDb; 9606-ENSP00000300107; -. DR PeptideAtlas; O76031; -. DR ProteomicsDB; 50351; -. DR Pumba; O76031; -. DR Antibodypedia; 51984; 116 antibodies from 26 providers. DR DNASU; 10845; -. DR Ensembl; ENST00000300107.7; ENSP00000300107.3; ENSG00000166855.9. DR GeneID; 10845; -. DR KEGG; hsa:10845; -. DR MANE-Select; ENST00000300107.7; ENSP00000300107.3; NM_006660.5; NP_006651.2. DR UCSC; uc002aom.4; human. DR AGR; HGNC:2088; -. DR CTD; 10845; -. DR DisGeNET; 10845; -. DR GeneCards; CLPX; -. DR HGNC; HGNC:2088; CLPX. DR HPA; ENSG00000166855; Low tissue specificity. DR MalaCards; CLPX; -. DR MIM; 615611; gene. DR MIM; 618015; phenotype. DR neXtProt; NX_O76031; -. DR OpenTargets; ENSG00000166855; -. DR PharmGKB; PA26614; -. DR VEuPathDB; HostDB:ENSG00000166855; -. DR eggNOG; KOG0745; Eukaryota. DR GeneTree; ENSGT00390000017625; -. DR HOGENOM; CLU_014218_0_1_1; -. DR InParanoid; O76031; -. DR OMA; ICDCNSL; -. DR OrthoDB; 452393at2759; -. DR PhylomeDB; O76031; -. DR TreeFam; TF312884; -. DR PathwayCommons; O76031; -. DR SignaLink; O76031; -. DR BioGRID-ORCS; 10845; 38 hits in 1168 CRISPR screens. DR ChiTaRS; CLPX; human. DR GenomeRNAi; 10845; -. DR Pharos; O76031; Tbio. DR PRO; PR:O76031; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; O76031; Protein. DR Bgee; ENSG00000166855; Expressed in sperm and 199 other cell types or tissues. DR ExpressionAtlas; O76031; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0009368; C:endopeptidase Clp complex; IDA:UniProtKB. DR GO; GO:0009841; C:mitochondrial endopeptidase Clp complex; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB. DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro. DR GO; GO:0016504; F:peptidase activator activity; IDA:UniProtKB. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0046034; P:ATP metabolic process; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IDA:ComplexPortal. DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:UniProtKB. DR CDD; cd19497; RecA-like_ClpX; 1. DR Gene3D; 1.10.8.60; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR003959; ATPase_AAA_core. DR InterPro; IPR019489; Clp_ATPase_C. DR InterPro; IPR004487; Clp_protease_ATP-bd_su_ClpX. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR010603; Znf_CppX_C4. DR NCBIfam; TIGR00382; clpX; 1. DR PANTHER; PTHR48102:SF7; ATP-DEPENDENT CLP PROTEASE ATP-BINDING SUBUNIT CLPX-LIKE, MITOCHONDRIAL; 1. DR PANTHER; PTHR48102; ATP-DEPENDENT CLP PROTEASE ATP-BINDING SUBUNIT CLPX-LIKE, MITOCHONDRIAL-RELATED; 1. DR Pfam; PF07724; AAA_2; 1. DR Pfam; PF10431; ClpB_D2-small; 1. DR SMART; SM00382; AAA; 1. DR SMART; SM01086; ClpB_D2-small; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51902; CLPX_ZB; 1. DR Genevisible; O76031; HS. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Chaperone; Disease variant; Metal-binding; KW Mitochondrion; Mitochondrion nucleoid; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Transit peptide; Zinc. FT TRANSIT 1..56 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 57..633 FT /note="ATP-dependent Clp protease ATP-binding subunit clpX- FT like, mitochondrial" FT /id="PRO_0000005518" FT DOMAIN 93..146 FT /note="ClpX-type ZB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01250" FT REGION 68..100 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 598..633 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 80..100 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 598..613 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 105 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01250" FT BINDING 108 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01250" FT BINDING 127 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01250" FT BINDING 130 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01250" FT BINDING 294..301 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT MOD_RES 437 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 617 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT VARIANT 298 FT /note="G -> D (in EPP2; results in decreased ATP FT hydrolysis; cells with the mutant protein show increased FT ALA levels and accumulation of the heme biosynthesis FT intermediate protoporphyrin IX)" FT /evidence="ECO:0000269|PubMed:28874591" FT /id="VAR_081001" FT VARIANT 488 FT /note="I -> T (in dbSNP:rs35754835)" FT /id="VAR_048826" FT MUTAGEN 359 FT /note="E->A: Abolishes ATP hydrolysis." FT /evidence="ECO:0000269|PubMed:22710082" FT CONFLICT 21 FT /note="L -> P (in Ref. 2; BAF85005)" FT /evidence="ECO:0000305" SQ SEQUENCE 633 AA; 69224 MW; CF46A6DC0DDBF022 CRC64; MPSCGACTCG AAAVRLITSS LASAQRGISG GRIHMSVLGR LGTFETQILQ RAPLRSFTET PAYFASKDGI SKDGSGDGNK KSASEGSSKK SGSGNSGKGG NQLRCPKCGD LCTHVETFVS STRFVKCEKC HHFFVVLSEA DSKKSIIKEP ESAAEAVKLA FQQKPPPPPK KIYNYLDKYV VGQSFAKKVL SVAVYNHYKR IYNNIPANLR QQAEVEKQTS LTPRELEIRR REDEYRFTKL LQIAGISPHG NALGASMQQQ VNQQIPQEKR GGEVLDSSHD DIKLEKSNIL LLGPTGSGKT LLAQTLAKCL DVPFAICDCT TLTQAGYVGE DIESVIAKLL QDANYNVEKA QQGIVFLDEV DKIGSVPGIH QLRDVGGEGV QQGLLKLLEG TIVNVPEKNS RKLRGETVQV DTTNILFVAS GAFNGLDRII SRRKNEKYLG FGTPSNLGKG RRAAAAADLA NRSGESNTHQ DIEEKDRLLR HVEARDLIEF GMIPEFVGRL PVVVPLHSLD EKTLVQILTE PRNAVIPQYQ ALFSMDKCEL NVTEDALKAI ARLALERKTG ARGLRSIMEK LLLEPMFEVP NSDIVCVEVD KEVVEGKKEP GYIRAPTKES SEEEYDSGVE EEGWPRQADA ANS //