ID PANK2_HUMAN Reviewed; 570 AA. AC Q9BZ23; B1AK33; B2Z3X0; D3DVZ0; Q5T7I2; Q5T7I4; Q7RTX5; Q8N7Q4; Q8TCR5; AC Q9BYW5; Q9HAF2; DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot. DT 28-NOV-2006, sequence version 3. DT 27-MAR-2024, entry version 194. DE RecName: Full=Pantothenate kinase 2, mitochondrial; DE Short=hPanK2; DE EC=2.7.1.33 {ECO:0000269|PubMed:15659606, ECO:0000269|PubMed:16272150, ECO:0000269|PubMed:17242360, ECO:0000269|PubMed:17825826}; DE AltName: Full=Pantothenic acid kinase 2; DE Contains: DE RecName: Full=Pantothenate kinase 2, mitochondrial intermediate form; DE Short=iPanK2; DE Contains: DE RecName: Full=Pantothenate kinase 2, mitochondrial mature form; DE Short=mPanK2; DE Flags: Precursor; GN Name=PANK2; Synonyms=C20orf48; 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), ALTERNATIVE SPLICING (ISOFORM 3), RP VARIANT ALA-126, AND SUBCELLULAR LOCATION (ISOFORMS 1 AND 3). RC TISSUE=Brain; RX PubMed=12554685; DOI=10.1093/hmg/ddg026; RA Hoertnagel K., Prokisch H., Meitinger T.; RT "An isoform of hPANK2, deficient in pantothenate kinase-associated RT neurodegeneration, localizes to mitochondria."; RL Hum. Mol. Genet. 12:321-327(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 106-570 (ISOFORM 1). 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 [GENOMIC DNA], AND VARIANTS PRO-94; GLN-111 AND RP ALA-126. RG NIEHS SNPs program; RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [5] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 406-570. RC TISSUE=Brain; 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 PROTEIN SEQUENCE OF N-TERMINUS, CHARACTERIZATION OF VARIANTS NBIA1 GLY-134; RP VAL-219; ALA-234; ASN-471; ARG-521 AND MET-528, PROTEOLYTIC PROCESSING BY RP MPP, CLEAVAGE SITE, FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY (ISOFORM 1), RP SUBCELLULAR LOCATION (ISOFORM 1), SUBUNIT, ACTIVITY REGULATION (ISOFORM 1), RP AND TISSUE SPECIFICITY. RX PubMed=15659606; DOI=10.1523/jneurosci.4265-04.2005; RA Kotzbauer P.T., Truax A.C., Trojanowski J.Q., Lee V.M.; RT "Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration RT with brain iron accumulation caused by abnormal processing, stability, and RT catalytic activity of mutant pantothenate kinase 2."; RL J. Neurosci. 25:689-698(2005). RN [8] RP IDENTIFICATION, ALTERNATIVE INITIATION AT LEU-111, VARIANTS GLN-111 AND RP ALA-126, VARIANTS NBIA1 VAL-219; ALA-234; TRP-264; CYS-278; VAL-282; RP CYS-286; ILE-327; PRO-351; SER-355; ILE-404; PRO-413; ASN-471; THR-497; RP ILE-500; ARG-521 AND MET-528, AND TISSUE SPECIFICITY. RX PubMed=11479594; DOI=10.1038/ng572; RA Zhou B., Westaway S.K., Levinson B., Johnson M.A., Gitschier J., RA Hayflick S.J.; RT "A novel pantothenate kinase gene (PANK2) is defective in Hallervorden- RT Spatz syndrome."; RL Nat. Genet. 28:345-349(2001). RN [9] RP INVOLVEMENT IN HARP. RX PubMed=12058097; DOI=10.1212/wnl.58.11.1673; RA Ching K.H.L., Westaway S.K., Gitschier J., Higgins J.J., Hayflick S.J.; RT "HARP syndrome is allelic with pantothenate kinase-associated RT neurodegeneration."; RL Neurology 58:1673-1674(2002). RN [10] RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY (ISOFORM 1), ACTIVITY REGULATION RP (ISOFORM 1), SUBCELLULAR LOCATION (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=17825826; DOI=10.1016/j.febslet.2007.08.056; RA Leonardi R., Zhang Y.M., Lykidis A., Rock C.O., Jackowski S.; RT "Localization and regulation of mouse pantothenate kinase 2."; RL FEBS Lett. 581:4639-4644(2007). RN [11] RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY (ISOFORM 1), SUBUNIT, AND ACTIVITY RP REGULATION (ISOFORM 1). RX PubMed=17242360; DOI=10.1073/pnas.0607621104; RA Leonardi R., Rock C.O., Jackowski S., Zhang Y.M.; RT "Activation of human mitochondrial pantothenate kinase 2 by RT palmitoylcarnitine."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1494-1499(2007). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-169 AND SER-189, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-169 AND SER-189, AND RP IDENTIFICATION BY 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-189, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168 AND SER-189, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [17] RP SUBCELLULAR LOCATION (ISOFORM 1), NUCLEAR LOCALIZATION SIGNAL, NUCLEAR RP EXPORT SIGNAL, AND MUTAGENESIS OF 82-ARG--ARG-94 AND 268-LEU--LEU-275. RX PubMed=23152917; DOI=10.1371/journal.pone.0049509; RA Alfonso-Pecchio A., Garcia M., Leonardi R., Jackowski S.; RT "Compartmentalization of mammalian pantothenate kinases."; RL PLoS ONE 7:e49509-e49509(2012). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168 AND SER-189, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168 AND SER-189, AND 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 [20] RP FUNCTION (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=30221726; DOI=10.3892/mmr.2018.9480; RA Pagani F., Trivedi A., Khatri D., Zizioli D., Garrafa E., Mitola S., RA Finazzi D.; RT "Silencing of pantothenate kinase 2 reduces endothelial cell RT angiogenesis."; RL Mol. Med. Report. 18:4739-4746(2018). RN [21] RP VARIANTS NBIA1 GLY-134; PRO-249; LEU-278; ASP-322; GLY-322; GLN-357; RP THR-398; LEU-425 DEL; TYR-428; ASN-447; THR-501; VAL-509; ASP-511; TRP-532; RP PRO-563 AND LEU-570. RX PubMed=12510040; DOI=10.1056/nejmoa020817; RA Hayflick S.J., Westaway S.K., Levinson B., Zhou B., Johnson M.A., RA Ching K.H., Gitschier J.; RT "Genetic, clinical, and radiographic delineation of Hallervorden-Spatz RT syndrome."; RL N. Engl. J. Med. 348:33-40(2003). RN [22] RP VARIANTS NBIA1 ARG-521 AND LEU-570. RX PubMed=15834858; DOI=10.1002/mds.20476; RA Nicholas A.P., Earnst K.S., Marson D.C.; RT "Atypical Hallervorden-Spatz disease with preserved cognition and obtrusive RT obsessions and compulsions."; RL Mov. Disord. 20:880-886(2005). RN [23] RP CHARACTERIZATION OF VARIANTS NBIA1 VAL-219; ALA-234; TRP-264; CYS-286; RP ILE-327; PRO-351; ILE-404; ASN-471; ILE-500; VAL-509; ARG-521; MET-528 AND RP TRP-532, FUNCTION (ISOFORMS 1 AND 4), CATALYTIC ACTIVITY (ISOFORMS 1 AND RP 4), SUBUNIT, ACTIVITY REGULATION (ISOFORM 1), PROTEOLYTIC PROCESSING, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=16272150; DOI=10.1074/jbc.m508825200; RA Zhang Y.M., Rock C.O., Jackowski S.; RT "Biochemical properties of human pantothenate kinase 2 isoforms and RT mutations linked to pantothenate kinase-associated neurodegeneration."; RL J. Biol. Chem. 281:107-114(2006). RN [24] RP VARIANTS NBIA1 ARG-521 AND SER-555. RX PubMed=24075960; DOI=10.1016/j.ejmg.2013.08.007; RA Perez-Gonzalez E.A., Chacon-Camacho O.F., Arteaga-Vazquez J., Zenteno J.C., RA Mutchinick O.M.; RT "A novel gene mutation in PANK2 in a patient with an atypical form of RT pantothenate kinase-associated neurodegeneration."; RL Eur. J. Med. Genet. 56:606-608(2013). RN [25] RP VARIANT NBIA1 SER-377. RX PubMed=22930366; DOI=10.1007/s10072-012-1177-8; RA Shan J., Wen B., Zhu J., Lin P., Zheng J., Yan C.; RT "Novel PANK2 gene mutations in two Chinese siblings with atypical RT pantothenate kinase-associated neurodegeneration."; RL Neurol. Sci. 34:561-563(2013). RN [26] RP VARIANT NBIA1 GLY-232. RX PubMed=24655737; DOI=10.1016/j.jns.2014.03.001; RA Tanteles G.A., Spanou-Aristidou E., Antoniou C., RA Christophidou-Anastasiadou V., Kleopa K.A.; RT "Novel homozygous PANK2 mutation causing atypical pantothenate kinase- RT associated neurodegeneration (PKAN) in a Cypriot family."; RL J. Neurol. Sci. 340:233-236(2014). RN [27] RP VARIANTS NBIA1 PRO-489 AND MET-528. RX PubMed=27185474; DOI=10.1016/j.braindev.2016.02.010; RA Yapici Z., Akcakaya N.H., Tekturk P., Iseri S.A., Ozbek U.; RT "A novel gene mutation in PANK2 in a patient with severe jaw-opening RT dystonia."; RL Brain Dev. 38:755-758(2016). CC -!- FUNCTION: [Isoform 1]: Mitochondrial isoform that catalyzes the CC phosphorylation of pantothenate to generate 4'-phosphopantothenate in CC the first and rate-determining step of coenzyme A (CoA) synthesis CC (PubMed:15659606, PubMed:17825826, PubMed:17242360, PubMed:16272150). CC Required for angiogenic activity of umbilical vein of endothelial cells CC (HUVEC) (PubMed:30221726). {ECO:0000269|PubMed:15659606, CC ECO:0000269|PubMed:16272150, ECO:0000269|PubMed:17242360, CC ECO:0000269|PubMed:17825826, ECO:0000269|PubMed:30221726}. CC -!- FUNCTION: [Isoform 4]: Cytoplasmic isoform that catalyzes the CC phosphorylation of pantothenate to generate 4'-phosphopantothenate in CC the first and rate-determining step of coenzyme A (CoA) synthesis. CC {ECO:0000269|PubMed:16272150}. CC -!- CATALYTIC ACTIVITY: [Isoform 1]: CC Reaction=(R)-pantothenate + ATP = (R)-4'-phosphopantothenate + ADP + CC H(+); Xref=Rhea:RHEA:16373, ChEBI:CHEBI:10986, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29032, ChEBI:CHEBI:30616, ChEBI:CHEBI:456216; CC EC=2.7.1.33; Evidence={ECO:0000269|PubMed:15659606, CC ECO:0000269|PubMed:16272150, ECO:0000269|PubMed:17242360, CC ECO:0000269|PubMed:17825826}; CC -!- CATALYTIC ACTIVITY: [Isoform 4]: CC Reaction=(R)-pantothenate + ATP = (R)-4'-phosphopantothenate + ADP + CC H(+); Xref=Rhea:RHEA:16373, ChEBI:CHEBI:10986, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29032, ChEBI:CHEBI:30616, ChEBI:CHEBI:456216; CC EC=2.7.1.33; Evidence={ECO:0000269|PubMed:16272150}; CC -!- ACTIVITY REGULATION: [Isoform 1]: Strongly inhibited by acetyl-CoA and CC its thioesters (PubMed:15659606, PubMed:17825826, PubMed:17242360, CC PubMed:16272150). Activated by palmitoylcarnitine (PubMed:17825826, CC PubMed:17242360). {ECO:0000269|PubMed:15659606, CC ECO:0000269|PubMed:16272150, ECO:0000269|PubMed:17242360, CC ECO:0000269|PubMed:17825826}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=25.4 uM for pantothenate {ECO:0000269|PubMed:16272150}; CC KM=63.6 uM for ATP {ECO:0000269|PubMed:16272150}; CC Vmax=92 pmol/min/mg enzyme for pantothenate CC {ECO:0000269|PubMed:16272150}; CC Vmax=90.2 pmol/min/mg enzyme for ATP {ECO:0000269|PubMed:16272150}; CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)- CC pantothenate: step 1/5. {ECO:0000269|PubMed:15659606, CC ECO:0000269|PubMed:16272150, ECO:0000269|PubMed:17242360, CC ECO:0000269|PubMed:17825826}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15659606, CC ECO:0000269|PubMed:16272150, ECO:0000269|PubMed:17242360}. CC -!- INTERACTION: CC Q9BZ23-2; Q6H8Q1-8: ABLIM2; NbExp=3; IntAct=EBI-25929070, EBI-16436655; CC Q9BZ23-2; P26436: ACRV1; NbExp=3; IntAct=EBI-25929070, EBI-25884472; CC Q9BZ23-2; Q8WXK3: ASB13; NbExp=3; IntAct=EBI-25929070, EBI-707573; CC Q9BZ23-2; Q8WXF7: ATL1; NbExp=3; IntAct=EBI-25929070, EBI-2410266; CC Q9BZ23-2; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-25929070, EBI-350590; CC Q9BZ23-2; Q99871: HAUS7; NbExp=3; IntAct=EBI-25929070, EBI-395719; CC Q9BZ23-2; Q6P1K2-3: PMF1; NbExp=3; IntAct=EBI-25929070, EBI-12906008; CC Q9BZ23-2; Q969K3: RNF34; NbExp=3; IntAct=EBI-25929070, EBI-2340642; CC Q9BZ23-2; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-25929070, EBI-358545; CC Q9BZ23-2; Q8WXH5: SOCS4; NbExp=3; IntAct=EBI-25929070, EBI-3942425; CC Q9BZ23-2; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-25929070, EBI-357085; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion CC {ECO:0000269|PubMed:12554685, ECO:0000269|PubMed:15659606, CC ECO:0000269|PubMed:17825826}. Mitochondrion intermembrane space CC {ECO:0000269|PubMed:23152917}. Nucleus {ECO:0000269|PubMed:23152917}. CC Note=Localizes predominantly to the mitochondria and to a lesser extent CC to the nucleus. Found in both the mitochondria and the nucleus CC throughout the cell cycle, with the exception of the G2/M phase when it CC is restricted to mitochdondria. {ECO:0000269|PubMed:23152917}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm CC {ECO:0000269|PubMed:12554685, ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=4; CC Name=1; CC IsoId=Q9BZ23-1; Sequence=Displayed; CC Name=3; CC IsoId=Q9BZ23-2; Sequence=VSP_007424; CC Name=2; CC IsoId=Q9BZ23-3; Sequence=VSP_018825; CC Name=4; CC IsoId=Q9BZ23-4; Sequence=VSP_038494, VSP_038495; CC -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level) CC (PubMed:15659606, PubMed:17825826). Ubiquitous (PubMed:11479594). CC Highly expressed in the testis (PubMed:17825826). Expressed in the CC umbilical vein endothelial cells (HUVEC) (PubMed:30221726). CC {ECO:0000269|PubMed:11479594, ECO:0000269|PubMed:15659606, CC ECO:0000269|PubMed:17825826, ECO:0000269|PubMed:30221726}. CC -!- PTM: Synthesized as a 62-kDa precursor which is proteolytically CC processed by the mitochondrial-processing peptidase (MPP) via a 59-kDa CC intermediate to yield the mature mitochondrial 48-kDa subunit. CC {ECO:0000269|PubMed:15659606, ECO:0000269|PubMed:16272150}. CC -!- DISEASE: Neurodegeneration with brain iron accumulation 1 (NBIA1) CC [MIM:234200]: Autosomal recessive neurodegenerative disorder associated CC with iron accumulation in the brain, primarily in the basal ganglia. CC Clinical manifestations include progressive muscle spasticity, CC hyperreflexia, muscle rigidity, dystonia, dysarthria, and intellectual CC deterioration which progresses to severe dementia over several years. CC It is clinically classified into classic, atypical, and intermediate CC phenotypes. Classic forms present with onset in first decade, rapid CC progression, loss of independent ambulation within 15 years. Atypical CC forms have onset in second decade, slow progression, maintenance of CC independent ambulation up to 40 years later. Intermediate forms CC manifest onset in first decade with slow progression or onset in second CC decade with rapid progression. Patients with early onset tend to also CC develop pigmentary retinopathy, whereas those with later onset tend to CC also have speech disorders and psychiatric features. All patients have CC the 'eye of the tiger' sign on brain MRI. {ECO:0000269|PubMed:11479594, CC ECO:0000269|PubMed:12510040, ECO:0000269|PubMed:15659606, CC ECO:0000269|PubMed:15834858, ECO:0000269|PubMed:16272150, CC ECO:0000269|PubMed:22930366, ECO:0000269|PubMed:24075960, CC ECO:0000269|PubMed:24655737, ECO:0000269|PubMed:27185474}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Hypoprebetalipoproteinemia, acanthocytosis, retinitis CC pigmentosa, and pallidal degeneration (HARP) [MIM:607236]: Rare CC syndrome with many clinical similarities to PKAN. CC {ECO:0000269|PubMed:12058097}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: The HSS syndrome has been proposed to be renamed because CC of the unethical activities of Julius Hallervorden and Hugo Spatz CC during world war II. CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative initiation at Met- CC 124 of isoform 1. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: May be produced by alternative initiation CC at Leu-111 of isoform 1. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the type II pantothenate kinase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC05173.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/pank2/"; 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; AF494409; AAN32907.1; -; mRNA. DR EMBL; AK021791; BAB13897.1; -; mRNA. DR EMBL; AK097796; BAC05173.1; ALT_INIT; mRNA. DR EMBL; EU595875; ACD11492.1; -; Genomic_DNA. DR EMBL; AL031670; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL353194; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471133; EAX10478.1; -; Genomic_DNA. DR EMBL; CH471133; EAX10476.1; -; Genomic_DNA. DR EMBL; AL713654; CAD28463.1; -; mRNA. DR EMBL; BK000010; DAA00004.1; -; mRNA. DR CCDS; CCDS13071.2; -. [Q9BZ23-1] DR CCDS; CCDS13072.1; -. [Q9BZ23-2] DR CCDS; CCDS93004.1; -. [Q9BZ23-4] DR RefSeq; NP_001311120.1; NM_001324191.1. [Q9BZ23-2] DR RefSeq; NP_079236.3; NM_024960.5. [Q9BZ23-2] DR RefSeq; NP_705902.2; NM_153638.3. [Q9BZ23-1] DR RefSeq; NP_705904.1; NM_153640.3. [Q9BZ23-2] DR RefSeq; XP_005260893.3; XM_005260836.4. DR PDB; 5E26; X-ray; 2.14 A; A/B/C/D=205-568. DR PDBsum; 5E26; -. DR AlphaFoldDB; Q9BZ23; -. DR SMR; Q9BZ23; -. DR BioGRID; 123079; 37. DR IntAct; Q9BZ23; 23. DR MINT; Q9BZ23; -. DR STRING; 9606.ENSP00000313377; -. DR BindingDB; Q9BZ23; -. DR ChEMBL; CHEMBL3407327; -. DR GlyCosmos; Q9BZ23; 1 site, 1 glycan. DR GlyGen; Q9BZ23; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9BZ23; -. DR PhosphoSitePlus; Q9BZ23; -. DR BioMuta; PANK2; -. DR DMDM; 118572682; -. DR EPD; Q9BZ23; -. DR jPOST; Q9BZ23; -. DR MassIVE; Q9BZ23; -. DR MaxQB; Q9BZ23; -. DR PaxDb; 9606-ENSP00000313377; -. DR PeptideAtlas; Q9BZ23; -. DR ProteomicsDB; 79754; -. [Q9BZ23-1] DR ProteomicsDB; 79755; -. [Q9BZ23-2] DR ProteomicsDB; 79756; -. [Q9BZ23-3] DR ProteomicsDB; 79757; -. [Q9BZ23-4] DR Pumba; Q9BZ23; -. DR TopDownProteomics; Q9BZ23-1; -. [Q9BZ23-1] DR Antibodypedia; 2051; 393 antibodies from 32 providers. DR DNASU; 80025; -. DR Ensembl; ENST00000316562.9; ENSP00000313377.4; ENSG00000125779.24. [Q9BZ23-1] DR Ensembl; ENST00000497424.5; ENSP00000417609.1; ENSG00000125779.24. [Q9BZ23-2] DR Ensembl; ENST00000610179.7; ENSP00000477429.2; ENSG00000125779.24. [Q9BZ23-4] DR Ensembl; ENST00000621507.1; ENSP00000481523.1; ENSG00000125779.24. [Q9BZ23-2] DR GeneID; 80025; -. DR KEGG; hsa:80025; -. DR MANE-Select; ENST00000610179.7; ENSP00000477429.2; NM_001386393.1; NP_001373322.1. [Q9BZ23-4] DR UCSC; uc002wkb.4; human. [Q9BZ23-1] DR AGR; HGNC:15894; -. DR CTD; 80025; -. DR DisGeNET; 80025; -. DR GeneCards; PANK2; -. DR GeneReviews; PANK2; -. DR HGNC; HGNC:15894; PANK2. DR HPA; ENSG00000125779; Low tissue specificity. DR MalaCards; PANK2; -. DR MIM; 234200; phenotype. DR MIM; 606157; gene. DR MIM; 607236; phenotype. DR neXtProt; NX_Q9BZ23; -. DR OpenTargets; ENSG00000125779; -. DR Orphanet; 216873; Atypical pantothenate kinase-associated neurodegeneration. DR Orphanet; 216866; Classic pantothenate kinase-associated neurodegeneration. DR PharmGKB; PA38048; -. DR VEuPathDB; HostDB:ENSG00000125779; -. DR eggNOG; KOG2201; Eukaryota. DR GeneTree; ENSGT00940000157626; -. DR HOGENOM; CLU_011154_0_1_1; -. DR InParanoid; Q9BZ23; -. DR OMA; WSKGAKQ; -. DR OrthoDB; 167164at2759; -. DR PhylomeDB; Q9BZ23; -. DR TreeFam; TF314866; -. DR BioCyc; MetaCyc:HS13177-MONOMER; -. DR BRENDA; 2.7.1.33; 2681. DR PathwayCommons; Q9BZ23; -. DR Reactome; R-HSA-196783; Coenzyme A biosynthesis. DR SABIO-RK; Q9BZ23; -. DR SignaLink; Q9BZ23; -. DR UniPathway; UPA00241; UER00352. DR BioGRID-ORCS; 80025; 9 hits in 1155 CRISPR screens. DR ChiTaRS; PANK2; human. DR GeneWiki; PANK2_(gene); -. DR GenomeRNAi; 80025; -. DR Pharos; Q9BZ23; Tbio. DR PRO; PR:Q9BZ23; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q9BZ23; Protein. DR Bgee; ENSG00000125779; Expressed in endothelial cell and 192 other cell types or tissues. DR ExpressionAtlas; Q9BZ23; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004594; F:pantothenate kinase activity; IMP:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; IEA:Ensembl. DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB. DR GO; GO:0015937; P:coenzyme A biosynthetic process; IBA:GO_Central. DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl. DR GO; GO:0015939; P:pantothenate metabolic process; NAS:ParkinsonsUK-UCL. DR GO; GO:0016310; P:phosphorylation; NAS:ParkinsonsUK-UCL. DR GO; GO:1904251; P:regulation of bile acid metabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Ensembl. DR GO; GO:0090207; P:regulation of triglyceride metabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:0007286; P:spermatid development; IEA:Ensembl. DR Gene3D; 3.30.420.40; -; 1. DR Gene3D; 3.30.420.510; -; 1. DR InterPro; IPR043129; ATPase_NBD. DR InterPro; IPR004567; Type_II_PanK. DR NCBIfam; TIGR00555; panK_eukar; 1. DR PANTHER; PTHR12280; PANTOTHENATE KINASE; 1. DR PANTHER; PTHR12280:SF25; PANTOTHENATE KINASE 2, MITOCHONDRIAL; 1. DR Pfam; PF03630; Fumble; 1. DR SUPFAM; SSF53067; Actin-like ATPase domain; 2. DR Genevisible; Q9BZ23; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative initiation; Alternative splicing; Angiogenesis; KW ATP-binding; Coenzyme A biosynthesis; Cytoplasm; Direct protein sequencing; KW Disease variant; Kinase; Mitochondrion; Neurodegeneration; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Transferase; Transit peptide. FT TRANSIT 1..31 FT /note="Mitochondrion" FT /evidence="ECO:0000269|PubMed:15659606" FT CHAIN 32..570 FT /note="Pantothenate kinase 2, mitochondrial intermediate FT form" FT /evidence="ECO:0000269|PubMed:15659606" FT /id="PRO_0000023201" FT CHAIN 141..570 FT /note="Pantothenate kinase 2, mitochondrial mature form" FT /evidence="ECO:0000269|PubMed:15659606" FT /id="PRO_0000452676" FT REGION 34..94 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 127..198 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 82..94 FT /note="Nucleolar localization signal" FT /evidence="ECO:0000269|PubMed:23152917" FT MOTIF 268..275 FT /note="Nuclear export signal" FT /evidence="ECO:0000269|PubMed:23152917" FT ACT_SITE 338 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:Q9H999" FT BINDING 392 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000250|UniProtKB:Q8TE04" FT BINDING 395 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000250|UniProtKB:Q8TE04" FT BINDING 407 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000250|UniProtKB:Q8TE04" FT SITE 140..141 FT /note="Cleavage; by MPP" FT /evidence="ECO:0000269|PubMed:15659606" FT MOD_RES 168 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 169 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 189 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT VAR_SEQ 1..291 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_007424" FT VAR_SEQ 1..123 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_018825" FT VAR_SEQ 1..110 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_038494" FT VAR_SEQ 111 FT /note="L -> M (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_038495" FT VARIANT 94 FT /note="R -> P (in dbSNP:rs71647827)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_054484" FT VARIANT 111 FT /note="L -> Q (in dbSNP:rs71647828)" FT /evidence="ECO:0000269|PubMed:11479594, ECO:0000269|Ref.3" FT /id="VAR_015152" FT VARIANT 126 FT /note="G -> A (in dbSNP:rs3737084)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:12554685, ECO:0000269|Ref.3" FT /id="VAR_015153" FT VARIANT 134 FT /note="E -> G (in NBIA1; no effect on enzyme activity or FT its mitochondrial localization; dbSNP:rs765679726)" FT /evidence="ECO:0000269|PubMed:12510040, FT ECO:0000269|PubMed:15659606" FT /id="VAR_060934" FT VARIANT 219 FT /note="G -> V (in NBIA1; loss of enzyme activity; no effect FT on its mitochondrial localization)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:15659606, ECO:0000269|PubMed:16272150" FT /id="VAR_015154" FT VARIANT 232 FT /note="D -> G (in NBIA1; uncertain significance)" FT /evidence="ECO:0000269|PubMed:24655737" FT /id="VAR_076594" FT VARIANT 234 FT /note="T -> A (in NBIA1; no effect on enzyme activity or FT its mitochondrial localization; dbSNP:rs137852965)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:15659606, ECO:0000269|PubMed:16272150" FT /id="VAR_015155" FT VARIANT 249 FT /note="R -> P (in NBIA1)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060935" FT VARIANT 264 FT /note="R -> W (in NBIA1; no effect on enzyme activity; FT dbSNP:rs137852961)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:16272150" FT /id="VAR_015156" FT VARIANT 278 FT /note="R -> C (in NBIA1; dbSNP:rs137852966)" FT /evidence="ECO:0000269|PubMed:11479594" FT /id="VAR_015157" FT VARIANT 278 FT /note="R -> L (in NBIA1; dbSNP:rs1348762206)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060936" FT VARIANT 282 FT /note="L -> V (in NBIA1)" FT /evidence="ECO:0000269|PubMed:11479594" FT /id="VAR_015158" FT VARIANT 286 FT /note="R -> C (in NBIA1; no effect on enzyme activity; FT dbSNP:rs137852962)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:16272150" FT /id="VAR_015159" FT VARIANT 322 FT /note="E -> D (in NBIA1; dbSNP:rs974575417)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060937" FT VARIANT 322 FT /note="E -> G (in NBIA1; dbSNP:rs768230831)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060938" FT VARIANT 327 FT /note="T -> I (in NBIA1; no effect on enzyme activity)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:16272150" FT /id="VAR_015160" FT VARIANT 351 FT /note="S -> P (in NBIA1; no effect on enzyme activity; FT dbSNP:rs137852964)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:16272150" FT /id="VAR_015161" FT VARIANT 355 FT /note="N -> S (in NBIA1; dbSNP:rs746484727)" FT /evidence="ECO:0000269|PubMed:11479594" FT /id="VAR_015162" FT VARIANT 357 FT /note="R -> Q (in NBIA1; dbSNP:rs754521581)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060939" FT VARIANT 377 FT /note="F -> S (in NBIA1; uncertain significance)" FT /evidence="ECO:0000269|PubMed:22930366" FT /id="VAR_076595" FT VARIANT 398 FT /note="A -> T (in NBIA1; dbSNP:rs759223327)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060940" FT VARIANT 404 FT /note="N -> I (in NBIA1; no effect on enzyme activity or FT its inhibition by acetyl CoA; dbSNP:rs752078407)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:16272150" FT /id="VAR_015163" FT VARIANT 413 FT /note="L -> P (in NBIA1; dbSNP:rs750176786)" FT /evidence="ECO:0000269|PubMed:11479594" FT /id="VAR_015164" FT VARIANT 425 FT /note="Missing (in NBIA1; dbSNP:rs1064794317)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060941" FT VARIANT 428 FT /note="C -> Y (in NBIA1; dbSNP:rs1012947103)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060942" FT VARIANT 447 FT /note="D -> N (in NBIA1)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060943" FT VARIANT 471 FT /note="S -> N (in NBIA1; significant loss of enzyme FT activity; no effect on its mitochondrial localization or FT its inhibition by acetyl CoA; dbSNP:rs137852963)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:15659606, ECO:0000269|PubMed:16272150" FT /id="VAR_015165" FT VARIANT 489 FT /note="L -> P (in NBIA1; uncertain significance)" FT /evidence="ECO:0000269|PubMed:27185474" FT /id="VAR_076596" FT VARIANT 497 FT /note="I -> T (in NBIA1)" FT /evidence="ECO:0000269|PubMed:11479594" FT /id="VAR_015166" FT VARIANT 500 FT /note="N -> I (in NBIA1; significant loss of enzyme FT activity; dbSNP:rs759332123)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:16272150" FT /id="VAR_015167" FT VARIANT 501 FT /note="I -> T (in NBIA1; dbSNP:rs775459398)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060944" FT VARIANT 509 FT /note="A -> V (in NBIA1; no effect on enzyme activity)" FT /evidence="ECO:0000269|PubMed:12510040, FT ECO:0000269|PubMed:16272150" FT /id="VAR_060945" FT VARIANT 511 FT /note="N -> D (in NBIA1; dbSNP:rs767653843)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060946" FT VARIANT 521 FT /note="G -> R (in NBIA1; loss of enzyme activity; no effect FT on its mitochondrial localization; loss of proteolytic FT cleavage to yield the mature form; dbSNP:rs137852959)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:15659606, ECO:0000269|PubMed:15834858, FT ECO:0000269|PubMed:16272150, ECO:0000269|PubMed:24075960" FT /id="VAR_015168" FT VARIANT 528 FT /note="T -> M (in NBIA1; uncertain significance; no effect FT on enzyme activity, mitochondrial localization or its FT inhibition by acetyl CoA; dbSNP:rs137852967)" FT /evidence="ECO:0000269|PubMed:11479594, FT ECO:0000269|PubMed:15659606, ECO:0000269|PubMed:16272150, FT ECO:0000269|PubMed:27185474" FT /id="VAR_015169" FT VARIANT 532 FT /note="R -> W (in NBIA1; no effect on enzyme activity)" FT /evidence="ECO:0000269|PubMed:12510040, FT ECO:0000269|PubMed:16272150" FT /id="VAR_060947" FT VARIANT 555 FT /note="G -> S (in NBIA1; uncertain significance)" FT /evidence="ECO:0000269|PubMed:24075960" FT /id="VAR_076597" FT VARIANT 563 FT /note="L -> P (in NBIA1; dbSNP:rs1324077575)" FT /evidence="ECO:0000269|PubMed:12510040" FT /id="VAR_060948" FT VARIANT 570 FT /note="P -> L (in NBIA1; dbSNP:rs41279408)" FT /evidence="ECO:0000269|PubMed:12510040, FT ECO:0000269|PubMed:15834858" FT /id="VAR_060949" FT MUTAGEN 82..94 FT /note="RWRNGRGGRPRAR->AWANGAGGAPAAA: Loss of nuclear FT localization." FT /evidence="ECO:0000269|PubMed:23152917" FT MUTAGEN 268..275 FT /note="LELKDLTL->AEAKDATA: Loss of export from nucleus." FT /evidence="ECO:0000269|PubMed:23152917" FT CONFLICT 460 FT /note="R -> G (in Ref. 2; BAB13897)" FT /evidence="ECO:0000305" FT CONFLICT 475 FT /note="M -> K (in Ref. 2; BAB13897)" FT /evidence="ECO:0000305" FT STRAND 213..218 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 220..231 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 235..240 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 243..254 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 256..258 FT /evidence="ECO:0007829|PDB:5E26" FT TURN 259..261 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 262..264 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 266..268 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 270..275 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 278..288 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 289..291 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 292..301 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 304..306 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 309..315 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 317..320 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 322..329 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 332..336 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 338..352 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 354..357 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 359..365 FT /evidence="ECO:0007829|PDB:5E26" FT TURN 369..371 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 373..377 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 384..403 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 405..412 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 415..426 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 431..439 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 443..445 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 447..449 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 450..454 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 459..461 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 467..470 FT /evidence="ECO:0007829|PDB:5E26" FT TURN 471..476 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 478..483 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 486..512 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 516..521 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 522..524 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 528..541 FT /evidence="ECO:0007829|PDB:5E26" FT TURN 542..544 FT /evidence="ECO:0007829|PDB:5E26" FT STRAND 547..553 FT /evidence="ECO:0007829|PDB:5E26" FT HELIX 557..566 FT /evidence="ECO:0007829|PDB:5E26" SQ SEQUENCE 570 AA; 62681 MW; 9061A60D6CA93BBB CRC64; MRRLGPFHPR VHWAAPPSLS SGLHRLLFLR GTRIPSSTTL SPPRHDSLSL DGGTVNPPRV REPTGREAFG PSPASSDWLP ARWRNGRGGR PRARLCSGWT AAEEARRNPT LGGLLGRQRL LLRMGGGRLG APMERHGRAS ATSVSSAGEQ AAGDPEGRRQ EPLRRRASSA SVPAVGASAE GTRRDRLGSY SGPTSVSRQR VESLRKKRPL FPWFGLDIGG TLVKLVYFEP KDITAEEEEE EVESLKSIRK YLTSNVAYGS TGIRDVHLEL KDLTLCGRKG NLHFIRFPTH DMPAFIQMGR DKNFSSLHTV FCATGGGAYK FEQDFLTIGD LQLCKLDELD CLIKGILYID SVGFNGRSQC YYFENPADSE KCQKLPFDLK NPYPLLLVNI GSGVSILAVY SKDNYKRVTG TSLGGGTFFG LCCLLTGCTT FEEALEMASR GDSTKVDKLV RDIYGGDYER FGLPGWAVAS SFGNMMSKEK REAVSKEDLA RATLITITNN IGSIARMCAL NENINQVVFV GNFLRINTIA MRLLAYALDY WSKGQLKALF SEHEGYFGAV GALLELLKIP //