PANK2_HUMAN
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 03-AUG-2022, entry version 185.
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=92.0 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; Q8WXH5: SOCS4; NbExp=3; IntAct=EBI-25929070, EBI-3942425;
CC Q9BZ23-2; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-25929070, EBI-357085;
CC Q9BZ23-2; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-25929070, EBI-358545;
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 ---------------------------------------------------------------------------
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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 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. [Q9BZ23-2]
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; 34.
DR IntAct; Q9BZ23; 23.
DR MINT; Q9BZ23; -.
DR STRING; 9606.ENSP00000313377; -.
DR BindingDB; Q9BZ23; -.
DR ChEMBL; CHEMBL3407327; -.
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; Q9BZ23; -.
DR PeptideAtlas; Q9BZ23; -.
DR PRIDE; Q9BZ23; -.
DR ProteomicsDB; 79754; -. [Q9BZ23-1]
DR ProteomicsDB; 79755; -. [Q9BZ23-2]
DR ProteomicsDB; 79756; -. [Q9BZ23-3]
DR ProteomicsDB; 79757; -. [Q9BZ23-4]
DR TopDownProteomics; Q9BZ23-1; -. [Q9BZ23-1]
DR Antibodypedia; 2051; 363 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 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; DDCVEFM; -.
DR OrthoDB; 865329at2759; -.
DR PhylomeDB; Q9BZ23; -.
DR TreeFam; TF314866; -.
DR BioCyc; MetaCyc:HS13177-MON; -.
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; 8 hits in 1074 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 190 other tissues.
DR ExpressionAtlas; Q9BZ23; baseline and differential.
DR Genevisible; Q9BZ23; HS.
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:0070584; P:mitochondrion morphogenesis; 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 InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR004567; Type_II_PanK.
DR PANTHER; PTHR12280; PTHR12280; 1.
DR Pfam; PF03630; Fumble; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
DR TIGRFAMs; TIGR00555; panK_eukar; 1.
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; atypical; loss of enzyme activity;
FT no effect 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; atypical; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24655737"
FT /id="VAR_076594"
FT VARIANT 234
FT /note="T -> A (in NBIA1; atypical; no effect on enzyme
FT activity or its mitochondrial localization;
FT 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; atypical; 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; atypical; 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; atypical; no effect on enzyme
FT activity; 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; atypical; 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; atypical; unknown pathological
FT 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; atypical; no effect on enzyme
FT activity or its inhibition by acetyl CoA;
FT 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; unknown pathological
FT 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; atypical; 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; classic and atypical forms; loss
FT of enzyme activity; no effect on its mitochondrial
FT localization; loss of proteolytic cleavage to yield the
FT 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; classic and atypical forms;
FT unknown pathological significance; no effect on enzyme
FT activity, mitochondrial localization or its inhibition by
FT 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; atypical; unknown pathological
FT 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; atypical; 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
