PANK2_MOUSE
ID PANK2_MOUSE Reviewed; 456 AA.
AC Q7M753; Q3U4S0;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Pantothenate kinase 2, mitochondrial;
DE Short=hPanK2;
DE EC=2.7.1.33 {ECO:0000269|PubMed:17379144, ECO:0000269|PubMed:17825826, ECO:0000269|PubMed:22815849};
DE AltName: Full=Pantothenic acid kinase 2;
GN Name=Pank2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhou B., Westaway S.K., Levinson B., Johnson M.A., Gitschier J.,
RA Hayflick S.J.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-456.
RC STRAIN=NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 7-456.
RC STRAIN=NOD; TISSUE=Thymus;
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, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=17379144; DOI=10.1016/j.chembiol.2007.01.013;
RA Zhang Y.M., Chohnan S., Virga K.G., Stevens R.D., Ilkayeva O.R.,
RA Wenner B.R., Bain J.R., Newgard C.B., Lee R.E., Rock C.O., Jackowski S.;
RT "Chemical knockout of pantothenate kinase reveals the metabolic and genetic
RT program responsible for hepatic coenzyme A homeostasis.";
RL Chem. Biol. 14:291-302(2007).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22815849; DOI=10.1371/journal.pone.0040871;
RA Garcia M., Leonardi R., Zhang Y.M., Rehg J.E., Jackowski S.;
RT "Germline deletion of pantothenate kinases 1 and 2 reveals the key roles
RT for CoA in postnatal metabolism.";
RL PLoS ONE 7:e40871-e40871(2012).
RN [9]
RP SUBCELLULAR LOCATION.
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).
CC -!- FUNCTION: Catalyzes the phosphorylation of pantothenate to generate 4'-
CC phosphopantothenate in the first and rate-determining step of coenzyme
CC A (CoA) synthesis. {ECO:0000269|PubMed:17379144,
CC ECO:0000269|PubMed:17825826, ECO:0000269|PubMed:22815849}.
CC -!- CATALYTIC ACTIVITY:
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:17379144,
CC ECO:0000269|PubMed:17825826, ECO:0000269|PubMed:22815849};
CC -!- ACTIVITY REGULATION: Inhibited by acetyl-CoA (PubMed:17825826).
CC Inhibited by calcium hopantenate (PubMed:17379144). Activated by
CC palmitoylcarnitine (PubMed:17825826). {ECO:0000269|PubMed:17379144,
CC ECO:0000269|PubMed:17825826}.
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-
CC pantothenate: step 1/5. {ECO:0000269|PubMed:17379144,
CC ECO:0000269|PubMed:17825826, ECO:0000269|PubMed:22815849}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9BZ23}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17825826,
CC ECO:0000269|PubMed:23152917}.
CC -!- DISRUPTION PHENOTYPE: Single knockout mice show a reduction in
CC pantothenate kinase (PANK) activity of about 30% and 60% in the liver
CC and brain respectively. Pank1 and Pank2 double knockout mice develop
CC progressively severe hypoglycemia and hyperketonemia by postnatal day
CC 10 leading to their death by day 17. A reduction in PANK activity of
CC about 90-95% seen in the liver and brain and hepatocytes show reduced
CC NADH levels. {ECO:0000269|PubMed:22815849}.
CC -!- SIMILARITY: Belongs to the type II pantothenate kinase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI06185.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE32361.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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; BK000014; DAA00008.1; -; mRNA.
DR EMBL; AL808128; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK154080; BAE32361.1; ALT_INIT; mRNA.
DR EMBL; BC106184; AAI06185.1; ALT_INIT; mRNA.
DR CCDS; CCDS16761.1; -.
DR RefSeq; NP_705721.2; NM_153501.2.
DR AlphaFoldDB; Q7M753; -.
DR SMR; Q7M753; -.
DR STRING; 10090.ENSMUSP00000119606; -.
DR iPTMnet; Q7M753; -.
DR PhosphoSitePlus; Q7M753; -.
DR SwissPalm; Q7M753; -.
DR PRIDE; Q7M753; -.
DR ProteomicsDB; 328865; -.
DR Antibodypedia; 2051; 363 antibodies from 32 providers.
DR DNASU; 74450; -.
DR Ensembl; ENSMUST00000150843; ENSMUSP00000119606; ENSMUSG00000037514.
DR GeneID; 74450; -.
DR KEGG; mmu:74450; -.
DR UCSC; uc008mlg.2; mouse.
DR CTD; 80025; -.
DR MGI; MGI:1921700; Pank2.
DR VEuPathDB; HostDB:ENSMUSG00000037514; -.
DR eggNOG; KOG2201; Eukaryota.
DR GeneTree; ENSGT00940000157626; -.
DR HOGENOM; CLU_011154_0_1_1; -.
DR OMA; DDCVEFM; -.
DR OrthoDB; 865329at2759; -.
DR PhylomeDB; Q7M753; -.
DR TreeFam; TF314866; -.
DR Reactome; R-MMU-196783; Coenzyme A biosynthesis.
DR UniPathway; UPA00241; UER00352.
DR BioGRID-ORCS; 74450; 0 hits in 75 CRISPR screens.
DR ChiTaRS; Pank2; mouse.
DR Proteomes; UP000000589; Chromosome 2.
DR Bgee; ENSMUSG00000037514; Expressed in spermatid and 227 other tissues.
DR ExpressionAtlas; Q7M753; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IMP:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004594; F:pantothenate kinase activity; IDA:MGI.
DR GO; GO:0009060; P:aerobic respiration; IMP:MGI.
DR GO; GO:0001525; P:angiogenesis; ISO:MGI.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IMP:MGI.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IMP:MGI.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:1904251; P:regulation of bile acid metabolic process; ISO:MGI.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; ISO:MGI.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IMP:MGI.
DR GO; GO:0090207; P:regulation of triglyceride metabolic process; ISO:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:MGI.
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 ATP-binding; Coenzyme A biosynthesis; Cytoplasm; Disease variant; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase;
KW Transit peptide.
FT CHAIN 1..456
FT /note="Pantothenate kinase 2, mitochondrial"
FT /id="PRO_0000452677"
FT REGION 16..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 154..161
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q9BZ23"
FT ACT_SITE 224
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9H999"
FT BINDING 278
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q8TE04"
FT BINDING 281
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q8TE04"
FT BINDING 293
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q8TE04"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZ23"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZ23"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZ23"
SQ SEQUENCE 456 AA; 50212 MW; 2A4565D99C471205 CRC64;
MGGWLGRQRR LLRMGAGRFG APMERQGRAA ATSAAVGESA DSEARRRDPL RRRASSAAPS
GSGEAESVRR ERPGSLGGST SAGRPRAEGL RKRRPLFPWF GLDIGGTLVK LVYFEPKDIT
AEEEKEEVES LKSIRKYLTS NVAYGSTGIR DVHLELKDLT LCGRKGNLHF IRFPTHDMPA
FIQMGRDKNF SSLHTVFCAT GGGSYKFEQD FLTIGDLQLR KLDELDCLIK GILYIDSVGF
NGRSQCYYFE NPADSEKCQK LPFDLKNPYP LLLVNIGSGV SILAVYSKDN YKRVTGTSLG
GGTFFGLCCL LTGCSTFEEA LEMASRGDST KVDKLVRDIY GGDYERFGLP GWAVASSFGN
MMSKEKREAA SKEDLARATL ITITNNIGSI ARMCALNENI NQVVFVGNFL RVNTIAMRLL
AYALDYWSKG QLKALFSEHE GYFGAVGALL ELLKIP
