PANK3_MOUSE
ID PANK3_MOUSE Reviewed; 370 AA.
AC Q8R2W9;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Pantothenate kinase 3;
DE Short=mPanK3;
DE EC=2.7.1.33 {ECO:0000269|PubMed:16040613, ECO:0000269|PubMed:17379144};
DE AltName: Full=Pantothenic acid kinase 3;
GN Name=Pank3;
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 [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [2]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16040613; DOI=10.1074/jbc.m506275200;
RA Zhang Y.M., Rock C.O., Jackowski S.;
RT "Feedback regulation of murine pantothenate kinase 3 by coenzyme A and
RT coenzyme A thioesters.";
RL J. Biol. Chem. 280:32594-32601(2005).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBUNIT.
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 [4]
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:16040613,
CC ECO:0000269|PubMed:17379144}.
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:16040613,
CC ECO:0000269|PubMed:17379144};
CC -!- ACTIVITY REGULATION: Subject to allosteric regulation, exists in two
CC distinct conformational states, a catalytically incompetent (or open)
CC conformation stabilized by the binding of acetyl(acyl)-CoA, and a
CC catalytically competent (or closed) conformation stabilized by ATP-
CC binding (By similarity). Acetyl-CoA and its thioesters act as
CC allosteric inhibitors and compete with the ATP-binding site (By
CC similarity). Strongly inhibited by acetyl-CoA, malonyl-CoA and
CC palmitoyl CoA and modestly inhibited by CoA (PubMed:16040613).
CC Inhibited by calcium hopantenate (PubMed:17379144).
CC {ECO:0000250|UniProtKB:Q9H999, ECO:0000269|PubMed:16040613,
CC ECO:0000269|PubMed:17379144}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.5 uM for pantothenate {ECO:0000269|PubMed:16040613};
CC KM=112.0 uM for ATP {ECO:0000269|PubMed:16040613};
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-
CC pantothenate: step 1/5. {ECO:0000269|PubMed:16040613,
CC ECO:0000269|PubMed:17379144}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16040613,
CC ECO:0000269|PubMed:17379144}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16040613,
CC ECO:0000269|PubMed:23152917, ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the liver.
CC {ECO:0000269|PubMed:16040613}.
CC -!- SIMILARITY: Belongs to the type II pantothenate kinase family.
CC {ECO:0000305}.
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DR EMBL; BC027089; AAH27089.1; -; mRNA.
DR EMBL; BC032188; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS24543.1; -.
DR RefSeq; NP_666074.1; NM_145962.2.
DR AlphaFoldDB; Q8R2W9; -.
DR SMR; Q8R2W9; -.
DR IntAct; Q8R2W9; 1.
DR MINT; Q8R2W9; -.
DR STRING; 10090.ENSMUSP00000018990; -.
DR iPTMnet; Q8R2W9; -.
DR PhosphoSitePlus; Q8R2W9; -.
DR EPD; Q8R2W9; -.
DR MaxQB; Q8R2W9; -.
DR PaxDb; Q8R2W9; -.
DR PRIDE; Q8R2W9; -.
DR ProteomicsDB; 294379; -.
DR Antibodypedia; 16804; 229 antibodies from 24 providers.
DR DNASU; 211347; -.
DR Ensembl; ENSMUST00000018990; ENSMUSP00000018990; ENSMUSG00000018846.
DR GeneID; 211347; -.
DR KEGG; mmu:211347; -.
DR UCSC; uc007ilf.1; mouse.
DR CTD; 79646; -.
DR MGI; MGI:2387464; Pank3.
DR VEuPathDB; HostDB:ENSMUSG00000018846; -.
DR eggNOG; KOG2201; Eukaryota.
DR GeneTree; ENSGT00940000156396; -.
DR HOGENOM; CLU_011154_0_1_1; -.
DR InParanoid; Q8R2W9; -.
DR OMA; WAQEGDN; -.
DR OrthoDB; 865329at2759; -.
DR PhylomeDB; Q8R2W9; -.
DR TreeFam; TF314866; -.
DR BRENDA; 2.7.1.33; 3474.
DR Reactome; R-MMU-196783; Coenzyme A biosynthesis.
DR SABIO-RK; Q8R2W9; -.
DR UniPathway; UPA00241; UER00352.
DR BioGRID-ORCS; 211347; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Pank3; mouse.
DR PRO; PR:Q8R2W9; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8R2W9; protein.
DR Bgee; ENSMUSG00000018846; Expressed in mammary gland and 254 other tissues.
DR ExpressionAtlas; Q8R2W9; baseline and differential.
DR Genevisible; Q8R2W9; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:1905502; F:acetyl-CoA binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0004594; F:pantothenate kinase activity; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019842; F:vitamin binding; ISS:UniProtKB.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IDA:MGI.
DR GO; GO:0016310; P:phosphorylation; ISO: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; Kinase;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..370
FT /note="Pantothenate kinase 3"
FT /id="PRO_0000161805"
FT ACT_SITE 138
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9H999"
FT BINDING 192
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q9H999"
FT BINDING 195
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q9H999"
FT BINDING 207
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:Q9H999"
SQ SEQUENCE 370 AA; 41120 MW; 61D982A619E83A78 CRC64;
MKIKDAKKPS FPWFGMDIGG TLVKLSYFEP IDITAEEEQE EVESLKSIRK YLTSNVAYGS
TGIRDVHLEL KDLTLFGRRG NLHFIRFPTQ DLPTFIQMGR DKNFSTLQTV LSATGGGAYK
FEKDFRTIGN LHLHKLDELD CLVKGLLYID SVSFNGQAEC YYFANASEPE RCQKMPFNLD
DPYPLLVVNI GSGVSILAVH SKDNYKRVTG TSLGGGTFLG LCSLLTGCES FEEALEMASK
GDSTQADRLV RDIYGGDYER FGLPGWAVAS SFGNMIYKEK RETVSKEDLA RATLVTITNN
IGSVARMCAV NEKINRVVFV GNFLRVNTLS MKLLAYALDY WSKGQLKALF LEHEGYFGAV
GALLGLPNFS
