FAHD1_MOUSE
ID FAHD1_MOUSE Reviewed; 227 AA.
AC Q8R0F8; Q3U020; Q3UQY4; Q8BLJ7; Q9JJB2;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Acylpyruvase FAHD1, mitochondrial;
DE EC=3.7.1.5;
DE AltName: Full=Fumarylacetoacetate hydrolase domain-containing protein 1;
DE AltName: Full=Oxaloacetate decarboxylase {ECO:0000250|UniProtKB:Q6P587};
DE Short=OAA decarboxylase {ECO:0000250|UniProtKB:Q6P587};
DE EC=4.1.1.112 {ECO:0000250|UniProtKB:Q6P587};
DE Flags: Precursor;
GN Name=Fahd1; ORFNames=MNCb-4134;
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 STRAIN=C57BL/6J; TISSUE=Brain;
RA Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation of full-length cDNA clones from mouse brain cDNA library made by
RT oligo-capping method.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryo, Spinal ganglion, and Spleen;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=21878618; DOI=10.1074/jbc.m111.264770;
RA Pircher H., Straganz G.D., Ehehalt D., Morrow G., Tanguay R.M.,
RA Jansen-Durr P.;
RT "Identification of human fumarylacetoacetate hydrolase domain containing
RT protein 1 (FAHD1) as a novel mitochondrial acylpyruvase.";
RL J. Biol. Chem. 286:36500-36508(2011).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-118, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-116, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25575590; DOI=10.1074/jbc.m114.609305;
RA Pircher H., von Grafenstein S., Diener T., Metzger C., Albertini E.,
RA Taferner A., Unterluggauer H., Kramer C., Liedl K.R., Jansen-Durr P.;
RT "Identification of FAH domain containing protein 1 (FAHD1) as oxaloacetate
RT decarboxylase.";
RL J. Biol. Chem. 290:6755-6762(2015).
CC -!- FUNCTION: Probable mitochondrial acylpyruvase which is able to
CC hydrolyze acetylpyruvate and fumarylpyruvate in vitro (By similarity).
CC Also has oxaloacetate decarboxylase activity (PubMed:25575590).
CC {ECO:0000250|UniProtKB:Q6P587, ECO:0000269|PubMed:25575590}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3-acylpyruvate + H2O = a carboxylate + H(+) + pyruvate;
CC Xref=Rhea:RHEA:19009, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29067, ChEBI:CHEBI:57278; EC=3.7.1.5;
CC Evidence={ECO:0000250|UniProtKB:Q6P587};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxaloacetate = CO2 + pyruvate; Xref=Rhea:RHEA:15641,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452,
CC ChEBI:CHEBI:16526; EC=4.1.1.112;
CC Evidence={ECO:0000250|UniProtKB:Q6P587};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q6P587};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q6P587};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q6P587}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q6P587}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q6P587}.
CC -!- TISSUE SPECIFICITY: Ubiquitous with higher expression in the liver and
CC the kidney (at protein level). {ECO:0000269|PubMed:21878618}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Elevated oxaloacetate
CC levels. {ECO:0000269|PubMed:25575590}.
CC -!- SIMILARITY: Belongs to the FAH family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC32142.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB041600; BAA95083.1; -; mRNA.
DR EMBL; AK044920; BAC32142.1; ALT_INIT; mRNA.
DR EMBL; AK157292; BAE34035.1; -; mRNA.
DR EMBL; AK141973; BAE24904.1; -; mRNA.
DR EMBL; AC166102; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026949; AAH26949.1; -; mRNA.
DR CCDS; CCDS37496.1; -.
DR RefSeq; NP_075969.1; NM_023480.2.
DR PDB; 6SBI; X-ray; 2.70 A; A/B/C/D=1-227.
DR PDB; 6SBJ; X-ray; 2.22 A; A/B/C/D=1-227.
DR PDBsum; 6SBI; -.
DR PDBsum; 6SBJ; -.
DR AlphaFoldDB; Q8R0F8; -.
DR SMR; Q8R0F8; -.
DR IntAct; Q8R0F8; 1.
DR STRING; 10090.ENSMUSP00000055827; -.
DR iPTMnet; Q8R0F8; -.
DR PhosphoSitePlus; Q8R0F8; -.
DR SwissPalm; Q8R0F8; -.
DR jPOST; Q8R0F8; -.
DR MaxQB; Q8R0F8; -.
DR PaxDb; Q8R0F8; -.
DR PeptideAtlas; Q8R0F8; -.
DR PRIDE; Q8R0F8; -.
DR ProteomicsDB; 271857; -.
DR Antibodypedia; 56108; 68 antibodies from 14 providers.
DR DNASU; 68636; -.
DR Ensembl; ENSMUST00000049642; ENSMUSP00000055827; ENSMUSG00000045316.
DR GeneID; 68636; -.
DR KEGG; mmu:68636; -.
DR UCSC; uc008ayl.1; mouse.
DR CTD; 81889; -.
DR MGI; MGI:1915886; Fahd1.
DR VEuPathDB; HostDB:ENSMUSG00000045316; -.
DR eggNOG; KOG1535; Eukaryota.
DR GeneTree; ENSGT00940000160452; -.
DR HOGENOM; CLU_028458_5_0_1; -.
DR InParanoid; Q8R0F8; -.
DR OMA; YALSIDM; -.
DR PhylomeDB; Q8R0F8; -.
DR TreeFam; TF300911; -.
DR Reactome; R-MMU-71403; Citric acid cycle (TCA cycle).
DR BioGRID-ORCS; 68636; 1 hit in 58 CRISPR screens.
DR PRO; PR:Q8R0F8; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8R0F8; protein.
DR Bgee; ENSMUSG00000045316; Expressed in ileal epithelium and 232 other tissues.
DR Genevisible; Q8R0F8; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0018773; F:acetylpyruvate hydrolase activity; ISS:UniProtKB.
DR GO; GO:0047621; F:acylpyruvate hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0034545; F:fumarylpyruvate hydrolase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008948; F:oxaloacetate decarboxylase activity; ISS:UniProtKB.
DR Gene3D; 3.90.850.10; -; 1.
DR InterPro; IPR011234; Fumarylacetoacetase-like_C.
DR InterPro; IPR036663; Fumarylacetoacetase_C_sf.
DR Pfam; PF01557; FAA_hydrolase; 1.
DR SUPFAM; SSF56529; SSF56529; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Calcium; Cytoplasm; Hydrolase; Lyase; Magnesium;
KW Metal-binding; Mitochondrion; Phosphoprotein; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 31..227
FT /note="Acylpyruvase FAHD1, mitochondrial"
FT /id="PRO_0000156830"
FT BINDING 74
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q6P587"
FT BINDING 76
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q6P587"
FT BINDING 105
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q6P587"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6AYQ8"
FT MOD_RES 116
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 118
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 1
FT /note="M -> R (in Ref. 2; BAC32142)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="I -> V (in Ref. 2; BAE34035 and 4; AAH26949)"
FT /evidence="ECO:0000305"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:6SBJ"
FT HELIX 16..19
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 23..27
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:6SBJ"
FT HELIX 52..54
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:6SBJ"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:6SBJ"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 97..104
FT /evidence="ECO:0007829|PDB:6SBJ"
FT HELIX 109..118
FT /evidence="ECO:0007829|PDB:6SBJ"
FT HELIX 123..126
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:6SBJ"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 158..164
FT /evidence="ECO:0007829|PDB:6SBJ"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:6SBJ"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 207..212
FT /evidence="ECO:0007829|PDB:6SBJ"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:6SBJ"
FT STRAND 216..224
FT /evidence="ECO:0007829|PDB:6SBJ"
SQ SEQUENCE 227 AA; 25172 MW; 62C5AEA14F8F38C5 CRC64;
MTQSCTMAST KPLSRFWEWG KNIVCVGRNY ADHVKEMRST VLSEPVLFLK PSTAYAPEGS
PVLMPAYCRN LHHEVELGVL LGKRGEAIPE AAAMDYVAGY ALCLDMTARD VQEECKKKGL
PWTLAKSFTS SCPVSAFVPK EKIPDPHALR LWLKVNGELR QEGKTSSMIF SIPYIISYVS
KIITLEEGDL ILTGTPKGVG PIKENDEIEA GIDGVVSMRF KVKRSEY
