NUDT8_HUMAN
ID NUDT8_HUMAN Reviewed; 236 AA.
AC Q8WV74; Q6ZW59;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Mitochondrial coenzyme A diphosphatase NUDT8;
DE EC=3.6.1.-;
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 8;
DE Short=Nudix motif 8;
GN Name=NUDT8;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Tongue;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Acyl-CoA diphosphatase that mediates the hydrolysis of a wide
CC range of CoA and CoA esters yielding 3',5'-ADP and the corresponding
CC 4'-phosphopantetheine derivative as products (By similarity).
CC Hydrolyzes short- and medium-chain acyl-CoAs, exhibiting the highest
CC activity toward free CoA, hexanoyl-CoA, and octanoyl-CoA and the lowest
CC activity against acetyl-CoA (By similarity). Exhibits decapping
CC activity towards dpCoA-capped RNAs in vitro (By similarity).
CC {ECO:0000250|UniProtKB:Q9CR24}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an acyl-CoA + H2O = adenosine 3',5'-bisphosphate + an acyl-4'-
CC phosphopantetheine + 2 H(+); Xref=Rhea:RHEA:50044, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58342, ChEBI:CHEBI:58343,
CC ChEBI:CHEBI:132023; Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50045;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CoA + H2O = (R)-4'-phosphopantetheine + adenosine 3',5'-
CC bisphosphate + 2 H(+); Xref=Rhea:RHEA:64988, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:58343,
CC ChEBI:CHEBI:61723; Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64989;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + H2O = adenosine 3',5'-bisphosphate + 2 H(+) + S-
CC acetyl-4'-phosphopantetheine; Xref=Rhea:RHEA:64992,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:156266;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64993;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=butanoyl-CoA + H2O = adenosine 3',5'-bisphosphate + 2 H(+) +
CC S-butanoyl-4'-phosphopantetheine; Xref=Rhea:RHEA:49976,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57371,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:132011;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49977;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexanoyl-CoA = adenosine 3',5'-bisphosphate + 2 H(+) +
CC hexanoyl-4'-phosphopantetheine; Xref=Rhea:RHEA:49980,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58343,
CC ChEBI:CHEBI:62620, ChEBI:CHEBI:132012;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49981;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + octanoyl-CoA = adenosine 3',5'-bisphosphate + 2 H(+) +
CC S-octanoyl-4'-phosphopantetheine; Xref=Rhea:RHEA:50016,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57386,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:132013;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50017;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + propanoyl-CoA = adenosine 3',5'-bisphosphate + 2 H(+) +
CC propanoyl-4'-phosphopantetheine; Xref=Rhea:RHEA:67464,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57392,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:172362;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67465;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + malonyl-CoA = adenosine 3',5'-bisphosphate + 2 H(+) +
CC malonyl-4'-phosphopantetheine; Xref=Rhea:RHEA:67468,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:172363;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67469;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + succinyl-CoA = adenosine 3',5'-bisphosphate + 2 H(+) +
CC succinyl-4'-phosphopantetheine; Xref=Rhea:RHEA:67472,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57292,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:172364;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67473;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end CoA-ribonucleoside in mRNA + H2O = (R)-4'-
CC phosphopantetheine + a 5'-end phospho-adenosine-phospho-
CC ribonucleoside in mRNA + 2 H(+); Xref=Rhea:RHEA:67592, Rhea:RHEA-
CC COMP:15719, Rhea:RHEA-COMP:17276, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:61723, ChEBI:CHEBI:144051,
CC ChEBI:CHEBI:172371; Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67593;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9CR24};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9CR24}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9CR24}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WV74-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WV74-2; Sequence=VSP_014282, VSP_014283;
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; AK123561; BAC85646.1; -; mRNA.
DR EMBL; BC018644; AAH18644.1; -; mRNA.
DR CCDS; CCDS58151.1; -. [Q8WV74-1]
DR CCDS; CCDS8174.1; -. [Q8WV74-2]
DR RefSeq; NP_001230679.1; NM_001243750.1. [Q8WV74-1]
DR RefSeq; NP_862826.1; NM_181843.2. [Q8WV74-2]
DR AlphaFoldDB; Q8WV74; -.
DR SMR; Q8WV74; -.
DR BioGRID; 129040; 24.
DR IntAct; Q8WV74; 10.
DR STRING; 9606.ENSP00000365883; -.
DR iPTMnet; Q8WV74; -.
DR PhosphoSitePlus; Q8WV74; -.
DR BioMuta; NUDT8; -.
DR DMDM; 68565920; -.
DR EPD; Q8WV74; -.
DR jPOST; Q8WV74; -.
DR MassIVE; Q8WV74; -.
DR MaxQB; Q8WV74; -.
DR PaxDb; Q8WV74; -.
DR PeptideAtlas; Q8WV74; -.
DR PRIDE; Q8WV74; -.
DR ProteomicsDB; 74757; -. [Q8WV74-1]
DR ProteomicsDB; 74758; -. [Q8WV74-2]
DR Antibodypedia; 30486; 130 antibodies from 23 providers.
DR DNASU; 254552; -.
DR Ensembl; ENST00000301490.8; ENSP00000301490.4; ENSG00000167799.10. [Q8WV74-2]
DR Ensembl; ENST00000376693.3; ENSP00000365883.2; ENSG00000167799.10. [Q8WV74-1]
DR GeneID; 254552; -.
DR KEGG; hsa:254552; -.
DR MANE-Select; ENST00000376693.3; ENSP00000365883.2; NM_001243750.2; NP_001230679.1.
DR UCSC; uc001omn.4; human. [Q8WV74-1]
DR CTD; 254552; -.
DR DisGeNET; 254552; -.
DR GeneCards; NUDT8; -.
DR HGNC; HGNC:8055; NUDT8.
DR HPA; ENSG00000167799; Tissue enhanced (heart).
DR neXtProt; NX_Q8WV74; -.
DR OpenTargets; ENSG00000167799; -.
DR PharmGKB; PA31841; -.
DR VEuPathDB; HostDB:ENSG00000167799; -.
DR eggNOG; KOG3069; Eukaryota.
DR GeneTree; ENSGT00940000163889; -.
DR HOGENOM; CLU_1834486_0_0_1; -.
DR InParanoid; Q8WV74; -.
DR OMA; YYIWGAT; -.
DR OrthoDB; 1253012at2759; -.
DR PhylomeDB; Q8WV74; -.
DR TreeFam; TF106350; -.
DR PathwayCommons; Q8WV74; -.
DR SignaLink; Q8WV74; -.
DR BioGRID-ORCS; 254552; 18 hits in 1076 CRISPR screens.
DR ChiTaRS; NUDT8; human.
DR GenomeRNAi; 254552; -.
DR Pharos; Q8WV74; Tdark.
DR PRO; PR:Q8WV74; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8WV74; protein.
DR Bgee; ENSG00000167799; Expressed in apex of heart and 94 other tissues.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0106399; F:acyl-coenzyme A diphosphatase activity; IEA:RHEA.
DR GO; GO:0010945; F:CoA pyrophosphatase activity; IEA:InterPro.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0046356; P:acetyl-CoA catabolic process; ISS:UniProtKB.
DR GO; GO:0044580; P:butyryl-CoA catabolic process; ISS:UniProtKB.
DR GO; GO:0015938; P:coenzyme A catabolic process; ISS:UniProtKB.
DR GO; GO:2001294; P:malonyl-CoA catabolic process; ISS:UniProtKB.
DR GO; GO:0036114; P:medium-chain fatty-acyl-CoA catabolic process; ISS:UniProtKB.
DR GO; GO:1902859; P:propionyl-CoA catabolic process; ISS:UniProtKB.
DR GO; GO:1901289; P:succinyl-CoA catabolic process; ISS:UniProtKB.
DR CDD; cd03426; CoAse; 1.
DR InterPro; IPR045121; CoAse.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR PANTHER; PTHR12992; PTHR12992; 1.
DR Pfam; PF00293; NUDIX; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Hydrolase; Magnesium; Manganese; Metal-binding;
KW Mitochondrion; Reference proteome.
FT CHAIN 1..236
FT /note="Mitochondrial coenzyme A diphosphatase NUDT8"
FT /id="PRO_0000019948"
FT DOMAIN 25..172
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 70..91
FT /note="Nudix box"
FT BINDING 85
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 89
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 70
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CR24"
FT VAR_SEQ 137..140
FT /note="DEVF -> SWGI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014282"
FT VAR_SEQ 141..236
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014283"
SQ SEQUENCE 236 AA; 25370 MW; 7DDD2A56010B4D9F CRC64;
MLPDCLSAEG ELRCRRLLAG ATARLRARPA SAAVLVPLCS VRGVPALLYT LRSSRLTGRH
KGDVSFPGGK CDPADQDVVH TALRETREEL GLAVPEEHVW GLLRPVYDPQ KATVVPVLAG
VGPLDPQSLR PNSEEVDEVF ALPLAHLLQT QNQGYTHFCR GGHFRYTLPV FLHGPHRVWG
LTAVITEFAL QLLAPGTYQP RLAGLTCSGA EGLARPKQPL ASPCQASSTP GLNKGL
