CBR4_MOUSE
ID CBR4_MOUSE Reviewed; 236 AA.
AC Q91VT4; Q3UBY4; Q8BXV1;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] reductase;
DE EC=1.1.1.100 {ECO:0000250|UniProtKB:Q8N4T8};
DE AltName: Full=3-ketoacyl-[acyl-carrier-protein] reductase beta subunit {ECO:0000250|UniProtKB:Q8N4T8};
DE Short=KAR beta subunit {ECO:0000250|UniProtKB:Q8N4T8};
DE AltName: Full=Carbonyl reductase family member 4;
DE Short=CBR4;
DE AltName: Full=Quinone reductase CBR4;
DE EC=1.6.5.10 {ECO:0000250|UniProtKB:Q8N4T8};
GN Name=Cbr4;
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=Bone marrow macrophage, and Cerebellum;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; TISSUE=Mammary tumor;
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].
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 [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-40; LYS-96 AND LYS-194, AND
RP IDENTIFICATION BY MASS 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).
CC -!- FUNCTION: Component of the heterotetramer complex KAR (3-ketoacyl-[acyl
CC carrier protein] reductase or 3-ketoacyl-[ACP] reductase) that forms
CC part of the mitochondrial fatty acid synthase (mtFAS). Beta-subunit of
CC the KAR heterotetramer complex, responsible for the 3-ketoacyl-ACP
CC reductase activity of the mtFAS, reduces 3-oxoacyl-[ACP] to (3R)-
CC hydroxyacyl-[ACP] in a NADPH-dependent manner with no chain length
CC preference, thereby participating in mitochondrial fatty acid
CC biosynthesis. The homotetramer has NADPH-dependent quinone reductase
CC activity (in vitro), hence could play a role in protection against
CC cytotoxicity of exogenous quinones. As a heterotetramer, it can also
CC reduce 9,10-phenanthrenequinone, 1,4-benzoquinone and various other o-
CC quinones and p-quinones (in vitro). {ECO:0000250|UniProtKB:Q8N4T8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + H(+)
CC + NADPH; Xref=Rhea:RHEA:17397, Rhea:RHEA-COMP:9916, Rhea:RHEA-
CC COMP:9945, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78776, ChEBI:CHEBI:78827; EC=1.1.1.100;
CC Evidence={ECO:0000250|UniProtKB:Q8N4T8};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17399;
CC Evidence={ECO:0000250|UniProtKB:Q8N4T8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + H(+) + NADPH = a quinol + NADP(+);
CC Xref=Rhea:RHEA:46164, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:132124;
CC EC=1.6.5.10; Evidence={ECO:0000250|UniProtKB:Q8N4T8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46165;
CC Evidence={ECO:0000250|UniProtKB:Q8N4T8};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000250|UniProtKB:Q8N4T8}.
CC -!- SUBUNIT: Homotetramer (in vitro). Heterotetramer with HSD17B8; contains
CC two molecules each of HSD17B8 and CBR4. Does not form homotetramers
CC when HSD17B8 is coexpressed, only heterotetramers (in vitro).
CC {ECO:0000250|UniProtKB:Q8N4T8}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q8N4T8}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC31519.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK043313; BAC31519.1; ALT_INIT; mRNA.
DR EMBL; AK150763; BAE29830.1; -; mRNA.
DR EMBL; BC009118; AAH09118.1; -; mRNA.
DR CCDS; CCDS40349.1; -.
DR RefSeq; NP_663570.2; NM_145595.2.
DR AlphaFoldDB; Q91VT4; -.
DR SMR; Q91VT4; -.
DR BioGRID; 231509; 5.
DR STRING; 10090.ENSMUSP00000034058; -.
DR iPTMnet; Q91VT4; -.
DR PhosphoSitePlus; Q91VT4; -.
DR SwissPalm; Q91VT4; -.
DR EPD; Q91VT4; -.
DR jPOST; Q91VT4; -.
DR MaxQB; Q91VT4; -.
DR PaxDb; Q91VT4; -.
DR PeptideAtlas; Q91VT4; -.
DR PRIDE; Q91VT4; -.
DR ProteomicsDB; 265568; -.
DR Antibodypedia; 28439; 178 antibodies from 24 providers.
DR DNASU; 234309; -.
DR Ensembl; ENSMUST00000034058; ENSMUSP00000034058; ENSMUSG00000031641.
DR GeneID; 234309; -.
DR KEGG; mmu:234309; -.
DR UCSC; uc009lub.2; mouse.
DR CTD; 84869; -.
DR MGI; MGI:2384567; Cbr4.
DR VEuPathDB; HostDB:ENSMUSG00000031641; -.
DR eggNOG; KOG1200; Eukaryota.
DR GeneTree; ENSGT00940000157620; -.
DR HOGENOM; CLU_010194_1_3_1; -.
DR InParanoid; Q91VT4; -.
DR OMA; KHMVDAG; -.
DR OrthoDB; 1226147at2759; -.
DR PhylomeDB; Q91VT4; -.
DR TreeFam; TF354265; -.
DR Reactome; R-MMU-75105; Fatty acyl-CoA biosynthesis.
DR UniPathway; UPA00094; -.
DR BioGRID-ORCS; 234309; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Cbr4; mouse.
DR PRO; PR:Q91VT4; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q91VT4; protein.
DR Bgee; ENSMUSG00000031641; Expressed in interventricular septum and 249 other tissues.
DR ExpressionAtlas; Q91VT4; baseline and differential.
DR Genevisible; Q91VT4; MM.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:1990204; C:oxidoreductase complex; ISS:UniProtKB.
DR GO; GO:0004316; F:3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; ISS:UniProtKB.
DR GO; GO:0003955; F:NAD(P)H dehydrogenase (quinone) activity; ISO:MGI.
DR GO; GO:0070402; F:NADPH binding; ISS:UniProtKB.
DR GO; GO:0008753; F:NADPH dehydrogenase (quinone) activity; ISS:UniProtKB.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0048038; F:quinone binding; ISS:UniProtKB.
DR GO; GO:0044597; P:daunorubicin metabolic process; ISO:MGI.
DR GO; GO:0044598; P:doxorubicin metabolic process; ISO:MGI.
DR GO; GO:0006633; P:fatty acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISO:MGI.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Mitochondrion; NAD; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..236
FT /note="3-oxoacyl-[acyl-carrier-protein] reductase"
FT /id="PRO_0000319879"
FT ACT_SITE 147
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 11..14
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT BINDING 34..35
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT BINDING 56
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT BINDING 83..85
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT BINDING 134
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT BINDING 147
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT BINDING 151
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT BINDING 180..182
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT SITE 168
FT /note="Important for interaction with acyl carrier protein
FT (ACP)"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q8N4T8"
FT MOD_RES 40
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 96
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 194
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CONFLICT 89
FT /note="D -> G (in Ref. 2; AAH09118)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 236 AA; 25415 MW; 546F400177DDC7F1 CRC64;
MDKVCAVFGG SRGIGRAVAQ LMAQKGYRLA IVSRNLEVAK VTAGELGGNH LAFRCDVAKE
QDVQSTFQEM EKHLGPVNFL VNAAGINRDS LLVRTKTEDM ISQLHTNLLG SMLTCKAAMK
TMIQQGGSIV NVGSIIGLKG NVGQSAYSAT KGGLVGFSRS LAKEVARKKI RVNVVAPGFI
RTDMTRHLKE EHFKKNIPLG RFGETLEVAH AVVFLLESPY ITGHVLIVDG GLQLTV
