Q8N4T8 (CBR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carbonyl reductase family member 4
EC=1.-.-.-

Alternative name(s):
3-oxoacyl-[acyl-carrier-protein] reductase
EC=1.1.1.-
Quinone reductase CBR4

Gene names

Name:

CBR4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	237 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The heteroteramer with HSD17B8 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity. May play a role in biosynthesis of fatty acids in mitochondria. The homotetramer may act as NADPH-dependent quinone reductase. Has broad substrate specificity and reduces 9,10-phenanthrenequinone, 1,4-benzoquinone and various other o-quinones and p-quinones (in vitro). Ref.6 Ref.7
Pathway	Lipid metabolism; fatty acid biosynthesis.
Subunit structure	Homotetramer. Heterotetramer with HSD17B8; contains two molecules of HSD17B8 and CBR4. Ref.6
Subcellular location	Mitochondrion matrix Ref.6 Ref.7.
Tissue specificity	Detected in liver and kidney (at protein level). Ref.6
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Biophysicochemical properties	Kinetic parameters: KM=11 µM for NADPH KM=1.6 µM for 9,10-phenanthrenequinone KM=1.9 µM for 1,4-benzoquinone pH dependence: Optimum pH is 6-8.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	NAD NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	daunorubicin metabolic process Inferred from mutant phenotype PubMed 20837989. Source: UniProtKB doxorubicin metabolic process Inferred from mutant phenotype PubMed 20837989. Source: UniProtKB fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway protein homotetramerization Inferred from physical interaction Ref.6. Source: UniProtKB
Cellular_component	mitochondrial matrix Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	NAD(P)H dehydrogenase (quinone) activity Inferred from direct assay PubMed 20837989. Source: UniProtKB NADPH binding Inferred from direct assay Ref.6. Source: UniProtKB NADPH dehydrogenase (quinone) activity Inferred from direct assay Ref.6. Source: UniProtKB quinone binding Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N4T8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8N4T8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     180-237: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 237	237	Carbonyl reductase family member 4		PRO_0000319878
Regions
	Nucleotide binding	7 – 31	25	NAD or NADP By similarity
Sites
	Active site	148	1	Proton acceptor By similarity
	Binding site	135	1	Substrate By similarity
Natural variations
	Alternative sequence	180 – 237	58	Missing in isoform 2.		VSP_031527
	Natural variant	70	1	L → M. Ref.1 Ref.2 Ref.5 Ref.8 Corresponds to variant rs2877380 [ dbSNP | Ensembl ].		VAR_039049

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 3. Checksum: 376FF5FA0CB9ABF0	FASTA	237	25,301
	10 20 30 40 50 60 MDKVCAVFGG SRGIGRAVAQ LMARKGYRLA VIARNLEGAK AAAGDLGGDH LAFSCDVAKE 70 80 90 100 110 120 HDVQNTFEEL EKHLGRVNFL VNAAGINRDG LLVRTKTEDM VSQLHTNLLG SMLTCKAAMR 130 140 150 160 170 180 TMIQQQGGSI VNVGSIVGLK GNSGQSVYSA SKGGLVGFSR ALAKEVARKK IRVNVVAPGF 190 200 210 220 230 VHTDMTKDLK EEHLKKNIPL GRFGETIEVA HAVVFLLESP YITGHVLVVD GGLQLIL
	Isoform 2 [UniParc]. Checksum: 6C43EAF3A2AFCEA0	FASTA	179	18,837
	10 20 30 40 50 60 MDKVCAVFGG SRGIGRAVAQ LMARKGYRLA VIARNLEGAK AAAGDLGGDH LAFSCDVAKE 70 80 90 100 110 120 HDVQNTFEEL EKHLGRVNFL VNAAGINRDG LLVRTKTEDM VSQLHTNLLG SMLTCKAAMR 130 140 150 160 170 TMIQQQGGSI VNVGSIVGLK GNSGQSVYSA SKGGLVGFSR ALAKEVARKK IRVNVVAPG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT MET-70. Tissue: Embryo and Placenta.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT MET-70. Tissue: Melanoma.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT MET-70. Tissue: Duodenum and Uterus.
[6]	"Human carbonyl reductase 4 is a mitochondrial NADPH-dependent quinone reductase." Endo S., Matsunaga T., Kitade Y., Ohno S., Tajima K., El-Kabbani O., Hara A. Biochem. Biophys. Res. Commun. 377:1326-1330(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MASS SPECTROMETRY, TISSUE SPECIFICITY.
[7]	"17beta-Hydroxysteroid dehydrogenase type 8 and carbonyl reductase type 4 assemble as a ketoacyl reductase of human mitochondrial FAS." Chen Z., Kastaniotis A.J., Miinalainen I.J., Rajaram V., Wierenga R.K., Hiltunen J.K. FASEB J. 23:3682-3691(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HSD17B8.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] MET-70, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK027337 mRNA. Translation: BAB55045.1. AK291756 mRNA. Translation: BAF84445.1. AL833393 mRNA. Translation: CAH10582.1. AC021151 Genomic DNA. No translation available. CH471056 Genomic DNA. Translation: EAX04797.1. BC021973 mRNA. Translation: AAH21973.1. BC033650 mRNA. Translation: AAH33650.1.
IPI	IPI00384297. IPI00884980.
RefSeq	NP_116172.2. NM_032783.4.
UniGene	Hs.659311.
3D structure databases
HSSP	HSSP built from PDB template 1YDE based on UniProtKB Q9BPX1.
ProteinModelPortal	Q8N4T8.
SMR	Q8N4T8. Positions 2-232.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000303525.
PTM databases
PhosphoSite	Q8N4T8.
Polymorphism databases
DMDM	269849708.
Proteomic databases
PaxDb	Q8N4T8.
PRIDE	Q8N4T8.
Protocols and materials databases
DNASU	84869.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000306193; ENSP00000303525; ENSG00000145439. ENST00000504480; ENSP00000427615; ENSG00000145439.
GeneID	84869.
KEGG	hsa:84869.
UCSC	uc003iry.3. human.
Organism-specific databases
CTD	84869.
GeneCards	GC04M169815.
H-InvDB	HIX0004629.
HGNC	HGNC:25891. CBR4.
HPA	HPA037499.
neXtProt	NX_Q8N4T8.
PharmGKB	PA144596471.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1028.
HOVERGEN	HBG002145.
InParanoid	Q8N4T8.
KO	K11539.
OMA	CHLAIIA.
Enzyme and pathway databases
SABIO-RK	Q8N4T8.
UniPathway	UPA00094.
Gene expression databases
ArrayExpress	Q8N4T8.
Bgee	Q8N4T8.
CleanEx	HS_CBR4.
Genevestigator	Q8N4T8.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
InterPro	IPR002198. DH_sc/Rdtase_SDR. IPR002347. Glc/ribitol_DH. IPR016040. NAD(P)-bd_dom. IPR020904. Sc_DH/Rdtase_CS. [Graphical view]
Pfam	PF00106. adh_short. 1 hit. [Graphical view]
PRINTS	PR00081. GDHRDH. PR00080. SDRFAMILY.
PROSITE	PS00061. ADH_SHORT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CBR4. human.
GenomeRNAi	84869.
NextBio	75151.

Entry information

Entry name

CBR4_HUMAN

Accession

Primary (citable) accession number: Q8N4T8
Secondary accession number(s): Q8WTW8, Q96K93

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	November 24, 2009
Last modified:	May 1, 2013
This is version 85 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.