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Q8N4T8

- CBR4_HUMAN

UniProt

Q8N4T8 - CBR4_HUMAN

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Protein

Carbonyl reductase family member 4

Gene

CBR4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).2 Publications

Kineticsi

  1. KM=11 µM for NADPH
  2. KM=1.6 µM for 9,10-phenanthrenequinone
  3. KM=1.9 µM for 1,4-benzoquinone

pH dependencei

Optimum pH is 6-8.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei135 – 1351SubstrateBy similarity
Active sitei148 – 1481Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi7 – 3125NAD or NADPBy similarityAdd
BLAST

GO - Molecular functioni

  1. NAD(P)H dehydrogenase (quinone) activity Source: UniProtKB
  2. NADPH binding Source: UniProtKB
  3. NADPH dehydrogenase (quinone) activity Source: UniProtKB
  4. quinone binding Source: UniProtKB

GO - Biological processi

  1. daunorubicin metabolic process Source: UniProtKB
  2. doxorubicin metabolic process Source: UniProtKB
  3. fatty acid biosynthetic process Source: UniProtKB-UniPathway
  4. protein homotetramerization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism

Keywords - Ligandi

NAD, NADP

Enzyme and pathway databases

SABIO-RKQ8N4T8.
UniPathwayiUPA00094.

Names & Taxonomyi

Protein namesi
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 namesi
Name:CBR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:25891. CBR4.

Subcellular locationi

Mitochondrion matrix 2 Publications

GO - Cellular componenti

  1. mitochondrial matrix Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA144596471.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 237237Carbonyl reductase family member 4PRO_0000319878Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication
Modified residuei40 – 401N6-acetyllysineBy similarity
Modified residuei96 – 961N6-acetyllysineBy similarity
Modified residuei195 – 1951N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ8N4T8.
PaxDbiQ8N4T8.
PRIDEiQ8N4T8.

PTM databases

PhosphoSiteiQ8N4T8.

Expressioni

Tissue specificityi

Detected in liver and kidney (at protein level).1 Publication

Gene expression databases

BgeeiQ8N4T8.
CleanExiHS_CBR4.
ExpressionAtlasiQ8N4T8. baseline and differential.
GenevestigatoriQ8N4T8.

Organism-specific databases

HPAiHPA037499.

Interactioni

Subunit structurei

Homotetramer. Heterotetramer with HSD17B8; contains two molecules of HSD17B8 and CBR4.1 Publication

Protein-protein interaction databases

BioGridi124314. 5 interactions.
STRINGi9606.ENSP00000303525.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4CQLX-ray2.85B/C/F/G/J/K/N/O1-237[»]
4CQMX-ray2.34B/C/F/G/J/K/N/O1-237[»]
ProteinModelPortaliQ8N4T8.
SMRiQ8N4T8. Positions 3-233.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG1028.
GeneTreeiENSGT00760000118868.
HOVERGENiHBG002145.
InParanoidiQ8N4T8.
KOiK11539.
OMAiPKVIAYS.
PhylomeDBiQ8N4T8.
TreeFamiTF354265.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]
PfamiPF00106. adh_short. 1 hit.
[Graphical view]
PRINTSiPR00081. GDHRDH.
PR00080. SDRFAMILY.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q8N4T8-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MDKVCAVFGG SRGIGRAVAQ LMARKGYRLA VIARNLEGAK AAAGDLGGDH
60 70 80 90 100
LAFSCDVAKE HDVQNTFEEL EKHLGRVNFL VNAAGINRDG LLVRTKTEDM
110 120 130 140 150
VSQLHTNLLG SMLTCKAAMR TMIQQQGGSI VNVGSIVGLK GNSGQSVYSA
160 170 180 190 200
SKGGLVGFSR ALAKEVARKK IRVNVVAPGF VHTDMTKDLK EEHLKKNIPL
210 220 230
GRFGETIEVA HAVVFLLESP YITGHVLVVD GGLQLIL
Length:237
Mass (Da):25,301
Last modified:November 24, 2009 - v3
Checksum:i376FF5FA0CB9ABF0
GO
Isoform 2 (identifier: Q8N4T8-2) [UniParc]FASTAAdd to Basket

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

Note: No experimental confirmation available.

Show »
Length:179
Mass (Da):18,837
Checksum:i6C43EAF3A2AFCEA0
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti70 – 701L → M.4 Publications
Corresponds to variant rs2877380 [ dbSNP | Ensembl ].
VAR_039049

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei180 – 23758Missing in isoform 2. 1 PublicationVSP_031527Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS3812.1. [Q8N4T8-1]
RefSeqiNP_116172.2. NM_032783.4. [Q8N4T8-1]
UniGeneiHs.659311.

Genome annotation databases

EnsembliENST00000306193; ENSP00000303525; ENSG00000145439. [Q8N4T8-1]
ENST00000504480; ENSP00000427615; ENSG00000145439. [Q8N4T8-2]
GeneIDi84869.
KEGGihsa:84869.
UCSCiuc003iry.3. human. [Q8N4T8-1]

Polymorphism databases

DMDMi269849708.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS3812.1. [Q8N4T8-1 ]
RefSeqi NP_116172.2. NM_032783.4. [Q8N4T8-1 ]
UniGenei Hs.659311.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4CQL X-ray 2.85 B/C/F/G/J/K/N/O 1-237 [» ]
4CQM X-ray 2.34 B/C/F/G/J/K/N/O 1-237 [» ]
ProteinModelPortali Q8N4T8.
SMRi Q8N4T8. Positions 3-233.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 124314. 5 interactions.
STRINGi 9606.ENSP00000303525.

PTM databases

PhosphoSitei Q8N4T8.

Polymorphism databases

DMDMi 269849708.

Proteomic databases

MaxQBi Q8N4T8.
PaxDbi Q8N4T8.
PRIDEi Q8N4T8.

Protocols and materials databases

DNASUi 84869.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000306193 ; ENSP00000303525 ; ENSG00000145439 . [Q8N4T8-1 ]
ENST00000504480 ; ENSP00000427615 ; ENSG00000145439 . [Q8N4T8-2 ]
GeneIDi 84869.
KEGGi hsa:84869.
UCSCi uc003iry.3. human. [Q8N4T8-1 ]

Organism-specific databases

CTDi 84869.
GeneCardsi GC04M169815.
H-InvDB HIX0004629.
HGNCi HGNC:25891. CBR4.
HPAi HPA037499.
neXtProti NX_Q8N4T8.
PharmGKBi PA144596471.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1028.
GeneTreei ENSGT00760000118868.
HOVERGENi HBG002145.
InParanoidi Q8N4T8.
KOi K11539.
OMAi PKVIAYS.
PhylomeDBi Q8N4T8.
TreeFami TF354265.

Enzyme and pathway databases

UniPathwayi UPA00094 .
SABIO-RK Q8N4T8.

Miscellaneous databases

ChiTaRSi CBR4. human.
GenomeRNAii 84869.
NextBioi 75151.
PROi Q8N4T8.

Gene expression databases

Bgeei Q8N4T8.
CleanExi HS_CBR4.
ExpressionAtlasi Q8N4T8. baseline and differential.
Genevestigatori Q8N4T8.

Family and domain databases

Gene3Di 3.40.50.720. 1 hit.
InterProi IPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view ]
Pfami PF00106. adh_short. 1 hit.
[Graphical view ]
PRINTSi PR00081. GDHRDH.
PR00080. SDRFAMILY.
PROSITEi PS00061. ADH_SHORT. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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, IDENTIFICATION BY 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. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. Cited for: VARIANT [LARGE SCALE ANALYSIS] MET-70, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiCBR4_HUMAN
AccessioniPrimary (citable) accession number: Q8N4T8
Secondary accession number(s): Q8WTW8, Q96K93
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: November 24, 2009
Last modified: October 29, 2014
This is version 98 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3