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Q8CG76 (ARK72_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aflatoxin B1 aldehyde reductase member 2

EC=1.1.1.n11
Alternative name(s):
Succinic semialdehyde reductase
Short name=SSA reductase
Gene names
Name:Akr7a2
Synonyms:Afar, Akr7a5
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length367 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen By similarity. Ref.11

Catalytic activity

4-hydroxybutanoate + NADP+ = succinate semialdehyde + NADPH. Ref.11

Enzyme regulation

Inhibited by citrate, succinate and tartrate. Ref.11

Subunit structure

Homodimer. Ref.11

Subcellular location

Golgi apparatus By similarity. Cytoplasm By similarity.

Tissue specificity

Expressed in liver, kidney, testis and brain with low levels in skeletal muscle, spleen, heart and lung. Ref.5

Sequence similarities

Belongs to the aldo/keto reductase family. Aldo/keto reductase 2 subfamily.

Biophysicochemical properties

Kinetic parameters:

KM=19.8 µM for succinic semialdehyde Ref.11

Sequence caution

The sequence AAH31857.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAC81077.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAC81078.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCytoplasm
Golgi apparatus
   LigandNADP
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay PubMed 14651853PubMed 18614015. Source: MGI

   Molecular_functionalditol:NADP+ 1-oxidoreductase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 367367Aflatoxin B1 aldehyde reductase member 2
PRO_0000070376

Regions

Nucleotide binding179 – 1802NADP
Nucleotide binding234 – 24411NADP UniProtKB P38918
Nucleotide binding326 – 3349NADP

Sites

Active site851Proton donor
Binding site801NADP
Binding site1491Substrate UniProtKB P38918
Binding site2051NADP
Binding site2581NADP
Binding site2681Substrate
Binding site2711Substrate
Binding site3671Substrate
Site1131Lowers pKa of active site Tyr By similarity UniProtKB O43488

Amino acid modifications

Modified residue1361N6-acetyllysine Ref.10
Modified residue2441N6-succinyllysine Ref.9

Experimental info

Sequence conflict51A → G in BAE25302. Ref.1
Sequence conflict91V → G in BAE25302. Ref.1
Sequence conflict121A → V in BAE25302. Ref.1
Sequence conflict171A → G in BAE25302. Ref.1
Sequence conflict1271I → V in AAH31857. Ref.3
Sequence conflict1271I → V in CAC81078. Ref.4
Sequence conflict1621R → C in AAO38437. Ref.5
Sequence conflict3541A → G in AAH31857. Ref.3

Secondary structure

......................................................... 367
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8CG76 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 1123BD7028D3FBDF

FASTA36740,612
        10         20         30         40         50         60 
MLRAASRAVG RAAVRSAQRS GTSVGRPLAM SRPPPPRAAS GAPLRPATVL GTMEMGRRMD 

        70         80         90        100        110        120 
ASASAASVRA FLERGHSELD TAFMYCDGQS ENILGGLGLG LGSGDCTVKI ATKANPWEGK 

       130        140        150        160        170        180 
SLKPDSIRSQ LETSLKRLQC PRVDLFYLHA PDHSTPVEET LRACHQLHQE GKFVELGLSN 

       190        200        210        220        230        240 
YASWEVAEIC TLCKSNGWIL PTVYQGMYNA TTRQVEAELL PCLRHFGLRF YAYNPLAGGL 

       250        260        270        280        290        300 
LTGKYKYEDK DGKQPVGRFF GNNWAETYRN RFWKEHHFEA IALVEKALQT TYGTNAPRMT 

       310        320        330        340        350        360 
SAALRWMYHH SQLQGTRGDA VILGMSSLEQ LEQNLAATEE GPLEPAVVEA FDQAWNMVAH 


ECPNYFR 

« Hide

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Eye.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"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] OF 5-367.
Strain: FVB/N.
Tissue: Liver.
[4]"Aflatoxin B1 aldehyde reductase (AFAR) genes cluster at 1p35-1p36.1 in a region frequently altered in human tumour cells."
Praml C., Savelyeva L., Schwab M.
Oncogene 22:4765-4773(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 25-367.
Strain: BALB/c.
[5]"Characterisation of a novel mouse liver aldo-keto reductase AKR7A5."
Hinshelwood A., McGarvie G., Ellis E.
FEBS Lett. 523:213-218(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-367, TISSUE SPECIFICITY.
Strain: CD-1.
Tissue: Liver.
[6]Ellis E.M., Hinshelwood A., McGarvie G.
Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 127 AND 162.
[7]"Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct subclass of aldo-keto reductase 7 family proteins."
Kelly V.P., Sherratt P.J., Crouch D.H., Hayes J.D.
Biochem. J. 366:847-861(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GENE STRUCTURE.
[8]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[9]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-244, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[10]"Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-136, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[11]"Crystal structure of mouse succinic semialdehyde reductase AKR7A5: structural basis for substrate specificity."
Zhu X., Lapthorn A.J., Ellis E.M.
Biochemistry 45:1562-1570(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 30-367 IN COMPLEX WITH NADP AND THE INHIBITOR TARTRATE, ENZYME REGULATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK143203 mRNA. Translation: BAE25302.1.
AL807811 Genomic DNA. Translation: CAM18543.1.
BC031857 mRNA. Translation: AAH31857.1. Different initiation.
AJ271800 mRNA. Translation: CAC81077.1. Different initiation.
AJ271801 mRNA. Translation: CAC81078.1. Different initiation.
AF525358 mRNA. Translation: AAO38437.2.
BK000393 mRNA. Translation: DAA00087.1.
CCDSCCDS18844.1.
RefSeqNP_079613.3. NM_025337.3.
UniGeneMm.482154.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2C91X-ray2.30A/B/C/D/E/F/G/H/I/J30-367[»]
ProteinModelPortalQ8CG76.
SMRQ8CG76. Positions 43-367.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8CG76. 3 interactions.
MINTMINT-1869477.

PTM databases

PhosphoSiteQ8CG76.

2D gel databases

REPRODUCTION-2DPAGEQ8CG76.

Proteomic databases

MaxQBQ8CG76.
PaxDbQ8CG76.
PRIDEQ8CG76.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000073787; ENSMUSP00000073459; ENSMUSG00000028743.
GeneID110198.
KEGGmmu:110198.
UCSCuc008vmc.2. mouse.

Organism-specific databases

CTD110198.
MGIMGI:107796. Akr7a5.

Phylogenomic databases

eggNOGCOG0667.
GeneTreeENSGT00550000074567.
HOGENOMHOG000250286.
HOVERGENHBG050576.
InParanoidA2AMV3.
KOK15303.
OMACTVKIAT.
OrthoDBEOG77127F.
TreeFamTF329173.

Enzyme and pathway databases

SABIO-RKQ8CG76.

Gene expression databases

BgeeQ8CG76.
GenevestigatorQ8CG76.

Family and domain databases

Gene3D3.20.20.100. 1 hit.
InterProIPR001395. Aldo/ket_red.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERPTHR11732. PTHR11732. 1 hit.
PfamPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
SUPFAMSSF51430. SSF51430. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ8CG76.
NextBio363519.
PROQ8CG76.
SOURCESearch...

Entry information

Entry nameARK72_MOUSE
AccessionPrimary (citable) accession number: Q8CG76
Secondary accession number(s): A2AMV3 expand/collapse secondary AC list , Q3UPU2, Q8CG77, Q8JZQ8, Q9D157
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 2003
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 107 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot