Full text data of AKR7A2
AKR7A2
(AFAR, AFAR1, AKR7)
[Confidence: low (only semi-automatic identification from reviews)]
Aflatoxin B1 aldehyde reductase member 2; 1.1.1.n11 (AFB1 aldehyde reductase 1; AFB1-AR 1; Aldoketoreductase 7; Succinic semialdehyde reductase; SSA reductase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Aflatoxin B1 aldehyde reductase member 2; 1.1.1.n11 (AFB1 aldehyde reductase 1; AFB1-AR 1; Aldoketoreductase 7; Succinic semialdehyde reductase; SSA reductase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O43488
ID ARK72_HUMAN Reviewed; 359 AA.
AC O43488; O75749; Q5TG63;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
read moreDT 14-NOV-2003, sequence version 3.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=Aflatoxin B1 aldehyde reductase member 2;
DE EC=1.1.1.n11;
DE AltName: Full=AFB1 aldehyde reductase 1;
DE Short=AFB1-AR 1;
DE AltName: Full=Aldoketoreductase 7;
DE AltName: Full=Succinic semialdehyde reductase;
DE Short=SSA reductase;
GN Name=AKR7A2; Synonyms=AFAR, AFAR1, AKR7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-359.
RC TISSUE=Pancreas, Skin, and Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-359, PARTIAL PROTEIN SEQUENCE,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP VARIANT THR-142.
RC TISSUE=Liver;
RX PubMed=9576847;
RA Ireland L.S., Harrison D.J., Neal G.E., Hayes J.D.;
RT "Molecular cloning, expression and catalytic activity of a human AKR7
RT member of the aldo-keto reductase superfamily: evidence that the major
RT 2-carboxybenzaldehyde reductase from human liver is a homologue of rat
RT aflatoxin B1-aldehyde reductase.";
RL Biochem. J. 332:21-34(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-359.
RC TISSUE=Brain;
RX PubMed=9823300;
RA Praml C., Savelyeva L., Perri P., Schwab M.;
RT "Cloning of the human aflatoxin B1-aldehyde reductase gene at 1p35-
RT 1p36.1 in a region frequently altered in human tumor cells.";
RL Cancer Res. 58:5014-5018(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 30-359.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 222-236; 251-261 AND 279-297, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [7]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RX PubMed=10510318; DOI=10.1042/0264-6021:3430487;
RA O'Connor T., Ireland L.S., Harrison D.J., Hayes J.D.;
RT "Major differences exist in the function and tissue-specific
RT expression of human aflatoxin B1 aldehyde reductase and the principal
RT human aldo-keto reductase AKR1 family members.";
RL Biochem. J. 343:487-504(1999).
RN [8]
RP GENE STRUCTURE.
RX PubMed=12071861; DOI=10.1042/BJ20020342;
RA Kelly V.P., Sherratt P.J., Crouch D.H., Hayes J.D.;
RT "Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate
RT synthases that associate with the Golgi apparatus define a distinct
RT subclass of aldo-keto reductase 7 family proteins.";
RL Biochem. J. 366:847-861(2002).
RN [9]
RP FUNCTION.
RX PubMed=17591773; DOI=10.1074/jbc.M702465200;
RA Lyon R.C., Johnston S.M., Watson D.G., McGarvie G., Ellis E.M.;
RT "Synthesis and catabolism of gamma-hydroxybutyrate in SH-SY5Y human
RT neuroblastoma cells: role of the aldo-keto reductase AKR7A2.";
RL J. Biol. Chem. 282:25986-25992(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NADP.
RG Structural genomics consortium (SGC);
RT "Structure of the aflatoxin aldehyde reductase in complex with
RT NADPH.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [12]
RP VARIANTS THR-142 AND HIS-157.
RX PubMed=18752886; DOI=10.1016/j.canlet.2008.07.013;
RA Praml C., Schulz W., Claas A., Mollenhauer J., Poustka A.,
RA Ackermann R., Schwab M., Henrich K.-O.;
RT "Genetic variation of aflatoxin B1 aldehyde reductase genes (AFAR) in
RT human tumour cells.";
RL Cancer Lett. 272:160-166(2008).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of succinic
CC semialdehyde to gamma-hydroxybutyrate. May have an important role
CC in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has
CC broad substrate specificity. Has NADPH-dependent aldehyde
CC reductase activity towards 2-carboxybenzaldehyde, 2-
CC nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce
CC 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can
CC reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1)
CC to the non-binding AFB1 dialcohol. May be involved in protection
CC of liver against the toxic and carcinogenic effects of AFB1, a
CC potent hepatocarcinogen.
CC -!- CATALYTIC ACTIVITY: 4-hydroxybutanoate + NADP(+) = succinate
CC semialdehyde + NADPH.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for succinic semialdehyde;
CC KM=17 uM for 2-carboxybenzaldehyde;
CC KM=8 uM for 9,10-phenanthrenequinone;
CC KM=102 uM for 1,2-naphthoquinone;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus (By similarity). Cytoplasm.
CC -!- TISSUE SPECIFICITY: Detected in brain, liver, small intestine and
CC testis, and at lower levels in heart, prostate, skeletal muscle
CC and spleen. Detected in kidney proximal and distal tubules,
CC endothelial cells lining the Bowman's capsules and some cysts.
CC Detected at low levels in lung and pancreas (at protein level).
CC Widely expressed.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto
CC reductase 2 subfamily.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-30 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC52104.1; Type=Erroneous initiation;
CC Sequence=AAH04111.3; Type=Erroneous initiation;
CC Sequence=AAH10852.1; Type=Erroneous initiation;
CC Sequence=AAH11586.1; Type=Erroneous initiation;
CC Sequence=AAH12171.1; Type=Erroneous initiation;
CC Sequence=AAH13996.1; Type=Erroneous initiation;
CC Sequence=AAP36011.1; Type=Erroneous initiation;
CC Sequence=CAA76347.1; Type=Erroneous initiation;
CC Sequence=CAB72321.1; Type=Erroneous initiation;
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DR EMBL; AL035413; CAB72321.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC004111; AAH04111.3; ALT_INIT; mRNA.
DR EMBL; BC007352; AAH07352.2; -; mRNA.
DR EMBL; BC010852; AAH10852.1; ALT_INIT; mRNA.
DR EMBL; BC011586; AAH11586.1; ALT_INIT; mRNA.
DR EMBL; BC012171; AAH12171.1; ALT_INIT; mRNA.
DR EMBL; BC013996; AAH13996.1; ALT_INIT; mRNA.
DR EMBL; AF026947; AAC52104.1; ALT_INIT; mRNA.
DR EMBL; Y16675; CAA76347.1; ALT_INIT; mRNA.
DR EMBL; BT007347; AAP36011.1; ALT_INIT; mRNA.
DR EMBL; BK000395; DAA00088.1; -; mRNA.
DR RefSeq; NP_003680.2; NM_003689.3.
DR UniGene; Hs.571886; -.
DR PDB; 2BP1; X-ray; 2.40 A; A/B/C/D=1-359.
DR PDBsum; 2BP1; -.
DR ProteinModelPortal; O43488; -.
DR SMR; O43488; 37-359.
DR IntAct; O43488; 2.
DR MINT; MINT-5002225; -.
DR STRING; 9606.ENSP00000235835; -.
DR PhosphoSite; O43488; -.
DR REPRODUCTION-2DPAGE; IPI00305978; -.
DR REPRODUCTION-2DPAGE; O43488; -.
DR UCD-2DPAGE; O43488; -.
DR PaxDb; O43488; -.
DR PRIDE; O43488; -.
DR DNASU; 8574; -.
DR Ensembl; ENST00000235835; ENSP00000235835; ENSG00000053371.
DR GeneID; 8574; -.
DR KEGG; hsa:8574; -.
DR UCSC; uc001bbw.3; human.
DR CTD; 8574; -.
DR GeneCards; GC01M019630; -.
DR H-InvDB; HIX0000198; -.
DR HGNC; HGNC:389; AKR7A2.
DR HPA; CAB032841; -.
DR MIM; 603418; gene.
DR neXtProt; NX_O43488; -.
DR PharmGKB; PA24682; -.
DR eggNOG; COG0667; -.
DR HOGENOM; HOG000250286; -.
DR HOVERGEN; HBG050576; -.
DR InParanoid; O43488; -.
DR KO; K15303; -.
DR OMA; CTVKIAT; -.
DR OrthoDB; EOG77127F; -.
DR PhylomeDB; O43488; -.
DR SABIO-RK; O43488; -.
DR EvolutionaryTrace; O43488; -.
DR GeneWiki; AKR7A2; -.
DR GenomeRNAi; 8574; -.
DR NextBio; 32161; -.
DR PMAP-CutDB; O43488; -.
DR PRO; PR:O43488; -.
DR ArrayExpress; O43488; -.
DR Bgee; O43488; -.
DR CleanEx; HS_AKR7A2; -.
DR Genevestigator; O43488; -.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; TAS:ProtInc.
DR GO; GO:0009055; F:electron carrier activity; TAS:UniProtKB.
DR GO; GO:0019119; F:phenanthrene-9,10-epoxide hydrolase activity; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; TAS:ProtInc.
DR GO; GO:0044597; P:daunorubicin metabolic process; IMP:UniProtKB.
DR GO; GO:0044598; P:doxorubicin metabolic process; IMP:UniProtKB.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR001395; Aldo/ket_red.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR PANTHER; PTHR11732; PTHR11732; 1.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR SUPFAM; SSF51430; SSF51430; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Golgi apparatus; NADP; Oxidoreductase;
KW Polymorphism; Reference proteome.
FT CHAIN 1 359 Aflatoxin B1 aldehyde reductase member 2.
FT /FTId=PRO_0000070375.
FT NP_BIND 171 172 NADP.
FT NP_BIND 226 236 NADP.
FT NP_BIND 318 326 NADP.
FT ACT_SITE 77 77 Proton donor (By similarity).
FT BINDING 72 72 NADP.
FT BINDING 141 141 Substrate (By similarity).
FT BINDING 197 197 NADP.
FT BINDING 250 250 NADP.
FT BINDING 260 260 Substrate (By similarity).
FT BINDING 263 263 Substrate (By similarity).
FT BINDING 359 359 Substrate (By similarity).
FT SITE 105 105 Lowers pKa of active site Tyr (By
FT similarity).
FT MOD_RES 128 128 N6-acetyllysine (By similarity).
FT VARIANT 135 135 V -> M (in dbSNP:rs6670759).
FT /FTId=VAR_048209.
FT VARIANT 142 142 A -> T (in dbSNP:rs1043657).
FT /FTId=VAR_017413.
FT VARIANT 157 157 Q -> H (in dbSNP:rs859208).
FT /FTId=VAR_017414.
FT VARIANT 180 180 E -> K (in dbSNP:rs859210).
FT /FTId=VAR_060222.
FT VARIANT 198 198 G -> S (in dbSNP:rs2231200).
FT /FTId=VAR_048210.
FT VARIANT 214 214 C -> Y (in dbSNP:rs2235794).
FT /FTId=VAR_017415.
FT VARIANT 255 255 S -> N (in dbSNP:rs2231203).
FT /FTId=VAR_048211.
FT STRAND 39 43
FT TURN 48 50
FT HELIX 53 65
FT STRAND 70 72
FT HELIX 77 80
FT HELIX 81 87
FT STRAND 101 106
FT HELIX 116 130
FT STRAND 135 140
FT HELIX 149 161
FT STRAND 164 172
FT HELIX 175 188
FT STRAND 193 199
FT HELIX 206 208
FT HELIX 211 218
FT STRAND 221 225
FT HELIX 229 234
FT HELIX 239 242
FT TURN 243 245
FT STRAND 252 254
FT HELIX 257 264
FT HELIX 267 284
FT HELIX 285 287
FT HELIX 291 302
FT HELIX 307 309
FT STRAND 312 315
FT HELIX 320 330
FT HELIX 337 350
FT HELIX 351 353
SQ SEQUENCE 359 AA; 39589 MW; 2C9775FE4B977D2A CRC64;
MLSAASRVVS RAAVHCALRS PPPEARALAM SRPPPPRVAS VLGTMEMGRR MDAPASAAAV
RAFLERGHTE LDTAFMYSDG QSETILGGLG LGLGGGDCRV KIATKANPWD GKSLKPDSVR
SQLETSLKRL QCPQVDLFYL HAPDHGTPVE ETLHACQRLH QEGKFVELGL SNYASWEVAE
ICTLCKSNGW ILPTVYQGMY NATTRQVETE LFPCLRHFGL RFYAYNPLAG GLLTGKYKYE
DKDGKQPVGR FFGNSWAETY RNRFWKEHHF EAIALVEKAL QAAYGASAPS VTSAALRWMY
HHSQLQGAHG DAVILGMSSL EQLEQNLAAT EEGPLEPAVV DAFNQAWHLV AHECPNYFR
//
ID ARK72_HUMAN Reviewed; 359 AA.
AC O43488; O75749; Q5TG63;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
read moreDT 14-NOV-2003, sequence version 3.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=Aflatoxin B1 aldehyde reductase member 2;
DE EC=1.1.1.n11;
DE AltName: Full=AFB1 aldehyde reductase 1;
DE Short=AFB1-AR 1;
DE AltName: Full=Aldoketoreductase 7;
DE AltName: Full=Succinic semialdehyde reductase;
DE Short=SSA reductase;
GN Name=AKR7A2; Synonyms=AFAR, AFAR1, AKR7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-359.
RC TISSUE=Pancreas, Skin, and Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-359, PARTIAL PROTEIN SEQUENCE,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP VARIANT THR-142.
RC TISSUE=Liver;
RX PubMed=9576847;
RA Ireland L.S., Harrison D.J., Neal G.E., Hayes J.D.;
RT "Molecular cloning, expression and catalytic activity of a human AKR7
RT member of the aldo-keto reductase superfamily: evidence that the major
RT 2-carboxybenzaldehyde reductase from human liver is a homologue of rat
RT aflatoxin B1-aldehyde reductase.";
RL Biochem. J. 332:21-34(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-359.
RC TISSUE=Brain;
RX PubMed=9823300;
RA Praml C., Savelyeva L., Perri P., Schwab M.;
RT "Cloning of the human aflatoxin B1-aldehyde reductase gene at 1p35-
RT 1p36.1 in a region frequently altered in human tumor cells.";
RL Cancer Res. 58:5014-5018(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 30-359.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 222-236; 251-261 AND 279-297, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [7]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RX PubMed=10510318; DOI=10.1042/0264-6021:3430487;
RA O'Connor T., Ireland L.S., Harrison D.J., Hayes J.D.;
RT "Major differences exist in the function and tissue-specific
RT expression of human aflatoxin B1 aldehyde reductase and the principal
RT human aldo-keto reductase AKR1 family members.";
RL Biochem. J. 343:487-504(1999).
RN [8]
RP GENE STRUCTURE.
RX PubMed=12071861; DOI=10.1042/BJ20020342;
RA Kelly V.P., Sherratt P.J., Crouch D.H., Hayes J.D.;
RT "Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate
RT synthases that associate with the Golgi apparatus define a distinct
RT subclass of aldo-keto reductase 7 family proteins.";
RL Biochem. J. 366:847-861(2002).
RN [9]
RP FUNCTION.
RX PubMed=17591773; DOI=10.1074/jbc.M702465200;
RA Lyon R.C., Johnston S.M., Watson D.G., McGarvie G., Ellis E.M.;
RT "Synthesis and catabolism of gamma-hydroxybutyrate in SH-SY5Y human
RT neuroblastoma cells: role of the aldo-keto reductase AKR7A2.";
RL J. Biol. Chem. 282:25986-25992(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NADP.
RG Structural genomics consortium (SGC);
RT "Structure of the aflatoxin aldehyde reductase in complex with
RT NADPH.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [12]
RP VARIANTS THR-142 AND HIS-157.
RX PubMed=18752886; DOI=10.1016/j.canlet.2008.07.013;
RA Praml C., Schulz W., Claas A., Mollenhauer J., Poustka A.,
RA Ackermann R., Schwab M., Henrich K.-O.;
RT "Genetic variation of aflatoxin B1 aldehyde reductase genes (AFAR) in
RT human tumour cells.";
RL Cancer Lett. 272:160-166(2008).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of succinic
CC semialdehyde to gamma-hydroxybutyrate. May have an important role
CC in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has
CC broad substrate specificity. Has NADPH-dependent aldehyde
CC reductase activity towards 2-carboxybenzaldehyde, 2-
CC nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce
CC 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can
CC reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1)
CC to the non-binding AFB1 dialcohol. May be involved in protection
CC of liver against the toxic and carcinogenic effects of AFB1, a
CC potent hepatocarcinogen.
CC -!- CATALYTIC ACTIVITY: 4-hydroxybutanoate + NADP(+) = succinate
CC semialdehyde + NADPH.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for succinic semialdehyde;
CC KM=17 uM for 2-carboxybenzaldehyde;
CC KM=8 uM for 9,10-phenanthrenequinone;
CC KM=102 uM for 1,2-naphthoquinone;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus (By similarity). Cytoplasm.
CC -!- TISSUE SPECIFICITY: Detected in brain, liver, small intestine and
CC testis, and at lower levels in heart, prostate, skeletal muscle
CC and spleen. Detected in kidney proximal and distal tubules,
CC endothelial cells lining the Bowman's capsules and some cysts.
CC Detected at low levels in lung and pancreas (at protein level).
CC Widely expressed.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto
CC reductase 2 subfamily.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-30 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC52104.1; Type=Erroneous initiation;
CC Sequence=AAH04111.3; Type=Erroneous initiation;
CC Sequence=AAH10852.1; Type=Erroneous initiation;
CC Sequence=AAH11586.1; Type=Erroneous initiation;
CC Sequence=AAH12171.1; Type=Erroneous initiation;
CC Sequence=AAH13996.1; Type=Erroneous initiation;
CC Sequence=AAP36011.1; Type=Erroneous initiation;
CC Sequence=CAA76347.1; Type=Erroneous initiation;
CC Sequence=CAB72321.1; Type=Erroneous initiation;
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DR EMBL; AL035413; CAB72321.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC004111; AAH04111.3; ALT_INIT; mRNA.
DR EMBL; BC007352; AAH07352.2; -; mRNA.
DR EMBL; BC010852; AAH10852.1; ALT_INIT; mRNA.
DR EMBL; BC011586; AAH11586.1; ALT_INIT; mRNA.
DR EMBL; BC012171; AAH12171.1; ALT_INIT; mRNA.
DR EMBL; BC013996; AAH13996.1; ALT_INIT; mRNA.
DR EMBL; AF026947; AAC52104.1; ALT_INIT; mRNA.
DR EMBL; Y16675; CAA76347.1; ALT_INIT; mRNA.
DR EMBL; BT007347; AAP36011.1; ALT_INIT; mRNA.
DR EMBL; BK000395; DAA00088.1; -; mRNA.
DR RefSeq; NP_003680.2; NM_003689.3.
DR UniGene; Hs.571886; -.
DR PDB; 2BP1; X-ray; 2.40 A; A/B/C/D=1-359.
DR PDBsum; 2BP1; -.
DR ProteinModelPortal; O43488; -.
DR SMR; O43488; 37-359.
DR IntAct; O43488; 2.
DR MINT; MINT-5002225; -.
DR STRING; 9606.ENSP00000235835; -.
DR PhosphoSite; O43488; -.
DR REPRODUCTION-2DPAGE; IPI00305978; -.
DR REPRODUCTION-2DPAGE; O43488; -.
DR UCD-2DPAGE; O43488; -.
DR PaxDb; O43488; -.
DR PRIDE; O43488; -.
DR DNASU; 8574; -.
DR Ensembl; ENST00000235835; ENSP00000235835; ENSG00000053371.
DR GeneID; 8574; -.
DR KEGG; hsa:8574; -.
DR UCSC; uc001bbw.3; human.
DR CTD; 8574; -.
DR GeneCards; GC01M019630; -.
DR H-InvDB; HIX0000198; -.
DR HGNC; HGNC:389; AKR7A2.
DR HPA; CAB032841; -.
DR MIM; 603418; gene.
DR neXtProt; NX_O43488; -.
DR PharmGKB; PA24682; -.
DR eggNOG; COG0667; -.
DR HOGENOM; HOG000250286; -.
DR HOVERGEN; HBG050576; -.
DR InParanoid; O43488; -.
DR KO; K15303; -.
DR OMA; CTVKIAT; -.
DR OrthoDB; EOG77127F; -.
DR PhylomeDB; O43488; -.
DR SABIO-RK; O43488; -.
DR EvolutionaryTrace; O43488; -.
DR GeneWiki; AKR7A2; -.
DR GenomeRNAi; 8574; -.
DR NextBio; 32161; -.
DR PMAP-CutDB; O43488; -.
DR PRO; PR:O43488; -.
DR ArrayExpress; O43488; -.
DR Bgee; O43488; -.
DR CleanEx; HS_AKR7A2; -.
DR Genevestigator; O43488; -.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; TAS:ProtInc.
DR GO; GO:0009055; F:electron carrier activity; TAS:UniProtKB.
DR GO; GO:0019119; F:phenanthrene-9,10-epoxide hydrolase activity; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; TAS:ProtInc.
DR GO; GO:0044597; P:daunorubicin metabolic process; IMP:UniProtKB.
DR GO; GO:0044598; P:doxorubicin metabolic process; IMP:UniProtKB.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR001395; Aldo/ket_red.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR PANTHER; PTHR11732; PTHR11732; 1.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR SUPFAM; SSF51430; SSF51430; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Golgi apparatus; NADP; Oxidoreductase;
KW Polymorphism; Reference proteome.
FT CHAIN 1 359 Aflatoxin B1 aldehyde reductase member 2.
FT /FTId=PRO_0000070375.
FT NP_BIND 171 172 NADP.
FT NP_BIND 226 236 NADP.
FT NP_BIND 318 326 NADP.
FT ACT_SITE 77 77 Proton donor (By similarity).
FT BINDING 72 72 NADP.
FT BINDING 141 141 Substrate (By similarity).
FT BINDING 197 197 NADP.
FT BINDING 250 250 NADP.
FT BINDING 260 260 Substrate (By similarity).
FT BINDING 263 263 Substrate (By similarity).
FT BINDING 359 359 Substrate (By similarity).
FT SITE 105 105 Lowers pKa of active site Tyr (By
FT similarity).
FT MOD_RES 128 128 N6-acetyllysine (By similarity).
FT VARIANT 135 135 V -> M (in dbSNP:rs6670759).
FT /FTId=VAR_048209.
FT VARIANT 142 142 A -> T (in dbSNP:rs1043657).
FT /FTId=VAR_017413.
FT VARIANT 157 157 Q -> H (in dbSNP:rs859208).
FT /FTId=VAR_017414.
FT VARIANT 180 180 E -> K (in dbSNP:rs859210).
FT /FTId=VAR_060222.
FT VARIANT 198 198 G -> S (in dbSNP:rs2231200).
FT /FTId=VAR_048210.
FT VARIANT 214 214 C -> Y (in dbSNP:rs2235794).
FT /FTId=VAR_017415.
FT VARIANT 255 255 S -> N (in dbSNP:rs2231203).
FT /FTId=VAR_048211.
FT STRAND 39 43
FT TURN 48 50
FT HELIX 53 65
FT STRAND 70 72
FT HELIX 77 80
FT HELIX 81 87
FT STRAND 101 106
FT HELIX 116 130
FT STRAND 135 140
FT HELIX 149 161
FT STRAND 164 172
FT HELIX 175 188
FT STRAND 193 199
FT HELIX 206 208
FT HELIX 211 218
FT STRAND 221 225
FT HELIX 229 234
FT HELIX 239 242
FT TURN 243 245
FT STRAND 252 254
FT HELIX 257 264
FT HELIX 267 284
FT HELIX 285 287
FT HELIX 291 302
FT HELIX 307 309
FT STRAND 312 315
FT HELIX 320 330
FT HELIX 337 350
FT HELIX 351 353
SQ SEQUENCE 359 AA; 39589 MW; 2C9775FE4B977D2A CRC64;
MLSAASRVVS RAAVHCALRS PPPEARALAM SRPPPPRVAS VLGTMEMGRR MDAPASAAAV
RAFLERGHTE LDTAFMYSDG QSETILGGLG LGLGGGDCRV KIATKANPWD GKSLKPDSVR
SQLETSLKRL QCPQVDLFYL HAPDHGTPVE ETLHACQRLH QEGKFVELGL SNYASWEVAE
ICTLCKSNGW ILPTVYQGMY NATTRQVETE LFPCLRHFGL RFYAYNPLAG GLLTGKYKYE
DKDGKQPVGR FFGNSWAETY RNRFWKEHHF EAIALVEKAL QAAYGASAPS VTSAALRWMY
HHSQLQGAHG DAVILGMSSL EQLEQNLAAT EEGPLEPAVV DAFNQAWHLV AHECPNYFR
//
MIM
603418
*RECORD*
*FIELD* NO
603418
*FIELD* TI
*603418 ALDO-KETO REDUCTASE FAMILY 7, MEMBER A2; AKR7A2
;;ALDO-KETO REDUCTASE 7; AKR7;;
read moreAFLATOXIN B1-ALDEHYDE REDUCTASE; AFAR
*FIELD* TX
DESCRIPTION
Aldo-keto reductases, such as AKR7A2, are involved in the detoxification
of aldehydes and ketones.
CLONING
Ireland et al. (1998) used a rat aflatoxin B1-aldehyde reductase (AFAR)
cDNA and a human EST sequence to isolate human AFAR cDNAs from
cerebellum and liver libraries. The full-length cDNA encodes a 330-amino
acid polypeptide with 78% identity to rat AFAR, 22% identity to a
Shaker-related voltage-gated potassium channel, and 16% identity to
aldose reductase (103880). Northern blot analysis revealed that AFAR is
expressed in a wide range of human tissues.
By EST database analysis, Kelly et al. (2002) identified an AKR7A2
splice variant that encodes a deduced 359-amino acid protein with an
N-terminal extension.
GENE FUNCTION
Ireland et al. (1998) showed that expressed AFAR can metabolize
aflatoxin, but its specificity for some substrates differs from that of
rat AFAR. They showed that AFAR is the principal human liver reductase
for 2-carboxybenzaldehyde.
GENE STRUCTURE
Praml et al. (2003) determined that the AKR7A2 gene contains 7 exons and
spans 7.8 kb.
MAPPING
By FISH and genomic sequence analysis, Praml et al. (2003) mapped the
AKR7A2 gene to chromosome 1p36.1-p35, where it lies in a gene cluster
with the AKR7A3 (608477) and AKR7A4 (608478) genes. The genes are
oriented in a head-to-tail tandem arrangement,
distal-5-prime-AKR7A2-AKR7A3-AKR7A4-3-prime-proximal. AKR7A pseudogenes
are located on chromosomes Xq25 and 1p12. Praml et al. (2003) mapped the
mouse Akr7a2 gene to chromosome 5, where it is proximal to the Pla2g2a
gene (172411).
*FIELD* RF
1. Ireland, L. S.; Harrison, D. J.; Neal, G. E.; Hayes, J. D.: Molecular
cloning, expression and catalytic activity of a human AKR7 member
of the aldo-keto reductase superfamily: evidence that the major 2-carboxybenzaldehyde
reductase from human liver is a homologue of rat aflatoxin B(1)-aldehyde
reductase. Biochem. J. 332: 21-34, 1998.
2. Kelly, V. P.; Sherratt, P. J.; Crouch, D. H.; Hayes, J. D.: Novel
homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases
that associate with the Golgi apparatus define a distinct subclass
of reductase 7 family proteins. Biochem. J. 366: 847-861, 2002.
3. Praml, C.; Savelyeva, L.; Schwab, M.: Aflatoxin B1 aldehyde reductase
(AFAR) genes cluster at 1p35-1p36.1 in a region frequently altered
in human tumour cells. Oncogene 22: 4765-4773, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 2/18/2004
*FIELD* CD
Jennifer P. Macke: 1/12/1999
*FIELD* ED
joanna: 05/23/2012
mgross: 2/20/2004
terry: 2/18/2004
alopez: 7/22/1999
alopez: 1/12/1999
*RECORD*
*FIELD* NO
603418
*FIELD* TI
*603418 ALDO-KETO REDUCTASE FAMILY 7, MEMBER A2; AKR7A2
;;ALDO-KETO REDUCTASE 7; AKR7;;
read moreAFLATOXIN B1-ALDEHYDE REDUCTASE; AFAR
*FIELD* TX
DESCRIPTION
Aldo-keto reductases, such as AKR7A2, are involved in the detoxification
of aldehydes and ketones.
CLONING
Ireland et al. (1998) used a rat aflatoxin B1-aldehyde reductase (AFAR)
cDNA and a human EST sequence to isolate human AFAR cDNAs from
cerebellum and liver libraries. The full-length cDNA encodes a 330-amino
acid polypeptide with 78% identity to rat AFAR, 22% identity to a
Shaker-related voltage-gated potassium channel, and 16% identity to
aldose reductase (103880). Northern blot analysis revealed that AFAR is
expressed in a wide range of human tissues.
By EST database analysis, Kelly et al. (2002) identified an AKR7A2
splice variant that encodes a deduced 359-amino acid protein with an
N-terminal extension.
GENE FUNCTION
Ireland et al. (1998) showed that expressed AFAR can metabolize
aflatoxin, but its specificity for some substrates differs from that of
rat AFAR. They showed that AFAR is the principal human liver reductase
for 2-carboxybenzaldehyde.
GENE STRUCTURE
Praml et al. (2003) determined that the AKR7A2 gene contains 7 exons and
spans 7.8 kb.
MAPPING
By FISH and genomic sequence analysis, Praml et al. (2003) mapped the
AKR7A2 gene to chromosome 1p36.1-p35, where it lies in a gene cluster
with the AKR7A3 (608477) and AKR7A4 (608478) genes. The genes are
oriented in a head-to-tail tandem arrangement,
distal-5-prime-AKR7A2-AKR7A3-AKR7A4-3-prime-proximal. AKR7A pseudogenes
are located on chromosomes Xq25 and 1p12. Praml et al. (2003) mapped the
mouse Akr7a2 gene to chromosome 5, where it is proximal to the Pla2g2a
gene (172411).
*FIELD* RF
1. Ireland, L. S.; Harrison, D. J.; Neal, G. E.; Hayes, J. D.: Molecular
cloning, expression and catalytic activity of a human AKR7 member
of the aldo-keto reductase superfamily: evidence that the major 2-carboxybenzaldehyde
reductase from human liver is a homologue of rat aflatoxin B(1)-aldehyde
reductase. Biochem. J. 332: 21-34, 1998.
2. Kelly, V. P.; Sherratt, P. J.; Crouch, D. H.; Hayes, J. D.: Novel
homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases
that associate with the Golgi apparatus define a distinct subclass
of reductase 7 family proteins. Biochem. J. 366: 847-861, 2002.
3. Praml, C.; Savelyeva, L.; Schwab, M.: Aflatoxin B1 aldehyde reductase
(AFAR) genes cluster at 1p35-1p36.1 in a region frequently altered
in human tumour cells. Oncogene 22: 4765-4773, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 2/18/2004
*FIELD* CD
Jennifer P. Macke: 1/12/1999
*FIELD* ED
joanna: 05/23/2012
mgross: 2/20/2004
terry: 2/18/2004
alopez: 7/22/1999
alopez: 1/12/1999