Reviewed, UniProtKB/Swiss-Prot O43488 (ARK72_HUMAN)

Names and origin

Protein names

Recommended name:
    Aflatoxin B1 aldehyde reductase member 2
    EC=1.1.1.n11
Alternative name(s):
    Succinic semialdehyde reductase
      Short name=SSA reductase
    AFB1-AR 1
    Aldoketoreductase 7

Gene names

Name:	AKR7A2
Synonyms:	AFAR, AFAR1, AKR7

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	359 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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. Has NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). 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. Ref.3 Ref.9
Subunit structure	Homodimer. Ref.3
Subcellular location	Golgi apparatus By similarity. Cytoplasm.
Tissue specificity	Detected in brain, liver, small intestine and testis, and at lower levels in heart, prostate, skeletal muscle and spleen. Detected in kidney proximal and distal tubules, endothelial cells lining the Bowman's capsules and some cysts. Detected at low levels in lung and pancreas (at protein level). Widely expressed. Ref.3 Ref.7
Sequence similarities	Belongs to the aldo/keto reductase 2 family.
Caution	It is uncertain whether Met-1 or Met-30 is the initiator.
Biophysicochemical properties	Kinetic parameters: KM=20 µM for succinic semialdehyde KM=17 µM for 2-carboxybenzaldehyde KM=8 µM for 9,10-phenanthrenequinone KM=102 µM for 1,2-naphthoquinone

Ontologies

Keywords
Cellular component	Cytoplasm Golgi apparatus
Coding sequence diversity	Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Ref.3 Traceable author statement. Source: ProtInc cellular aldehyde metabolic process Ref.3 Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aldehyde reductase activity Ref.3 Traceable author statement. Source: ProtInc electron carrier activity Ref.3 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 359

359

Aflatoxin B1 aldehyde reductase member 2

PRO_0000070375

Regions

Nucleotide binding

171 – 172

2

NADP

Nucleotide binding

226 – 236

11

NADP

Nucleotide binding

318 – 326

9

NADP

Sites

Active site

77

1

Proton donor By similarity

Binding site

72

1

NADP

Binding site

141

1

Substrate By similarity

Binding site

197

1

NADP

Binding site

250

1

NADP

Binding site

260

1

Substrate By similarity

Binding site

263

1

Substrate By similarity

Binding site

359

1

Substrate By similarity

Site

105

1

Lowers pKa of active site Tyr By similarity

Amino acid modifications

Modified residue

40

1

Phosphoserine By similarity

Modified residue

255

1

Phosphoserine

Natural variations

Natural variant

135

1

V → M: dbSNP rs6670759.

VAR_048209

Natural variant

142

1

A → T: dbSNP rs1043657. Ref.3 Ref.13

VAR_017413

Natural variant

157

1

Q → H: dbSNP rs859208. Ref.13

VAR_017414

Natural variant

180

1

E → K: dbSNP rs859210.

VAR_060222

Natural variant

198

1

G → S: dbSNP rs2231200.

VAR_048210

Natural variant

214

1

C → Y: dbSNP rs2235794.

VAR_017415

Natural variant

255

1

S → N: dbSNP rs2231203.

VAR_048211

Secondary structure

1

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359

Helix Strand Turn

Details...

Beta strand

39 – 43

5

Turn

48 – 50

3

Helix

53 – 65

13

Beta strand

70 – 72

3

Helix

77 – 80

4

Helix

81 – 87

7

Beta strand

101 – 106

6

Helix

116 – 130

15

Beta strand

135 – 140

6

Helix

149 – 161

13

Beta strand

164 – 172

9

Helix

175 – 188

14

Beta strand

193 – 199

7

Helix

206 – 208

3

Helix

211 – 218

8

Beta strand

221 – 225

5

Helix

229 – 234

6

Helix

239 – 242

4

Turn

243 – 245

3

Beta strand

252 – 254

3

Helix

257 – 264

8

Helix

267 – 284

18

Helix

285 – 287

3

Helix

291 – 302

12

Helix

307 – 309

3

Beta strand

312 – 315

4

Helix

320 – 330

11

Helix

337 – 350

14

Helix

351 – 353

3

Sequences

	Sequence		Length	Mass (Da)
	O43488-1 [UniParc]. Last modified November 14, 2003. Version 3. Checksum: 2C9775FE4B977D2A	FASTA	359	39,589
	10 20 30 40 50 60 MLSAASRVVS RAAVHCALRS PPPEARALAM SRPPPPRVAS VLGTMEMGRR MDAPASAAAV 70 80 90 100 110 120 RAFLERGHTE LDTAFMYSDG QSETILGGLG LGLGGGDCRV KIATKANPWD GKSLKPDSVR 130 140 150 160 170 180 SQLETSLKRL QCPQVDLFYL HAPDHGTPVE ETLHACQRLH QEGKFVELGL SNYASWEVAE 190 200 210 220 230 240 ICTLCKSNGW ILPTVYQGMY NATTRQVETE LFPCLRHFGL RFYAYNPLAG GLLTGKYKYE 250 260 270 280 290 300 DKDGKQPVGR FFGNSWAETY RNRFWKEHHF EAIALVEKAL QAAYGASAPS VTSAALRWMY 310 320 330 340 350 HHSQLQGAHG DAVILGMSSL EQLEQNLAAT EEGPLEPAVV DAFNQAWHLV AHECPNYFR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-359. Tissue: Pancreas, Skin and Uterus.
[3]	"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 B1-aldehyde reductase." Ireland L.S., Harrison D.J., Neal G.E., Hayes J.D. Biochem. J. 332:21-34(1998) [PubMed: 9576847] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-359, PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT THR-142. Tissue: Liver.
[4]	"Cloning of the human aflatoxin B1-aldehyde reductase gene at 1p35-1p36.1 in a region frequently altered in human tumor cells." Praml C., Savelyeva L., Perri P., Schwab M. Cancer Res. 58:5014-5018(1998) [PubMed: 9823300] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-359. Tissue: Brain.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 30-359.
[6]	Lubec G., Vishwanath V. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 222-236; 251-261 AND 279-297, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[7]	"Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members." O'Connor T., Ireland L.S., Harrison D.J., Hayes J.D. Biochem. J. 343:487-504(1999) [PubMed: 10510318] [Abstract] Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
[8]	"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: 12071861] [Abstract] Cited for: GENE STRUCTURE.
[9]	"Synthesis and catabolism of gamma-hydroxybutyrate in SH-SY5Y human neuroblastoma cells: role of the aldo-keto reductase AKR7A2." Lyon R.C., Johnston S.M., Watson D.G., McGarvie G., Ellis E.M. J. Biol. Chem. 282:25986-25992(2007) [PubMed: 17591773] [Abstract] Cited for: FUNCTION.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255, MASS SPECTROMETRY. Tissue: T-cell.
[12]	"Structure of the aflatoxin aldehyde reductase in complex with NADPH." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NADP.
[13]	"Genetic variation of aflatoxin B1 aldehyde reductase genes (AFAR) in human tumour cells." Praml C., Schulz W., Claas A., Mollenhauer J., Poustka A., Ackermann R., Schwab M., Henrich K.-O. Cancer Lett. 272:160-166(2008) [PubMed: 18752886] [Abstract] Cited for: VARIANTS THR-142 AND HIS-157.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AL035413 Genomic DNA. Translation: CAB72321.1. Different initiation.
BC004111 mRNA. Translation: AAH04111.3. Different initiation.
BC007352 mRNA. Translation: AAH07352.2.
BC010852 mRNA. Translation: AAH10852.1. Different initiation.
BC011586 mRNA. Translation: AAH11586.1. Different initiation.
BC012171 mRNA. Translation: AAH12171.1. Different initiation.
BC013996 mRNA. Translation: AAH13996.1. Different initiation.
AF026947 mRNA. Translation: AAC52104.1. Different initiation.
Y16675 mRNA. Translation: CAA76347.1. Different initiation.
BT007347 mRNA. Translation: AAP36011.1. Different initiation.
BK000395 mRNA. Translation: DAA00088.1.

IPI

IPI00305978.

RefSeq

NP_003680.2.

UniGene

Hs.571886

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BP1	X-ray	2.40	A/B/C/D	1-359	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O43488. 2 interactions.

STRING

O43488.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00305978.
O43488.

Proteomic databases

PRIDE

O43488.

Genome annotation databases

Ensembl

ENST00000235835; ENSP00000235835; ENSG00000053371; Homo sapiens. [Genome view]

GeneID

8574.

KEGG

hsa:8574.

UCSC

uc001bbw.1. human.

Organism-specific databases

CTD

8574.

GeneCards

GC01M019503.

H-InvDB

HIX0000198.

HGNC

HGNC:389. AKR7A2.

MIM

603418. gene.

PharmGKB

PA24682.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG605727.

HOVERGEN

O43488.

InParanoid

O43488.

OMA

HHFEAIA.

OrthoDB

EOG9VT8GK.

Gene expression databases

ArrayExpress

O43488.

Bgee

O43488.

CleanEx

HS_AKR7A2.

Genevestigator

O43488.

GermOnline

ENSG00000053371. Homo sapiens.

Family and domain databases

InterPro

IPR001395. Aldo/ket_red.
[Graphical view]

Gene3D

G3DSA:3.20.20.100. Aldo/ket_red. 1 hit.

PANTHER

PTHR11732. Aldo/ket_red. 1 hit.

Pfam

PF00248. Aldo_ket_red. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

32161.

PMAP-CutDB

O43488.

SOURCE

Search...

Entry information

Entry name

ARK72_HUMAN

Accession

Primary (citable) accession number: O43488
Secondary accession number(s): O75749, Q5TG63

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 14, 2003
Last modified:	December 15, 2009
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.