Reviewed, UniProtKB/Swiss-Prot Q8NHP1 (ARK74_HUMAN)

Names and origin

Protein names

Recommended name:
    Aflatoxin B1 aldehyde reductase member 4
    EC=1.-.-.-

Gene names

Name:	AKR7A4
Synonyms:	AFAR3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	331 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	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.
Tissue specificity	Mainly expressed in uterus.
Sequence similarities	Belongs to the aldo/keto reductase 2 family.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism Selenocysteine
Ligand	NAD NADP Selenium
Molecular function	Oxidoreductase
Gene Ontology (GO)
None. [Check GOA]

Alternative products

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

Isoform 1 (identifier: Q8NHP1-1)

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: Q8NHP1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-178: Missing.
     179-235: VETELFPCLR...TQWAEIYRNS → MHLTTAPRWK...TAGSCPLCTS

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 331	331	Aflatoxin B1 aldehyde reductase member 4
Regions
	Nucleotide binding	198 – 208	11	NADP By similarity
Sites
	Active site	49	1	Proton donor By similarity
	Binding site	113	1	Substrate By similarity
	Site	77	1	Lowers pKa of active site Tyr By similarity
Amino acid modifications
	Non-standard residue	106	1	Selenocysteine Probable
Natural variations
	Alternative sequence	1 – 178	178	Missing in isoform 2.
	Alternative sequence	179 – 235	57	VETEL…IYRNS → MHLTTAPRWKRHCVPATSCT RRASSWSLASPTMPPGKWPR SVPSARATAGSCPLCTS in isoform 2.
	Natural variant	255	1	A → T: dbSNP rs2235795.
	Natural variant	322	1	F → V: dbSNP rs2982534.
Experimental info
	Sequence conflict	186	1	C → Y in CAC79668. Ref.3
	Sequence conflict	235	1	S → H in CAC79668. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 2, 2008. Version 5. Checksum: 7610FBDD2FAD98A2	FASTA	331	36,914
	10 20 30 40 50 60 MSRQLSRARP ATVLGAMEMG RRMDAPTSAA VTRAFLERGH TEIDTAFLYS DGQSETILGG 70 80 90 100 110 120 LGLRMGSSDC RVKIATKANP WIGNSLKPDS VRSQLETSLK RLQCPUVDLF YLHAPDHSAP 130 140 150 160 170 180 VEETLRACHQ LHQEGKFVEL GLSNYAAWEV AEICTLCKSN GWILPTVYQG MYSATTRQVE 190 200 210 220 230 240 TELFPCLRHF GLRFYAYNPL AGGLLTGKYK YEDKDGKQPV GRFFGTQWAE IYRNSFWKEH 250 260 270 280 290 300 HFEGIALVEK ALQAAYGASA PSMTSAALRW MYHHSQLQGA HGDAVILGMS SLEQLEQNLA 310 320 330 AAEEGPLEPA VVDAFNQAWH LFAHECPNYF I
	Isoform 2 [UniParc]. Checksum: 3C29E1ADB792AD73		153	16,724
	10 20 30 40 50 60 MHLTTAPRWK RHCVPATSCT RRASSWSLAS PTMPPGKWPR SVPSARATAG SCPLCTSFWK 70 80 90 100 110 120 EHHFEGIALV EKALQAAYGA SAPSMTSAAL RWMYHHSQLQ GAHGDAVILG MSSLEQLEQN 130 140 150 LAAAEEGPLE PAVVDAFNQA WHLFAHECPN YFI

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] (ISOFORM 2). Tissue: Colon.
[3]	"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: 12879023] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 73-331, VARIANT THR-255, TISSUE SPECIFICITY, PROBABLE SELENOCYSTEINE AT SEC-106. Tissue: Uterus.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AL035413 Genomic DNA. No translation available. BC035351 mRNA. Translation: AAH35351.1. AJ278012 mRNA. Translation: CAC79668.1.
RefSeq	NP_957704.1.
UniGene	Hs.662342
3D structure databases
HSSP	HSSP built from PDB template 1GVE based on UniProtKB P38918.
SMR	Q8NHP1. Positions 9-330.
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000211454. Homo sapiens. [Contig view]
GeneID	246181.
Organism-specific databases
MIM	608478. gene.
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q8NHP1.
HOVERGEN	Q8NHP1.
Gene expression databases
GermOnline	ENSG00000211454. 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]
ProDom	PD000288. Aldo/ket_red. 1 hit. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ARK74_HUMAN

Accession

Primary (citable) accession number: Q8NHP1
Secondary accession number(s): Q5U614

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 2003
Last sequence update:	September 2, 2008
Last modified:	September 23, 2008
This is version 47 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)