Reviewed, UniProtKB/Swiss-Prot Q96JD6 (AKCL2_HUMAN)

Names and origin

Protein names

Recommended name:
    1,5-anhydro-D-fructose reductase
      Short name=AF reductase
    EC=1.1.1.263
Alternative name(s):
    Aldo-keto reductase family 1 member C-like protein 2
    Aldo-keto reductase family 1 member E2
    Testis-specific protein
    HTSP
    LoopADR

Gene names

Name:	AKR1E2
Synonyms:	AKR1CL2, AKRDC1

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	320 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 1,5-anhydro-D-fructose (AF) to 1,5-anhydro-D-glucitol. Can also catalyze the reduction of various aldehydes and quinones By similarity. Has low NADPH-dependent reductase activity towards 9,10-phenanthrenequinone (in vitro).
Catalytic activity	1,5-anhydro-D-glucitol + NADP+ = 1,5-anhydro-D-fructose + NADPH.
Subcellular location	Cytoplasm Potential.
Tissue specificity	Testis-specific. Ref.1
Sequence similarities	Belongs to the aldo/keto reductase family.
Biophysicochemical properties	Kinetic parameters: KM=6.1 µM for 9,10-phenanthrenequinone with NADPH as cofactor Vmax=0.42 nmol/min/mg enzyme towards 9,10-phenanthrenequinone with NADPH as cofactor

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	1,5-anhydro-D-fructose reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96JD6-1)

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: Q96JD6-2)

Also known as: HTSP2;

The sequence of this isoform differs from the canonical sequence as follows:
     194-250: Missing.

Isoform 3 (identifier: Q96JD6-3)

Also known as: HTSP1;

The sequence of this isoform differs from the canonical sequence as follows:
     194-250: Missing.
     307-307: I → M
     308-320: Missing.

Isoform 4 (identifier: Q96JD6-4)

Also known as: HTSP4;

The sequence of this isoform differs from the canonical sequence as follows:
     307-307: I → M
     308-320: Missing.

Isoform 5 (identifier: Q96JD6-5)

Also known as: HTSP3;

The sequence of this isoform differs from the canonical sequence as follows:
     154-251: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 320	320	1,5-anhydro-D-fructose reductase		PRO_0000287880
Regions
	Nucleotide binding	269 – 277	9	NADP By similarity
Sites
	Active site	40	1	Proton donor By similarity
	Binding site	35	1	NADP By similarity
	Binding site	102	1	Substrate By similarity
	Binding site	193	1	NADP By similarity
	Site	69	1	Lowers pKa of active site Tyr By similarity
Natural variations
	Alternative sequence	154 – 251	98	Missing in isoform 5.		VSP_025614
	Alternative sequence	194 – 250	57	Missing in isoform 2 and isoform 3.		VSP_025615
	Alternative sequence	307	1	I → M in isoform 3 and isoform 4.		VSP_025616
	Alternative sequence	308 – 320	13	Missing in isoform 3 and isoform 4.		VSP_025617
	Natural variant	52	1	C → G: dbSNP rs35429729.		VAR_032356
	Natural variant	86	1	K → R: dbSNP rs17133693.		VAR_032357
Experimental info
	Sequence conflict	312	1	K → N in AAK58523. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 2. Checksum: A73E06225E7F15DD	FASTA	320	36,589
	10 20 30 40 50 60 MGDIPAVGLS SWKASPGKVT EAVKEAIDAG YRHFDCAYFY HNEREVGAGI RCKIKEGAVR 70 80 90 100 110 120 REDLFIATKL WCTCHKKSLV ETACRKSLKA LKLNYLDLYL IHWPMGFKPP HPEWIMSCSE 130 140 150 160 170 180 LSFCLSHPRV QDLPLDESNM VIPSDTDFLD TWEAMEDLVI TGLVKNIGVS NFNHEQLERL 190 200 210 220 230 240 LNKPGLRFKP LTNQIECHPY LTQKNLISFC QSRDVSVTAY RPLGGSCEGV DLIDNPVIKR 250 260 270 280 290 300 IAKEHGKSPA QILIRFQIQR NVIVIPGSIT PSHIKENIQV FDFELTQHDM DNILSLNRNL 310 320 RLAMFPITKN HKDYPFHIEY
	Isoform 2 (HTSP2). Checksum: 024E146FABDEBA9F	FASTA	263	30,323
	10 20 30 40 50 60 MGDIPAVGLS SWKASPGKVT EAVKEAIDAG YRHFDCAYFY HNEREVGAGI RCKIKEGAVR 70 80 90 100 110 120 REDLFIATKL WCTCHKKSLV ETACRKSLKA LKLNYLDLYL IHWPMGFKPP HPEWIMSCSE 130 140 150 160 170 180 LSFCLSHPRV QDLPLDESNM VIPSDTDFLD TWEAMEDLVI TGLVKNIGVS NFNHEQLERL 190 200 210 220 230 240 LNKPGLRFKP LTNQILIRFQ IQRNVIVIPG SITPSHIKEN IQVFDFELTQ HDMDNILSLN 250 260 RNLRLAMFPI TKNHKDYPFH IEY
	Isoform 3 (HTSP1). Checksum: 241A3E8125FDE258	FASTA	250	28,667
	10 20 30 40 50 60 MGDIPAVGLS SWKASPGKVT EAVKEAIDAG YRHFDCAYFY HNEREVGAGI RCKIKEGAVR 70 80 90 100 110 120 REDLFIATKL WCTCHKKSLV ETACRKSLKA LKLNYLDLYL IHWPMGFKPP HPEWIMSCSE 130 140 150 160 170 180 LSFCLSHPRV QDLPLDESNM VIPSDTDFLD TWEAMEDLVI TGLVKNIGVS NFNHEQLERL 190 200 210 220 230 240 LNKPGLRFKP LTNQILIRFQ IQRNVIVIPG SITPSHIKEN IQVFDFELTQ HDMDNILSLN 250 RNLRLAMFPM
	Isoform 4 (HTSP4). Checksum: 4DEEDE07568D2F03	FASTA	307	34,933
	10 20 30 40 50 60 MGDIPAVGLS SWKASPGKVT EAVKEAIDAG YRHFDCAYFY HNEREVGAGI RCKIKEGAVR 70 80 90 100 110 120 REDLFIATKL WCTCHKKSLV ETACRKSLKA LKLNYLDLYL IHWPMGFKPP HPEWIMSCSE 130 140 150 160 170 180 LSFCLSHPRV QDLPLDESNM VIPSDTDFLD TWEAMEDLVI TGLVKNIGVS NFNHEQLERL 190 200 210 220 230 240 LNKPGLRFKP LTNQIECHPY LTQKNLISFC QSRDVSVTAY RPLGGSCEGV DLIDNPVIKR 250 260 270 280 290 300 IAKEHGKSPA QILIRFQIQR NVIVIPGSIT PSHIKENIQV FDFELTQHDM DNILSLNRNL RLAMFPM
	Isoform 5 (HTSP3). Checksum: 388A3D53CEA44BE4	FASTA	222	25,693
	10 20 30 40 50 60 MGDIPAVGLS SWKASPGKVT EAVKEAIDAG YRHFDCAYFY HNEREVGAGI RCKIKEGAVR 70 80 90 100 110 120 REDLFIATKL WCTCHKKSLV ETACRKSLKA LKLNYLDLYL IHWPMGFKPP HPEWIMSCSE 130 140 150 160 170 180 LSFCLSHPRV QDLPLDESNM VIPSDTDFLD TWEILIRFQI QRNVIVIPGS ITPSHIKENI 190 200 210 220 QVFDFELTQH DMDNILSLNR NLRLAMFPIT KNHKDYPFHI EY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human testis specific protein: a new member of aldo-keto reductase superfamily." Nishinaka T., Azuma Y., Ushijima S., Miki T., Yabe-Nishimura C. Chem. Biol. Interact. 143:299-305(2003) [PubMed: 12604216] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 5), BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Tissue: Testis.
[2]	"LoopADR: a novel human aldo-keto reductase." Hyndman D.J., Li L., Flynn T.G. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Small intestine.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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 4). Tissue: Lung.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB040820 mRNA. Translation: BAC54565.1. AB040821 mRNA. Translation: BAC54566.1. AB040822 mRNA. Translation: BAC54567.1. AB055603 mRNA. Translation: BAC54568.1. AF263242 mRNA. Translation: AAK58523.1. AC091817 Genomic DNA. No translation available. BC002862 mRNA. Translation: AAH02862.1.
IPI	IPI00153045. IPI00384751. IPI00384752. IPI00644253. IPI00845396.
RefSeq	NP_001035267.1.
UniGene	Hs.657944
3D structure databases
HSSP	HSSP built from PDB template 1PWM based on UniProtKB P15121.
ModBase	Search...
Proteomic databases
PRIDE	Q96JD6.
Genome annotation databases
Ensembl	ENST00000298375; ENSP00000298375; ENSG00000165568; Homo sapiens. [Genome view]
GeneID	83592.
KEGG	hsa:83592.
UCSC	uc001ihh.1. human. uc001ihi.1. human. uc009xhw.1. human.
Organism-specific databases
CTD	83592.
GeneCards	GC10P004858.
HGNC	HGNC:23437. AKR1E2.
PharmGKB	PA134910506.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q96JD6.
HOVERGEN	Q96JD6.
Gene expression databases
ArrayExpress	Q96JD6.
Bgee	Q96JD6.
CleanEx	HS_AKR1CL2.
Genevestigator	Q96JD6.
Family and domain databases
InterPro	IPR001395. Aldo/ket_red. IPR018170. Aldo/ket_reductase_CS. IPR020471. Aldo/keto_reductase_sg. [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]
PRINTS	PR00069. ALDKETRDTASE.
PROSITE	PS00798. ALDOKETO_REDUCTASE_1. 1 hit. PS00062. ALDOKETO_REDUCTASE_2. 1 hit. PS00063. ALDOKETO_REDUCTASE_3. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	72513.

Entry information

Entry name

AKCL2_HUMAN

Accession

Primary (citable) accession number: Q96JD6
Secondary accession number(s): Q86Z16 , Q86Z17, Q86Z18, Q9BU71

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	November 24, 2009
Last modified:	November 24, 2009
This is version 52 of the entry and version 2 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.