Q16698 (DECR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
2,4-dienoyl-CoA reductase, mitochondrial
EC=1.3.1.34

Alternative name(s):
2,4-dienoyl-CoA reductase [NADPH]
Short name=4-enoyl-CoA reductase [NADPH]

Gene names

Name:	DECR1
Synonyms:	DECR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	335 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Auxiliary enzyme of beta-oxidation. It participates in the metabolism of unsaturated fatty enoyl-CoA esters having double bonds in both even- and odd-numbered positions. Catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to yield trans-3-enoyl-CoA.
Catalytic activity	Trans-2,3-didehydroacyl-CoA + NADP+ = trans,trans-2,3,4,5-tetradehydroacyl-CoA + NADPH. Ref.8
Subunit structure	Homotetramer. Ref.8
Subcellular location	Mitochondrion.
Tissue specificity	Heart = liver = pancreas > kidney >> skeletal muscle = lung. Ref.1
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family. 2,4-dienoyl-CoA reductase subfamily.
Biophysicochemical properties	Kinetic parameters: KM=7.7 µM for NADPH Ref.8 KM=14.3 µM for trans-2,trans-4-hexadienoyl-CoA Vmax=30.3 µmol/min/mg enzyme

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fatty acid beta-oxidation Inferred from direct assay Ref.8. Source: UniProtKB protein homotetramerization Inferred from direct assay Ref.8. Source: UniProtKB
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA
Molecular_function	2,4-dienoyl-CoA reductase (NADPH) activity Inferred from direct assay Ref.8. Source: UniProtKB NADPH binding Inferred from direct assay Ref.8. Source: UniProtKB oxidoreductase activity, acting on NAD(P)H Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 34

34

Mitochondrion By similarity

Chain

35 – 335

301

2,4-dienoyl-CoA reductase, mitochondrial

PRO_0000031965

Regions

Nucleotide binding

66 – 71

6

NADP

Nucleotide binding

240 – 243

4

NADP

Sites

Active site

199

1

Proton acceptor Potential

Binding site

91

1

NADP

Binding site

91

1

Substrate By similarity

Binding site

117

1

NADP

Binding site

119

1

Substrate

Binding site

149

1

Substrate

Binding site

157

1

Substrate

Binding site

214

1

NADP

Binding site

251

1

Substrate By similarity

Amino acid modifications

Modified residue

110

1

N6-acetyllysine By similarity

Modified residue

230

1

N6-acetyllysine Ref.6

Natural variations

Natural variant

333

1

K → N.
Corresponds to variant rs15094 [ dbSNP | Ensembl ].

VAR_012034

Experimental info

Mutagenesis

148

1

N → A: Reduces enzyme activity by 97%. Ref.8

Mutagenesis

199

1

Y → A: Reduces enzyme activity by 99%. Strongly reduced affinity for substrate and for NADP. Ref.8

Mutagenesis

210

1

S → A: Reduces enzyme activity by over 99%. Ref.8

Mutagenesis

214

1

K → A: Reduces enzyme activity by over 99%. Ref.8

Sequence conflict

287

1

D → G in AAB09423. Ref.2

Sequence conflict

292

1

I → V in AAB09423. Ref.2

Sequence conflict

303

1

E → G in AAB09423. Ref.2

Sequence conflict

311

1

F → G in AAB09423. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

335

Helix Strand Turn

Details...

Helix

36 – 43

8

Turn

54 – 59

6

Beta strand

61 – 65

5

Turn

66 – 68

3

Helix

70 – 81

12

Beta strand

85 – 91

7

Helix

93 – 107

15

Beta strand

111 – 115

5

Helix

121 – 134

14

Beta strand

139 – 143

5

Helix

153 – 155

3

Helix

158 – 185

28

Beta strand

190 – 195

6

Helix

199 – 202

4

Helix

208 – 228

21

Helix

229 – 231

3

Beta strand

233 – 240

8

Beta strand

254 – 256

3

Helix

257 – 263

7

Helix

274 – 284

11

Helix

287 – 289

3

Beta strand

296 – 300

5

Helix

303 – 308

6

Helix

312 – 316

5

Helix

319 – 325

7

Sequences

	Sequence		Length	Mass (Da)
	Q16698 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: F04E72AACB718430	FASTA	335	36,068
	10 20 30 40 50 60 MKLPARVFFT LGSRLPCGLA PRRFFSYGTK ILYQNTEALQ SKFFSPLQKA MLPPNSFQGK 70 80 90 100 110 120 VAFITGGGTG LGKGMTTLLS SLGAQCVIAS RKMDVLKATA EQISSQTGNK VHAIQCDVRD 130 140 150 160 170 180 PDMVQNTVSE LIKVAGHPNI VINNAAGNFI SPTERLSPNA WKTITDIVLN GTAFVTLEIG 190 200 210 220 230 240 KQLIKAQKGA AFLSITTIYA ETGSGFVVPS ASAKAGVEAM SKSLAAEWGK YGMRFNVIQP 250 260 270 280 290 300 GPIKTKGAFS RLDPTGTFEK EMIGRIPCGR LGTVEELANL AAFLCSDYAS WINGAVIKFD 310 320 330 GGEEVLISGE FNDLRKVTKE QWDTIEELIR KTKGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of cDNA for human 120 kDa mitochondrial 2,4-dienoyl-coenzyme A reductase." Koivuranta K.T., Hakkola E.H., Hiltunen J.K. Biochem. J. 304:787-792(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Liver.
[2]	Ding J.H., Yang B.Z., Roe C.R. Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Molecular cloning and characterization of the human mitochondrial 2,4-dienoyl-CoA reductase gene (DECR)." Helander H.M., Koivuranta K.T., Horelli-Kuitunen N., Palvimo J.J., Palotie A., Hiltunen J.K. Genomics 46:112-119(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Brain.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-230, MASS SPECTROMETRY.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Structure and reactivity of human mitochondrial 2,4-dienoyl-CoA reductase: enzyme-ligand interactions in a distinctive short-chain reductase active site." Alphey M.S., Yu W., Byres E., Li D., Hunter W.N. J. Biol. Chem. 280:3068-3077(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 35-335 IN COMPLEX WITH NADP AND SUBSTRATE, CATALYTIC ACTIVITY, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASN-148; TYR-199; SER-210 AND LYS-214.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L26050 mRNA. Translation: AAA67551.1.
U49352 mRNA. Translation: AAB09423.1.
U78302 , U94980, U94981, U94982, U94983, U94984, U94985, U94986, U94987 Genomic DNA. Translation: AAB88724.1.
AC004612 Genomic DNA. Translation: AAC14671.1.
AF049895 Genomic DNA. No translation available.
BC105080 mRNA. Translation: AAI05081.1.
BC105082 mRNA. Translation: AAI05083.1.

IPI

IPI00003482.

PIR

S53352.

RefSeq

NP_001350.1. NM_001359.1.

UniGene

Hs.492212.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W6U	X-ray	1.75	A/B/C/D	35-335	[»]
1W73	X-ray	2.10	A/B/C/D	35-335	[»]
1W8D	X-ray	2.20	A/B/C/D	35-335	[»]

ProteinModelPortal

Q16698.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16698. 5 interactions.

STRING

9606.ENSP00000220764.

PTM databases

PhosphoSite

Q16698.

Polymorphism databases

DMDM

3913456.

2D gel databases

UCD-2DPAGE

Q16698.

Proteomic databases

PaxDb

Q16698.

PeptideAtlas

Q16698.

PRIDE

Q16698.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000220764; ENSP00000220764; ENSG00000104325.

GeneID

1666.

KEGG

hsa:1666.

UCSC

uc003yek.1. human.

Organism-specific databases

CTD

1666.

GeneCards

GC08P091082.

HGNC

HGNC:2753. DECR1.

HPA

HPA023160.
HPA023162.
HPA023238.

MIM

222745. gene+phenotype.

neXtProt

NX_Q16698.

PharmGKB

PA141.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1028.

HOVERGEN

HBG005465.

InParanoid

Q16698.

KO

K13236.

OMA

TGAFEKE.

OrthoDB

EOG4C2HB7.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q16698.

Gene expression databases

ArrayExpress

Q16698.

Bgee

Q16698.

CleanEx

HS_DECR1.

Genevestigator

Q16698.

GermOnline

ENSG00000104325. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

PRINTS

PR00081. GDHRDH.

PROSITE

PS00061. ADH_SHORT. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

DECR1. human.

EvolutionaryTrace

Q16698.

GenomeRNAi

1666.

NextBio

6856.

SOURCE

Search...

Entry information

Entry name

DECR_HUMAN

Accession

Primary (citable) accession number: Q16698
Secondary accession number(s): Q2M304, Q93085

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.