Reviewed, UniProtKB/Swiss-Prot Q08426 (ECHP_HUMAN)

Names and origin

Protein names

Recommended name:
    Peroxisomal bifunctional enzyme
      Short name=PBE
      Short name=PBFE
Including the following 2 domains:
    1- Recommended name:
            Enoyl-CoA hydratase/3,2-trans-enoyl-CoA isomerase
              EC=4.2.1.17
              EC=5.3.3.8
    2- Recommended name:
            3-hydroxyacyl-CoA dehydrogenase
              EC=1.1.1.35

Gene names

Name:	EHHADH
Synonyms:	ECHD

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	723 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)

Catalytic activity	(3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H2O. (3Z)-dodec-3-enoyl-CoA = (2E)-dodec-2-enoyl-CoA. (S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH.
Pathway	Lipid metabolism; fatty acid beta-oxidation.
Subunit structure	Monomer.
Subcellular location	Peroxisome.
Tissue specificity	Liver and kidney. Lower amounts seen in the brain.
Sequence similarities	In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family. In the C-terminal section; belongs to the 3-hydroxyacyl-CoA dehydrogenase family.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Peroxisome
Coding sequence diversity	Polymorphism
Ligand	NAD
Molecular function	Isomerase Lyase Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	peroxisome Ref.1 Traceable author statement. Source: ProtInc
Molecular function	3-hydroxyacyl-CoA dehydrogenase activity Ref.1 Traceable author statement. Source: ProtInc coenzyme binding Inferred from electronic annotation. Source: InterPro dodecenoyl-CoA delta-isomerase activity Inferred from electronic annotation. Source: EC enoyl-CoA hydratase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 723	722	Peroxisomal bifunctional enzyme		PRO_0000109247
Regions
	Region	2 – 282	281	Enoyl-CoA hydratase / isomerase
	Region	283 – 572	290	3-hydroxyacyl-CoA dehydrogenase
	Motif	721 – 723	3	Microbody targeting signal
Sites
	Binding site	101	1	Substrate; via amide nitrogen By similarity
	Site	124	1	Important for catalytic activity By similarity
Amino acid modifications
	Modified residue	359	1	Phosphoserine Ref.8
	Modified residue	584	1	N6-acetyllysine Ref.10
Natural variations
	Natural variant	40	1	V → G: dbSNP rs1062551. Ref.1		VAR_054329
	Natural variant	41	1	I → R: dbSNP rs1062552. Ref.1		VAR_054330
	Natural variant	75	1	T → I: dbSNP rs1062553. Ref.1		VAR_047132
	Natural variant	274	1	A → T: dbSNP rs2302819. Ref.3		VAR_047133
	Natural variant	325	1	A → G: dbSNP rs1062555. Ref.1		VAR_054331
	Natural variant	598	1	K → T: dbSNP rs1042437. Ref.1 Ref.7		VAR_054332
	Natural variant	606	1	T → P: dbSNP rs1042438. Ref.1 Ref.7		VAR_047134
	Natural variant	685	1	Q → K: dbSNP rs11919970.		VAR_047135
	Natural variant	715	1	L → S: dbSNP rs11927618.		VAR_047136
Experimental info
	Sequence conflict	117	1	E → D in AAA53289. Ref.1
	Sequence conflict	656 – 657	2	WP → CA in AAA53289. Ref.1
	Sequence conflict	656 – 657	2	WP → CA in AAB19482. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q08426-1 [UniParc]. Last modified February 10, 2009. Version 3. Checksum: FC3B44B030A7BCBD	FASTA	723	79,495
	10 20 30 40 50 60 MAEYTRLHNA LALIRLRNPP VNAISTTLLR DIKEGLQKAV IDHTIKAIVI CGAEGKFSAG 70 80 90 100 110 120 ADIRGFSAPR TFGLTLGHVV DEIQRNEKPV VAAIQGMAFG GGLELALGCH YRIAHAEAQV 130 140 150 160 170 180 GLPEVTLGLL PGARGTQLLP RLTGVPAALD LITSGRRILA DEALKLGILD KVVNSDPVEE 190 200 210 220 230 240 AIRFAQRVSD QPLESRRLCN KPIQSLPNMD SIFSEALLKM RRQHPGCLAQ EACVRAVQAA 250 260 270 280 290 300 VQYPYEVGIK KEEELFLYLL QSGQARALQY AFFAERKANK WSTPSGASWK TASARPVSSV 310 320 330 340 350 360 GVVGLGTMGR GIVISFARAR IPVIAVDSDK NQLATANKMI TSVLEKEASK MQQSGHPWSG 370 380 390 400 410 420 PKPRLTSSVK ELGGVDLVIE AVFEEMSLKK QVFAELSAVC KPEAFLCTNT SALDVDEIAS 430 440 450 460 470 480 STDRPHLVIG THFFSPAHVM KLLEVIPSQY SSPTTIATVM NLSKKIKKIG VVVGNCFGFV 490 500 510 520 530 540 GNRMLNPYYN QAYFLLEEGS KPEEVDQVLE EFGFKMGPFR VSDLAGLDVG WKSRKGQGLT 550 560 570 580 590 600 GPTLLPGTPA RKRGNRRYCP IPDVLCELGR FGQKTGKGWY QYDKPLGRIH KPDPWLSKFL 610 620 630 640 650 660 SRYRKTHHIE PRTISQDEIL ERCLYSLINE AFRILGEGIA ASPEHIDVVY LHGYGWPRHK 670 680 690 700 710 720 GGPMFYASTV GLPTVLEKLQ KYYRQNPDIP QLEPSDYLKK LASQGNPPLK EWQSLAGSPS SKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of the human peroxisomal enoyl-CoA hydratase: 3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme and localization to chromosome 3q26.3-3q28: a free left Alu Arm is inserted in the 3' noncoding region." Hoefler G., Forstner M., McGuinness M.C., Hulla W., Hiden M., Krisper P., Kenner L., Ried T., Lengauer C., Zechner R., Moser H.W., Chen G.L. Genomics 19:60-67(1994) [PubMed: 8188243] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLY-40; ARG-41; ILE-75; GLY-325; THR-598 AND PRO-606. Tissue: Liver.
[2]	"Structural organization of gene for human peroxisomal enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase: L-bifunctional enzyme (L-PBE)." Cherkaoui-Malki M., Surapureddi S., Yeldandi A.V., Rao S.M., Zhu Y., Reddy J.K. Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-274. Tissue: Placenta.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Uterus.
[7]	"Import of human bifunctional enzyme into peroxisomes of human hepatoma cells in vitro." Chen G.L., Balfe A., Erwa W., Hoefler G., Gaertner J., Aikawa J., Chen W.W. Biochem. Biophys. Res. Commun. 178:1084-1091(1991) [PubMed: 1651711] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 502-723, VARIANTS THR-598 AND PRO-606. Tissue: Liver.
[8]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-359, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-584, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L07077 mRNA. Translation: AAA53289.1. AJ427345 , AJ427346, AJ427347, AJ427348, AJ427349, AJ427350, AJ427351 Genomic DNA. Translation: CAD22483.1. AK291798 mRNA. Translation: BAF84487.1. AK223460 mRNA. Translation: BAD97180.1. CH471052 Genomic DNA. Translation: EAW78229.1. BC038948 mRNA. Translation: AAH38948.1. BC110460 mRNA. Translation: AAI10461.1. S50245 mRNA. Translation: AAB19482.1.
IPI	IPI00216164.
PIR	A49613.
RefSeq	NP_001159887.1. NP_001957.2.
UniGene	Hs.429879
3D structure databases
SMR	Q08426. Positions 262-717.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q08426. 1 interaction.
STRING	Q08426.
PTM databases
PhosphoSite	Q08426.
Proteomic databases
PRIDE	Q08426.
Genome annotation databases
Ensembl	ENST00000231887; ENSP00000231887; ENSG00000113790; Homo sapiens. [Genome view]
GeneID	1962.
Organism-specific databases
CTD	1962.
GeneCards	GC03M186391.
HGNC	HGNC:3247. EHHADH.
MIM	607037. gene.
Orphanet	50812. Zellweger-like syndrome, without peroxisomal anomalies.
PharmGKB	PA27682.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG691737.
HOVERGEN	Q08426.
InParanoid	Q08426.
OMA	PYYNQTY.
OrthoDB	EOG93JFQ9.
PhylomeDB	Q08426.
Enzyme and pathway databases
BRENDA	1.1.1.35. 247. 4.2.1.17. 247. 5.3.3.8. 247.
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q08426.
Bgee	Q08426.
CleanEx	HS_EHHADH.
Genevestigator	Q08426.
GermOnline	ENSG00000113790. Homo sapiens.
Family and domain databases
InterPro	IPR006180. 3-OHacyl-CoA_DH_CS. IPR006176. 3-OHacyl-CoA_DH_NAD-bd. IPR006108. 3HC_DH_C. IPR008927. 6-PGluconate_DH_C-like. IPR001753. Crotonase_core. IPR013328. DH_multihelical. IPR018376. Enoyl-CoA_hyd/isom_CS. IPR016040. NAD(P)-bd_dom. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit. G3DSA:1.10.1040.10. Opine_DH. 2 hits.
Pfam	PF00725. 3HCDH. 2 hits. PF02737. 3HCDH_N. 1 hit. PF00378. ECH. 1 hit. [Graphical view]
PROSITE	PS00067. 3HCDH. 1 hit. PS00166. ENOYL_COA_HYDRATASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00157. NADH.
SOURCE	Search...

Entry information

Entry name

ECHP_HUMAN

Accession

Primary (citable) accession number: Q08426
Secondary accession number(s): A8K6Y3, Q58EZ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	February 10, 2009
Last modified:	February 9, 2010
This is version 107 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.