Reviewed, UniProtKB/Swiss-Prot P00363 (FRDA_ECOLI)

Names and origin

Protein names

Recommended name:
    Fumarate reductase flavoprotein subunit
    EC=1.3.99.1

Gene names

Name:	frdA
Ordered Locus Names:	b4154, JW4115

Organism

Escherichia coli (strain K12) [Complete proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	602 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	Two distinct, membrane-bound, FAD-containing enzymes are responsible for the catalysis of fumarate and succinate interconversion; the fumarate reductase is used in anaerobic growth, and the succinate dehydrogenase is used in aerobic growth.
Catalytic activity	Succinate + acceptor = fumarate + reduced acceptor.
Cofactor	Binds 1 FAD covalently per subunit.
Subunit structure	Fumarate dehydrogenase forms part of an enzyme complex containing four subunits: a flavoprotein, an iron-sulfur, and two hydrophobic anchor proteins.
Sequence similarities	Belongs to the FAD-dependent oxidoreductase 2 family. FRD/SDH subfamily.

Ontologies

Keywords
Biological process	Electron transport Transport
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	anaerobic respiration Inferred from electronic annotation. Source: InterPro electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	membrane Inferred from direct assay. Source: UniProtKB
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro electron carrier activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct succinate dehydrogenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ydcZ	P76111	1	EBI-550480,EBI-550492

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 602

601

Fumarate reductase flavoprotein subunit

PRO_0000158660

Regions

Nucleotide binding

9 – 23

15

FAD Potential

Sites

Active site

233

1

Active site

249

1

Amino acid modifications

Modified residue

45

1

Tele-8alpha-FAD histidine

Experimental info

Mutagenesis

45

1

H → R: Inactivates enzyme. Ref.5

Mutagenesis

45

1

H → S, C or Y: Decreased ability (greater than 70%) to reduce fumarate. Ref.5

Mutagenesis

233

1

H → S: Severely affect succinate oxidation and decrease fumarate oxidation by 75%. Ref.6

Mutagenesis

248

1

C → S or A: Does not inactivate enzyme. Ref.6

Mutagenesis

249

1

R → H or L: Inactivates enzyme. Ref.6

Sequence conflict

386

1

L → P in AAA23437. Ref.1

Secondary structure

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602

Helix Strand Turn

Details...

Beta strand

2 – 5

4

Beta strand

7 – 11

5

Helix

15 – 27

13

Beta strand

33 – 39

7

Helix

41 – 43

3

Helix

45 – 48

4

Helix

63 – 73

11

Turn

74 – 76

3

Helix

80 – 99

20

Beta strand

110 – 112

3

Helix

132 – 144

13

Beta strand

150 – 154

5

Beta strand

156 – 164

9

Beta strand

167 – 175

9

Turn

176 – 179

4

Beta strand

180 – 185

6

Beta strand

189 – 191

3

Helix

197 – 199

3

Beta strand

200 – 205

6

Helix

212 – 218

7

Turn

219 – 221

3

Beta strand

224 – 226

3

Beta strand

230 – 236

7

Turn

238 – 240

3

Helix

247 – 250

4

Beta strand

254 – 256

3

Helix

263 – 266

4

Turn

267 – 269

3

Helix

283 – 285

3

Helix

288 – 301

14

Beta strand

312 – 316

5

Helix

318 – 320

3

Helix

322 – 328

7

Helix

330 – 340

11

Turn

344 – 346

3

Beta strand

349 – 358

10

Beta strand

361 – 363

3

Beta strand

371 – 373

3

Beta strand

375 – 377

3

Helix

379 – 381

3

Beta strand

385 – 387

3

Helix

395 – 416

22

Helix

423 – 442

20

Helix

449 – 463

15

Beta strand

464 – 468

5

Helix

470 – 487

18

Helix

501 – 525

25

Turn

545 – 547

3

Beta strand

550 – 556

7

Beta strand

562 – 568

7

Sequences

	Sequence		Length	Mass (Da)
	P00363-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 3306D7FF6E198AE9	FASTA	602	65,972
	10 20 30 40 50 60 MQTFQADLAI VGAGGAGLRA AIAAAQANPN AKIALISKVY PMRSHTVAAE GGSAAVAQDH 70 80 90 100 110 120 DSFEYHFHDT VAGGDWLCEQ DVVDYFVHHC PTEMTQLELW GCPWSRRPDG SVNVRRFGGM 130 140 150 160 170 180 KIERTWFAAD KTGFHMLHTL FQTSLQFPQI QRFDEHFVLD ILVDDGHVRG LVAMNMMEGT 190 200 210 220 230 240 LVQIRANAVV MATGGAGRVY RYNTNGGIVT GDGMGMALSH GVPLRDMEFV QYHPTGLPGS 250 260 270 280 290 300 GILMTEGCRG EGGILVNKNG YRYLQDYGMG PETPLGEPKN KYMELGPRDK VSQAFWHEWR 310 320 330 340 350 360 KGNTISTPRG DVVYLDLRHL GEKKLHERLP FICELAKAYV GVDPVKEPIP VRPTAHYTMG 370 380 390 400 410 420 GIETDQNCET RIKGLFAVGE CSSVGLHGAN RLGSNSLAEL VVFGRLAGEQ ATERAATAGN 430 440 450 460 470 480 GNEAAIEAQA AGVEQRLKDL VNQDGGENWA KIRDEMGLAM EEGCGIYRTP ELMQKTIDKL 490 500 510 520 530 540 AELQERFKRV RITDTSSVFN TDLLYTIELG HGLNVAECMA HSAMARKESR GAHQRLDEGC 550 560 570 580 590 600 TERDDVNFLK HTLAFRDADG TTRLEYSDVK ITTLPPAKRV YGGEADAADK AEAANKKEKA NG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence coding for the flavoprotein subunit of the fumarate reductase of Escherichia coli." Cole S.T. Eur. J. Biochem. 122:479-484(1982) [PubMed: 7037404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[2]	"Analysis of the Escherichia coli genome VI: DNA sequence of the region from 92.8 through 100 minutes." Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L., Blattner F.R. Nucleic Acids Res. 23:2105-2119(1995) [PubMed: 7610040] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[3]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed: 9278503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]	"Fumarate reductase mutants of Escherichia coli that lack covalently bound flavin." Blaut M., Whittaker K., Valdovinos A., Ackrell B.A., Gunsalus R.P., Cecchini G. J. Biol. Chem. 264:13599-13604(1989) [PubMed: 2668268] [Abstract] Cited for: MUTAGENESIS OF HIS-45.
[6]	"Identification of active site residues of Escherichia coli fumarate reductase by site-directed mutagenesis." Schroeder I., Gunsalus R.P., Ackrell B.A.C., Cochran B., Cecchini G. J. Biol. Chem. 266:13572-13579(1991) [PubMed: 1856194] [Abstract] Cited for: MUTAGENESIS OF HIS-233; CYS-248 AND ARG-249.
[7]	"Replacement of the proximal heme thiolate ligand in chloroperoxidase with a histidine residue." Yi X., Mroczko M., Manoj K.M., Wang X., Hager L.P. Proc. Natl. Acad. Sci. U.S.A. 96:12412-12417(1999) [PubMed: 10535936] [Abstract] Cited for: MUTAGENESIS OF CYS-51.
[8]	"Structure of the Escherichia coli fumarate reductase respiratory complex." Iverson T.M., Luna-Chavez C., Cecchini G., Rees D.C. Science 284:1961-1966(1999) [PubMed: 10373108] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS).
[9]	"Crystallographic studies of the Escherichia coli quinol-fumarate reductase with inhibitors bound to the quinol-binding site." Iverson T.M., Luna-Chavez C., Croal L.R., Cecchini G., Rees D.C. J. Biol. Chem. 277:16124-16130(2002) [PubMed: 11850430] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

J01611 Genomic DNA. Translation: AAA23437.1.
U14003 Genomic DNA. Translation: AAA97053.1.
U00096 Genomic DNA. Translation: AAC77114.1.
AP009048 Genomic DNA. Translation: BAE78158.1.

PIR

RDECFF. A00376.

RefSeq

AP_004657.1.
NP_418578.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KF6	X-ray	2.70	A/M	1-602	[»]
1KFY	X-ray	3.60	A/M	1-602	[»]
1L0V	X-ray	3.30	A/M	1-602	[»]
2B76	X-ray	3.30	A/M	1-602	[»]
3CIR	X-ray	3.65	A/M	1-602	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:9681N.

IntAct

P00363. 14 interactions.

2-D gel databases

ECO2DBASE

G063.2. 6TH EDITION.

Genome annotation databases

GeneID

948667.

GenomeReviews

Gene locus JW4115 in contig AP009048_GR.
Gene locus b4154 in contig U00096_GR.

KEGG

ecj:JW4115.
eco:b4154.

Organism-specific databases

EchoBASE

EB0326.

EcoGene

EG10330. frdA.

CMR

Search...

Phylogenomic databases

HOGENOM

P00363.

OMA

P00363. CMAHSAI.

Enzyme and pathway databases

BioCyc

EcoCyc:FUM-FLAVO.
MetaCyc:FUM-FLAVO.

Family and domain databases

InterPro

IPR003953. FAD_bind2_N.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR003952. FRD_SDH_FAD_BS.
IPR004112. Fum_Rdtase/Succ_DH_flav_C.
IPR005884. Fum_red_fp.
IPR014006. Succ_Dhase_frdA_Gneg.
[Graphical view]

Pfam

PF00890. FAD_binding_2. 1 hit.
PF02910. Succ_DH_flav_C. 1 hit.
[Graphical view]

PRINTS

PR00368. FADPNR.

TIGRFAMs

TIGR01176. fum_red_Fp. 1 hit.
TIGR01812. sdhA_frdA_Gneg. 1 hit.

PROSITE

PS00504. FRD_SDH_FAD_BINDING. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00730. Thiabendazole.

Entry information

Entry name

FRDA_ECOLI

Accession

Primary (citable) accession number: P00363
Secondary accession number(s): Q2M6E8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 111 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)