P0A574 (FABH_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
3-oxoacyl-[acyl-carrier-protein] synthase 3
EC=2.3.1.180

Alternative name(s):
3-oxoacyl-[acyl-carrier-protein] synthase III
Beta-ketoacyl-ACP synthase III
Short name=KAS III
MtFabH

Gene names

Name:	fabH
Ordered Locus Names:	Rv0533c, MT0557
ORF Names:	MTCY25D10.12c

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	335 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for long chain acyl-CoA such as myristoyl-CoA. Does not use acyl-CoA as primer. Its substrate specificity determines the biosynthesis of mycolic acid fatty acid chain, which is characteristic of mycobacterial cell wall. Ref.3
Catalytic activity	Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacetyl-[acyl-carrier-protein] + CoA + CO2. HAMAP MF_01815
Pathway	Lipid metabolism; fatty acid biosynthesis. HAMAP MF_01815
Subunit structure	Homodimer.
Subcellular location	Cytoplasm HAMAP MF_01815.
Domain	The last Arg residue of the ACP-binding site is essential for the weak association between ACP/AcpP and FabH By similarity. HAMAP MF_01815
Miscellaneous	Inhibited by thiolactomycin. Not sensitive to cerulenin. HAMAP MF_01815 Was identified as a high-confidence drug target. HAMAP MF_01815
Sequence similarities	Belongs to the FabH family.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Lipid synthesis
Cellular component	Cytoplasm
Molecular function	Acyltransferase Transferase
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	fatty acid elongation Inferred from direct assay Ref.3. Source: MTBBASE long-chain fatty-acyl-CoA metabolic process Inferred from direct assay. Source: MTBBASE
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	3-oxoacyl-[acyl-carrier-protein] synthase activity Inferred from direct assay Ref.5. Source: MTBBASE beta-ketoacyl-acyl-carrier-protein synthase III activity Inferred from direct assay Ref.3. Source: MTBBASE fatty-acyl-CoA binding Inferred from direct assay. Source: MTBBASE protein homodimerization activity Inferred from physical interaction Ref.5. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 335

335

3-oxoacyl-[acyl-carrier-protein] synthase 3 HAMAP MF_01815

PRO_0000110443

Regions

Region

259 – 263

5

ACP-binding By similarity

Sites

Active site

122

1

Active site

258

1

Active site

289

1

Secondary structure

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335

Helix Strand Turn

Details...

Beta strand

13 – 21

9

Beta strand

24 – 28

5

Helix

29 – 32

4

Beta strand

35 – 37

3

Helix

40 – 47

8

Beta strand

50 – 54

5

Helix

61 – 75

15

Helix

80 – 82

3

Beta strand

85 – 89

5

Beta strand

96 – 98

3

Helix

100 – 107

8

Beta strand

114 – 119

6

Helix

121 – 123

3

Helix

124 – 137

14

Beta strand

142 – 151

10

Helix

153 – 155

3

Turn

161 – 166

6

Beta strand

169 – 178

10

Beta strand

188 – 191

4

Helix

193 – 198

6

Beta strand

199 – 203

5

Helix

205 – 209

5

Beta strand

219 – 221

3

Helix

223 – 244

22

Helix

249 – 251

3

Beta strand

254 – 257

4

Helix

262 – 271

10

Helix

284 – 287

4

Helix

291 – 293

3

Helix

294 – 304

11

Beta strand

313 – 320

8

Turn

321 – 323

3

Beta strand

324 – 331

8

Sequences

	Sequence		Length	Mass (Da)
	P0A574 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: 6573BE1FAE5BCFB6	FASTA	335	34,873
	10 20 30 40 50 60 MTEIATTSGA RSVGLLSVGA YRPERVVTND EICQHIDSSD EWIYTRTGIK TRRFAADDES 70 80 90 100 110 120 AASMATEACR RALSNAGLSA ADIDGVIVTT NTHFLQTPPA APMVAASLGA KGILGFDLSA 130 140 150 160 170 180 GCAGFGYALG AAADMIRGGG AATMLVVGTE KLSPTIDMYD RGNCFIFADG AAAVVVGETP 190 200 210 220 230 240 FQGIGPTVAG SDGEQADAIR QDIDWITFAQ NPSGPRPFVR LEGPAVFRWA AFKMGDVGRR 250 260 270 280 290 300 AMDAAGVRPD QIDVFVPHQA NSRINELLVK NLQLRPDAVV ANDIEHTGNT SAASIPLAMA 310 320 330 ELLTTGAAKP GDLALLIGYG AGLSYAAQVV RMPKG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed: 9634230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Identification and substrate specificity of beta -ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis." Choi K.-H., Kremer L., Besra G.S., Rock C.O. J. Biol. Chem. 275:28201-28207(2000) [PubMed: 10840036] [Abstract] Cited for: FUNCTION, SUBSTRATE SPECIFICITY.
[4]	"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed: 19099550] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
[5]	"Crystal structure of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III." Scarsdale J.N., Kazanina G., He X., Reynolds K.A., Wright H.T. J. Biol. Chem. 276:20516-20522(2001) [PubMed: 11278743] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[6]	"X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (MtFabH)." Sacchettini J.C., Sridharan S. Submitted (JUN-2002) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842573 Genomic DNA. Translation: CAB08984.1.
AE000516 Genomic DNA. Translation: AAK44780.1.

PIR

H70545.

RefSeq

NP_215047.1. NC_000962.2.
NP_334966.1. NC_002755.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HZP	X-ray	2.10	A/B	1-335	[»]
1M1M	X-ray	2.70	A/B	1-335	[»]
1U6E	X-ray	1.85	A/B	1-334	[»]
1U6S	X-ray	2.30	A/B	1-335	[»]
2AHB	X-ray	2.00	A/B	1-335	[»]
2AJ9	X-ray	2.50	A/B	1-335	[»]
2QNX	X-ray	2.70	A/B	1-335	[»]
2QNY	X-ray	2.15	A/B	1-335	[»]
2QNZ	X-ray	2.30	A/B	1-335	[»]
2QO0	X-ray	1.85	A/B	1-335	[»]
2QO1	X-ray	2.60	A/B	1-335	[»]
2QX1	X-ray	2.60	A/B	1-335	[»]

ProteinModelPortal

P0A574.

SMR

P0A574. Positions 1-334.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBMYCT00000003040; EBMYCP00000003040; EBMYCG00000003038.
EBMYCT00000070625; EBMYCP00000068684; EBMYCG00000070620.

GeneID

887381.
924839.

GenomeReviews

Gene locus MT0557 in contig AE000516_GR.
Gene locus Rv0533c in contig AL123456_GR.

KEGG

mtc:MT0557.
mtu:Rv0533c.

PATRIC

18122930. VBIMycTub22151_0599.

TIGR

MT0557.

Organism-specific databases

TubercuList

Rv0533c.

Phylogenomic databases

GeneTree

EBGT00050000016069.

HOGENOM

HBG649927.

OMA

TIWGSDG.

PhylomeDB

P0A574.

ProtClustDB

PRK09352.

Family and domain databases

HAMAP

MF_01815. FabH.
[Tree]

InterPro

IPR013751. ACP_syn_III.
IPR013747. ACP_syn_III_C.
IPR004655. FabH_synth.
IPR016039. Thiolase-like.
IPR016038. Thiolase-like_subgr.
[Graphical view]

Gene3D

G3DSA:3.40.47.10. Thiolase-like_subgr. 2 hits.

KO

K11608.

Pfam

PF08545. ACP_syn_III. 1 hit.
PF08541. ACP_syn_III_C. 1 hit.
[Graphical view]

SUPFAM

SSF53901. Thiolase-like. 1 hit.

TIGRFAMs

TIGR00747. FabH. 1 hit.

ProtoNet

Search...

Entry information

Entry name

FABH_MYCTU

Accession

Primary (citable) accession number: P0A574
Secondary accession number(s): O06399

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	January 25, 2012
This is version 56 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program