P0A5H3 (ACEA_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Isocitrate lyase
Short name=ICL
Short name=Isocitrase
Short name=Isocitratase
EC=4.1.3.1

Gene names

Name:	icl
Ordered Locus Names:	Rv0467, MT0483
ORF Names:	MTV038.11

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	428 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle. May be involved in the assimilation of one-carbon compounds via the isocitrate lyase-positive serine pathway By similarity.
Catalytic activity	Isocitrate = succinate + glyoxylate.
Pathway	Carbohydrate metabolism; glyoxylate cycle; (S)-malate from isocitrate: step 1/2.
Subunit structure	Homotetramer By similarity.
Subcellular location	Cytoplasm.
Post-translational modification	Pupylated at Lys-334 by the prokaryotic ubiquitin-like protein Pup, which leads to its degradation by the proteasome. Ref.3
Miscellaneous	Was identified as a natural substrate of the M.tuberculosis proteasome.
Sequence similarities	Belongs to the isocitrate lyase/PEP mutase superfamily. Isocitrate lyase family.

Ontologies

Keywords
Biological process	Glyoxylate bypass Tricarboxylic acid cycle
Cellular component	Cytoplasm
Molecular function	Lyase
PTM	Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to hypoxia Inferred from expression pattern PubMed 18434250. Source: MTBBASE glyoxylate cycle Inferred from direct assay PubMed 10572116. Source: MTBBASE isocitrate metabolic process Inferred from direct assay PubMed 10572116. Source: MTBBASE maintenance of symbiont tolerance to host environment Inferred from mutant phenotype PubMed 10963599. Source: MTBBASE pathogenesis Inferred from direct assay PubMed 21203517. Source: MTBBASE response to acetate Inferred from direct assay PubMed 10572116. Source: MTBBASE response to acid Inferred from expression pattern PubMed 12081975. Source: MTBBASE response to fatty acid Inferred from direct assay PubMed 10572116. Source: MTBBASE response to host immune response Inferred from expression pattern PubMed 10500215PubMed 12010964PubMed 12953091. Source: MTBBASE tricarboxylic acid cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Inferred from direct assay PubMed 15525680. Source: MTBBASE plasma membrane Inferred from direct assay PubMed 15525680. Source: MTBBASE
Molecular_function	isocitrate lyase activity Inferred from direct assay PubMed 10572116PubMed 16689789. Source: MTBBASE methylisocitrate lyase activity Inferred from direct assay PubMed 16689789PubMed 16879647. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 428

428

Isocitrate lyase

PRO_0000068779

Sites

Active site

191

1

Amino acid modifications

Cross-link

334

Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-Cter in protein Pup)

Secondary structure

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428

Helix Strand Turn

Details...

Helix

10 – 19

10

Helix

21 – 23

3

Helix

32 – 38

7

Helix

47 – 62

16

Beta strand

66 – 70

5

Helix

74 – 82

9

Beta strand

88 – 90

3

Helix

92 – 98

7

Beta strand

108 – 110

3

Helix

116 – 138

23

Beta strand

150 – 153

4

Turn

155 – 158

4

Helix

161 – 173

13

Beta strand

177 – 182

6

Helix

186 – 188

3

Helix

202 – 218

17

Beta strand

224 – 229

6

Turn

231 – 233

3

Beta strand

236 – 238

3

Turn

243 – 245

3

Helix

246 – 248

3

Beta strand

249 – 253

5

Beta strand

259 – 261

3

Helix

265 – 275

11

Helix

276 – 278

3

Beta strand

280 – 284

5

Helix

291 – 302

12

Beta strand

309 – 313

5

Beta strand

316 – 318

3

Helix

320 – 323

4

Helix

326 – 338

13

Beta strand

341 – 346

6

Helix

349 – 368

20

Helix

370 – 383

14

Helix

384 – 386

3

Helix

393 – 396

4

Helix

399 – 409

11

Helix

422 – 426

5

Sequences

	Sequence		Length	Mass (Da)
	P0A5H3 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: E5223F38CB5D9E8B	FASTA	428	47,087
	10 20 30 40 50 60 MSVVGTPKSA EQIQQEWDTN PRWKDVTRTY SAEDVVALQG SVVEEHTLAR RGAEVLWEQL 70 80 90 100 110 120 HDLEWVNALG ALTGNMAVQQ VRAGLKAIYL SGWQVAGDAN LSGHTYPDQS LYPANSVPQV 130 140 150 160 170 180 VRRINNALQR ADQIAKIEGD TSVENWLAPI VADGEAGFGG ALNVYELQKA LIAAGVAGSH 190 200 210 220 230 240 WEDQLASEKK CGHLGGKVLI PTQQHIRTLT SARLAADVAD VPTVVIARTD AEAATLITSD 250 260 270 280 290 300 VDERDQPFIT GERTREGFYR TKNGIEPCIA RAKAYAPFAD LIWMETGTPD LEAARQFSEA 310 320 330 340 350 360 VKAEYPDQML AYNCSPSFNW KKHLDDATIA KFQKELAAMG FKFQFITLAG FHALNYSMFD 370 380 390 400 410 420 LAYGYAQNQM SAYVELQERE FAAEERGYTA TKHQREVGAG YFDRIATTVD PNSSTTALTG STEEGQFH

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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Prokayrotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis." Festa R.A., McAllister F., Pearce M.J., Mintseris J., Burns K.E., Gygi S.P., Darwin K.H. PLoS ONE 5:E8589-E8589(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEASOME SUBSTRATE, PUPYLATION AT LYS-334, IDENTIFICATION BY MASS SPECTROMETRY. Strain: ATCC 25618 / H37Rv.
[4]	"Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis." Sharma V., Sharma S., zu Bentrup K.H., McKinney J.D., Russell D.G., Jacobs W.R. Jr., Sacchettini J.C. Nat. Struct. Biol. 7:663-668(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842573 Genomic DNA. Translation: CAE55284.1.
AE000516 Genomic DNA. Translation: AAK44707.1.
AL123456 Genomic DNA. Translation: CCP43200.1.

PIR

G70828.

RefSeq

NP_334893.1. NC_002755.2.
YP_006513796.1. NC_018143.1.
YP_177728.1. NC_000962.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F61	X-ray	2.00	A/B	2-428	[»]
1F8I	X-ray	2.25	A/B/C/D	2-428	[»]
1F8M	X-ray	1.80	A/B/C/D	2-428	[»]

ProteinModelPortal

P0A5H3.

SMR

P0A5H3. Positions 2-427.

ModBase

Search...

Protein-protein interaction databases

STRING

83332.Rv0467.

Proteomic databases

PaxDb

P0A5H3.

PRIDE

P0A5H3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK44707; AAK44707; MT0483.

GeneID

13318337.
886291.
923830.

KEGG

mtc:MT0483.
mtu:Rv0467.
mtv:RVBD_0467.

PATRIC

18122774. VBIMycTub22151_0521.

Organism-specific databases

TubercuList

Rv0467.

Phylogenomic databases

eggNOG

COG2224.

HOGENOM

HOG000238475.

KO

K01637.

OMA

QAVQQVK.

ProtClustDB

PRK15063.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-11952.

UniPathway

UPA00703; UER00719.

Family and domain databases

Gene3D

3.20.20.60. 1 hit.

InterPro

IPR006254. Isocitrate_lyase.
IPR000918. Isocitrate_lyase/Pmutase.
IPR018523. Isocitrate_lyase_ph_CS.
IPR015813. Pyrv/PenolPyrv_Kinase.
[Graphical view]

PANTHER

PTHR21631:SF3. PTHR21631:SF3. 1 hit.

Pfam

PF00463. ICL. 1 hit.
[Graphical view]

PIRSF

PIRSF001362. Isocit_lyase. 1 hit.

SUPFAM

SSF51621. Pyrv/PenolPyrv_Kinase_cat. 1 hit.

TIGRFAMs

TIGR01346. isocit_lyase. 2 hits.

PROSITE

PS00161. ISOCITRATE_LYASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P0A5H3.

ChEMBL

CHEMBL1667699.

EvolutionaryTrace

P0A5H3.

Entry information

Entry name

ACEA_MYCTU

Accession

Primary (citable) accession number: P0A5H3
Secondary accession number(s): L0T3N9, O53752

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	May 1, 2013
This is version 62 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program