Reviewed, UniProtKB/Swiss-Prot Q58991 (AKSF_METJA)

Names and origin

Protein names

Recommended name:
    Homoisocitrate dehydrogenase
      Short name=HICDH
    EC=1.1.1.87
Alternative name(s):
    Isohomocitrate dehydrogenase
      Short name=IHDH
    NAD-dependent threo-isohomocitrate dehydrogenase

Gene names

Name:	aksF
Synonyms:	icd
Ordered Locus Names:	MJ1596

Organism

Methanocaldococcus jannaschii (Methanococcus jannaschii) [Complete proteome] [HAMAP]

Taxonomic identifier

2190 [NCBI]

Taxonomic lineage

Archaea › Euryarchaeota › Methanococci › Methanococcales › Methanocaldococcaceae › Methanocaldococcus

Protein attributes

Sequence length	347 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the NAD-dependent oxidation and decarboxylation of (2R,3S)-homoisocitrate ((1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate), (2R,3S)-homo(2)-isocitrate and (2R,3S)-homo(3)-isocitrate, into 2-oxoadipate, 2-oxopimelate, and 2-oxosuberate, respectively. This last compound is a precursor to coenzyme B and biotin in methanoarchaea. Is also able to produce 2-oxoazelate from (2R,3S)-homo(4)-isocitrate. Is not able to use NADP as an oxidant. Ref.1
Catalytic activity	(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+ = 2-oxoadipate + CO2 + NADH. Ref.1
Cofactor	Binds 1 magnesium or manganese ion per subunit By similarity.
Pathway	Organic acid metabolism; 2-ketosuberic acid biosynthesis.
Sequence similarities	Belongs to the isocitrate and isopropylmalate dehydrogenases family.
Biophysicochemical properties	Kinetic parameters: KM=0.037 mM for (2R,3S)-homoisocitrate KM=0.016 mM for (2R,3S)-homo(2)-isocitrate KM=0.021 mM for (2R,3S)-homo(3)-isocitrate Vmax=2.6 µmol/min/mg enzyme with (2R,3S)-homoisocitrate as substrate Vmax=8.7 µmol/min/mg enzyme with (2R,3S)-homo(2)-isocitrate as substrate Vmax=7.1 µmol/min/mg enzyme with (2R,3S)-homo(3)-isocitrate as substrate Temperature dependence: Stable at 100 degrees Celsius for 10 min.

Ontologies

Keywords
Ligand	Magnesium Manganese Metal-binding NAD
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	leucine biosynthetic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	3-isopropylmalate dehydrogenase activity Inferred from electronic annotation. Source: InterPro NAD or NADH binding Inferred from electronic annotation. Source: InterPro homoisocitrate dehydrogenase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 347	347	Homoisocitrate dehydrogenase		PRO_0000083574
Sites
	Metal binding	213	1	Magnesium or manganese By similarity
	Metal binding	237	1	Magnesium or manganese By similarity
	Metal binding	241	1	Magnesium or manganese By similarity
	Binding site	81	1	Substrate By similarity
	Binding site	87	1	Substrate By similarity
	Binding site	97	1	Substrate By similarity
	Binding site	128	1	Substrate By similarity
	Binding site	213	1	Substrate By similarity
	Site	135	1	Critical for catalysis By similarity
	Site	181	1	Critical for catalysis By similarity
Amino acid modifications
	Modified residue	81	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	77	1	K → Q in AAB99614. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q58991-1 [UniParc]. Last modified March 24, 2009. Version 3. Checksum: 20D7BF9FDA451116	FASTA	347	38,536
	10 20 30 40 50 60 MMKVCVIEGD GIGKEVIPEA IKILNELGEF EIIKGEAGLE CLKKYGNALP EDTIEKAKEA 70 80 90 100 110 120 DIILFGAITS PKPGEVKNYK SPIITLRKMF HLYANVRPIN NFGIGQLIGK IADYEFLNAK 130 140 150 160 170 180 NIDIVIIREN TEDLYVGRER LENDTAIAER VITRKGSERI IRFAFEYAIK NNRKKVSCIH 190 200 210 220 230 240 KANVLRITDG LFLEVFNEIK KHYNIEADDY LVDSTAMNLI KHPEKFDVIV TTNMFGDILS 250 260 270 280 290 300 DEASALIGGL GLAPSANIGD DKALFEPVHG SAPDIAGKGI ANPMASILSI AMLFDYIGEK 310 320 330 340 EKGDLIREAV KYCLINKKVT PDLGGDLKTK DVGDEILNYI RKKLKGY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Methanogen homoaconitase catalyzes both hydrolyase reactions in coenzyme B biosynthesis." Drevland R.M., Jia Y., Palmer D.R.J., Graham D.E. J. Biol. Chem. 283:28888-28896(2008) [PubMed: 18765671] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY. Strain: ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440.
[2]	"Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii." Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G., Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R., Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R., Kirkness E.F., Weinstock K.G. , Merrick J.M., Glodek A., Scott J.L., Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R., Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D., Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P., Fraser C.M., Smith H.O., Woese C.R., Venter J.C. Science 273:1058-1073(1996) [PubMed: 8688087] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440.
[3]	"Identification of enzymes homologous to isocitrate dehydrogenase that are involved in coenzyme B and leucine biosynthesis in methanoarchaea." Howell D.M., Graupner M., Xu H., White R.H. J. Bacteriol. 182:5013-5016(2000) [PubMed: 10940051] [Abstract] Cited for: CHARACTERIZATION, BIOPHYSICOCHEMICAL PROPERTIES.

Cross-references

Sequence databases
EMBLGenBankDDBJ	EU447775 Genomic DNA. Translation: ACA28837.1. L77117 Genomic DNA. Translation: AAB99614.1.
RefSeq	NP_248605.1.
3D structure databases
HSSP	HSSP built from PDB template 1IPD based on UniProtKB P00351.
ModBase	Search...
Genome annotation databases
GeneID	1452504.
GenomeReviews	Gene locus MJ1596 in contig L77117_GR.
KEGG	mja:MJ1596.
NMPDR	fig|243232.1.peg.1642.
TIGR	MJ1596.
Phylogenomic databases
HOGENOM	Q58991.
Enzyme and pathway databases
BioCyc	MetaCyc:MON-2004. MJAN243232:MJ_1596-MON.
Family and domain databases
InterPro	IPR019818. IsoCit/isopropylmalate_DH_CS. IPR001804. Isocitrate/isopropylmalate_DH. IPR011828. LEU3_arc. [Graphical view]
Gene3D	G3DSA:3.40.718.10. IDH_IMDH. 1 hit.
PANTHER	PTHR11835. IDH_IMDH_dimeric. 1 hit.
Pfam	PF00180. Iso_dh. 1 hit. [Graphical view]
TIGRFAMs	TIGR02088. LEU3_arch. 1 hit.
PROSITE	PS00470. IDH_IMDH. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

AKSF_METJA

Accession

Primary (citable) accession number: Q58991
Secondary accession number(s): B1PL93

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	March 24, 2009
Last modified:	June 16, 2009
This is version 64 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)