P48735 (IDHP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Isocitrate dehydrogenase [NADP], mitochondrial
Short name=IDH
EC=1.1.1.42

Alternative name(s):
ICD-M
IDP
NADP(+)-specific ICDH
Oxalosuccinate decarboxylase

Gene names

Name:

IDH2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	452 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	Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex.
Catalytic activity	Isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH.
Cofactor	Binds 1 magnesium or manganese ion per subunit By similarity.
Subunit structure	Homodimer.
Subcellular location	Mitochondrion.
Involvement in disease	D-2-hydroxyglutaric aciduria 2 (D2HGA2) [MIM:613657]: A neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Ontologies

Keywords
Biological process	Glyoxylate bypass Tricarboxylic acid cycle
Cellular component	Mitochondrion
Disease	Disease mutation
Domain	Transit peptide
Ligand	Magnesium Manganese Metal-binding NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	2-oxoglutarate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB carbohydrate metabolic process Non-traceable author statement PubMed 8954790. Source: ProtInc glyoxylate cycle Inferred from electronic annotation. Source: UniProtKB-KW isocitrate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB tricarboxylic acid cycle Traceable author statement. Source: Reactome
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: Compara mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	NAD binding Inferred from electronic annotation. Source: InterPro isocitrate dehydrogenase (NADP+) activity Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 39	39	Mitochondrion By similarity
	Chain	40 – 452	413	Isocitrate dehydrogenase [NADP], mitochondrial		PRO_0000014420
Regions
	Nucleotide binding	115 – 117	3	NADP By similarity
	Nucleotide binding	349 – 354	6	NADP By similarity
	Region	134 – 140	7	Substrate binding By similarity
Sites
	Metal binding	291	1	Magnesium or manganese By similarity
	Metal binding	314	1	Magnesium or manganese By similarity
	Binding site	117	1	Substrate By similarity
	Binding site	122	1	NADP By similarity
	Binding site	149	1	Substrate By similarity
	Binding site	172	1	Substrate By similarity
	Binding site	299	1	NADP By similarity
	Binding site	367	1	NADP; via amide nitrogen and carbonyl oxygen By similarity
	Site	179	1	Critical for catalysis By similarity
	Site	251	1	Critical for catalysis By similarity
Amino acid modifications
	Modified residue	67	1	N6-acetyllysine Ref.5
	Modified residue	106	1	N6-acetyllysine Ref.5
	Modified residue	155	1	N6-acetyllysine Ref.5
	Modified residue	166	1	N6-acetyllysine Ref.5
	Modified residue	180	1	N6-acetyllysine Ref.5
	Modified residue	256	1	N6-acetyllysine Ref.5
	Modified residue	263	1	N6-acetyllysine Ref.5
	Modified residue	272	1	N6-acetyllysine Ref.5
	Modified residue	275	1	N6-acetyllysine Ref.5
	Modified residue	282	1	N6-acetyllysine Ref.5
	Modified residue	442	1	N6-acetyllysine Ref.5
Natural variations
	Natural variant	140	1	R → G in D2HGA2. Ref.7		VAR_065174
	Natural variant	140	1	R → Q in D2HGA2. Ref.7		VAR_065175
Experimental info
	Sequence conflict	34	1	Q → H in CAA49208. Ref.1
	Sequence conflict	435	1	T → M in CAA49208. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P48735 [UniParc]. Last modified April 3, 2002. Version 2. Checksum: 4DDC830AFC06AB52	FASTA	452	50,909
	10 20 30 40 50 60 MAGYLRVVRS LCRASGSRPA WAPAALTAPT SQEQPRRHYA DKRIKVAKPV VEMDGDEMTR 70 80 90 100 110 120 IIWQFIKEKL ILPHVDIQLK YFDLGLPNRD QTDDQVTIDS ALATQKYSVA VKCATITPDE 130 140 150 160 170 180 ARVEEFKLKK MWKSPNGTIR NILGGTVFRE PIICKNIPRL VPGWTKPITI GRHAHGDQYK 190 200 210 220 230 240 ATDFVADRAG TFKMVFTPKD GSGVKEWEVY NFPAGGVGMG MYNTDESISG FAHSCFQYAI 250 260 270 280 290 300 QKKWPLYMST KNTILKAYDG RFKDIFQEIF DKHYKTDFDK NKIWYEHRLI DDMVAQVLKS 310 320 330 340 350 360 SGGFVWACKN YDGDVQSDIL AQGFGSLGLM TSVLVCPDGK TIEAEAAHGT VTRHYREHQK 370 380 390 400 410 420 GRPTSTNPIA SIFAWTRGLE HRGKLDGNQD LIRFAQMLEK VCVETVESGA MTKDLAGCIH 430 440 450 GLSNVKLNEH FLNTTDFLDT IKSNLDRALG RQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Huh T.-L., Oh I.-U., Kim Y.O., Huh J.-W., Song B.J. Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[3]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon and Skin.
[5]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-67; LYS-106; LYS-155; LYS-166; LYS-180; LYS-256; LYS-263; LYS-272; LYS-275; LYS-282 AND LYS-442, MASS SPECTROMETRY.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"IDH2 mutations in patients with D-2-hydroxyglutaric aciduria." Kranendijk M., Struys E.A., van Schaftingen E., Gibson K.M., Kanhai W.A., van der Knaap M.S., Amiel J., Buist N.R., Das A.M., de Klerk J.B., Feigenbaum A.S., Grange D.K., Hofstede F.C., Holme E., Kirk E.P., Korman S.H., Morava E., Morris A. , Smeitink J., Sukhai R.N., Vallance H., Jakobs C., Salomons G.S. Science 330:336-336(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS D2HGA2 GLN-140 AND GLY-140.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X69433 mRNA. Translation: CAA49208.1. AK312627 mRNA. Translation: BAG35513.1. CH471101 Genomic DNA. Translation: EAX02082.1. BC009244 mRNA. Translation: AAH09244.1. BC071828 mRNA. Translation: AAH71828.1.
IPI	IPI00011107.
PIR	S57499.
RefSeq	NP_002159.2. NM_002168.2.
UniGene	Hs.596461.
3D structure databases
ProteinModelPortal	P48735.
ModBase	Search...
Protein-protein interaction databases
IntAct	P48735. 1 interaction.
STRING	9606.ENSP00000331897.
PTM databases
PhosphoSite	P48735.
Polymorphism databases
DMDM	20141568.
2D gel databases
OGP	P48735.
UCD-2DPAGE	P48735.
Proteomic databases
PaxDb	P48735.
PeptideAtlas	P48735.
PRIDE	P48735.
Protocols and materials databases
DNASU	3418.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000330062; ENSP00000331897; ENSG00000182054.
GeneID	3418.
KEGG	hsa:3418.
UCSC	uc002box.3. human.
Organism-specific databases
CTD	3418.
GeneCards	GC15M090626.
HGNC	HGNC:5383. IDH2.
HPA	HPA007831.
MIM	147650. gene. 613657. phenotype.
neXtProt	NX_P48735.
Orphanet	79315. D-2-hydroxyglutaric aciduria.
PharmGKB	PA29631.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0538.
HOGENOM	HOG000019858.
HOVERGEN	HBG006119.
InParanoid	P48735.
KO	K00031.
OMA	QHQQGKP.
OrthoDB	EOG42V8G4.
PhylomeDB	P48735.
Enzyme and pathway databases
BioCyc	MetaCyc:HS00021-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P48735.
Bgee	P48735.
CleanEx	HS_IDH2.
Genevestigator	P48735.
GermOnline	ENSG00000182054. Homo sapiens.
Family and domain databases
Gene3D	3.40.718.10. 1 hit.
InterPro	IPR019818. IsoCit/isopropylmalate_DH_CS. IPR004790. Isocitrate_DH_NADP. IPR024084. IsoPropMal-DH-like_dom. [Graphical view]
PANTHER	PTHR11822. PTHR11822. 1 hit.
Pfam	PF00180. Iso_dh. 1 hit. [Graphical view]
PIRSF	PIRSF000108. IDH_NADP. 1 hit.
TIGRFAMs	TIGR00127. nadp_idh_euk. 1 hit.
PROSITE	PS00470. IDH_IMDH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	IDH2. human.
GenomeRNAi	3418.
NextBio	13474.
SOURCE	Search...

Entry information

Entry name

IDHP_HUMAN

Accession

Primary (citable) accession number: P48735
Secondary accession number(s): B2R6L6, Q96GT3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	April 3, 2002
Last modified:	May 1, 2013
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.