Reviewed, UniProtKB/Swiss-Prot O43837 (IDH3B_HUMAN)

Names and origin

Protein names

Recommended name:
    Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial
    EC=1.1.1.41
Alternative name(s):
    Isocitric dehydrogenase
    NAD(+)-specific ICDH

Gene names

Name:

IDH3B

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	385 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)

Catalytic activity	Isocitrate + NAD+ = 2-oxoglutarate + CO2 + NADH.
Cofactor	Binds 1 magnesium or manganese ion per subunit By similarity.
Subunit structure	Heterooligomer of subunits alpha, beta, and gamma in the apparent ratio of 2:1:1 By similarity.
Subcellular location	Mitochondrion.
Involvement in disease	Defects in IDH3B are the cause of retinitis pigmentosa type 46 (RP46) [MIM:612572]. RP is a retinal dystrophy belonging to the group of pigmentary retinopathies. RP is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Ref.10
Sequence similarities	Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Ontologies

Keywords
Biological process	Sensory transduction Tricarboxylic acid cycle Vision
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Retinitis pigmentosa
Domain	Transit peptide
Ligand	Magnesium Manganese Metal-binding NAD
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	isocitrate metabolic process Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW tricarboxylic acid cycle Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Inferred from Experiment. Source: Reactome
Molecular function	NAD or NADH binding Inferred from electronic annotation. Source: InterPro electron carrier activity Traceable author statement. Source: UniProtKB isocitrate dehydrogenase (NAD+) activity Traceable author statement. Source: ProtInc magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform B (identifier: O43837-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform A (identifier: O43837-2)

The sequence of this isoform differs from the canonical sequence as follows:
     361-385: RDMGGYSTTTDFIKSVIGHLQTKGS → SDMGGYATCHDFTEAVIAALPHP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 34	34	Mitochondrion By similarity
	Chain	35 – 385	351	Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial		PRO_0000014444
Sites
	Metal binding	251	1	Magnesium or manganese By similarity
	Binding site	133	1	Substrate By similarity
	Binding site	164	1	Substrate By similarity
	Binding site	251	1	Substrate By similarity
	Site	171	1	Critical for catalysis By similarity
	Site	218	1	Critical for catalysis By similarity
Amino acid modifications
	Modified residue	146	1	N6-acetyllysine Ref.9
	Modified residue	199	1	N6-acetyllysine Ref.9
	Modified residue	374	1	N6-acetyllysine Ref.9
Natural variations
	Alternative sequence	361 – 385	25	RDMGG…QTKGS → SDMGGYATCHDFTEAVIAAL PHP in isoform A.		VSP_002462
	Natural variant	3	1	A → V: dbSNP rs3178817. Ref.1 Ref.2		VAR_022660
	Natural variant	132	1	L → P in RP46. Ref.10		VAR_054851
	Natural variant	166	1	Q → H: dbSNP rs11542741.		VAR_049781
	Natural variant	360	1	T → A: dbSNP rs8296.		VAR_056005
Experimental info
	Sequence conflict	127 – 130	4	SYDM → RTLV Ref.7
	Sequence conflict	385	1	S → SNL in AAD09340. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform B [UniParc]. Last modified May 1, 2007. Version 2. Checksum: 7324E6CC30A68EE2	FASTA	385	42,184
	10 20 30 40 50 60 MAALSGVRWL TRALVSAGNP GAWRGLSTSA AAHAASRSQA EDVRVEGSFP VTMLPGDGVG 70 80 90 100 110 120 PELMHAVKEV FKAAAVPVEF QEHHLSEVQN MASEEKLEQV LSSMKENKVA IIGKIHTPME 130 140 150 160 170 180 YKGELASYDM RLRRKLDLFA NVVHVKSLPG YMTRHNNLDL VIIREQTEGE YSSLEHESAR 190 200 210 220 230 240 GVIECLKIVT RAKSQRIAKF AFDYATKKGR GKVTAVHKAN IMKLGDGLFL QCCEEVAELY 250 260 270 280 290 300 PKIKFETMII DNCCMQLVQN PYQFDVLVMP NLYGNIIDNL AAGLVGGAGV VPGESYSAEY 310 320 330 340 350 360 AVFETGARHP FAQAVGRNIA NPTAMLLSAS NMLRHLNLEY HSSMIADAVK KVIKVGKVRT 370 380 RDMGGYSTTT DFIKSVIGHL QTKGS
	Isoform A. Checksum: 6B5A3D3F82CCDB34	FASTA	383	41,887
	10 20 30 40 50 60 MAALSGVRWL TRALVSAGNP GAWRGLSTSA AAHAASRSQA EDVRVEGSFP VTMLPGDGVG 70 80 90 100 110 120 PELMHAVKEV FKAAAVPVEF QEHHLSEVQN MASEEKLEQV LSSMKENKVA IIGKIHTPME 130 140 150 160 170 180 YKGELASYDM RLRRKLDLFA NVVHVKSLPG YMTRHNNLDL VIIREQTEGE YSSLEHESAR 190 200 210 220 230 240 GVIECLKIVT RAKSQRIAKF AFDYATKKGR GKVTAVHKAN IMKLGDGLFL QCCEEVAELY 250 260 270 280 290 300 PKIKFETMII DNCCMQLVQN PYQFDVLVMP NLYGNIIDNL AAGLVGGAGV VPGESYSAEY 310 320 330 340 350 360 AVFETGARHP FAQAVGRNIA NPTAMLLSAS NMLRHLNLEY HSSMIADAVK KVIKVGKVRT 370 380 SDMGGYATCH DFTEAVIAAL PHP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mitochondrial NAD+-specific isocitrate dehydrogenase." Ko H.-J., Kim Y.-O., Park H., Oh I., Yeo S., Hong S., Chae B., Kim S., Son B., Lee Y., Yeo H., Huh T.-L. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), VARIANT VAL-3. Tissue: Heart.
[2]	Ko H.-J., Kim Y.-O., Huh T.-L. Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), VARIANT VAL-3.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). Tissue: Synovium.
[4]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). Tissue: Lung.
[7]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-385 (ISOFORM B). Tissue: Uterus.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-146; LYS-199 AND LYS-374, MASS SPECTROMETRY.
[10]	"Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle." Hartong D.T., Dange M., McGee T.L., Berson E.L., Dryja T.P., Colman R.F. Nat. Genet. 40:1230-1234(2008) [PubMed: 18806796] [Abstract] Cited for: VARIANT RP46 PRO-132.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U49283 mRNA. Translation: AAB94295.1. AF023265 mRNA. Translation: AAD09339.1. AF023266 mRNA. Translation: AAD09340.1. AK315641 mRNA. Translation: BAG38008.1. AL049712 Genomic DNA. Translation: CAC01442.2. AL049712 Genomic DNA. Translation: CAC01443.1. CH471133 Genomic DNA. Translation: EAX10580.1. BC001960 mRNA. Translation: AAH01960.1. AL050094 mRNA. Translation: CAB43266.1.
IPI	IPI00304417. IPI00304419.
PIR	T08743. T13147.
RefSeq	NP_008830.2. NP_777280.1. NP_777281.1.
UniGene	Hs.436405
3D structure databases
HSSP	HSSP built from PDB template 1HQS based on UniProtKB P39126.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43837. 8 interactions.
STRING	O43837.
PTM databases
PhosphoSite	O43837.
Proteomic databases
PRIDE	O43837.
Genome annotation databases
Ensembl	ENST00000341825; ENSP00000343215; ENSG00000101365; Homo sapiens. [Genome view] ENST00000380843; ENSP00000370223; ENSG00000101365; Homo sapiens. [Genome view] ENST00000380851; ENSP00000370232; ENSG00000101365; Homo sapiens. [Genome view] ENST00000435594; ENSP00000410058; ENSG00000101365; Homo sapiens. [Genome view] ENST00000445490; ENSP00000396957; ENSG00000101365; Homo sapiens. [Genome view]
GeneID	3420.
KEGG	hsa:3420.
NMPDR	fig|9606.3.peg.19736.
UCSC	uc002wgp.1. human. uc002wgq.1. human.
Organism-specific databases
CTD	3420.
GeneCards	GC20M002587.
H-InvDB	HIX0015578.
HGNC	HGNC:5385. IDH3B.
MIM	604526. gene. 612572. phenotype.
Orphanet	791. Retinitis pigmentosa.
PharmGKB	PA29633.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O43837.
OMA	TTTDFIK.
Enzyme and pathway databases
BRENDA	1.1.1.41. 247.
Reactome	REACT_1046. Pyruvate metabolism and TCA cycle. REACT_1505. Integration of energy metabolism. REACT_15380. Diabetes pathways.
Gene expression databases
ArrayExpress	O43837.
Bgee	O43837.
CleanEx	HS_IDH3B.
Genevestigator	O43837.
GermOnline	ENSG00000101365. Homo sapiens.
Family and domain databases
InterPro	IPR019818. IsoCit/isopropylmalate_DH_CS. IPR001804. Isocitrate/isopropylmalate_DH. IPR004434. Isocitrate_DH_NAD_mit. [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	TIGR00175. mito_nad_idh. 1 hit.
PROSITE	PS00470. IDH_IMDH. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00157. NADH.
NextBio	13482.
SOURCE	Search...

Entry information

Entry name

IDH3B_HUMAN

Accession

Primary (citable) accession number: O43837
Secondary accession number(s): B2RDR1 , O95106, Q5JXS8, Q9NQ06, Q9NQ07, Q9UEX0, Q9UG99

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	May 1, 2007
Last modified:	November 3, 2009
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.