O43837 (IDH3B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial
EC=1.1.1.41

Alternative name(s):
Isocitric dehydrogenase subunit beta
NAD(+)-specific ICDH subunit beta

Gene names

Name:

IDH3B

Organism

Homo sapiens (Human)

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.9
Sequence similarities	Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Ontologies

Keywords
Biological process	Tricarboxylic acid cycle
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 Reference proteome
Gene Ontology (GO)
Biological process	isocitrate metabolic process Traceable author statement. Source: ProtInc tricarboxylic acid cycle Traceable author statement. Source: Reactome
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	NAD binding Inferred from electronic annotation. Source: InterPro electron carrier activity Traceable author statement Ref.1. Source: UniProtKB isocitrate dehydrogenase (NAD+) activity Traceable author statement. Source: ProtInc magnesium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 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

Isoform C (identifier: O43837-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-177: MAALSGVRWL...EGEYSSLEHE → MKMGERWSSLFPFPVSPSCCFLLTQ

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.7
	Modified residue	199	1	N6-acetyllysine Ref.7
	Modified residue	374	1	N6-acetyllysine Ref.7
Natural variations
	Alternative sequence	1 – 177	177	MAALS…SLEHE → MKMGERWSSLFPFPVSPSCC FLLTQ in isoform C.		VSP_041335
	Alternative sequence	361 – 385	25	RDMGG…QTKGS → SDMGGYATCHDFTEAVIAAL PHP in isoform A.		VSP_002462
	Natural variant	3	1	A → V. Ref.1 Corresponds to variant rs3178817 [ dbSNP | Ensembl ].		VAR_022660
	Natural variant	132	1	L → P in RP46. Ref.9		VAR_054851
	Natural variant	166	1	Q → H. Corresponds to variant rs11542741 [ dbSNP | Ensembl ].		VAR_049781
	Natural variant	360	1	T → A. Corresponds to variant rs8296 [ dbSNP | Ensembl ].		VAR_056005
Experimental info
	Sequence conflict	127 – 130	4	SYDM → RTLV in CAB43266. Ref.6
	Sequence conflict	250	1	I → V in BAA91971. Ref.2
	Sequence conflict	385	1	S → SNL in AAD09340. Ref.1

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 [UniParc]. 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
	Isoform C [UniParc]. Checksum: 7036C0A641A17E2D	FASTA	233	25,555
	10 20 30 40 50 60 MKMGERWSSL FPFPVSPSCC FLLTQSARGV IECLKIVTRA KSQRIAKFAF DYATKKGRGK 70 80 90 100 110 120 VTAVHKANIM KLGDGLFLQC CEEVAELYPK IKFETMIIDN CCMQLVQNPY QFDVLVMPNL 130 140 150 160 170 180 YGNIIDNLAA GLVGGAGVVP GESYSAEYAV FETGARHPFA QAVGRNIANP TAMLLSASNM 190 200 210 220 230 LRHLNLEYHS SMIADAVKKV IKVGKVRTRD MGGYSTTTDF IKSVIGHLQT KGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and functional characterization of a novel, tissue-specific NAD+-dependent isocitrate dehydrogenase beta subunit isoform." Kim Y.-O., Koh H.-J., Kim S.-H., Jo S.-H., Huh J.-W., Jeong K.-S., Lee I.J., Song B.J., Huh T.-L. J. Biol. Chem. 274:36866-36875(1999) [PubMed: 10601238] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), VARIANT VAL-3, ALTERNATIVE SPLICING. 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS B AND C). Tissue: Placenta and Synovium.
[3]	"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].
[4]	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].
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"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
EMBL GenBank DDBJ	U49283 mRNA. Translation: AAB94295.1. AF023265 mRNA. Translation: AAD09339.1. AF023266 mRNA. Translation: AAD09340.1. AK001905 mRNA. Translation: BAA91971.1. AK315641 mRNA. Translation: BAG38008.1. AL049712 Genomic DNA. Translation: CAC01442.2. AL049712 Genomic DNA. Translation: CAC01443.1. CH471133 Genomic DNA. Translation: EAX10579.1. CH471133 Genomic DNA. Translation: EAX10580.1. CH471133 Genomic DNA. Translation: EAX10582.1. CH471133 Genomic DNA. Translation: EAX10583.1. BC001960 mRNA. Translation: AAH01960.1. AL050094 mRNA. Translation: CAB43266.1.
IPI	IPI00304417. IPI00304419. IPI00871304.
PIR	T08743. T13147.
RefSeq	NP_008830.2. NM_006899.2. NP_777280.1. NM_174855.1. NP_777281.1. NM_174856.1.
UniGene	Hs.436405.
3D structure databases
ProteinModelPortal	O43837.
SMR	O43837. Positions 43-382.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43837. 5 interactions.
MINT	MINT-1431659.
STRING	O43837.
PTM databases
PhosphoSite	O43837.
Proteomic databases
PRIDE	O43837.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000380843; ENSP00000370223; ENSG00000101365.
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.
neXtProt	NX_O43837.
Orphanet	791. Retinitis pigmentosa.
PharmGKB	PA29633.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18474.
HOVERGEN	HBG052080.
InParanoid	O43837.
OMA	NPGAWRG.
PhylomeDB	O43837.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
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. IPR024084. IsoPropMal-DH-like_dom. [Graphical view]
Gene3D	G3DSA:3.40.718.10. IDH_IMDH. 1 hit.
KO	K00030.
PANTHER	PTHR11835. IDH_IMDH_dimeric. 1 hit. PTHR11835:SF5. PTHR11835:SF5. 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
DrugBank	DB00157. NADH.
NextBio	13482.
SOURCE	Search...

Entry information

Entry name

IDH3B_HUMAN

Accession

Primary (citable) accession number: O43837
Secondary accession number(s): B2RDR1 , D3DVX2, D3DVX3, O95106, Q5JXS8, Q9NQ06, Q9NQ07, Q9NUZ0, Q9UEX0, Q9UG99

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	May 1, 2007
Last modified:	January 25, 2012
This is version 123 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.