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Protein

Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial

Gene

IDH3B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a structural role to facilitate the assembly and ensure the full activity of the enzyme catalyzing the decarboxylation of isocitrate (ICT) into alpha-ketoglutarate. The heterodimer composed of the alpha (IDH3A) and beta (IDH3B) subunits and the heterodimer composed of the alpha (IDH3A) and gamma (IDH3G) subunits, have considerable basal activity but the full activity of the heterotetramer (containing two subunits of IDH3A, one of IDH3B and one of IDH3G) requires the assembly and cooperative function of both heterodimers.1 Publication

Enzyme regulationi

The heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits can be allosterically activated by citrate (CIT) or/and ADP, and the two activators can act independently or synergistically. The heterodimer composed of IDH3A and IDH3B subunits cannot be allosterically regulated and the allosteric regulation of the heterotetramer is through the IDH3G subunit and not the IDH3B subunit. The IDH3G subunit contains the allosteric site which consists of a CIT-binding site and an ADP-binding site, and the binding of CIT and ADP causes conformational changes at the allosteric site which are transmitted to the active site in the catalytic subunit (IDH3A) through a cascade of conformational changes at the heterodimer interface, leading to stabilization of the isocitrate-binding at the active site and thus activation of the enzyme. ATP can activate the heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits at low concentrations but inhibits their activities at high concentrations, whereas ATP exhibits only inhibitory effect on the heterodimer composed of IDH3A and IDH3B subunits.2 Publications

GO - Molecular functioni

  • electron carrier activity Source: UniProtKB
  • isocitrate dehydrogenase (NAD+) activity Source: ProtInc
  • magnesium ion binding Source: InterPro
  • NAD binding Source: InterPro

GO - Biological processi

  • isocitrate metabolic process Source: ProtInc
  • tricarboxylic acid cycle Source: Reactome

Keywordsi

Biological processTricarboxylic acid cycle

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000101365-MONOMER.
BRENDAi1.1.1.41. 2681.
ReactomeiR-HSA-71403. Citric acid cycle (TCA cycle).
SABIO-RKiO43837.

Names & Taxonomyi

Protein namesi
Recommended name:
Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial
Alternative name(s):
Isocitric dehydrogenase subunit beta
NAD(+)-specific ICDH subunit beta
Gene namesi
Name:IDH3B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000101365.20.
HGNCiHGNC:5385. IDH3B.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Retinitis pigmentosa 46 (RP46)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa 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.
See also OMIM:612572
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054851132L → P in RP46. 1 PublicationCorresponds to variant dbSNP:rs137853020Ensembl.1

Keywords - Diseasei

Disease mutation, Retinitis pigmentosa

Organism-specific databases

DisGeNETi3420.
GeneReviewsiIDH3B.
MalaCardsiIDH3B.
MIMi612572. phenotype.
OpenTargetsiENSG00000101365.
Orphaneti791. Retinitis pigmentosa.
PharmGKBiPA29633.

Chemistry databases

DrugBankiDB00157. NADH.

Polymorphism and mutation databases

BioMutaiIDH3B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 34MitochondrionBy similarityAdd BLAST34
ChainiPRO_000001444435 – 385Isocitrate dehydrogenase [NAD] subunit beta, mitochondrialAdd BLAST351

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei199N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO43837.
MaxQBiO43837.
PaxDbiO43837.
PeptideAtlasiO43837.
PRIDEiO43837.

PTM databases

iPTMnetiO43837.
PhosphoSitePlusiO43837.

Expressioni

Gene expression databases

BgeeiENSG00000101365.
CleanExiHS_IDH3B.
ExpressionAtlasiO43837. baseline and differential.
GenevisibleiO43837. HS.

Organism-specific databases

HPAiHPA049387.
HPA054180.

Interactioni

Subunit structurei

Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer containing one IDH3A and one IDH3B subunit and the heterodimer containing one IDH3A and one IDH3G subunit assemble into a heterotetramer (which contains two subunits of IDH3A, one of IDH3B and one of IDH3G) and further into the heterooctamer.1 Publication

Protein-protein interaction databases

BioGridi109646. 32 interactors.
IntActiO43837. 18 interactors.
MINTiMINT-5003855.
STRINGi9606.ENSP00000370223.

Structurei

3D structure databases

ProteinModelPortaliO43837.
SMRiO43837.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0784. Eukaryota.
COG0473. LUCA.
GeneTreeiENSGT00590000083091.
HOVERGENiHBG052080.
InParanoidiO43837.
KOiK00030.
PhylomeDBiO43837.
TreeFamiTF315033.

Family and domain databases

InterProiView protein in InterPro
IPR019818. IsoCit/isopropylmalate_DH_CS.
IPR004434. Isocitrate_DH_NAD.
IPR024084. IsoPropMal-DH-like_dom.
PfamiView protein in Pfam
PF00180. Iso_dh. 1 hit.
SMARTiView protein in SMART
SM01329. Iso_dh. 1 hit.
TIGRFAMsiTIGR00175. mito_nad_idh. 1 hit.
PROSITEiView protein in PROSITE
PS00470. IDH_IMDH. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform B (identifier: O43837-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAALSGVRWL TRALVSAGNP GAWRGLSTSA AAHAASRSQA EDVRVEGSFP
60 70 80 90 100
VTMLPGDGVG PELMHAVKEV FKAAAVPVEF QEHHLSEVQN MASEEKLEQV
110 120 130 140 150
LSSMKENKVA IIGKIHTPME YKGELASYDM RLRRKLDLFA NVVHVKSLPG
160 170 180 190 200
YMTRHNNLDL VIIREQTEGE YSSLEHESAR GVIECLKIVT RAKSQRIAKF
210 220 230 240 250
AFDYATKKGR GKVTAVHKAN IMKLGDGLFL QCCEEVAELY PKIKFETMII
260 270 280 290 300
DNCCMQLVQN PYQFDVLVMP NLYGNIIDNL AAGLVGGAGV VPGESYSAEY
310 320 330 340 350
AVFETGARHP FAQAVGRNIA NPTAMLLSAS NMLRHLNLEY HSSMIADAVK
360 370 380
KVIKVGKVRT RDMGGYSTTT DFIKSVIGHL QTKGS
Length:385
Mass (Da):42,184
Last modified:May 1, 2007 - v2
Checksum:i7324E6CC30A68EE2
GO
Isoform A (identifier: O43837-2) [UniParc]FASTAAdd to basket

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

Show »
Length:383
Mass (Da):41,887
Checksum:i6B5A3D3F82CCDB34
GO
Isoform C (identifier: O43837-3) [UniParc]FASTAAdd to basket

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

Show »
Length:233
Mass (Da):25,555
Checksum:i7036C0A641A17E2D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti127 – 130SYDM → RTLV in CAB43266 (PubMed:17974005).Curated4
Sequence conflicti250I → V in BAA91971 (PubMed:14702039).Curated1
Sequence conflicti385S → SNL in AAD09340 (PubMed:10601238).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0226603A → V1 PublicationCorresponds to variant dbSNP:rs3178817Ensembl.1
Natural variantiVAR_054851132L → P in RP46. 1 PublicationCorresponds to variant dbSNP:rs137853020Ensembl.1
Natural variantiVAR_049781166Q → H. Corresponds to variant dbSNP:rs11542741Ensembl.1
Natural variantiVAR_056005360T → A. Corresponds to variant dbSNP:rs8296Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0413351 – 177MAALS…SLEHE → MKMGERWSSLFPFPVSPSCC FLLTQ in isoform C. 1 PublicationAdd BLAST177
Alternative sequenceiVSP_002462361 – 385RDMGG…QTKGS → SDMGGYATCHDFTEAVIAAL PHP in isoform A. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13031.1. [O43837-2]
CCDS13032.1. [O43837-1]
PIRiT08743.
T13147.
RefSeqiNP_001317692.1. NM_001330763.1.
NP_008830.2. NM_006899.4. [O43837-1]
NP_777280.1. NM_174855.3. [O43837-2]
UniGeneiHs.436405.

Genome annotation databases

EnsembliENST00000380843; ENSP00000370223; ENSG00000101365. [O43837-1]
ENST00000380851; ENSP00000370232; ENSG00000101365. [O43837-2]
GeneIDi3420.
KEGGihsa:3420.
UCSCiuc002wgp.4. human. [O43837-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIDH3B_HUMAN
AccessioniPrimary (citable) accession number: O43837
Secondary accession number(s): B2RDR1
, D3DVX2, D3DVX3, O95106, Q5JXS8, Q9NQ06, Q9NQ07, Q9NUZ0, Q9UEX0, Q9UG99
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 2007
Last modified: October 25, 2017
This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families