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SDHD (succinate dehydrogenase complex II, subunit D, integral membrane protein)

Identity

Other namesSDH4 (succinate dehydrogenase 4)
HGNC (Hugo) SDHD
Location 11q23
Location_base_pair Starts at 111462781 and ends at 111471727 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

Description 8895 bp, 4 exons
Transcription A non transcribed sequence highly homologous to SDHD cDNA is present on chromosome 1p36-p34

Protein

Description 159 amino acids and 17 kDa
Expression widely expressed
Localisation mitochondrial inner membrane
Function Complex II (succinate-ubiquinone oxidoreductase) of the respiratory chain is involved in the oxidation of succinate, carries electrons from FADH to CoQ. It is composed of four nuclear-encoded subunits. The subunit D protein or small subunit (cybS) is one of two integral membrane proteins anchoring the complex to membrane.
Homology The complex II includes SDHC (cybL) and SDHB (iron-sulfur protein) which are also implicated in paragangliomas and pheochromocytomas.

Mutations

Germinal Germline mutations cause hereditary paraganglioma. Different types of mutations are described. False-sense mutations, insertions and deletions leading to protein truncation and missense mutations.
Somatic Loss of wild type allele in tumor DNA is usually observed.

Implicated in

Entity Hereditary paraganglioma type 1 (also called familial non chromaffin paragangliomas 1, or familial glomus tumor)
Disease Hereditary paraganglioma type 1 (PGL1) is a rare autosomal dominant disorder. The disease is transmitted through fathers and no disease phenotype is transmetted maternally in accordance with a maternal genomic imprinting. Paragangliomas are slow growing highly vascular tumor, usually benign, derived from crest-neural cells. They are preferentially located in the neck (carotid body and glomus vagal) and head (glomus jugulare and tympanicum). They may be associated with pheochromocytomas.
Prognosis It depends on extent of the disease at the time of diagnosis.
  

External links

Nomenclature
HGNC (Hugo)SDHD   10683
Entrez_Gene (NCBI)SDHD  6392  succinate dehydrogenase complex, subunit D, integral membrane protein
Cards
AtlasSDHDID390
GeneCards (Weizmann)SDHD
Ensembl (Hinxton)ENSG00000204370 [Gene_View]  SDHD [Vega]
AceView (NCBI)SDHD
Genatlas (Paris)SDHD
euGene (Indiana)6392
SOURCE (Stanford)NM_003002
Genomic and cartography
GoldenPath (UCSC)SDHD  -  11q23   chr11:111462781-111471727 +  11q23   [Description]    (hg18-Mar_2006)
EnsemblSDHD - 11q23 [CytoView]
Mapping of homologs : NCBISDHD [Mapview]
OMIM114900   168000   171300   602690   606864   612359   
Gene and transcription
Gene : Genbank (Entrez)AA374642 AB006202 AK075360 BC005263 BC009574
Reference sequence (RefSeq transcript) :SRSNM_003002
Reference transcript : EntrezNM_003002
RefSeq genomic : SRSAC_000054 AC_000143 NC_000011 NT_033899 NW_001838042 NW_925173
RefSeq genomic : EntrezAC_000054 AC_000143 NC_000011 NT_033899 NW_001838042 NW_925173
Consensus coding sequences : CCDS NCBISDHD
Cluster EST : UnigeneHs.356270 [ SRS ] Hs.356270 [ NCBI ]
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtO14521 (SRS) O14521 (Expasy) O14521 (Uniprot)
With graphics : InterProO14521
Splice isoforms : VarSplice FASTAO14521(VarSplice FASTA)
Domains : Interpro (SRS)CybS   
Domains : Interpro (EBI)CybS   
Related proteins : CluSTrO14521
Domain families : Pfam SRSCybS (PF05328)   
Domain families : Pfam SangerCybS (PF05328)   
Domain families : Pfam NCBIpfam05328   
Blocks (Seattle)O14521
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD04069
Protein Interaction databases
DIP (DOE-UCLA)O14521
IntAct (EBI)O14521
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBISDHD
SNP : GeneSNP UtahSDHD
SNP : HGBaseSDHD
Genetic variants : HAPMAPSDHD
Somatic Mutations in Cancer : COSMICSDHD 
Mutations and Diseases : HGMDSDHD
Hereditary diseases : OMIM114900    168000    171300    602690    606864    612359   
Hereditary diseases : GENETests114900    168000    171300    602690    606864    612359   
Diseases : Genetic AssociationSDHD
General knowledge
Homologs : HomoloGeneSDHD
Homology/Alignments : Family Browser UCSCSDHD
Phylogenetic Trees/Animal Genes : TreeFamSDHD
Chemical/Protein Interactions : CTD6392
Keywords Ontology : AmiGOsuccinate dehydrogenase activity  mitochondrion  mitochondrial envelope  mitochondrial inner membrane  mitochondrial inner membrane  tricarboxylic acid cycle  transport  electron carrier activity  membrane  integral to membrane  heme binding  electron transport chain  metal ion binding  
Keywords Ontology : EGO-EBIsuccinate dehydrogenase activity  mitochondrion  mitochondrial envelope  mitochondrial inner membrane  mitochondrial inner membrane  tricarboxylic acid cycle  transport  electron carrier activity  membrane  integral to membrane  heme binding  electron transport chain  metal ion binding  
Pathways : BIOCARTAElectron Transport Reaction in Mitochondria [Genes]   
Pathways : KEGGCitrate cycle (TCA cycle)Oxidative phosphorylation
Other databases
Probes
Probes : ImagenesSDHD Related clones (RZPD - Berlin)
Literature
PubMed57 Pubmed reference(s) in Entrez
PubGeneSDHD

Bibliography

Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23.
Hirawake H, Taniwaki M, Tamura A, Kojima S, Kita K
Cytogenetics and cell genetics. 1997 ; 79 (1-2) : 132-138.
PMID 9533030
 
Characterization of the human SDHD gene encoding the small subunit of cytochrome b (cybS) in mitochondrial succinate-ubiquinone oxidoreductase.
Hirawake H, Taniwaki M, Tamura A, Amino H, Tomitsuka E, Kita K
Biochimica et biophysica acta. 1999 ; 1412 (3) : 295-300.
PMID 10482792
 
Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.
Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, Richard CW 3rd, Cornelisse CJ, Devilee P, Devlin B
Science (New York, N.Y.). 2000 ; 287 (5454) : 848-851.
PMID 10657297
 
Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma.
Gimm O, Armanios M, Dziema H, Neumann HP, Eng C
Cancer research. 2000 ; 60 (24) : 6822-6825.
PMID 11156372
 
Germline SDHD mutation in familial phaeochromocytoma.
Astuti D, Douglas F, Lennard TW, Aligianis IA, Woodward ER, Evans DG, Eng C, Latif F, Maher ER
Lancet. 2001 ; 357 (9263) : 1181-1182.
PMID 11323050
 
A high-resolution integrated map spanning the SDHD gene at 11q23: a 1.1-Mb BAC contig, a partial transcript map and 15 new repeat polymorphisms in a tumour-suppressor region.
Baysal BE, Willett-Brozick JE, Taschner PE, Dauwerse JG, Devilee P, Devlin B
European journal of human genetics : EJHG. 2001 ; 9 (2) : 121-129.
PMID 11313745
 
Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma.
Milunsky JM, Maher TA, Michels VV, Milunsky A
American journal of medical genetics. 2001 ; 100 (4) : 311-314.
PMID 11343322
 
Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene.
Taschner PE, Jansen JC, Baysal BE, Bosch A, Rosenberg EH, Brcker-Vriends AH, van Der Mey AG, van Ommen GJ, Cornelisse CJ, Devilee P
Genes, chromosomes & cancer. 2001 ; 31 (3) : 274-281.
PMID 11391798
 
The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway.
Gimenez-Roqueplo AP, Favier J, Rustin P, Mourad JJ, Plouin PF, Corvol P, Rtig A, Jeunemaitre X
American journal of human genetics. 2001 ; 69 (6) : 1186-1197.
PMID 11605159
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written02-2002Anne-Paule Gimenez-Roqueplo

Citation

This paper should be referenced as such :
Gimenez-Roqueplo AP . SDHD (succinate dehydrogenase complex II, subunit D, integral membrane protein). Atlas Genet Cytogenet Oncol Haematol. February 2002 .
URL : http://AtlasGeneticsOncology.org/Genes/SDHDID390.html

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indexed on : Sat Jun 27 16:39:43 CEST 2009

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