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UniProtKB/Swiss-Prot entry P21912


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name DHSB_HUMAN
Primary accession number P21912
Secondary accession number Q9NQ12
Integrated into Swiss-Prot on May 1, 1991
Sequence was last modified on May 2, 2002 (Sequence version 3)
Annotations were last modified on    November 25, 2008 (Entry version 107)
Name and origin of the protein
Protein name Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial [Precursor]
Synonyms EC 1.3.5.1
Iron-sulfur subunit of complex II
Ip
Gene name
Name: SDHB
Synonyms: SDH, SDH1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
TISSUE=Liver;
DOI=10.1016/0378-1119(95)00162-Y; PubMed=7622059 [NCBI, ExPASy, EBI, Israel, Japan]
Au H.C., Ream-Robinson D., Bellew L.A., Broomfield P.L.E., Saghbini M., Scheffler I.E.;
"Structural organization of the gene encoding the human iron-sulfur subunit of succinate dehydrogenase.";
Gene 159:249-253(1995).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan]
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 19-280.
TISSUE=Liver;
DOI=10.1016/0006-291X(90)91916-G; PubMed=2302193 [NCBI, ExPASy, EBI, Israel, Japan]
Kita K., Oya H., Gennis R.B., Ackrell B.A.C., Kasahara M.;
"Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of iron sulfur (Ip) subunit of liver mitochondria.";
Biochem. Biophys. Res. Commun. 166:101-108(1990).
[5]
NUCLEOTIDE SEQUENCE [MRNA] OF 107-249.
TISSUE=Fibroblast;
PubMed=2494655 [NCBI, ExPASy, EBI, Israel, Japan]
Gould S.J., Subramani S., Scheffler I.E.;
"Use of the DNA polymerase chain reaction for homology probing: isolation of partial cDNA or genomic clones encoding the iron-sulfur protein of succinate dehydrogenase from several species.";
Proc. Natl. Acad. Sci. U.S.A. 86:1934-1938(1989).
[6]
ERRATUM.
Gould S.J., Subramani S., Scheffler I.E.;
Proc. Natl. Acad. Sci. U.S.A. 90:2556-2556(1993).
[7]
VARIANT FAMILIAL EXTRAADRENAL PHEOCHROMOCYTOMA ARG-197, AND VARIANT PHEOCHROMOCYTOMA SER-87.
DOI=10.1086/321282; PubMed=11404820 [NCBI, ExPASy, EBI, Israel, Japan]
Astuti D., Latif F., Dallol A., Dahia P.L.M., Douglas F., George E., Skoeldberg F., Husebye E.S., Eng C., Maher E.R.;
"Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.";
Am. J. Hum. Genet. 69:49-54(2001).
[8]
VARIANT FAMILIAL MALIGNANT PARAGANGLIOMA HIS-242.
DOI=10.1210/jc.2002-020312; PubMed=12213855 [NCBI, ExPASy, EBI, Israel, Japan]
Young A.L., Baysal B.E., Deb A., Young W.F. Jr.;
"Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene.";
J. Clin. Endocrinol. Metab. 87:4101-4105(2002).
[9]
VARIANT PGL4 ARG-131.
DOI=10.1136/jmg.39.3.178; PubMed=11897817 [NCBI, ExPASy, EBI, Israel, Japan]
Baysal B.E., Willett-Brozick J.E., Lawrence E.C., Drovdlic C.M., Savul S.A., McLeod D.R., Yee H.A., Brackmann D.E., Slattery W.H. III, Myers E.N., Ferrell R.E., Rubinstein W.S.;
"Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas.";
J. Med. Genet. 39:178-183(2002).
[10]
VARIANTS PHEOCHROMOCYTOMA GLN-29 INS; GLY-46; TYR-101; ARG-192; TYR-196 AND HIS-242.
DOI=10.1056/NEJMoa020152; PubMed=12000816 [NCBI, ExPASy, EBI, Israel, Japan]
The Freiburg-Warsaw-Columbus pheochromocytoma study group;
Neumann H.P.H., Bausch B., McWhinney S.R., Bender B.U., Gimm O., Franke G., Schipper J., Klisch J., Altehoefer C., Zerres K., Januszewicz A., Smith W.M., Munk R., Manz T., Glaesker S., Apel T.W., Treier M., Reineke M., Walz M.K., Hoang-Vu C., Brauckhoff M., Klein-Franke A., Klose P., Schmidt H., Maier-Woelfle M., Peczkowska M., Szmigielski C., Eng C.;
"Germ-line mutations in nonsyndromic pheochromocytoma.";
N. Engl. J. Med. 346:1459-1466(2002).
[11]
VARIANT PLG4 PRO-132.
DOI=10.1210/jc.2003-031236; PubMed=14715873 [NCBI, ExPASy, EBI, Israel, Japan]
Maier-Woelfle M., Braendle M., Komminoth P., Saremaslani P., Schmid S., Locher T., Heitz P.U., Krull I., Galeazzi R.L., Schmid C., Perren A.;
"A novel succinate dehydrogenase subunit B gene mutation, H132P, causes familial malignant sympathetic extraadrenal paragangliomas.";
J. Clin. Endocrinol. Metab. 89:362-367(2004).
[12]
VARIANT PHEOCHROMOCYTOMA PHE-100.
DOI=10.1056/NEJMc070010; PubMed=17634472 [NCBI, ExPASy, EBI, Israel, Japan]
van Nederveen F.H., Korpershoek E., Lenders J.W.M., de Krijger R.R., Dinjens W.N.M.;
"Somatic SDHB mutation in an extraadrenal pheochromocytoma.";
N. Engl. J. Med. 357:306-308(2007).
[13]
INVOLVEMENT IN PARAGANGLIOMA AND GASTRIC STROMAL SARCOMA.
DOI=10.1056/NEJMc071191; PubMed=17804857 [NCBI, ExPASy, EBI, Israel, Japan]
McWhinney S.R., Pasini B., Stratakis C.A.;
"Familial gastrointestinal stromal tumors and germ-line mutations.";
N. Engl. J. Med. 357:1054-1056(2007).
Comments
  • FUNCTION: Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
  • CATALYTIC ACTIVITY: Succinate + ubiquinone = fumarate + ubiquinol.
  • COFACTOR: Binds 1 2Fe-2S cluster (By similarity).
  • COFACTOR: Binds 1 3Fe-4S cluster (By similarity).
  • COFACTOR: Binds 1 4Fe-4S cluster (By similarity).
  • PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle.
  • SUBUNIT: Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD.
  • SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.
  • DISEASE: Defects in SDHB are a cause of pheochromocytoma [MIM:171300]. The pheochromocytomas are catecholamine-producing, chromaffin tumors that arise in the adrenal medulla in 90% of cases. In the remaining 10% of cases, they develop in extra-adrenal sympathetic ganglia and may be referred to as "paraganglioma." Pheochromocytoma usually presents with hypertension. Approximately 10% of pheochromocytoma is hereditary. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of non-syndromic familial pheochromocytoma is unknown.
  • DISEASE: Defects in SDHB are the cause of hereditary paragangliomas type 4 (PLG4) [MIM:115310]; also known as familial non-chromaffin paragangliomas type 4. Paragangliomas refer to rare and mostly benign tumors that arise from any component of the neuroendocrine system. PLG4 is characterized by the development of mostly benign, highly vascular, slow growing tumors in the head and neck. In the head and neck region, the carotid body is the largest of all paraganglia and is also the most common site of the tumors.
  • DISEASE: Defects in SDHB are a cause of paraganglioma and gastric stromal sarcoma [MIM:606864]; also called Carney-Stratakis syndrome. Gastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance.
  • SIMILARITY: Belongs to the succinate dehydrogenase/fumarate reductase iron-sulfur protein family.
  • SIMILARITY: Contains 1 2Fe-2S ferredoxin-type domain.
  • SIMILARITY: Contains 1 4Fe-4S ferredoxin-type domain.
  • WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/SDHBID388.html";.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=SDHB";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
U17248; AAA81167.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U17886; AAA80581.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U17296; AAA80581.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U17880; AAA80581.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U17881; AAA80581.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U17882; AAA80581.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U17883; AAA80581.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U17884; AAA80581.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U17885; AAA80581.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL049569; CAB96822.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC007840; AAH07840.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
D10245; BAA01089.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M32246; AAA35708.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR I38895; I38895.
RefSeq NP_002991.2; -.
UniGene Hs.465924
3D structure databases
HSSP P07014; 1NEK. [HSSP ENTRY / PDB]
SMR P21912; 37-275.
ModBase P21912.
Protein-protein interaction databases
IntAct P21912; -.
PTM databases
PhosphoSite P21912; -.
Enzyme and pathway databases
Reactome REACT_1046; Pyruvate metabolism and TCA cycle.
REACT_6305; Electron Transport Chain.
Organism-specific databases
H-InvDB HIX0000179; -.
HGNC HGNC:10681; SDHB.
GenAtlas SDHB.
HPA CAB009822; -.
HPA002867; -.
HPA002868; -.
MIM 115310; phenotype. [NCBI / EBI]
171300; phenotype. [NCBI / EBI]
185470; gene. [NCBI / EBI]
606864; phenotype. [NCBI / EBI]
Orphanet 29072; Paraganglioma, hereditary.
PharmGKB PA35606; -.
GeneCards P21912.
Gene expression databases
ArrayExpress P21912; -.
CleanEx HS_SDHB; -.
GermOnline ENSG00000117118; Homo sapiens.
Ontologies
GO
GO:0005743; Cellular component: mitochondrial inner membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0051537; Molecular function: 2 iron, 2 sulfur cluster binding (inferred from electronic annotation from UniProtKB-KW).
GO:0051538; Molecular function: 3 iron, 4 sulfur cluster binding (inferred from electronic annotation from UniProtKB-KW).
GO:0051539; Molecular function: 4 iron, 4 sulfur cluster binding (inferred from electronic annotation from UniProtKB-KW).
GO:0009055; Molecular function: electron carrier activity (inferred from electronic annotation from InterPro).
GO:0005506; Molecular function: iron ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0008177; Molecular function: succinate dehydrogenase (ubiquinone) activity (inferred from electronic annotation from EC).
GO:0022900; Biological process: electron transport chain (inferred from electronic annotation from UniProtKB-KW).
GO:0006810; Biological process: transport (inferred from electronic annotation from UniProtKB-KW).
GO:0006099; Biological process: tricarboxylic acid cycle (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR006058; 2Fe2S_fd_BS.
IPR001450; 4Fe4S_Fe_S_bd.
IPR012675; b-grasp_ferredoxin-like.
IPR001041; Ferredoxin.
IPR012285; Fum_reductase_C.
IPR004489; Succ_DHase/fum_Rdtase_Fe-S.
Graphical view of domain structure.
Gene3D G3DSA:3.10.20.30; Ferredoxin_fold; 1.
G3DSA:1.10.1060.10; Fum_reductase_C; 1.
Pfam PF00111; Fer2; 1.
Pfam graphical view of domain structure.
TIGRFAMs TIGR00384; dhsB; 1.
PROSITE PS00197; 2FE2S_FER_1; 1.
PS51085; 2FE2S_FER_2; 1.
PS00198; 4FE4S_FER_1; 1.
PS51379; 4FE4S_FER_2; 1.
PROSITE graphical view of domain structure (profiles).
ProtoNet P21912.
Proteomic databases
PeptideAtlas P21912; -.
Genome annotation databases
Ensembl ENSG00000117118; Homo sapiens. [Contig view]
GeneID 6390; -.
KEGG hsa:6390; -.
Phylogenomic databases
HOGENOM P21912; -.
HOVERGEN P21912; -.
Other
DrugBank DB00139; Succinic acid.
LinkHub P21912; -.
NextBio 24824; -.
SOURCE SDHB; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
2Fe-2S; 3Fe-4S; 4Fe-4S; Disease mutation; Electron transport; Iron; Iron-sulfur; Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; Oxidoreductase; Transit peptide; Transport; Tricarboxylic acid cycle.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
TRANSIT   1    28  28     Mitochondrion. 
CHAIN   29   280  252     Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial. PRO_0000010355
DOMAIN   40   133  94     2Fe-2S ferredoxin-type. 
DOMAIN   176   206  31     4Fe-4S ferredoxin-type. 
METAL   93    93        Iron-sulfur 1 (2Fe-2S) (By similarity). 
METAL   98    98        Iron-sulfur 1 (2Fe-2S) (By similarity). 
METAL   101   101        Iron-sulfur 1 (2Fe-2S) (By similarity). 
METAL   113   113        Iron-sulfur 1 (2Fe-2S) (By similarity). 
METAL   186   186        Iron-sulfur 2 (4Fe-4S) (By similarity). 
METAL   189   189        Iron-sulfur 2 (4Fe-4S) (By similarity). 
METAL   192   192        Iron-sulfur 2 (4Fe-4S) (By similarity). 
METAL   196   196        Iron-sulfur 3 (3Fe-4S) (By similarity). 
METAL   243   243        Iron-sulfur 3 (3Fe-4S) (By similarity). 
METAL   249   249        Iron-sulfur 3 (3Fe-4S) (By similarity). 
METAL   253   253        Iron-sulfur 2 (4Fe-4S) (By similarity). 
BINDING   201   201        Ubiquinone; shared with DHSD (By similarity). 
VARIANT   29    29  1     A -> AQ (in pheochromocytoma). VAR_035063
VARIANT   46    46  1     R -> G (in pheochromocytoma). VAR_035064 [3D]
VARIANT   87    87  1     L -> S (in pheochromocytoma). VAR_018517 [3D]
VARIANT   100   100  1     S -> F (in pheochromocytoma; absence of expression in tumor cells indicating complete loss of SDHB function). VAR_037620 [3D]
VARIANT   101   101  1     C -> Y (in pheochromocytoma). VAR_035065 [3D]
VARIANT   131   131  1     P -> R (in PGL4). VAR_018518 [3D]
VARIANT   132   132  1     H -> P (in PLG4). VAR_037621 [3D]
VARIANT   192   192  1     C -> R (in pheochromocytoma). VAR_035066 [3D]
VARIANT   196   196  1     C -> Y (in pheochromocytoma). VAR_035067 [3D]
VARIANT   197   197  1     P -> R (in familial extraadrenal pheochromocytoma). VAR_017868 [3D]
VARIANT   242   242  1     R -> H (in familial malignant paraganglioma and pheochromocytoma). VAR_017869 [3D]
CONFLICT   19    21        GGA -> WRT (in Ref. 4). 
CONFLICT   62    62        E -> K (in Ref. 1; AAA81167). 
CONFLICT   67    67        K -> NR (in Ref. 1; AAA80581). 
CONFLICT   151   151        K -> R (in Ref. 5). 
CONFLICT   172   172        Q -> E (in Ref. 5). 
Sequence information
Length: 280 AA [This is the length of the unprocessed precursor] Molecular weight: 31630 Da [This is the MW of the unprocessed precursor] CRC64: ED12E7C3BA7B6D13 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MAAVVALSLR RRLPATTLGG ACLQASRGAQ TAAATAPRIK KFAIYRWDPD KAGDKPHMQT 

        70         80         90        100        110        120 
YEVDLNKCGP MVLDALIKIK NEVDSTLTFR RSCREGICGS CAMNINGGNT LACTRRIDTN 

       130        140        150        160        170        180 
LNKVSKIYPL PHMYVIKDLV PDLSNFYAQY KSIEPYLKKK DESQEGKQQY LQSIEEREKL 

       190        200        210        220        230        240 
DGLYECILCA CCSTSCPSYW WNGDKYLGPA VLMQAYRWMI DSRDDFTEER LAKLQDPFSL 

       250        260        270        280 
YRCHTIMNCT RTCPKGLNPG KAIAEIKKMM ATYKEKKASV 

P21912 in FASTA format

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