Reviewed,
UniProtKB/Swiss-Prot P21912 (DHSB_HUMAN)
Last modified
June 16, 2009.
Version 114.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial EC=1.3.5.1 Alternative name(s): Iron-sulfur subunit of complex II Short name=Ip | ||||
| Gene names |
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| 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 | 280 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)
| 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. Binds 1 3Fe-4S cluster By similarity. Binds 1 4Fe-4S cluster By similarity. |
| Pathway | |
| Subunit structure | 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. |
| Involvement in 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. Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.19 Ref.21 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. Ref.8 Ref.13 Ref.16 Ref.21 Ref.18 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. Ref.21 Defects in SDHB are a cause of Cowden-like syndrome [MIM:612359]. Cowden-like syndrome is a cancer predisposition syndrome associated with elevated risk for tumors of the breast, thyroid, kidney and uterus. |
| Sequence similarities | Belongs to the succinate dehydrogenase/fumarate reductase iron-sulfur protein family. Contains 1 2Fe-2S ferredoxin-type domain. Contains 1 4Fe-4S ferredoxin-type domain. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Transit peptide | 1 – 28 | 28 | Mitochondrion | ||||||
| Chain | 29 – 280 | 252 | Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial | PRO_0000010355 | |||||
Regions | |||||||||
| Domain | 40 – 133 | 94 | 2Fe-2S ferredoxin-type | ||||||
| Domain | 176 – 206 | 31 | 4Fe-4S ferredoxin-type | ||||||
Sites | |||||||||
| Metal binding | 93 | 1 | Iron-sulfur 1 (2Fe-2S) By similarity | ||||||
| Metal binding | 98 | 1 | Iron-sulfur 1 (2Fe-2S) By similarity | ||||||
| Metal binding | 101 | 1 | Iron-sulfur 1 (2Fe-2S) By similarity | ||||||
| Metal binding | 113 | 1 | Iron-sulfur 1 (2Fe-2S) By similarity | ||||||
| Metal binding | 186 | 1 | Iron-sulfur 2 (4Fe-4S) By similarity | ||||||
| Metal binding | 189 | 1 | Iron-sulfur 2 (4Fe-4S) By similarity | ||||||
| Metal binding | 192 | 1 | Iron-sulfur 2 (4Fe-4S) By similarity | ||||||
| Metal binding | 196 | 1 | Iron-sulfur 3 (3Fe-4S) By similarity | ||||||
| Metal binding | 243 | 1 | Iron-sulfur 3 (3Fe-4S) By similarity | ||||||
| Metal binding | 249 | 1 | Iron-sulfur 3 (3Fe-4S) By similarity | ||||||
| Metal binding | 253 | 1 | Iron-sulfur 2 (4Fe-4S) By similarity | ||||||
| Binding site | 201 | 1 | Ubiquinone; shared with DHSD By similarity | ||||||
Natural variations | |||||||||
| Natural variant | 3 | 1 | A → G Found in an individual with features of Cowden-like syndrome and absence of PTEN mutations; associated with increased manganese superoxide dismutase expression; associated with normal reactive oxygen species; associated with a 1.2-fold increase in AKT expression and 1.3-fold change in MAPK expression. dbSNP rs11203289. | VAR_054374 | |||||
| Natural variant | 29 | 1 | A → AQ in pheochromocytoma. Ref.11 | VAR_035063 | |||||
| Natural variant | 40 | 1 | K → E Ref.11 Ref.15 | VAR_054375 | |||||
| Natural variant | 43 | 1 | A → P in pheochromocytoma. Ref.12 | VAR_054376 | |||||
| Natural variant | 46 | 1 | R → G in pheochromocytoma. Ref.11 Ref.12 Ref.14 Ref.16 | VAR_035064 | |||||
| Natural variant | 46 | 1 | R → Q in pheochromocytoma and PLG4. Ref.11 Ref.12 Ref.14 Ref.16 | VAR_054377 | |||||
| Natural variant | 53 | 1 | G → R in pheochromocytoma. Ref.16 | VAR_054378 | |||||
| Natural variant | 65 | 1 | L → H in pheochromocytoma. Ref.14 Ref.16 | VAR_054379 | |||||
| Natural variant | 65 | 1 | L → P in pheochromocytoma. Ref.14 Ref.16 | VAR_054380 | |||||
| Natural variant | 87 | 1 | L → S in pheochromocytoma. Ref.8 Ref.16 | VAR_018517 | |||||
| Natural variant | 100 | 1 | S → F in pheochromocytoma; absence of expression in tumor cells indicating complete loss of SDHB function. Ref.11 Ref.19 | VAR_037620 | |||||
| Natural variant | 101 | 1 | C → Y in pheochromocytoma. Ref.11 Ref.16 | VAR_035065 | |||||
| Natural variant | 127 | 1 | I → N in pheochromocytoma. Ref.13 | VAR_054381 | |||||
| Natural variant | 131 | 1 | P → R in PGL4. Ref.10 | VAR_018518 | |||||
| Natural variant | 132 | 1 | H → P in PLG4. Ref.18 | VAR_037621 | |||||
| Natural variant | 163 | 1 | S → P Found in two individuals with features of Cowden-like syndrome and absence of PTEN mutations; associated with increased manganese superoxide dismutase function; associated with increased reactive oxygen species; associated with a 2.7-fold change in AKT expression and a 1.7-fold increase in MAPK expression. dbSNP rs33927012. | VAR_054382 | |||||
| Natural variant | 192 | 1 | C → R in pheochromocytoma. Ref.11 Ref.16 | VAR_035066 | |||||
| Natural variant | 196 | 1 | C → Y in pheochromocytoma. Ref.11 Ref.16 | VAR_035067 | |||||
| Natural variant | 197 | 1 | P → R in PLG4. Ref.8 Ref.13 | VAR_017868 | |||||
| Natural variant | 230 | 1 | R → C in pheochromocytoma. Ref.11 Ref.12 | VAR_054383 | |||||
| Natural variant | 242 | 1 | R → H in familial malignant paraganglioma and pheochromocytoma, pheochromocytoma and PLG4. Ref.11 Ref.16 Ref.9 | VAR_017869 | |||||
Experimental info | |||||||||
| Sequence conflict | 19 – 21 | 3 | GGA → WRT Ref.4 | ||||||
| Sequence conflict | 62 | 1 | E → K in AAA81167. Ref.1 | ||||||
| Sequence conflict | 67 | 1 | K → NR in AAA80581. Ref.1 | ||||||
| Sequence conflict | 151 | 1 | K → R Ref.5 | ||||||
| Sequence conflict | 172 | 1 | Q → E Ref.5 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Structural organization of the gene encoding the human iron-sulfur subunit of succinate dehydrogenase." Au H.C., Ream-Robinson D., Bellew L.A., Broomfield P.L.E., Saghbini M., Scheffler I.E. Gene 159:249-253(1995) [PubMed: 7622059] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Liver. |
| [2] | "The DNA sequence and biological annotation of human chromosome 1." 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. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | "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]. Tissue: Brain. |
| [4] | "Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of iron sulfur (Ip) subunit of liver mitochondria." Kita K., Oya H., Gennis R.B., Ackrell B.A.C., Kasahara M. Biochem. Biophys. Res. Commun. 166:101-108(1990) [PubMed: 2302193] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-280. Tissue: Liver. |
| [5] | "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." Gould S.J., Subramani S., Scheffler I.E. Proc. Natl. Acad. Sci. U.S.A. 86:1934-1938(1989) [PubMed: 2494655] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 107-249. Tissue: Fibroblast. |
| [6] | Erratum Gould S.J., Subramani S., Scheffler I.E. Proc. Natl. Acad. Sci. U.S.A. 90:2556-2556(1993) |
| [7] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [8] | "Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma." Astuti D., Latif F., Dallol A., Dahia P.L.M., Douglas F., George E., Skoeldberg F., Husebye E.S., Eng C., Maher E.R. Am. J. Hum. Genet. 69:49-54(2001) [PubMed: 11404820] [Abstract] Cited for: VARIANT PLG4 ARG-197, VARIANT PHEOCHROMOCYTOMA SER-87. |
| [9] | "Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene." Young A.L., Baysal B.E., Deb A., Young W.F. Jr. J. Clin. Endocrinol. Metab. 87:4101-4105(2002) [PubMed: 12213855] [Abstract] Cited for: VARIANT FAMILIAL MALIGNANT PARAGANGLIOMA HIS-242. |
| [10] | "Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas." 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. J. Med. Genet. 39:178-183(2002) [PubMed: 11897817] [Abstract] Cited for: VARIANT PGL4 ARG-131. |
| [11] | "Germ-line mutations in nonsyndromic pheochromocytoma." 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. Eng C.N. Engl. J. Med. 346:1459-1466(2002) [PubMed: 12000816] [Abstract] Cited for: VARIANTS PHEOCHROMOCYTOMA GLN-29 INS; GLY-46; TYR-101; ARG-192; TYR-196 AND HIS-242. |
| [12] | "Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas." Gimenez-Roqueplo A.-P., Favier J., Rustin P., Rieubland C., Crespin M., Nau V., Khau Van Kien P., Corvol P., Plouin P.-F., Jeunemaitre X. Cancer Res. 63:5615-5621(2003) [PubMed: 14500403] [Abstract] Cited for: VARIANTS PHEOCHROMOCYTOMA PRO-43; GLN-46; GLY-46 AND CYS-230. |
| [13] | "Genetic analysis of mitochondrial complex II subunits SDHD, SDHB and SDHC in paraganglioma and phaeochromocytoma susceptibility." Astuti D., Hart-Holden N., Latif F., Lalloo F., Black G.C., Lim C., Moran A., Grossman A.B., Hodgson S.V., Freemont A., Ramsden R., Eng C., Evans D.G.R., Maher E.R. Clin. Endocrinol. (Oxf.) 59:728-733(2003) [PubMed: 14974914] [Abstract] Cited for: VARIANT PHEOCHROMOCYTOMA ASN-127, VARIANT PLG4 ARG-197. |
| [14] | "Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas." Benn D.E., Croxson M.S., Tucker K., Bambach C.P., Richardson A.L., Delbridge L., Pullan P.T., Hammond J., Marsh D.J., Robinson B.G. Oncogene 22:1358-1364(2003) [PubMed: 12618761] [Abstract] Cited for: VARIANTS PHEOCHROMOCYTOMA GLN-46 AND HIS-65. |
| [15] | "K40E: a novel succinate dehydrogenase (SDH)B mutation causing familial phaeochromocytoma and paraganglioma." McDonnell C.M., Benn D.E., Marsh D.J., Robinson B.G., Zacharin M.R. Clin. Endocrinol. (Oxf.) 61:510-514(2004) [PubMed: 15473885] [Abstract] Cited for: VARIANT GLU-40. |
| [16] | "Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations." Neumann H.P.H., Pawlu C., Peczkowska M., Bausch B., McWhinney S.R., Muresan M., Buchta M., Franke G., Klisch J., Bley T.A., Hoegerle S., Boedeker C.C., Opocher G., Schipper J., Januszewicz A., Eng C. JAMA 292:943-951(2004) [PubMed: 15328326] [Abstract] Cited for: VARIANTS PHEOCHROMOCYTOMA GLY-46; GLN-46; ARG-53; PRO-65; SER-87; TYR-101; ARG-192; TYR-196 AND HIS-242, VARIANTS PLG4 GLN-46 AND HIS-242. |
| [17] | Erratum Neumann H.P.H., Pawlu C., Peczkowska M., Bausch B., McWhinney S.R., Muresan M., Buchta M., Franke G., Klisch J., Bley T.A., Hoegerle S., Boedeker C.C., Opocher G., Schipper J., Januszewicz A., Eng C. JAMA 292:1686-1686(2004) |
| [18] | "A novel succinate dehydrogenase subunit B gene mutation, H132P, causes familial malignant sympathetic extraadrenal paragangliomas." 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. J. Clin. Endocrinol. Metab. 89:362-367(2004) [PubMed: 14715873] [Abstract] Cited for: VARIANT PLG4 PRO-132. |
| [19] | "Somatic SDHB mutation in an extraadrenal pheochromocytoma." van Nederveen F.H., Korpershoek E., Lenders J.W.M., de Krijger R.R., Dinjens W.N.M. N. Engl. J. Med. 357:306-308(2007) [PubMed: 17634472] [Abstract] Cited for: VARIANT PHEOCHROMOCYTOMA PHE-100. |
| [20] | "Familial gastrointestinal stromal tumors and germ-line mutations." McWhinney S.R., Pasini B., Stratakis C.A. N. Engl. J. Med. 357:1054-1056(2007) [PubMed: 17804857] [Abstract] Cited for: INVOLVEMENT IN PARAGANGLIOMA AND GASTRIC STROMAL SARCOMA. |
| [21] | "Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes." Ni Y., Zbuk K.M., Sadler T., Patocs A., Lobo G., Edelman E., Platzer P., Orloff M.S., Waite K.A., Eng C. Am. J. Hum. Genet. 83:261-268(2008) [PubMed: 18678321] [Abstract] Cited for: VARIANTS GLY-3 AND PRO-163, CHARACTERIZATION OF VARIANTS GLY-3 AND PRO-163, INVOLVEMENT IN COWDEN-LIKE DISEASE. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U17248 mRNA. Translation: AAA81167.1. U17886 U17885 Genomic DNA. Translation: AAA80581.1. AL049569 Genomic DNA. Translation: CAB96822.1. BC007840 mRNA. Translation: AAH07840.1. D10245 mRNA. Translation: BAA01089.1. M32246 mRNA. Translation: AAA35708.1. | |
| IPI | IPI00294911. |
| PIR | I38895. |
| RefSeq | NP_002991.2. |
| UniGene | Hs.465924 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1NEK based on UniProtKB P07014. |
| SMR | P21912. Positions 37-275. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P21912. 6 interactions. |
Proteomic databases | |
| PeptideAtlas | P21912. |
| PRIDE | P21912. |
Genome annotation databases | |
| Ensembl | ENSG00000117118. Homo sapiens. [Contig view] |
| GeneID | 6390. |
| KEGG | hsa:6390. |
Organism-specific databases | |
| GeneCards | GC01M017217. |
| H-InvDB | HIX0000179. |
| HGNC | HGNC:10681. SDHB. |
| HPA | CAB009822. HPA002867. HPA002868. |
| MIM | 115310. phenotype. 171300. phenotype. 185470. gene. 606864. phenotype. 612359. phenotype. |
| Orphanet | 97286. Carney-Stratakis syndrome. 201. Cowden syndrome. 29072. Hereditary pheochromocytoma-paraganglioma syndrome. |
| PharmGKB | PA35606. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | P21912. |
| HOVERGEN | P21912. |
| OMA | P21912. ASIEPWL. |
Enzyme and pathway databases | |
| BRENDA | 1.3.5.1. 247. |
| Reactome | REACT_6305. Electron Transport Chain. |
Gene expression databases | |
| ArrayExpress | P21912. |
| Bgee | P21912. |
| CleanEx | HS_SDHB. |
| GermOnline | ENSG00000117118. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR006058. 2Fe2S_fd_BS. IPR017896. 4Fe4S_Fe-S-bd. IPR017900. 4Fe4S_Fe_S_CS. IPR012675. b-grasp_ferredoxin-like. IPR001041. Ferredoxin. IPR012285. Fum_reductase_C. IPR004489. Succ_DH/fum_Rdtase_Fe-S. [Graphical view] |
| Gene3D | G3DSA:3.10.20.30. Ferredoxin_fold. 1 hit. G3DSA:1.10.1060.10. Fum_reductase_C. 1 hit. |
| TIGRFAMs | TIGR00384. dhsB. 1 hit. |
| PROSITE | PS00197. 2FE2S_FER_1. 1 hit. PS51085. 2FE2S_FER_2. 1 hit. PS00198. 4FE4S_FER_1. 1 hit. PS51379. 4FE4S_FER_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00139. Succinic acid. |
| NextBio | 24824. |
| SOURCE | Search... |
Entry information
| Entry name | DHSB_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P21912 Secondary accession number(s): Q9NQ12 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| SIMILARITY comments Index of protein domains and families |

Clusters with


