Reviewed,
UniProtKB/Swiss-Prot O14521 (DHSD_HUMAN)
Last modified
January 19, 2010.
Version 110.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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Names and origin
| Protein names | Recommended name: Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial Short name=CybS Alternative name(s): Succinate-ubiquinone reductase membrane anchor subunit QPs3 CII-4 Succinate dehydrogenase complex subunit D Succinate-ubiquinone oxidoreductase cytochrome b small subunit | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 159 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 | Membrane-anchoring 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) 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 | |
| Involvement in disease | Defects in SDHD are a cause of hereditary paragangliomas type 1 (PGL1) [MIM:168000]; also known as familial non-chromaffin paragangliomas type 1. Paragangliomas refer to rare and mostly benign tumors that arise from any component of the neuroendocrine system. PGL1 is a rare autosomal dominant disorder which is characterized by the development of mostly benign, highly vascular, slowly 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. Penetrance of PLG1 is incomplete when the disease is transmitted through fathers. No disease phenotype is transmitted maternally. Ref.11 Ref.12 Ref.13 Ref.14 Ref.24 Defects in SDHD 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.24 Ref.10 Ref.18 Ref.20 Defects in SDHD are involved in intestinal carcinoid tumor [MIM:114900]. A carcinoid tumor is a yellow circumscribed tumor arising from enterochromaffin cells, in the small intestine. Ref.24 Defects in SDHD 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.24 Defects in SDHD 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. Ref.24 |
| Sequence similarities | Belongs to the CybS family. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Transit peptide | 1 – 56 | 56 | Mitochondrion Potential | ||||||
| Chain | 57 – 159 | 103 | Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial | PRO_0000006487 | |||||
Regions | |||||||||
| Topological domain | 57 – 63 | 7 | Mitochondrial matrix By similarity | ||||||
| Transmembrane | 64 – 85 | 22 | By similarity | ||||||
| Topological domain | 86 – 90 | 5 | Mitochondrial intermembrane By similarity | ||||||
| Transmembrane | 91 – 111 | 21 | By similarity | ||||||
| Topological domain | 112 – 120 | 9 | Mitochondrial matrix By similarity | ||||||
| Transmembrane | 121 – 142 | 22 | By similarity | ||||||
| Topological domain | 143 – 159 | 17 | Mitochondrial intermembrane By similarity | ||||||
Sites | |||||||||
| Metal binding | 102 | 1 | Iron (heme axial ligand); shared with SDHC By similarity | ||||||
| Binding site | 114 | 1 | Ubiquinone; shared with IP/SDHB By similarity | ||||||
Natural variations | |||||||||
| Natural variant | 12 | 1 | G → S Polymorphism that may increase susceptibility for developing pheochromocytoma, paraganglioma, intestinal carcinoid tumor and breast, renal and uterus carcinoma; associated with features of Cowden-like syndrome; associated with increased manganese superoxide dismutase expression; associated with increased reactive oxygen species; associated with 1.9-fold increase in both AKT and MAPK expression. dbSNP rs34677591. Ref.24 Ref.15 Ref.16 Ref.17 Ref.19 Ref.22 Ref.25 | VAR_017870 | |||||
| Natural variant | 50 | 1 | H → R Polymorphism that may increase susceptibility for developing paraganglioma, breast and tyroid carcinoma; may be involved in somatic Merkel cell carcinoma; associated with features of Cowden-like syndrome; associated with increased manganese superoxide dismutase expression; associated with increased reactive oxygen species; associated with a 2.0-fold increase in AKT expression and a 1.7-fold increase in MAPK expression. dbSNP rs11214077. Ref.24 Ref.16 Ref.17 Ref.19 | VAR_017871 | |||||
| Natural variant | 81 | 1 | P → L in PGL1 and pheochromocytoma. Ref.11 Ref.10 Ref.20 | VAR_010038 | |||||
| Natural variant | 92 | 1 | D → Y in PGL1 and pheochromocytoma. Ref.11 Ref.14 Ref.18 Ref.20 | VAR_010039 | |||||
| Natural variant | 93 | 1 | Missing in PGL1. | VAR_018519 | |||||
| Natural variant | 102 | 1 | H → L in PGL1. Ref.11 | VAR_010040 | |||||
| Natural variant | 114 | 1 | Y → C in PGL1. Ref.12 Ref.20 | VAR_017872 | |||||
| Natural variant | 139 | 1 | L → P in PGL1. Ref.14 | VAR_017873 | |||||
| Natural variant | 145 | 1 | H → N Found in an individual with features of Cowden-like syndrome; associated with increased manganese superoxide dismutase expression; asociated with normal reactive oxygen species; associated with no change in AKT expression but a 1.2-fold increase of MAPK expression. Ref.24 | VAR_054384 | |||||
| Natural variant | 148 | 1 | G → V in PLG1. Ref.20 | VAR_054385 | |||||
Experimental info | |||||||||
| Sequence conflict | 74 | 1 | V → F in AAH70307. Ref.8 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "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. Cytogenet. Cell Genet. 79:132-138(1997) [PubMed: 9533030] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver. |
| [2] | "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. Biochim. Biophys. Acta 1412:295-300(1999) [PubMed: 10482792] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. Isogai T.DNA Res. 12:117-126(2005) [PubMed: 16303743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [4] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [5] | "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [6] | "Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. Sakaki Y.Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | 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. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | "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: Bone marrow, Brain, Lung and Skeletal muscle. |
| [9] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [10] | "Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma." Gimm O., Armanios M., Dziema H., Neumann H.P.H., Eng C. Cancer Res. 60:6822-6825(2000) [PubMed: 11156372] [Abstract] Cited for: VARIANT PHEOCHROMOCYTOMA LEU-81. |
| [11] | "Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma." Baysal B.E., Ferrell R.E., Willett-Brozick J.E., Lawrence E.C., Myssiorek D., Bosch A., van der Mey A., Taschner P.E.M., Rubinstein W.S., Myers E.N., Richard C.W. III, Cornelisse C.J., Devilee P., Devlin B. Science 287:848-851(2000) [PubMed: 10657297] [Abstract] Cited for: VARIANTS PGL1 LEU-81; TYR-92 AND LEU-102. |
| [12] | "Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma." Milunsky J.M., Maher T.A., Michels V.V., Milunsky A. Am. J. Med. Genet. 100:311-314(2001) [PubMed: 11343322] [Abstract] Cited for: VARIANT PGL1 CYS-114. |
| [13] | "Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss." Badenhop R.F., Cherian S., Lord R.S.A., Baysal B.E., Taschner P.E.M., Schofield P.R. Genes Chromosomes Cancer 31:255-263(2001) [PubMed: 11391796] [Abstract] Cited for: VARIANT PGL1 TYR-93 DEL. |
| [14] | "Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene." Taschner P.E.M., Jansen J.C., Baysal B.E., Bosch A., Rosenberg E.H., Broecker-Vriends A.H.J.T., van Der Mey A.G.L., van Ommen G.-J.B., Cornelisse C.J., Devilee P. Genes Chromosomes Cancer 31:274-281(2001) [PubMed: 11391798] [Abstract] Cited for: VARIANTS PGL1 TYR-92 AND PRO-139. |
| [15] | "Germline SDHD mutation in paraganglioma of the spinal cord." Masuoka J., Brandner S., Paulus W., Soffer D., Vital A., Chimelli L., Jouvet A., Yonekawa Y., Kleihues P., Ohgaki H. Oncogene 20:5084-5086(2001) [PubMed: 11526495] [Abstract] Cited for: VARIANT SER-12. |
| [16] | "Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas." Kytoelae S., Nord B., Elder E.E., Carling T., Kjellman M., Cedermark B., Juhlin C., Hoeoeg A., Isola J., Larsson C. Genes Chromosomes Cancer 34:325-332(2002) [PubMed: 12007193] [Abstract] Cited for: INVOLVEMENT IN INTESTINAL CARCINOID TUMOR, VARIANTS SER-12 AND ARG-50. |
| [17] | "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 SER-12 AND ARG-50. |
| [18] | "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: VARIANT PHEOCHROMOCYTOMA TYR-92. |
| [19] | "G12S and H50R variations are polymorphisms in the SDHD gene." Cascon A., Ruiz-Llorente S., Cebrian A., Leton R., Telleria D., Benitez J., Robledo M. Genes Chromosomes Cancer 37:220-221(2003) [PubMed: 12696072] [Abstract] Cited for: DISCUSSION OF PATHOGENIC ROLE OF VARIANTS SER-12 AND ARG-50. |
| [20] | "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 PLG1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92. |
| [21] | 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) |
| [22] | "SDHD mutation analysis in seven German patients with sporadic carotid body paraganglioma: one novel mutation, no Dutch founder mutation and further evidence that G12S is a polymorphism." Leube B., Huber R., Goecke T.O., Sandmann W., Royer-Pokora B. Clin. Genet. 65:61-63(2004) [PubMed: 15032977] [Abstract] Cited for: VARIANT SER-12. |
| [23] | "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. |
| [24] | "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 SER-12; ARG-50 AND ASN-145, CHARACTERIZATION OF VARIANTS SER-12; ARG-50 AND ASN-145, INVOLVEMENT IN COWDEN-LIKE DISEASE. |
| [25] | "DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome." Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. Wilson R.K.Nature 456:66-72(2008) [PubMed: 18987736] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-12. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AB006202 mRNA. Translation: BAA22054.1. AB026906 Genomic DNA. Translation: BAA81889.1. AK075360 mRNA. Translation: BAG52120.1. BT007238 mRNA. Translation: AAP35902.1. CR456932 mRNA. Translation: CAG33213.1. AP002007 Genomic DNA. No translation available. CH471065 Genomic DNA. Translation: EAW67181.1. BC005263 mRNA. Translation: AAH05263.1. BC009574 mRNA. Translation: AAH09574.1. BC012603 mRNA. Translation: AAH12603.1. BC015188 mRNA. Translation: AAH15188.1. BC015992 mRNA. Translation: AAH15992.1. BC022350 mRNA. Translation: AAH22350.1. BC070307 mRNA. Translation: AAH70307.1. BC071755 mRNA. Translation: AAH71755.1. BC071756 mRNA. Translation: AAH71756.1. |
| IPI | IPI00297325. |
| RefSeq | NP_002993.1. |
| UniGene | Hs.356270 |
3D structure databases | |
| SMR | O14521. Positions 59-159. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | O14521. |
Proteomic databases | |
| PRIDE | O14521. |
Genome annotation databases | |
| Ensembl | ENST00000375549; ENSP00000364699; ENSG00000204370; Homo sapiens. [Genome view] |
| GeneID | 6392. |
| KEGG | hsa:6392. |
| UCSC | uc001pmz.1. human. |
Organism-specific databases | |
| CTD | 6392. |
| GeneCards | GC11P111462. GC11P111463. |
| H-InvDB | HIX0010122. HIX0029526. HIX0057022. |
| HGNC | HGNC:10683. SDHD. |
| MIM | 114900. phenotype. 168000. phenotype. 171300. phenotype. 602690. gene. 606864. phenotype. 612359. phenotype. |
| Orphanet | 97286. Carney-Stratakis syndrome. 201. Cowden syndrome. 877. Endocrine tumor. 29072. Hereditary pheochromocytoma-paraganglioma syndrome. |
| PharmGKB | PA35608. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG04089. |
| HOGENOM | HBG714119. |
| HOVERGEN | O14521. |
| InParanoid | O14521. |
| OMA | HWGLGQV. |
| OrthoDB | EOG9R52N6. |
Enzyme and pathway databases | |
| BioCyc | MetaCyc:ENSG00000150781-MONOMER. |
| Reactome | REACT_1046. Pyruvate metabolism and TCA cycle. REACT_1505. Integration of energy metabolism. REACT_15380. Diabetes pathways. |
Gene expression databases | |
| ArrayExpress | O14521. |
| Bgee | O14521. |
| CleanEx | HS_SDHD. |
| Genevestigator | O14521. |
| GermOnline | ENSG00000204370. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR007992. Cyt_b_succ_DH_CybS. [Graphical view] |
| PANTHER | PTHR13337. CybS. 1 hit. |
| Pfam | PF05328. CybS. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00139. Succinic acid. |
| NextBio | 24838. |
| SOURCE | Search... |
Entry information
| Entry name | DHSD_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O14521 Secondary accession number(s): A6ND90 Q6IRW2 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 11 Human chromosome 11: 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


