<p>Provides any useful information about the protein, mostly biological knowledge.</p><p><a href='../manual/function_section' target='_top'>More...</a></p>Functionⁱ

<p>Describes the metabolic pathway(s) associated with a protein.</p><p><a href='../manual/pathway' target='_top'>More...</a></p>Pathwayⁱ

Sites

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.</p><p><a href='../manual/metal' target='_top'>More...</a></p>Metal bindingi	102 – 102	1	Iron (heme axial ligand); shared with SDHCBy similarity
<p>Describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.</p><p><a href='../manual/binding' target='_top'>More...</a></p>Binding sitei	114 – 114	1	Ubiquinone; shared with IP/SDHBBy similarity

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

1. electron carrier activity Source: UniProtKB

   <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

   • 9533030

2. heme binding Source: UniProtKB
3. metal ion binding Source: UniProtKB-KW
4. succinate dehydrogenase activity Source: UniProtKB

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 9533030

5. ubiquinone binding Source: UniProtKB

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Biological processⁱ

1. cellular metabolic process Source: Reactome
2. respiratory electron transport chain Source: Reactome
3. small molecule metabolic process Source: Reactome
4. tricarboxylic acid cycle Source: UniProtKB

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 9533030

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Biological processⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Ligandⁱ

Enzyme and pathway databases

<p>Provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.</p><p><a href='../manual/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>Provides information on the location and the topology of the mature protein in the cell.</p><p><a href='../manual/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Topology

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.</p><p><a href='../manual/topo_dom' target='_top'>More...</a></p>Topological domaini	57 – 63	7	Mitochondrial matrixBy similarity
<p>Describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.</p><p><a href='../manual/transmem' target='_top'>More...</a></p>Transmembranei	64 – 85	22	HelicalBy similarity			Add BLAST
<p>Describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.</p><p><a href='../manual/topo_dom' target='_top'>More...</a></p>Topological domaini	86 – 90	5	Mitochondrial intermembraneBy similarity
<p>Describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.</p><p><a href='../manual/transmem' target='_top'>More...</a></p>Transmembranei	91 – 111	21	HelicalBy similarity			Add BLAST
<p>Describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.</p><p><a href='../manual/topo_dom' target='_top'>More...</a></p>Topological domaini	112 – 120	9	Mitochondrial matrixBy similarity
<p>Describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.</p><p><a href='../manual/transmem' target='_top'>More...</a></p>Transmembranei	121 – 142	22	HelicalBy similarity			Add BLAST
<p>Describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.</p><p><a href='../manual/topo_dom' target='_top'>More...</a></p>Topological domaini	143 – 159	17	Mitochondrial intermembraneBy similarity			Add BLAST

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Cellular componentⁱ

1. integral component of membrane Source: UniProtKB-KW
2. mitochondrial envelope Source: ProtInc

   <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

   • 9533030

3. mitochondrial inner membrane Source: UniProtKB

   <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ

   • 9533030

4. mitochondrial respiratory chain complex II Source: UniProtKB
5. mitochondrion Source: ProtInc

   <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ

   • 2302193

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Cellular componentⁱ

<p>Provides information on the disease(s) and phenotype(s) associated with the deficiency of a protein.</p><p><a href='../manual/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>Provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim"><span class="caps">OMIM</span></a> database are represented with a <a href="/diseases">controlled vocabulary</a> in the following way:</p><p><a href='../manual/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Paragangliomas 1 (PGL1)

[MIM:168000]: A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. 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.5 Publications

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.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] [Europe PMC] [Abstract]

  Cited for: VARIANTS PGL1 LEU-81; TYR-92 AND LEU-102.
• Ref.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] [Europe PMC] [Abstract]

  Cited for: VARIANT PGL1 CYS-114.
• Ref.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] [Europe PMC] [Abstract]

  Cited for: VARIANT PGL1 TYR-93 DEL.
• Ref.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] [Europe PMC] [Abstract]

  Cited for: VARIANTS PGL1 TYR-92 AND PRO-139.
• Ref.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] [Europe PMC] [Abstract]

  Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.

Note: The disease is caused by mutations affecting the gene represented in this entry.

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	81 – 81	1	P → L in PGL1 and pheochromocytoma. 3 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANT PHEOCHROMOCYTOMA LEU-81. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; TYR-92 AND LEU-102. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.		VAR_010038
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	92 – 92	1	D → Y in PGL1 and pheochromocytoma. 4 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; TYR-92 AND LEU-102. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 TYR-92 AND PRO-139. Ref.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. , Walz M.K., Hoang-Vu C., Brauckhoff M., Klein-Franke A., Klose P., Schmidt H., Maier-Woelfle M., Peczkowska M., Szmigielski C., Eng C. N. Engl. J. Med. 346:1459-1466(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PHEOCHROMOCYTOMA TYR-92. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.		VAR_010039
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	93 – 93	1	Missing in PGL1. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANT PGL1 TYR-93 DEL.		VAR_018519
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	102 – 102	1	H → L in PGL1. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; TYR-92 AND LEU-102.		VAR_010040
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	114 – 114	1	Y → C in PGL1. 2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANT PGL1 CYS-114. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.		VAR_017872
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	139 – 139	1	L → P in PGL1. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 TYR-92 AND PRO-139.		VAR_017873
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	148 – 148	1	G → V in PGL1. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.		VAR_054385

Pheochromocytoma (PCC)

[MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.3 Publications

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.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] [Europe PMC] [Abstract]

  Cited for: VARIANT PHEOCHROMOCYTOMA LEU-81.
• Ref.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.

  , Walz M.K., Hoang-Vu C., Brauckhoff M., Klein-Franke A., Klose P., Schmidt H., Maier-Woelfle M., Peczkowska M., Szmigielski C., Eng C.
  N. Engl. J. Med. 346:1459-1466(2002) [PubMed] [Europe PMC] [Abstract]

  Cited for: VARIANT PHEOCHROMOCYTOMA TYR-92.
• Ref.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] [Europe PMC] [Abstract]

  Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.

Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Intestinal carcinoid tumor (ICT)

[MIM:114900]: A yellow, well-differentiated, circumscribed tumor that arises from enterochromaffin cells in the small intestine or, less frequently, in other parts of the gastrointestinal tract.1 Publication

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.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] [Europe PMC] [Abstract]

  Cited for: INVOLVEMENT IN INTESTINAL CARCINOID TUMOR, VARIANTS SER-12 AND ARG-50.

Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Paraganglioma and gastric stromal sarcoma (PGGSS)

[MIM:606864]: 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.1 Publication

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.22

  "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] [Europe PMC] [Abstract]

  Cited for: INVOLVEMENT IN PGGSS.

Note: The disease is caused by mutations affecting the gene represented in this entry.

Cowden syndrome 3 (CWS3)

[MIM:615106]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid.1 Publication

<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment inⁱ

• Ref.23

  "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] [Europe PMC] [Abstract]

  Cited for: VARIANTS SER-12; ARG-50 AND ASN-145, CHARACTERIZATION OF VARIANTS SER-12; ARG-50 AND ASN-145, INVOLVEMENT IN CWS3.

Note: The disease may be caused by mutations affecting the gene represented in this entry.

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Diseaseⁱ

Organism-specific databases

<p>Describes post-translational modifications (PTMs) and/or processing events.</p><p><a href='../manual/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the extent of a transit peptide.</p><p><a href='../manual/transit' target='_top'>More...</a></p>Transit peptidei	1 – 56	56	MitochondrionSequence Analysis			Add BLAST
<p>Describes the extent of a polypeptide chain in the mature protein following processing.</p><p><a href='../manual/chain' target='_top'>More...</a></p>Chaini	57 – 159	103	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial		PRO_0000006487	Add BLAST

Proteomic databases

<p>Provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.</p><p><a href='../manual/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

Organism-specific databases

<p>Provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.</p><p><a href='../manual/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>Provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the ‘Function’ section).</p><p><a href='../manual/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

Protein-protein interaction databases

<p>Provides information on the tertiary structure of a protein.</p><p><a href='../manual/structure_section' target='_top'>More...</a></p>Structureⁱ

3D structure databases

<p>Provides information on sequence similarities with other proteins and the domain(s) present in a protein.</p><p><a href='../manual/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

<p>Provides information about the sequence similarity with other proteins.</p><p><a href='../manual/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>Displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.</p><p><a href='../manual/sequences_section' target='_top'>More...</a></p>Sequences (4)ⁱ

<p>Indicates if the canonical sequence displayed by default in the entry is complete or not.</p><p><a href='../manual/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>Indicates if the canonical sequence displayed by default in the entry is in its mature form or if it represents the precursor.</p><p><a href='../manual/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 4<p>Lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.</p><p><a href='../manual/alternative_products' target='_top'>More...</a></p> isoformsⁱ produced by alternative splicing. Align

        10         20         30         40         50
MAVLWRLSAV CGALGGRALL LRTPVVRPAH ISAFLQDRPI PEWCGVQHIH 
        60         70         80         90        100
LSPSHHSGSK AASLHWTSER VVSVLLLGLL PAAYLNPCSA MDYSLAAALT 
       110        120        130        140        150
LHGHWGLGQV VTDYVHGDAL QKAAKAGLLA LSALTFAGLC YFNYHDVGIC 

KAVAMLWKL                                             

        10         20         30         40         50
MAVLWRLSAV CGALGGRAGS KAASLHWTSE RVVSVLLLGL LPAAYLNPCS 
        60         70         80         90        100
AMDYSLAAAL TLHGHWGLGQ VVTDYVHGDA LQKAAKAGLL ALSALTFAGL 
       110        120
CYFNYHDVGI CKAVAMLWKL                                  

        10         20         30         40         50
MAVLWRLSAV CGALGGRALL LRTPVVRPAH ISAFLQDRPI PEWCGVQHIH 
        60         70         80 
LSPSHHWALD KLLLTMFMGM PCRKLPRQGF WHFQL            

        10         20         30         40         50
MAVLWRLSAV CGALGGRALL LRTPVVRPAH ISAFLQDRPI PEWCGVQHIH 
        60         70         80         90        100
LSPSHHSGSK AASLHWTSER VVSVLLLGLL PAAYLNPCSA MDYSLAAALT 
       110        120        130        140 
LHGHWLECNG AILARHDLGS ARSQLTATSA FRVQAILLPQ PPK 

Experimental Info

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.</p><p><a href='../manual/conflict' target='_top'>More...</a></p>Sequence conflicti	74 – 74	1	V → F in AAH70307. (PubMed:15489334)Curated

Natural variant

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	12 – 12	1	G → S Polymorphism that may increase susceptibility for developing pheochromocytoma, paraganglioma, intestinal carcinoid tumor and breast, renal and uterus carcinoma; may be associated with Cowden 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. 6 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANT SER-12. Ref.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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN INTESTINAL CARCINOID TUMOR, VARIANTS SER-12 AND ARG-50. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS SER-12 AND ARG-50. Ref.21 "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] [Europe PMC] [Abstract] Cited for: VARIANT SER-12. Ref.23 "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] [Europe PMC] [Abstract] Cited for: VARIANTS SER-12; ARG-50 AND ASN-145, CHARACTERIZATION OF VARIANTS SER-12; ARG-50 AND ASN-145, INVOLVEMENT IN CWS3. Ref.24 "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. , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K. Nature 456:66-72(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-12. Corresponds to variant rs34677591 [ dbSNP | Ensembl ].		VAR_017870
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	50 – 50	1	H → R Polymorphism that may increase susceptibility for developing paraganglioma, breast and thyroid carcinoma; may be involved in somatic Merkel cell carcinoma; may be associated with Cowden 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. 3 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN INTESTINAL CARCINOID TUMOR, VARIANTS SER-12 AND ARG-50. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS SER-12 AND ARG-50. Ref.23 "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] [Europe PMC] [Abstract] Cited for: VARIANTS SER-12; ARG-50 AND ASN-145, CHARACTERIZATION OF VARIANTS SER-12; ARG-50 AND ASN-145, INVOLVEMENT IN CWS3. Corresponds to variant rs11214077 [ dbSNP | Ensembl ].		VAR_017871
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	81 – 81	1	P → L in PGL1 and pheochromocytoma. 3 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANT PHEOCHROMOCYTOMA LEU-81. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; TYR-92 AND LEU-102. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.		VAR_010038
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	92 – 92	1	D → Y in PGL1 and pheochromocytoma. 4 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; TYR-92 AND LEU-102. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 TYR-92 AND PRO-139. Ref.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. , Walz M.K., Hoang-Vu C., Brauckhoff M., Klein-Franke A., Klose P., Schmidt H., Maier-Woelfle M., Peczkowska M., Szmigielski C., Eng C. N. Engl. J. Med. 346:1459-1466(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PHEOCHROMOCYTOMA TYR-92. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.		VAR_010039
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	93 – 93	1	Missing in PGL1. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANT PGL1 TYR-93 DEL.		VAR_018519
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	102 – 102	1	H → L in PGL1. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; TYR-92 AND LEU-102.		VAR_010040
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	114 – 114	1	Y → C in PGL1. 2 Publications <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANT PGL1 CYS-114. Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.		VAR_017872
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	139 – 139	1	L → P in PGL1. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 TYR-92 AND PRO-139.		VAR_017873
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	145 – 145	1	H → N Found in an individual with features of Cowden syndrome; associated with increased manganese superoxide dismutase expression; associated with normal reactive oxygen species; associated with no change in AKT expression but a 1.2-fold increase of MAPK expression. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.23 "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] [Europe PMC] [Abstract] Cited for: VARIANTS SER-12; ARG-50 AND ASN-145, CHARACTERIZATION OF VARIANTS SER-12; ARG-50 AND ASN-145, INVOLVEMENT IN CWS3. Corresponds to variant rs11214077 [ dbSNP | Ensembl ].		VAR_054384
<p>Describes natural variant(s) of the protein sequence.</p><p><a href='../manual/variant' target='_top'>More...</a></p>Natural varianti	148 – 148	1	G → V in PGL1. 1 Publication <p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More…</a></p> Manual assertion based on experiment ini Ref.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] [Europe PMC] [Abstract] Cited for: VARIANTS PGL1 LEU-81; CYS-114 AND VAL-148, VARIANT PHEOCHROMOCYTOMA TYR-92.		VAR_054385

Alternative sequence

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	19 – 57	39	Missing in isoform 2. Curated		VSP_054744	Add BLAST
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	56 – 158	103	HSGSK…AMLWK → HWALDKLLLTMFMGMPCRKL PRQGFWHFQ in isoform 3. Curated		VSP_054745	Add BLAST
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	106 – 143	38	GLGQV…LCYFN → LECNGAILARHDLGSARSQL TATSAFRVQAILLPQPPK in isoform 4. Curated		VSP_054746	Add BLAST
<p>Describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.</p><p><a href='../manual/var_seq' target='_top'>More...</a></p>Alternative sequencei	144 – 159	16	Missing in isoform 4. Curated		VSP_054747	Add BLAST

Sequence databases

Genome annotation databases

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Coding sequence diversityⁱ

<p>Is used to point to information related to entries and found in data collections other than UniProtKB.</p><p><a href='../manual/cross_references_section' target='_top'>More...</a></p> Cross-referencesⁱ

<p>Provides links to various web resources that are relevant for a specific protein.</p><p><a href='../manual/web_resource' target='_top'>More...</a></p> Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>Contains the literature citations that are the sources of data used to annotate the entry. Each reference is numbered and contains several subsections allowing a precise description of a given citation.</p><p><a href='../manual/publications_section' target='_top'>More...</a></p>Publicationsⁱ

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] [Europe PMC] [Abstract]
   Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
   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] [Europe PMC] [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.

   , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
   DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
   Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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] (ISOFORM 1).
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] (ISOFORM 1).
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.

   , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
   Nature 440:497-500(2006) [PubMed] [Europe PMC] [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.

   , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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] [Europe PMC] [Abstract]
   Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
   Tissue: Bone marrow, Brain, Lung and Skeletal muscle.
   
9. "Initial characterization of the human central proteome."
   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
   BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
   Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.

    , Walz M.K., Hoang-Vu C., Brauckhoff M., Klein-Franke A., Klose P., Schmidt H., Maier-Woelfle M., Peczkowska M., Szmigielski C., Eng C.
    N. Engl. J. Med. 346:1459-1466(2002) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: VARIANTS PGL1 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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN PGGSS.
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] [Europe PMC] [Abstract]
    Cited for: VARIANTS SER-12; ARG-50 AND ASN-145, CHARACTERIZATION OF VARIANTS SER-12; ARG-50 AND ASN-145, INVOLVEMENT IN CWS3.
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.

    , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K.
    Nature 456:66-72(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-12.

<p>Provides general information on the entry.</p><p><a href='../manual/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>Contains any relevant information that doesn’t fit in any other defined sections</p><p><a href='../manual/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

<p>UniProtKB Keywords constitute a <a target="_top" href="/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='../help/keywords' target='_top'>More...</a></p>Keywords - Technical termⁱ

Documents

1. Human chromosome 11
   Human chromosome 11: 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. PATHWAY comments
   Index of metabolic and biosynthesis pathways
6. SIMILARITY comments
   Index of protein domains and families

External Data

<p>Provides links to the UniProt Reference Clusters (<a href="/help/uniref">UniRef</a>). UniRef consists of clusters for UniProtKB sequences (including isoforms) and selected UniParc sequences, in order to obtain complete coverage of the sequence space at resolutions of 100%, 90% and 50% identity.</p><p><a href='../manual/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ