Q99643 (C560_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Succinate dehydrogenase cytochrome b560 subunit, mitochondrial

Alternative name(s):
Integral membrane protein CII-3
QPs-1
Short name=QPs1
Succinate dehydrogenase complex subunit C
Succinate-ubiquinone oxidoreductase cytochrome B large subunit
Short name=CYBL

Gene names

Name:	SDHC
Synonyms:	CYB560, SDH3

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	169 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).
Cofactor	Heme group. The heme is bound between the two transmembrane subunits SDHC and SDHD By similarity.
Pathway	Carbohydrate metabolism; tricarboxylic acid cycle.
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; Multi-pass membrane protein.
Involvement in disease	Defects in SDHC are the cause of paragangliomas type 3 (PGL3) [MIM:605373]. A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. Paragangliomas are most commonly located in the head and neck region, specifically at the carotid bifurcation, the jugular foramen, the vagal nerve, and in the middle ear. Ref.10 Defects in SDHC are a cause of paraganglioma and gastric stromal sarcoma (PGGSS) [MIM:606864]; also known as 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.11
Sequence similarities	Belongs to the cytochrome b560 family.

Ontologies

Keywords
Biological process	Electron transport Transport Tricarboxylic acid cycle
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing
Domain	Transit peptide Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	respiratory electron transport chain Traceable author statement. Source: Reactome transport Inferred from electronic annotation. Source: UniProtKB-KW tricarboxylic acid cycle Traceable author statement Ref.2. Source: UniProtKB
Cellular component	integral to membrane Traceable author statement Ref.2. Source: UniProtKB mitochondrial respiratory chain complex II Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane succinate dehydrogenase complex Inferred from electronic annotation. Source: InterPro
Molecular function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from sequence or structural similarity. Source: UniProtKB succinate dehydrogenase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99643-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q99643-2)

The sequence of this isoform differs from the canonical sequence as follows:
     81-169: GVSLFGMSAL...VLSSMGLAAM → DVGPRKRPED...PAWEKFSLFV

Isoform 3 (identifier: Q99643-3)

Also known as: CII-3b;

The sequence of this isoform differs from the canonical sequence as follows:
     27-60: Missing.

Isoform 4 (identifier: Q99643-4)

The sequence of this isoform differs from the canonical sequence as follows:
     27-60: Missing.
     81-169: GVSLFGMSAL...VLSSMGLAAM → DVGPRKRPED...PAWEKFSLFV

Isoform 5 (identifier: Q99643-5)

The sequence of this isoform differs from the canonical sequence as follows:
     7-59: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 29	29	Mitochondrion By similarity
	Chain	30 – 169	140	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial		PRO_0000003634
Regions
	Topological domain	30 – 62	33	Mitochondrial matrix By similarity
	Transmembrane	63 – 92	30	Helical; By similarity
	Topological domain	93 – 112	20	Mitochondrial intermembrane By similarity
	Transmembrane	113 – 137	25	Helical; By similarity
	Topological domain	138 – 144	7	Mitochondrial matrix By similarity
	Transmembrane	145 – 166	22	Helical; By similarity
	Topological domain	167 – 169	3	Mitochondrial intermembrane By similarity
Sites
	Metal binding	127	1	Iron (heme axial ligand); shared with SDHD By similarity
Natural variations
	Alternative sequence	7 – 59	53	Missing in isoform 5.		VSP_041381
	Alternative sequence	27 – 60	34	Missing in isoform 3 and isoform 4.		VSP_041382
	Alternative sequence	81 – 169	89	GVSLF…GLAAM → DVGPRKRPEDSPAIPVWSGC PGSYCVVLYGAGSHVKKGGS QHHLPTHYYIHPSFCLSFLS PAWEKFSLFV in isoform 2 and isoform 4.		VSP_041383

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: DF7CBD6D0CD49500	FASTA	169	18,610
	10 20 30 40 50 60 MAALLLRHVG RHCLRAHFSP QLCIRNAVPL GTTAKEEMER FWNKNIGSNR PLSPHITIYS 70 80 90 100 110 120 WSLPMAMSIC HRGTGIALSA GVSLFGMSAL LLPGNFESYL ELVKSLCLGP ALIHTAKFAL 130 140 150 160 VFPLMYHTWN GIRHLMWDLG KGLKIPQLYQ SGVVVLVLTV LSSMGLAAM
	Isoform 2 [UniParc]. Checksum: 971579A96F795D90	FASTA	150	16,650
	10 20 30 40 50 60 MAALLLRHVG RHCLRAHFSP QLCIRNAVPL GTTAKEEMER FWNKNIGSNR PLSPHITIYS 70 80 90 100 110 120 WSLPMAMSIC HRGTGIALSA DVGPRKRPED SPAIPVWSGC PGSYCVVLYG AGSHVKKGGS 130 140 150 QHHLPTHYYI HPSFCLSFLS PAWEKFSLFV
	Isoform 3 (CII-3b) [UniParc]. Checksum: 5F7A8BC812112D75	FASTA	135	14,770
	10 20 30 40 50 60 MAALLLRHVG RHCLRAHFSP QLCIRNWSLP MAMSICHRGT GIALSAGVSL FGMSALLLPG 70 80 90 100 110 120 NFESYLELVK SLCLGPALIH TAKFALVFPL MYHTWNGIRH LMWDLGKGLK IPQLYQSGVV 130 VLVLTVLSSM GLAAM
	Isoform 4 [UniParc]. Checksum: 36DFFD8CC2E6D4E8	FASTA	116	12,810
	10 20 30 40 50 60 MAALLLRHVG RHCLRAHFSP QLCIRNWSLP MAMSICHRGT GIALSADVGP RKRPEDSPAI 70 80 90 100 110 PVWSGCPGSY CVVLYGAGSH VKKGGSQHHL PTHYYIHPSF CLSFLSPAWE KFSLFV
	Isoform 5 [UniParc]. Checksum: AC702AE33DD1F118	FASTA	116	12,474
	10 20 30 40 50 60 MAALLLSWSL PMAMSICHRG TGIALSAGVS LFGMSALLLP GNFESYLELV KSLCLGPALI 70 80 90 100 110 HTAKFALVFP LMYHTWNGIR HLMWDLGKGL KIPQLYQSGV VVLVLTVLSS MGLAAM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The cDNA sequence of human CII-3, an integral membrane protein subunit of complex II of the mitochondria electron transport chain." Au H.C., Raval P.J., Scheffler I.E. Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"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] (ISOFORM 1). Tissue: Liver.
[3]	"Characterization of the human SDHC gene encoding one of the integral membrane proteins of succinate-quinone oxidoreductase in mitochondria." Elbehti-Green A., Au H.C., Mascarello J.T., Ream-Robinson D., Scheffler I.E. Gene 213:133-140(1998) [PubMed: 9714607] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"A human succinate-ubiquinone oxidoreductase CII-3 subunit gene ending in a polymorphic dinucleotide repeat is located within the sulfonylurea receptor (SUR) gene." Wohllk N., Thomas P.M., Huang E., Cote G.J. Mol. Genet. Metab. 65:187-190(1998) [PubMed: 9851882] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Peripheral blood.
[5]	"Homo sapiens succinate dehydrogenase complex, subunit C mRNA, alternative splicing variants." Hiatomi H., Kitano S., Kawano K., Hibi N. Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 5).
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Amygdala.
[7]	"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. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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] (ISOFORM 1). Tissue: Brain, Mammary gland and Skeletal muscle.
[10]	"Mutations in SDHC cause autosomal dominant paraganglioma, type 3." Niemann S., Mueller U. Nat. Genet. 26:268-270(2000) [PubMed: 11062460] [Abstract] Cited for: INVOLVEMENT IN PGL3.
[11]	"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 PGGSS.
[12]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Wikipedia

SDHC entry

TCA Cycle Gene Mutation Database

Cross-references

Sequence databases
EMBL GenBank DDBJ	U57877 mRNA. Translation: AAB41838.1. D49737 mRNA. Translation: BAA31998.1. AF039594 , AF039589, AF039590, AF039591, AF039592, AF039593 Genomic DNA. Translation: AAC27993.1. AF081495 Genomic DNA. Translation: AAC31940.1. AB201252 mRNA. Translation: BAE46977.1. AB211234 mRNA. Translation: BAE46978.1. AB211235 mRNA. Translation: BAE46979.1. AB212048 mRNA. Translation: BAE46980.1. AK294305 mRNA. Translation: BAG57586.1. AL592295 Genomic DNA. Translation: CAH70271.1. CH471121 Genomic DNA. Translation: EAW52600.1. CH471121 Genomic DNA. Translation: EAW52604.1. BC020808 mRNA. Translation: AAH20808.1. BC033626 mRNA. Translation: AAH33626.1. BC066329 mRNA. Translation: AAH66329.1.
IPI	IPI00016968. IPI00655605. IPI00655681. IPI00655889. IPI00943958.
RefSeq	NP_001030588.1. NM_001035511.1. NP_001030589.1. NM_001035512.1. NP_001030590.1. NM_001035513.1. NP_002992.1. NM_003001.3.
UniGene	Hs.444472.
3D structure databases
ProteinModelPortal	Q99643.
SMR	Q99643. Positions 32-169.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99643. 1 interaction.
STRING	Q99643.
Polymorphism databases
DMDM	5915811.
Proteomic databases
PRIDE	Q99643.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367975; ENSP00000356953; ENSG00000143252.
GeneID	6391.
KEGG	hsa:6391.
NMPDR	fig|9606.3.peg.2487.
UCSC	uc001gag.1. human.
Organism-specific databases
CTD	6391.
GeneCards	GC01P161285.
H-InvDB	HIX0001245.
HGNC	HGNC:10682. SDHC.
MIM	602413. gene. 605373. phenotype. 606864. phenotype.
neXtProt	NX_Q99643.
Orphanet	97286. Carney-Stratakis syndrome. 44890. Gastrointestinal stromal tumor. 29072. Hereditary pheochromocytoma-paraganglioma.
PharmGKB	PA35607.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000000566.
HOGENOM	HBG734972.
HOVERGEN	HBG003187.
InParanoid	Q99643.
OMA	FHRISGC.
OrthoDB	EOG4BCDP5.
PhylomeDB	Q99643.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000143252-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q99643.
Bgee	Q99643.
CleanEx	HS_SDHC.
Genevestigator	Q99643.
GermOnline	ENSG00000143252. Homo sapiens.
Family and domain databases
InterPro	IPR018495. Succ_DH_cyt_bsu_CS. IPR014314. Succ_DH_cytb556. IPR014361. Succ_DH_cytb560. IPR000701. Succ_DH_Fumarate_Rdtase_TM-su. [Graphical view]
KO	K00236.
Pfam	PF01127. Sdh_cyt. 1 hit. [Graphical view]
PIRSF	PIRSF000178. SDH_cyt_b560. 1 hit.
TIGRFAMs	TIGR02970. Succ_dehyd_cytB. 1 hit.
PROSITE	PS01000. SDH_CYT_1. 1 hit. PS01001. SDH_CYT_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00139. Succinic acid.
NextBio	24828.
SOURCE	Search...

Entry information

Entry name

C560_HUMAN

Accession

Primary (citable) accession number: Q99643
Secondary accession number(s): O75609 , Q3C259, Q3C2D8, Q3C2H4, Q5VTH3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	May 1, 1997
Last modified:	January 25, 2012
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.