Q9P2R7 (SUCB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Succinyl-CoA ligase [ADP-forming] subunit beta, mitochondrial
EC=6.2.1.5

Alternative name(s):
ATP-specific succinyl-CoA synthetase subunit beta
Renal carcinoma antigen NY-REN-39
Succinyl-CoA synthetase beta-A chain
Short name=SCS-betaA

Gene names

Name:

SUCLA2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	463 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	Catalyzes the ATP-dependent ligation of succinate and CoA to form succinyl-CoA By similarity.
Catalytic activity	ATP + succinate + CoA = ADP + phosphate + succinyl-CoA.
Pathway	Carbohydrate metabolism; tricarboxylic acid cycle; succinate from succinyl-CoA (ligase route): step 1/1.
Subunit structure	Heterodimer of an alpha and a beta subunit. Interacts with ALAS2. Ref.8
Subcellular location	Mitochondrion.
Tissue specificity	Widely expressed. Not expressed in liver and lung. Ref.6
Involvement in disease	Mitochondrial DNA depletion syndrome 5 (MTDPS5) [MIM:612073]: A disorder due to mitochondrial dysfunction. It is characterized by infantile onset of hypotonia, neurologic deterioration, a hyperkinetic-dystonic movement disorder, external ophthalmoplegia, deafness, variable renal tubular dysfunction, and mild methylmalonic aciduria. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.11 Ref.14
Sequence similarities	Belongs to the succinate/malate CoA ligase beta subunit family. Contains 1 ATP-grasp domain.

Ontologies

Keywords
Biological process	Tricarboxylic acid cycle
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	succinate metabolic process Inferred from electronic annotation. Source: Compara succinyl-CoA pathway Non-traceable author statement Ref.1. Source: UniProtKB tricarboxylic acid cycle Traceable author statement. Source: Reactome
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: InterPro succinate-CoA ligase (ADP-forming) activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9P2R7-1)

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: Q9P2R7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     26-47: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 52	52	Mitochondrion By similarity
	Chain	53 – 463	411	Succinyl-CoA ligase [ADP-forming] subunit beta, mitochondrial		PRO_0000033352
Regions
	Domain	61 – 288	228	ATP-grasp
Amino acid modifications
	Modified residue	78	1	N6-acetyllysine Ref.12
	Modified residue	84	1	Phosphotyrosine Ref.10
	Modified residue	143	1	N6-acetyllysine Ref.12
	Modified residue	279	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	26 – 47	22	Missing in isoform 2.		VSP_006292
	Natural variant	13	1	V → M. Corresponds to variant rs35201084 [ dbSNP | Ensembl ].		VAR_046214
	Natural variant	118	1	G → R in MTDPS5. Ref.14		VAR_046215
	Natural variant	199	1	S → T. Ref.2 Ref.4 Ref.6 Corresponds to variant rs7320366 [ dbSNP | Ensembl ].		VAR_013459
	Natural variant	284	1	R → C in MTDPS5. Ref.14		VAR_046216
Experimental info
	Sequence conflict	40	1	N → D in BAA91939. Ref.2
	Sequence conflict	203	1	I → V in BAA91939. Ref.2
	Sequence conflict	323	1	N → S in BAA91703. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 2, 2006. Version 3. Checksum: 1E1651728AF3B5CD	FASTA	463	50,317
	10 20 30 40 50 60 MAASMFYGRL VAVATLRNHR PRTAQRAAAQ VLGSSGLFNN HGLQVQQQQQ RNLSLHEYMS 70 80 90 100 110 120 MELLQEAGVS VPKGYVAKSP DEAYAIAKKL GSKDVVIKAQ VLAGGRGKGT FESGLKGGVK 130 140 150 160 170 180 IVFSPEEAKA VSSQMIGKKL FTKQTGEKGR ICNQVLVCER KYPRREYYFA ITMERSFQGP 190 200 210 220 230 240 VLIGSSHGGV NIEDVAAESP EAIIKEPIDI EEGIKKEQAL QLAQKMGFPP NIVESAAENM 250 260 270 280 290 300 VKLYSLFLKY DATMIEINPM VEDSDGAVLC MDAKINFDSN SAYRQKKIFD LQDWTQEDER 310 320 330 340 350 360 DKDAAKANLN YIGLDGNIGC LVNGAGLAMA TMDIIKLHGG TPANFLDVGG GATVHQVTEA 370 380 390 400 410 420 FKLITSDKKV LAILVNIFGG IMRCDVIAQG IVMAVKDLEI KIPVVVRLQG TRVDDAKALI 430 440 450 460 ADSGLKILAC DDLDEAARMV VKLSEIVTLA KQAHVDVKFQ LPI
	Isoform 2 [UniParc]. Checksum: B0B5E3CA063BEAD1	FASTA	441	48,040
	10 20 30 40 50 60 MAASMFYGRL VAVATLRNHR PRTAQQQQRN LSLHEYMSME LLQEAGVSVP KGYVAKSPDE 70 80 90 100 110 120 AYAIAKKLGS KDVVIKAQVL AGGRGKGTFE SGLKGGVKIV FSPEEAKAVS SQMIGKKLFT 130 140 150 160 170 180 KQTGEKGRIC NQVLVCERKY PRREYYFAIT MERSFQGPVL IGSSHGGVNI EDVAAESPEA 190 200 210 220 230 240 IIKEPIDIEE GIKKEQALQL AQKMGFPPNI VESAAENMVK LYSLFLKYDA TMIEINPMVE 250 260 270 280 290 300 DSDGAVLCMD AKINFDSNSA YRQKKIFDLQ DWTQEDERDK DAAKANLNYI GLDGNIGCLV 310 320 330 340 350 360 NGAGLAMATM DIIKLHGGTP ANFLDVGGGA TVHQVTEAFK LITSDKKVLA ILVNIFGGIM 370 380 390 400 410 420 RCDVIAQGIV MAVKDLEIKI PVVVRLQGTR VDDAKALIAD SGLKILACDD LDEAARMVVK 430 440 LSEIVTLAKQ AHVDVKFQLP I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia." Furuyama K., Shigeru S. J. Clin. Invest. 105:757-764(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT THR-199. Tissue: Placenta and Tongue.
[3]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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], VARIANT THR-199.
[5]	"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: Testis.
[6]	"Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes." Johnson J.D., Mehus J.G., Tews K., Milavetz B.I., Lambeth D.O. J. Biol. Chem. 273:27580-27586(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 38-463 (ISOFORM 1), TISSUE SPECIFICITY, VARIANT THR-199. Tissue: Liver.
[7]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[8]	"The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis." Cox T.C., Sadlon T.J., Schwarz Q.P., Matthews C.S., Wise P.D., Cox L.L., Bottomley S.S., May B.K. Int. J. Biochem. Cell Biol. 36:281-295(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ALAS2.
[9]	"Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion." Elpeleg O., Miller C., Hershkovitz E., Bitner-Glindzicz M., Bondi-Rubinstein G., Rahman S., Pagnamenta A., Eshhar S., Saada A. Am. J. Hum. Genet. 76:1081-1086(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MTDPS5.
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-84, MASS SPECTROMETRY.
[11]	"Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations." Ostergaard E., Hansen F.J., Sorensen N., Duno M., Vissing J., Larsen P.L., Faeroe O., Thorgrimsson S., Wibrand F., Christensen E., Schwartz M. Brain 130:853-861(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MTDPS5.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-78 AND LYS-143, MASS SPECTROMETRY.
[13]	"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].
[14]	"SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness." Carrozzo R., Dionisi-Vici C., Steuerwald U., Lucioli S., Deodato F., Di Giandomenico S., Bertini E., Franke B., Kluijtmans L.A., Meschini M.C., Rizzo C., Piemonte F., Rodenburg R., Santer R., Santorelli F.M., van Rooij A., Vermunt-de Koning D., Morava E., Wevers R.A. Brain 130:862-874(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MTDPS5 ARG-118 AND CYS-284.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB035863 mRNA. Translation: BAA92873.1. AK001458 mRNA. Translation: BAA91703.1. AK001847 mRNA. Translation: BAA91939.1. AK315513 mRNA. Translation: BAG37894.1. AL157369 Genomic DNA. Translation: CAI15149.1. AL157369 Genomic DNA. Translation: CAI15153.1. CH471075 Genomic DNA. Translation: EAX08777.1. BC027587 mRNA. Translation: AAH27587.1. AF058953 mRNA. Translation: AAC64396.1.
IPI	IPI00217232. IPI00464979.
RefSeq	NP_003841.1. NM_003850.2.
UniGene	Hs.546323.
3D structure databases
ProteinModelPortal	Q9P2R7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9P2R7. 5 interactions.
STRING	9606.ENSP00000367923.
PTM databases
PhosphoSite	Q9P2R7.
Polymorphism databases
DMDM	94730427.
Proteomic databases
PaxDb	Q9P2R7.
PRIDE	Q9P2R7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378645; ENSP00000367912; ENSG00000136143. ENST00000378654; ENSP00000367923; ENSG00000136143.
GeneID	8803.
KEGG	hsa:8803.
UCSC	uc001vbs.3. human.
Organism-specific databases
CTD	8803.
GeneCards	GC13M048510.
HGNC	HGNC:11448. SUCLA2.
HPA	HPA039435.
MIM	603921. gene. 612073. phenotype.
neXtProt	NX_Q9P2R7.
Orphanet	1933. Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria.
PharmGKB	PA36245.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0045.
HOVERGEN	HBG055555.
InParanoid	Q9P2R7.
KO	K01900.
OMA	QPVTKIL.
OrthoDB	EOG4RBQJQ.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000136143-MONOMER.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00223; UER00999.
Gene expression databases
ArrayExpress	Q9P2R7.
Bgee	Q9P2R7.
CleanEx	HS_SUCLA2.
Genevestigator	Q9P2R7.
GermOnline	ENSG00000136143. Homo sapiens.
Family and domain databases
Gene3D	3.30.1490.20. 1 hit. 3.30.470.20. 1 hit. 3.40.50.261. 1 hit.
InterPro	IPR011761. ATP-grasp. IPR013650. ATP-grasp_succ-CoA_synth-type. IPR013815. ATP_grasp_subdomain_1. IPR013816. ATP_grasp_subdomain_2. IPR005811. CoA_ligase. IPR017866. Succ-CoA_synthase_bsu_CS. IPR005809. Succ_CoA_synthase_bsu. IPR016102. Succinyl-CoA_synth-like. [Graphical view]
PANTHER	PTHR11815. PTHR11815. 1 hit.
Pfam	PF08442. ATP-grasp_2. 1 hit. PF00549. Ligase_CoA. 1 hit. [Graphical view]
PIRSF	PIRSF001554. SucCS_beta. 1 hit.
SUPFAM	SSF52210. CoA_ligase. 1 hit.
TIGRFAMs	TIGR01016. sucCoAbeta. 1 hit.
PROSITE	PS50975. ATP_GRASP. 1 hit. PS01217. SUCCINYL_COA_LIG_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SUCLA2. human.
DrugBank	DB00139. Succinic acid.
GenomeRNAi	8803.
NextBio	33020.
SOURCE	Search...

Entry information

Entry name

SUCB1_HUMAN

Accession

Primary (citable) accession number: Q9P2R7
Secondary accession number(s): B2RDE7 , O95194, Q5T9Q4, Q5T9Q6, Q9NV21, Q9NVP7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 27, 2002
Last sequence update:	May 2, 2006
Last modified:	May 1, 2013
This is version 135 of the entry and version 3 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.