P53597 (SUCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Succinyl-CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial
EC=6.2.1.4
EC=6.2.1.5

Alternative name(s):
Succinyl-CoA synthetase subunit alpha
Short name=SCS-alpha

Gene names

Name:

SUCLG1

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	346 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- or GTP-dependent ligation of succinate and CoA to form succinyl-CoA. The nature of the beta subunit determines the nucleotide specificity By similarity.
Catalytic activity	GTP + succinate + CoA = GDP + phosphate + succinyl-CoA. ATP + succinate + CoA = ADP + phosphate + succinyl-CoA.
Pathway	Carbohydrate metabolism; tricarboxylic acid cycle.
Subunit structure	Heterodimer of an alpha and a beta subunit.
Subcellular location	Mitochondrion.
Involvement in disease	Mitochondrial DNA depletion syndrome 9 (MTDPS9) [MIM:245400]: A severe disorder due to mitochondrial dysfunction. It is characterized by infantile onset of hypotonia, lactic acidosis, severe psychomotor retardation, progressive neurologic deterioration, and excretion of methylmalonic acid. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the succinate/malate CoA ligase alpha subunit family.
Sequence caution	The sequence AAD17940.2 differs from that shown. Reason: Erroneous initiation. The sequence AAH00504.1 differs from that shown. Reason: Erroneous initiation. The sequence CAA92426.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Tricarboxylic acid cycle
Cellular component	Mitochondrion
Disease	Disease mutation
Domain	Transit peptide
Ligand	GTP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	small molecule metabolic process Traceable author statement. Source: Reactome succinate metabolic process Inferred from electronic annotation. Source: Compara succinyl-CoA metabolic process Inferred from electronic annotation. Source: Compara tricarboxylic acid cycle Traceable author statement. Source: Reactome
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: Compara mitochondrial matrix Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay. Source: HPA succinate-CoA ligase complex (GDP-forming) Inferred from electronic annotation. Source: Compara
Molecular_function	ATP citrate synthase activity Inferred from electronic annotation. Source: InterPro GDP binding Inferred from electronic annotation. Source: Compara GTP binding Inferred from electronic annotation. Source: UniProtKB-KW cofactor binding Inferred from electronic annotation. Source: InterPro succinate-CoA ligase (ADP-forming) activity Inferred from electronic annotation. Source: EC succinate-CoA ligase (GDP-forming) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 40	40	Mitochondrion By similarity
	Chain	41 – 346	306	Succinyl-CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial		PRO_0000033340
Sites
	Active site	299	1	Tele-phosphohistidine intermediate By similarity
Amino acid modifications
	Modified residue	54	1	N6-acetyllysine Ref.6
	Cross-link	280		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Natural variations
	Natural variant	14	1	M → L in MTDPS9; with progressive liver disease and recurrent hepatic failure. Ref.10		VAR_065120
	Natural variant	85	1	G → A in MTDPS9. Ref.8		VAR_065157
	Natural variant	170	1	P → R in MTDPS9. Ref.9		VAR_065121
Experimental info
	Sequence conflict	19	1	S → N in CAA92426. Ref.4
	Sequence conflict	34	1	P → Q in CAA92426. Ref.4
	Sequence conflict	39	1	R → Q in CAA92426. Ref.4
	Sequence conflict	87	1	T → L in AAD17940. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P53597 [UniParc]. Last modified February 10, 2009. Version 4. Checksum: 76EF06F323CD5188	FASTA	346	36,250
	10 20 30 40 50 60 MTATLAAAAD IATMVSGSSG LAAARLLSRS FLLPQNGIRH CSYTASRQHL YVDKNTKIIC 70 80 90 100 110 120 QGFTGKQGTF HSQQALEYGT KLVGGTTPGK GGQTHLGLPV FNTVKEAKEQ TGATASVIYV 130 140 150 160 170 180 PPPFAAAAIN EAIEAEIPLV VCITEGIPQQ DMVRVKHKLL RQEKTRLIGP NCPGVINPGE 190 200 210 220 230 240 CKIGIMPGHI HKKGRIGIVS RSGTLTYEAV HQTTQVGLGQ SLCVGIGGDP FNGTDFIDCL 250 260 270 280 290 300 EIFLNDSATE GIILIGEIGG NAEENAAEFL KQHNSGPNSK PVVSFIAGLT APPGRRMGHA 310 320 330 340 GAIIAGGKGG AKEKISALQS AGVVVSMSPA QLGTTIYKEF EKRKML

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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] OF 3-346. Tissue: Lung.
[3]	"Sequence of the alpha subunit of succinyl-CoA synthetase in human." Tews K.N., Mehus J.G., Johnson J.D., Milavetz B.I., Lambeth D.O. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-346.
[4]	"The molecular basis for cross-reaction anti-dystrophin antibody with alpha-actinin." James M., Man N.T., Edwards Y.H., Morris G.E. Biochim. Biophys. Acta 1360:169-176(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-145. Tissue: Brain and Skeletal muscle.
[5]	"Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion." Ostergaard E., Christensen E., Kristensen E., Mogensen B., Duno M., Shoubridge E.A., Wibrand F. Am. J. Hum. Genet. 81:383-387(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MTDPS9.
[6]	"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-54, MASS SPECTROMETRY.
[7]	"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].
[8]	"A novel missense mutation in SUCLG1 associated with mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduria." Ostergaard E., Schwartz M., Batbayli M., Christensen E., Hjalmarson O., Kollberg G., Holme E. Eur. J. Pediatr. 169:201-205(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MTDPS9 ALA-85.
[9]	"The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein." Rouzier C., Le Guedard-Mereuze S., Fragaki K., Serre V., Miro J., Tuffery-Giraud S., Chaussenot A., Bannwarth S., Caruba C., Ostergaard E., Pellissier J.F., Richelme C., Espil C., Chabrol B., Paquis-Flucklinger V. J. Med. Genet. 47:670-676(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MTDPS9 ARG-170.
[10]	"Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy." Van Hove J.L., Saenz M.S., Thomas J.A., Gallagher R.C., Lovell M.A., Fenton L.Z., Shanske S., Myers S.M., Wanders R.J., Ruiter J., Turkenburg M., Waterham H.R. Pediatr. Res. 68:159-164(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MTDPS9 LEU-14.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC096770 Genomic DNA. No translation available. BC000504 mRNA. Translation: AAH00504.1. Different initiation. AF104921 mRNA. Translation: AAD17940.2. Different initiation. Z68204 mRNA. Translation: CAA92426.1. Different initiation.
IPI	IPI00872762.
RefSeq	NP_003840.2. NM_003849.3.
UniGene	Hs.270428.
3D structure databases
ProteinModelPortal	P53597.
ModBase	Search...
Protein-protein interaction databases
IntAct	P53597. 1 interaction.
MINT	MINT-137948.
STRING	9606.ENSP00000377446.
PTM databases
PhosphoSite	P53597.
Polymorphism databases
DMDM	223634731.
2D gel databases
UCD-2DPAGE	P53597.
Proteomic databases
PaxDb	P53597.
PRIDE	P53597.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000393868; ENSP00000377446; ENSG00000163541.
GeneID	8802.
KEGG	hsa:8802.
UCSC	uc002son.3. human.
Organism-specific databases
CTD	8802.
GeneCards	GC02M084562.
HGNC	HGNC:11449. SUCLG1.
HPA	HPA036683.
MIM	245400. phenotype. 611224. gene.
neXtProt	NX_P53597.
Orphanet	17. Fatal infantile lactic acidosis with methylmalonic aciduria.
PharmGKB	PA36246.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0074.
HOGENOM	HOG000239685.
HOVERGEN	HBG000957.
InParanoid	P53597.
KO	K01899.
OMA	KGRKKPM.
OrthoDB	EOG4WQ136.
Enzyme and pathway databases
BioCyc	MetaCyc:HS08877-MONOMER.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00223.
Gene expression databases
ArrayExpress	P53597.
Bgee	P53597.
CleanEx	HS_SUCLG1.
Genevestigator	P53597.
GermOnline	ENSG00000163541. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.261. 1 hit. 3.40.50.720. 1 hit.
InterPro	IPR017440. Cit_synth/succinyl-CoA_lig_AS. IPR003781. CoA-bd. IPR005810. CoA_lig_alpha. IPR005811. CoA_ligase. IPR016040. NAD(P)-bd_dom. IPR016102. Succinyl-CoA_synth-like. [Graphical view]
Pfam	PF02629. CoA_binding. 1 hit. PF00549. Ligase_CoA. 1 hit. [Graphical view]
PIRSF	PIRSF001553. SucCS_alpha. 1 hit.
PRINTS	PR01798. SCOASYNTHASE.
SMART	SM00881. CoA_binding. 1 hit. [Graphical view]
SUPFAM	SSF52210. CoA_ligase. 1 hit.
TIGRFAMs	TIGR01019. sucCoAalpha. 1 hit.
PROSITE	PS01216. SUCCINYL_COA_LIG_1. 1 hit. PS00399. SUCCINYL_COA_LIG_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SUCLG1. human.
DrugBank	DB00139. Succinic acid.
GenomeRNAi	8802.
NextBio	33016.
SOURCE	Search...

Entry information

Entry name

SUCA_HUMAN

Accession

Primary (citable) accession number: P53597
Secondary accession number(s): Q9BWB0, Q9UNP6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	February 10, 2009
Last modified:	May 1, 2013
This is version 135 of the entry and version 4 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.