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P53597 (SUCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length346 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processTricarboxylic acid cycle
   Cellular componentMitochondrion
   DiseaseDisease mutation
   DomainTransit peptide
   LigandGTP-binding
Nucleotide-binding
   Molecular functionLigase
   PTMAcetylation
Isopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular metabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

succinate metabolic process

Inferred from electronic annotation. Source: Ensembl

succinyl-CoA metabolic process

Inferred from electronic annotation. Source: Ensembl

tricarboxylic acid cycle

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrion

Traceable author statement Ref.4. Source: ProtInc

succinate-CoA ligase complex (GDP-forming)

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP citrate synthase activity

Inferred from electronic annotation. Source: InterPro

GDP binding

Inferred from electronic annotation. Source: Ensembl

GTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cofactor binding

Inferred from electronic annotation. Source: InterPro

poly(A) RNA binding

Inferred from direct assay PubMed 22658674. Source: UniProtKB

succinate-CoA ligase (ADP-forming) activity

Inferred from electronic annotation. Source: UniProtKB-EC

succinate-CoA ligase (GDP-forming) activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4040Mitochondrion By similarity
Chain41 – 346306Succinyl-CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial
PRO_0000033340

Sites

Active site2991Tele-phosphohistidine intermediate By similarity

Amino acid modifications

Modified residue541N6-acetyllysine Ref.6
Modified residue571N6-acetyllysine; alternate By similarity
Modified residue571N6-succinyllysine; alternate By similarity
Modified residue661N6-acetyllysine; alternate By similarity
Modified residue661N6-succinyllysine; alternate By similarity
Modified residue811N6-acetyllysine By similarity
Modified residue1051N6-acetyllysine By similarity
Modified residue3381N6-succinyllysine By similarity
Cross-link280Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Natural variant141M → L in MTDPS9; with progressive liver disease and recurrent hepatic failure. Ref.10
VAR_065120
Natural variant851G → A in MTDPS9. Ref.8
VAR_065157
Natural variant1701P → R in MTDPS9. Ref.9
VAR_065121

Experimental info

Sequence conflict191S → N in CAA92426. Ref.4
Sequence conflict341P → Q in CAA92426. Ref.4
Sequence conflict391R → Q in CAA92426. Ref.4
Sequence conflict871T → L in AAD17940. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P53597 [UniParc].

Last modified February 10, 2009. Version 4.
Checksum: 76EF06F323CD5188

FASTA34636,250
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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.
CCDSCCDS1967.2.
RefSeqNP_003840.2. NM_003849.3.
UniGeneHs.270428.

3D structure databases

ProteinModelPortalP53597.
SMRP53597. Positions 41-346.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114330. 13 interactions.
IntActP53597. 1 interaction.
MINTMINT-137948.
STRING9606.ENSP00000377446.

Chemistry

DrugBankDB00139. Succinic acid.

PTM databases

PhosphoSiteP53597.

Polymorphism databases

DMDM223634731.

2D gel databases

UCD-2DPAGEP53597.

Proteomic databases

MaxQBP53597.
PaxDbP53597.
PRIDEP53597.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000393868; ENSP00000377446; ENSG00000163541.
GeneID8802.
KEGGhsa:8802.
UCSCuc002son.3. human.

Organism-specific databases

CTD8802.
GeneCardsGC02M084562.
HGNCHGNC:11449. SUCLG1.
HPAHPA036683.
MIM245400. phenotype.
611224. gene.
neXtProtNX_P53597.
Orphanet17. Fatal infantile lactic acidosis with methylmalonic aciduria.
PharmGKBPA36246.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0074.
HOGENOMHOG000239685.
HOVERGENHBG000957.
InParanoidP53597.
KOK01899.
OMAQNGVRHC.
OrthoDBEOG74BJSG.
PhylomeDBP53597.
TreeFamTF300666.

Enzyme and pathway databases

BioCycMetaCyc:HS08877-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00223.

Gene expression databases

ArrayExpressP53597.
BgeeP53597.
CleanExHS_SUCLG1.
GenevestigatorP53597.

Family and domain databases

Gene3D3.40.50.261. 1 hit.
3.40.50.720. 1 hit.
InterProIPR017440. 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]
PfamPF02629. CoA_binding. 1 hit.
PF00549. Ligase_CoA. 1 hit.
[Graphical view]
PIRSFPIRSF001553. SucCS_alpha. 1 hit.
PRINTSPR01798. SCOASYNTHASE.
SMARTSM00881. CoA_binding. 1 hit.
[Graphical view]
SUPFAMSSF52210. SSF52210. 1 hit.
TIGRFAMsTIGR01019. sucCoAalpha. 1 hit.
PROSITEPS01216. SUCCINYL_COA_LIG_1. 1 hit.
PS00399. SUCCINYL_COA_LIG_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSUCLG1. human.
GeneWikiSUCLG1.
GenomeRNAi8802.
NextBio33016.
PROP53597.
SOURCESearch...

Entry information

Entry nameSUCA_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 147 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM