SUCLA2

Protein identityUniProt · HPA

UniProt accession

Q9P2R7

Gene

SUCLA2

Ensembl

ENSG00000136143

Chromosome

13

Canonical length

463 aa

Protein class

Citric acid cycle related proteins, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

Succinyl-CoA synthetase (SCS) is a mitochondrial matrix enzyme that acts as a heterodimer, being composed of an invariant alpha subunit and a substrate-specific beta subunit. The protein encoded by this gene is an ATP-specific SCS beta subunit that dimerizes with the SCS alpha subunit to form SCS-A, an essential component of the tricarboxylic acid cycle. SCS-A hydrolyzes ATP to convert succinate to succinyl-CoA. Defects in this gene are a cause of myopathic mitochondrial DNA depletion syndrome. A pseudogene of this gene has been found on chromosome 6. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

463 residues, UniProt reviewed canonical sequence.

>Q9P2R7|SUCLA2
     1  MAASMFYGRL VAVATLRNHR PRTAQRAAAQ VLGSSGLFNN HGLQVQQQQQ RNLSLHEYMS
    61  MELLQEAGVS VPKGYVAKSP DEAYAIAKKL GSKDVVIKAQ VLAGGRGKGT FESGLKGGVK
   121  IVFSPEEAKA VSSQMIGKKL FTKQTGEKGR ICNQVLVCER KYPRREYYFA ITMERSFQGP
   181  VLIGSSHGGV NIEDVAAESP EAIIKEPIDI EEGIKKEQAL QLAQKMGFPP NIVESAAENM
   241  VKLYSLFLKY DATMIEINPM VEDSDGAVLC MDAKINFDSN SAYRQKKIFD LQDWTQEDER
   301  DKDAAKANLN YIGLDGNIGC LVNGAGLAMA TMDIIKLHGG TPANFLDVGG GATVHQVTEA
   361  FKLITSDKKV LAILVNIFGG IMRCDVIAQG IVMAVKDLEI KIPVVVRLQG TRVDDAKALI
   421  ADSGLKILAC DDLDEAARMV VKLSEIVTLA KQAHVDVKFQ LPI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SUCLA2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

254 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SUCLA2.

Disease | AllUniProt

Conditions SUCLA2 is implicated in, by any mechanism.

• Mitochondrial DNA depletion syndrome 5 (MTDPS5) MIM:612073

Disease | GeneticClinVar

34 pathogenic / likely-pathogenic of 493 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria
• Inborn genetic diseases
• SUCLA2-related disorder
• Familial prostate cancer

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.63

gnomAD pLI

0

gnomAD missense Z

1.02

DepMap mean gene effect

-0.18

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• succinate metabolic process
• succinyl-CoA catabolic process
• succinyl-CoA metabolic process
• tricarboxylic acid cycle
• succinyl-CoA pathway

Molecular functions

• ATP binding
• magnesium ion binding
• succinate-CoA ligase (ADP-forming) activity

Cellular components

• extracellular exosome
• mitochondrial matrix
• mitochondrion
• succinate-CoA ligase complex
• succinate-CoA ligase complex (ADP-forming)

Protein domainsUniProt · Pfam · InterPro

• Succinate--CoA ligase-like, beta subunit
• ATP-citrate synthase/succinyl-CoA ligase, C-terminal domain
• ATP-grasp fold
• ATP-grasp fold, succinyl-CoA synthetase-type
• ATP-grasp fold, subdomain 1
• Succinyl-CoA synthetase-like
• Succinyl-CoA synthetase, beta subunit, conserved site
• CoA-ligase
• ATP-grasp domain
• Succinate--CoA ligase [ADP-forming] subunit beta, mitochondrial

KeywordsUniProt

• Acetylation
• ATP-binding
• Ligase
• Magnesium
• Metal-binding
• Mitochondrion
• Nucleotide-binding
• Phosphoprotein
• Primary mitochondrial disease
• Transit peptide
• Tricarboxylic acid cycle

InteractionsUniProt · HPA

Protein binding partners of SUCLA2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ALAS2