ATP5SL

Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia

ATP synthase subunit s-like protein is a protein that in humans is encoded by the DMAC2 gene.[5] It has a role in the assembly of the distal portion of the Mitochondiral Respiratory Complex 1 (NADH: ubiquinone oxidoreductase) membrane arm. Complex 1 is the largest respiratory complex of the mitochondrial electron transport chain.

AliasesDMAC2, ATP5SL, ATP5S like, distal membrane arm assembly complex 2, distal membrane arm assembly component 2
End41,440,717 bp[1]
Quick facts DMAC2, Identifiers ...
DMAC2
Identifiers
AliasesDMAC2, ATP5SL, ATP5S like, distal membrane arm assembly complex 2, distal membrane arm assembly component 2
External IDsOMIM: 617262; MGI: 1913599; HomoloGene: 9973; GeneCards: DMAC2; OMA:DMAC2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001290487
NM_025504

RefSeq (protein)

NP_001277416
NP_079780

Location (UCSC)Chr 19: 41.43 – 41.44 MbChr 7: 25.32 – 25.32 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
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Gene

ATP5SL’s preferred name is DMAC2, Distal membrane arm assembly complex 2. DMAC2 is on the minus strand of Chromosome 19 and spans 9400 base pairs.[6]

mRNA

There are 6 exons within ATP5SL's mRNA sequence and 12 known transcript variants that span between 1489 and 2515 nucleotides.[7]

The 3' untranslated region sequence has 8 large stem loops with 3 overlapping miRNA target binding sites: hsa-miR-4731-5p, hsa-miR-671-5p, and hsa-miR-4786-3p. This site is almost fully conserved in primates; it differs by one base pair. A secondary site of hsa-miR-4731-5p is fully conserved among Primates.

More information miRNA name, Target sequence ...
Caption text
miRNA nameTarget sequenceAssociation
hsa-miR-4731-5pCCCCAGCATumor suppressive activity [8]
hsa-miR-671-5pGGCTTCCTumor suppressor in breast cancer [9]
hsa-miR-4786-3pGGCTTCCImmune system; antiviral potential
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Expression

Normal RNA expression of DMAC2 in 27 various human tissues. Graph obtained from DMAC2 NCBI gene page
NCBI GEO Entry on ATP5SL from Normal tissue expression profiling (HG-U95E)

It is ubiquitously expressed at moderate levels in all tissues, with occasional high expression levels in the heart and skeletal muscle.

Protein

There are 11 different isoforms[10]. DMAC2 Isoform 1 is the longest, with a predicted molecular weight of about 3.2 kDa and a theoretical isoelectric point of about 5.85, making it negatively charged under basic conditions. It is localized in the mitochondria.

More information Protein Isoform, Accession ID ...
Table 1. DMAC2 Isoform table. Data obtained from NCBI
Protein IsoformAccession IDLength (amino acids)Difference
1NP_001161339263
2NP_001161340.1191Lacks an exon in the 3’ coding region. distinct C-terminus
3NP_001161341.1185Different 5’ untranslated region length and protein coding region
4NP_060505.2257Has an alternate in-frame exon in the 5' coding region
5NP_001161343.1230Different N-termini
6NP_001161342.1158Different N- and C-termini
7NP_001307767.1170different 5’ Untranslated region length, translation initiation at a different start codon
8NP_001307768.1178Missing multiple exons and 3' terminal exon extends past a splice site; different 3' coding region and 3' Untranslated region
9NP_001307769.1236Lacks an alternate in-frame exon
10NP_001307770.1164Missing two alternate exons in the coding region
11NP_001307773.1172Distinct different N- and C- termini
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Amino Acid Composition

Compositional analysis of Human DMAC2 isoform 1 protein made via SAPS

Source:[11]

  • DMAC2 isoform 1 sequence contains 5 Threonines, which is fewer than the average human protein has.
  • It has no charged segments or charge clusters.
  • There are more acidic residues than basic ones.
  • No significant hydrophobic segments.

Regions

There are two different 15-amino acid segments that repeat a Leucine every third amino acid. DMAC2 isoform 1 contains a Leucine-rich repeat domain of unknown function, DUF7885, which spans 94 amino acids.[12] Leucine-rich repeats are commonly composed of 2-45 motifs of 20-30 residues in length.[13] This motif is highly conserved in ATP5SL’s strict and distant orthologs. It has no transmembrane domains.

Post-translational modification

ATP5SL is predicted to undergo phosphorylation at multiple Serine, Threonine, and Tyrosine sites.[14] The kinases associated with the phosphorylation sites are Protein kinase A, cdc1, cdc2, EGFR, andATM. Serines have the highest amount of predicted phosphorylation sites in ATP5SL.

It has 2 predicted propeptide cleavage sites at Arginines.[15] In order to establish a mature protein, these sections are cut off and inactivated by proteases. Propeptides assist precursor proteins in remaining inactive until the right signal to move to their correct destination.[16]

More information Position, Context ...
Predicted propeptide cleavage sites in ATP5SL.
PositionContextScore
45GNQKKKR~TI0.796
255GPEEQPR~DT0.627
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Cleavage site is indicated by ~.

It contains a Mitochondrial transit peptide sorting signal at the N-terminus,[17] which directs proteins to the Chloroplast and Mitochondria. There are no signal proteins present.

There are no N-glycosylation or N-acetylation sites.

Protein Structure

Tertiary structure of DMAC2 isoform 1 made via icn3d

Tertiary structure can be visualized using I-Tasser and iCn3D. ATP5SL's structure is indicative of a Leucine-rich repeat region, which typically folds into a horseshoe (or arc) shape with a parallel beta-sheet on the concave face and different secondary helices structures on the convex face.[18] ATP5SL has alpha helices on the convex face and 3 parallel beta-sheets on the concave face.

ATP5SL is predicted to be soluble or globular,[19] it can diffuse through aqueous environments.[20] Commonly, in globular proteins, hydrophobic amino acid side chains are buried in the interior of the protein, and the hydrophilic amino acid side chains lie on the surface exposed to the water.[21] Interactions between amino acid residues stabilize globular protein structure.

Protein Interactions

More information Protein, IDs ...
Table 3. Proteins that are found to interact with ATP5SL
ProteinIDsIdentificationFunctionSubcellular Location
Mitochondria-localized glutamic acid-rich proteinMGARPAffinity Capture-MSRegulates the morphology and distribution of mitochondriaMitochondria
FAD-dependent oxidoreductase domain containing 1FOXRED1Cross-LinkingInvolved in the mid-late stages of complex I assemblyMitochondria
Transmembrane Protein 70TMEM70TextminingBiogenesis of mitochondrial ATP synthaseMitochondria
Distal membrane-arm assembly complex protein 1DMAC1GEO microarray Co-expressionInvolved in the assembly of the distal region of complex I)Mitochondria
Mov10 RISC complex RNA helicaseMOV10Affinity Capture-RNAPromotes type I interferon production in innate antiviral immunity Cytosol
Kelch-like family member 20KLHL20Two-HybridSubstrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexCytosol, Golgi Apparatus
Kinesin family member 14KIF14Affinity Capture-MSRegulates cell growth through regulation of cell cycle progression and cytokinesisExample
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Conceptual translation

Conceptual translation of ATP5SL by Berit Hansen

Shown on the right is a PDF of the full conceptual translation of Human DMAC2 isoform 1 (full mRNA) with annotations on the right side and an annotation legend below.

Homology

There are no known paralogs to this gene. DMAC2 evolutionary history spans approximately 563 million years (MYA); it was first found in jawless vertebrates, but not invertebrates.

Mammal, non-primate orthologs sequence identity ranged from 52% to 74%, and 72-86% sequence similarity.

More information taxonomic group, Genus and species ...
Caption text
taxonomic groupGenus and speciesCommon nametaxonomic ordermedian date of divergence from humans (MYA)Accession #Sequence Length (aa)Sequence identity (%)

Sequence similarity(%)

MammaliaHomo SapiensHumanPrimates0NP_001161339.1263100100
MammaliaMacaca fascicularisCrab Eating macaquePrimates28.8XP_045236960.12538992
MammaliaCarlito syrichtaPhilippine tariserPrimates69XP_021568406.13027788
MammaliaMus musculusHouse mouseRodentia87NP_001277416.12506782
MammaliaBos taurusDomestic cattleUngulates94NP_001258937.13017486
MammaliaMacrotis lagotisBilbyPeramelemorphia160XP_074075255.12815272
ReptiliaCiconia boycianaOriental storkCiconiiformes319XP_072704911.12604663
ReptiliaRhineura floridanaFlorida worm lizardSquamata319XP_061454037.12714764
ReptiliaTrachemys scripta elegansRed-eared terrapinTestudines319XP_034648456.12294763
ReptiliaAnas acutaNorthern PintailAnseriformes319XP_068524425.12355067
AmphibiaRhinatrema bivittatumTwo lined caecilianGumnophiona352XP_029475261.12805272
AmphibiaAscaphus trueiTailed frogAnura352XP_075463000.12124867
ActinopterygiiConger congerConger eelAnguilliformes429XP_061073726.12734362
ActinopterygiiAcipenser ruthenus Sterlet sturgeonAcipenseriformes429XP_033914069.32624864
ChondrichthyesScyliorhinus caniculaSmall-spotted catsharkCarcharhiniformes462XP_038642055.12624866
ChondrichthyesNarcine bancroftiiCaribbean electric rayTorpediniformes462XP_069763551.12615470
CephalaspidomorphiLethenteron reissneriFar Eastern brook lampreyPetromyzontiformes563XP_061415248.12454565
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Clinical Significance

Publications and databases have linked or associated ATP5SL with diseases related to the dysfunction of Complex I.

In Ovarian cancer, there is a large copy number variation on chromosome 19, which includes the deletion of ATP5SL.[22] In Breast cancer, there is a copy number variation that is thought to either gain or lose a copy of ATP5SL.[23]

SNPs

There are 5,917 catalogued SNPs on the NCBI Variation Viewer, many of which are intron variants. rs7259208 is associated with Type 2 diabetes in African Americans, but its role in the pathophysiology of Type 2 diabetes remains unknown.[24]


References

Further reading

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