ATP5SL
ATP synthase subunit s-like protein is a protein that in humans is encoded by the DMAC2 gene. It has a role in the assembly of the distal portion of the Mitochondiral Respiratory Complex 1 membrane arm. Complex 1 is the largest respiratory complex of the mitochondrial electron transport chain.
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.mRNA
There are 6 exons within ATP5SL's mRNA sequence and 12 known transcript variants that span between 1489 and 2515 nucleotides.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.
| miRNA name | Target sequence | Association |
| hsa-miR-4731-5p | CCCCAGCA | Tumor suppressive activity |
| hsa-miR-671-5p | GGCTTCC | Tumor suppressor in breast cancer |
| hsa-miR-4786-3p | GGCTTCC | Immune system; antiviral potential |
Expression
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. 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.| Protein Isoform | Accession ID | Length | Difference |
| 1 | NP_001161339 | 263 | |
| 2 | NP_001161340.1 | 191 | Lacks an exon in the 3’ coding region. distinct C-terminus |
| 3 | NP_001161341.1 | 185 | Different 5’ untranslated region length and protein coding region |
| 4 | NP_060505.2 | 257 | Has an alternate in-frame exon in the 5' coding region |
| 5 | NP_001161343.1 | 230 | Different N-termini |
| 6 | NP_001161342.1 | 158 | Different N- and C-termini |
| 7 | NP_001307767.1 | 170 | different 5’ Untranslated region length, translation initiation at a different start codon |
| 8 | NP_001307768.1 | 178 | Missing multiple exons and 3' terminal exon extends past a splice site; different 3' coding region and 3' Untranslated region |
| 9 | NP_001307769.1 | 236 | Lacks an alternate in-frame exon |
| 10 | NP_001307770.1 | 164 | Missing two alternate exons in the coding region |
| 11 | NP_001307773.1 | 172 | Distinct different N- and C- termini |
Amino Acid Composition
Source:- 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. Leucine-rich repeats are commonly composed of 2-45 motifs of 20-30 residues in length. 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. 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. 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.
| Position | Context | Score |
| 45 | GNQKKKR~TI | 0.796 |
| 255 | GPEEQPR~DT | 0.627 |
It contains a Mitochondrial transit peptide sorting signal at the N-terminus, 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 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 shape with a parallel beta-sheet on the concave face and different secondary helices structures on the convex face. 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, it can diffuse through aqueous environments. 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. Interactions between amino acid residues stabilize globular protein structure.
Protein Interactions
| Protein | IDs | Identification | Function | Subcellular Location |
| Mitochondria-localized glutamic acid-rich protein | MGARP | Affinity Capture-MS | Regulates the morphology and distribution of mitochondria | Mitochondria |
| FAD-dependent oxidoreductase domain containing 1 | FOXRED1 | Cross-Linking | Involved in the mid-late stages of complex I assembly | Mitochondria |
| Transmembrane Protein 70 | TMEM70 | Textmining | Biogenesis of mitochondrial ATP synthase | Mitochondria |
| Distal membrane-arm assembly complex protein 1 | DMAC1 | GEO microarray Co-expression | Involved in the assembly of the distal region of complex I) | Mitochondria |
| Mov10 RISC complex RNA helicase | MOV10 | Affinity Capture-RNA | Promotes type I interferon production in innate antiviral immunity | Cytosol |
| Kelch-like family member 20 | KLHL20 | Two-Hybrid | Substrate-specific adapter of a BCR E3 ubiquitin-protein ligase complex | Cytosol, Golgi Apparatus |
| Kinesin family member 14 | KIF14 | Affinity Capture-MS | Regulates cell growth through regulation of cell cycle progression and cytokinesis | Example |
Conceptual translation
Shown on the right is a PDF of the full conceptual translation of Human DMAC2 isoform 1 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 ; 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.
| taxonomic group | Genus and species | Common name | taxonomic order | median date of divergence from humans | Accession # | Sequence Length | Sequence identity | Sequence similarity |
| Mammalia | Homo Sapiens | Human | Primates | 0 | NP_001161339.1 | 263 | 100 | 100 |
| Mammalia | Macaca fascicularis | Crab Eating macaque | Primates | 28.8 | XP_045236960.1 | 253 | 89 | 92 |
| Mammalia | Carlito syrichta | Phillipine tariser | Primates | 69 | XP_021568406.1 | 302 | 77 | 88 |
| Mammalia | Mus musculus | House mouse | Rodentia | 87 | NP_001277416.1 | 250 | 67 | 82 |
| Mammalia | Bos taurus | Domestic cattle | Ungulates | 94 | NP_001258937.1 | 301 | 74 | 86 |
| Mammalia | Macrotis lagotis | Bilby | Peramelemorphia | 160 | XP_074075255.1 | 281 | 52 | 72 |
| Reptilia | Ciconia boyciana | Oriental stork | Ciconiiformes | 319 | XP_072704911.1 | 260 | 46 | 63 |
| Reptilia | Rhineura floridana | Florida worm lizard | Squamata | 319 | XP_061454037.1 | 271 | 47 | 64 |
| Reptilia | Trachemys scripta elegans | Red-eared terrapin | Testudines | 319 | XP_034648456.1 | 229 | 47 | 63 |
| Reptilia | Anas acuta | Northern Pintail | Anseriformes | 319 | XP_068524425.1 | 235 | 50 | 67 |
| Amphibia | Rhinatrema bivittatum | Two lined caecilian | Gumnophiona | 352 | XP_029475261.1 | 280 | 52 | 72 |
| Amphibia | Ascaphus truei | Tailed frog | Anura | 352 | XP_075463000.1 | 212 | 48 | 67 |
| Actinopterygii | Conger conger | Conger eel | Anguilliformes | 429 | XP_061073726.1 | 273 | 43 | 62 |
| Actinopterygii | Acipenser ruthenus | Sterlet sturgeon | Acipenseriformes | 429 | XP_033914069.3 | 262 | 48 | 64 |
| Chondrichthyes | Scyliorhinus canicula | Small-spotted catshark | Carcharhiniformes | 462 | XP_038642055.1 | 262 | 48 | 66 |
| Chondrichthyes | Narcine bancroftii | Caribbean electric ray | Torpediniformes | 462 | XP_069763551.1 | 261 | 54 | 70 |
| Cephalaspidomorphi | Lethenteron reissneri | Far Eastern brook lamprey | Petromyzontiformes | 563 | XP_061415248.1 | 245 | 45 | 65 |
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. In Breast cancer, there is a copy number variation that is thought to either gain or lose a copy of ATP5SL.