DMAC2
Identifiers
Aliases	DMAC2, ATP5SL, ATP5S like, distal membrane arm assembly complex 2, distal membrane arm assembly component 2
External IDs	OMIM: 617262; MGI: 1913599; GeneCards: DMAC2
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.2 Start 41,431,318 bp[1] End 41,440,717 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 A3 Start 25,318,839 bp[2] End 25,324,976 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart left ventricle jejunal mucosa parotid gland right auricle of heart myocardium of left ventricle right ventricle duodenum thoracic diaphragm muscle of thigh Top expressed in neural layer of retina interventricular septum right kidney muscle of thigh superior frontal gyrus primary visual cortex spermatocyte cerebellar cortex epiblast skeletal muscle tissue More reference expression data BioGPS n/a
Gene ontology Molecular function ubiquitin-protein transferase activity Cellular component mitochondrion mitochondrial respiratory chain complex I SCF ubiquitin ligase complex Biological process mitochondrial respiratory chain complex I assembly ubiquitin-dependent protein catabolic process protein ubiquitination SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 55101 66349 Ensembl ENSG00000105341 ENSMUSG00000057229 UniProt Q9NW81 Q9D7K5 RefSeq (mRNA) NM_001167867 NM_001167868 NM_001167869 NM_001167870 NM_001167871 NM_018035 NM_001320838 NM_001320839 NM_001320840 NM_001320841 NM_001320844 NM_001290487 NM_025504 RefSeq (protein) NP_001161339 NP_001161340 NP_001161341 NP_001161342 NP_001161343 NP_001307767 NP_001307768 NP_001307769 NP_001307770 NP_001307773 NP_060505 NP_001277416 NP_079780 Location (UCSC) Chr 19: 41.43 – 41.44 Mb Chr 7: 25.32 – 25.32 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

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]

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

The 3' untranslated region sequence has eight large stem loops with three 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 target binding sites

miRNA name	Target sequence	Association
hsa-miR-4731-5p	CCCCAGCA	Tumor suppressive activity [8]
hsa-miR-671-5p	GGCTTCC	Tumor suppressor in breast cancer [9]
hsa-miR-4786-3p	GGCTTCC	Immune system; antiviral potential

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

There are eleven 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.

Table 1. DMAC2 Isoform table. Data obtained from NCBI

Protein Isoform	Accession ID	Length (amino acids)	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

Source:^[11]

• DMAC2 isoform 1 sequence contains five 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.

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.

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, and ATM. Serines have the highest amount of predicted phosphorylation sites in ATP5SL.

It has two 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]

Predicted propeptide cleavage sites in ATP5SL.

Position	Context	Score
45	GNQKKKR~TI	0.796
255	GPEEQPR~DT	0.627

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.

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 three 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.

Table 3. Proteins that are found to interact with ATP5SL

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 (BTB-CUL3-RBX1) 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

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.

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.

Homology

Taxonomic group	Taxonomic order	Genus and species	Common name	Median date of divergence from humans (MYA)	Accession #	Sequence Length (aa)	Sequence identity (%)	Sequence similarity(%)
Mammalia	Primates	Homo Sapiens	Human	0	NP_001161339.1	263	100	100
Mammalia	Primates	Macaca fascicularis	Crab Eating macaque	28.8	XP_045236960.1	253	89	92
Mammalia	Primates	Carlito syrichta	Philippine tariser	69	XP_021568406.1	302	77	88
Mammalia	Rodentia	Mus musculus	House mouse	87	NP_001277416.1	250	67	82
Mammalia	Ungulates	Bos taurus	Domestic cattle	94	NP_001258937.1	301	74	86
Mammalia	Peramelemorphia	Macrotis lagotis	Bilby	160	XP_074075255.1	281	52	72
Reptilia	Ciconiiformes	Ciconia boyciana	Oriental stork	319	XP_072704911.1	260	46	63
Reptilia	Squamata	Rhineura floridana	Florida worm lizard	319	XP_061454037.1	271	47	64
Reptilia	Testudines	Trachemys scripta elegans	Red-eared terrapin	319	XP_034648456.1	229	47	63
Reptilia	Anseriformes	Anas acuta	Northern Pintail	319	XP_068524425.1	235	50	67
Amphibia	Gumnophiona	Rhinatrema bivittatum	Two lined caecilian	352	XP_029475261.1	280	52	72
Amphibia	Anura	Ascaphus truei	Tailed frog	352	XP_075463000.1	212	48	67
Actinopterygii	Anguilliformes	Conger conger	Conger eel	429	XP_061073726.1	273	43	62
Actinopterygii	Acipenseriformes	Acipenser ruthenus	Sterlet sturgeon	429	XP_033914069.3	262	48	64
Chondrichthyes	Carcharhiniformes	Scyliorhinus canicula	Small-spotted catshark	462	XP_038642055.1	262	48	66
Chondrichthyes	Torpediniformes	Narcine bancroftii	Caribbean electric ray	462	XP_069763551.1	261	54	70
Cephalaspidomorphi	Petromyzontiformes	Lethenteron reissneri	Far Eastern brook lamprey	563	XP_061415248.1	245	45	65

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]

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]

• Human ATP5SL genome location and ATP5SL gene details page in the UCSC Genome Browser.