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    Alas2 aminolevulinic acid synthase 2, erythroid [ Mus musculus (house mouse) ]

    Gene ID: 11656, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Alas2provided by MGI
    Official Full Name
    aminolevulinic acid synthase 2, erythroidprovided by MGI
    Primary source
    MGI:MGI:87990
    See related
    Ensembl:ENSMUSG00000025270 AllianceGenome:MGI:87990
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    ALAS; ALASE; ALAS-E; Alas-2
    Summary
    Enables 5-aminolevulinate synthase activity. Involved in erythrocyte differentiation; heme biosynthetic process; and hemoglobin biosynthetic process. Acts upstream of or within cellular iron ion homeostasis. Located in mitochondrion. Is expressed in several structures, including alimentary system; brain; genitourinary system; hemolymphoid system gland; and liver and biliary system. Human ortholog(s) of this gene implicated in cutaneous porphyria; erythropoietic protoporphyria; hemochromatosis; sideroblastic anemia; and sideroblastic anemia 1. Orthologous to human ALAS2 (5'-aminolevulinate synthase 2). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Biased expression in liver E14.5 (RPKM 488.3), liver E14 (RPKM 440.7) and 5 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    X F3; X 68.46 cM
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) X NC_000086.8 (149330443..149353614)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) X NC_000086.7 (150547417..150570622)

    Chromosome X - NC_000086.8Genomic Context describing neighboring genes Neighboring gene VCP nuclear cofactor family member 2 Neighboring gene zinc finger CCCH type containing 14 pseudogene Neighboring gene STARR-seq mESC enhancer starr_48069 Neighboring gene apurinic/apyrimidinic endonuclease 2 Neighboring gene STARR-seq mESC enhancer starr_48070 Neighboring gene microRNA 3620 Neighboring gene Alas2R1 erythroid cis-regulatory module Neighboring gene Alas2R3 erythroid cis-regulatory module Neighboring gene 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 Neighboring gene trophinin

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation. Saito K, et al. Mol Cell Biol, 2019 Apr 1. PMID 30670569, Free PMC Article
    2. Molecular dynamics analysis of the structural and dynamic properties of the functionally enhanced hepta-variant of mouse 5-aminolevulinate synthase. Na I, et al. J Biomol Struct Dyn, 2018 Jan. PMID 27928941
    3. Murine erythroid 5-aminolevulinate synthase: Truncation of a disordered N-terminal extension is not detrimental for catalysis. Stojanovski BM, et al. Biochim Biophys Acta, 2016 May. PMID 26854603
    4. Asn-150 of Murine Erythroid 5-Aminolevulinate Synthase Modulates the Catalytic Balance between the Rates of the Reversible Reaction. Stojanovski BM, et al. J Biol Chem, 2015 Dec 25. PMID 26511319, Free PMC Article
    5. Catalytically active alkaline molten globular enzyme: Effect of pH and temperature on the structural integrity of 5-aminolevulinate synthase. Stojanovski BM, et al. Biochim Biophys Acta, 2014 Dec. PMID 25240868, Free PMC Article

    See all (70) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. we used bioinformatics and computational biology tools to evaluate the role(s) of the C-terminal tail dynamics in the structure and conformational dynamics of the murine ALAS2 homodimer active site loop.
      Title: Anti-Correlation between the Dynamics of the Active Site Loop and C-Terminal Tail in Relation to the Homodimer Asymmetry of the Mouse Erythroid 5-Aminolevulinate Synthase.
    2. Data indicate that the 5-aminolevulinate synthase (mALAS2) active site loop harboring the simultaneous seven amino acid mutations was less flexible than the wild type loop.
      Title: Molecular dynamics analysis of the structural and dynamic properties of the functionally enhanced hepta-variant of mouse 5-aminolevulinate synthase.
    3. We propose that the N-terminal truncation offers a cell-specific ALAS2 regulatory mechanism without hindering heme synthesis
      Title: Murine erythroid 5-aminolevulinate synthase: Truncation of a disordered N-terminal extension is not detrimental for catalysis.
    4. N150F ALAS variant catalyzes the forward reaction at a mere 1.2-fold faster rate than that of the reverse reaction.
      Title: Asn-150 of Murine Erythroid 5-Aminolevulinate Synthase Modulates the Catalytic Balance between the Rates of the Reversible Reaction.
    5. Light treatments revealed that ALAS2 expression results in an increase in cell death in comparison to aminolevulinic acid (ALA) treatment producing a similar amount of protoprophyrin IX.
      Title: Expression of murine 5-aminolevulinate synthase variants causes protoporphyrin IX accumulation and light-induced mammalian cell death.
    6. The rate of ALA release is also controlled by a hysteretic kinetic mechanism (observed as a lag in the ALA external aldimine formation progress curve), consistent with conformational changes governing the dissociation of ALA from ALAS.
      Title: Unstable reaction intermediates and hysteresis during the catalytic cycle of 5-aminolevulinate synthase: implications from using pseudo and alternate substrates and a promiscuous enzyme variant.
    7. impaired mitochondrial [Fe-S] cluster biogenesis in Mfrn1(gt/gt) cells results in elevated IRP1 RNA-binding that attenuates ALAS2 mRNA translation and protoporphyrin accumulation
      Title: Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria.
    8. Gene expression and enzymatic assays indicate that erythroid 5-aminolevulinic acid synthase (Alas2) is decreased in hem6 animals, suggesting a mechanism that could account for the anemia.
      Title: hem6: an ENU-induced recessive hypochromic microcytic anemia mutation in the mouse.
    9. These findings thus suggest that heme may regulate a wide variety of hitherto unrecognized genes, and further analysis of these genes may clarify their role in erythroid cell differentiation.
      Title: Differential gene expression profiling between wild-type and ALAS2-null erythroblasts: identification of novel heme-regulated genes.
    10. Data suggest the reaction of glycine with ALAS follows a three-step kinetic process, and the substrate 5-aminolevulinate induces a conformational change in ALAS which may modulate product release.
      Title: Transient state kinetic investigation of 5-aminolevulinate synthase reaction mechanism.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Targeted (1)  1 citation
    • Endonuclease-mediated (1) 

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables 5-aminolevulinate synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 5-aminolevulinate synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables 5-aminolevulinate synthase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables 5-aminolevulinate synthase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables acyltransferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables coenzyme A binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables pyridoxal phosphate binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in erythrocyte development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in erythrocyte differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in heme biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in heme biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in hemoglobin biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in hemoglobin biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within intracellular iron ion homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in porphyrin-containing compound metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to hypoxia ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in tetrapyrrole biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial inner membrane ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in mitochondrial matrix IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrion HDA PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    5-aminolevulinate synthase, erythroid-specific, mitochondrial
    Names
    5-aminolevulinic acid synthase 2
    delta-ALA synthase 2
    delta-aminolevulinate synthase 2
    erythroid-specific ALAS
    NP_001095916.1
    NP_001396401.1
    NP_001396402.1
    NP_001396403.1
    NP_001396404.1
    NP_001396405.1
    NP_001396406.1
    NP_033783.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001102446.2 → NP_001095916.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform b

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the end of an exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
      Source sequence(s)
      AL672150, AL808140
      Consensus CDS
      CCDS53220.1
      UniProtKB/TrEMBL
      A2AFM1, Q3TA47, Q3TNI1
      Related
      ENSMUSP00000108335.2, ENSMUST00000112715.2
      Conserved Domains (3) summary
      COG0156
      Location:130 → 529
      BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]
      TIGR01821
      Location:128 → 533
      5aminolev_synth; 5-aminolevulinic acid synthase
      pfam09029
      Location:5 → 85
      Preseq_ALAS; 5-aminolevulinate synthase presequence

    2. NM_001409472.1 → NP_001396401.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform c precursor

      Status: VALIDATED

      Source sequence(s)
      AL672150, AL808140

    3. NM_001409473.1 → NP_001396402.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform d

      Status: VALIDATED

      Source sequence(s)
      AL672150, AL808140

    4. NM_001409474.1 → NP_001396403.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform e

      Status: VALIDATED

      Source sequence(s)
      AL672150, AL808140

    5. NM_001409475.1 → NP_001396404.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform f

      Status: VALIDATED

      Source sequence(s)
      AL672150, AL808140

    6. NM_001409476.1 → NP_001396405.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform g

      Status: VALIDATED

      Source sequence(s)
      AL672150, AL808140

    7. NM_001409477.1 → NP_001396406.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform h

      Status: VALIDATED

      Source sequence(s)
      AL672150, AL808140

    8. NM_009653.4 → NP_033783.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform a

      See identical proteins and their annotated locations for NP_033783.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
      Source sequence(s)
      AL672150, AL808140
      Consensus CDS
      CCDS41173.1
      UniProtKB/Swiss-Prot
      P08680, Q64452, Q9DCN0
      UniProtKB/TrEMBL
      A2AFM0, Q3TA47, Q3TNI1
      Related
      ENSMUSP00000066040.7, ENSMUST00000066337.13
      Conserved Domains (3) summary
      COG0156
      Location:145 → 544
      BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]
      TIGR01821
      Location:143 → 548
      5aminolev_synth; 5-aminolevulinic acid synthase
      pfam09029
      Location:5 → 100
      Preseq_ALAS; 5-aminolevulinate synthase presequence

    RNA

    1. NR_176852.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AL672150, AL808140

    2. NR_176853.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AL672150, AL808140

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000086.8 Reference GRCm39 C57BL/6J

      Range
      149330443..149353614
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P08680.3 GenPept UniProtKB/Swiss-Prot:P08680

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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