ALAS1

Identifiers

ALAS1, ALAS, ALAS3, ALASH, MIG4, ALAS-H, 5'-aminolevulinate synthase 1

External IDs

OMIM: 125290 MGI: 87989 HomoloGene: 55478 GeneCards: ALAS1

Gene location (Human)

Chr.	Chromosome 3 (human)^[1]

Band	3p21.2	Start	52,198,086 bp^[1]
Band	3p21.2	End	52,214,327 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 9 (mouse)^[2]

Band	9\|9 F1	Start	106,110,654 bp^[2]
Band	9\|9 F1	End	106,125,853 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

left adrenal gland

oocyte

secondary oocyte

right lobe of liver

right ventricle

parotid gland

gastrocnemius muscle

vastus lateralis muscle

biceps brachii

jejunal mucosa

Top expressed in

adrenal gland

right lung

right lung lobe

lacrimal gland

brown adipose tissue

right ventricle

soleus muscle

olfactory epithelium

left lobe of liver

digastric muscle

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	transferase activity pyridoxal phosphate binding acyltransferase activity protein binding catalytic activity 5-aminolevulinate synthase activity identical protein binding
Cellular component	mitochondrial matrix mitochondrion nucleoplasm cytosol
Biological process	heme biosynthetic process mitochondrion organization metabolism protoporphyrinogen IX biosynthetic process biosynthesis tetrapyrrole biosynthetic process porphyrin-containing compound metabolic process regulation of lipid metabolic process
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


211


11655

Ensembl


ENSG00000023330


ENSMUSG00000032786

UniProt


P13196


Q8VC19

RefSeq (mRNA)


NM_000688 NM_001304443 NM_001304444 NM_199166


NM_001291835 NM_020559

RefSeq (protein)


NP_000679 NP_001291372 NP_001291373 NP_954635


NP_001278764 NP_065584

Location (UCSC)

Chr 3: 52.2 – 52.21 Mb

Chr 9: 106.11 – 106.13 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Delta-aminolevulinate synthase 1 also known as ALAS1 is a protein that in humans is encoded by the ALAS1 gene.^[5]^[6] ALAS1 is an aminolevulinic acid synthase.

Delta-aminolevulinate synthase catalyzes the condensation of glycine with succinyl-CoA to form delta-aminolevulinic acid. This nuclear-encoded mitochondrial enzyme is the first and rate-limiting enzyme in the mammalian heme biosynthetic pathway. There are 2 tissue-specific isozymes: a housekeeping enzyme encoded by the ALAS1 gene and an erythroid tissue-specific enzyme encoded by ALAS2.^[6]

Mice lacking this gene exhibit embryonic lethality, indicating that ALAS is essential for early embryogenesis.^[7]

References

External links

Goodfellow BJ, Dias JS, Ferreira GC, et al. (2001). "The solution structure and heme binding of the presequence of murine 5-aminolevulinate synthase". FEBS Lett. 505 (2): 325–31. doi:10.1016/S0014-5793(01)02818-6. PMID 11566198. S2CID 34879759.
Cortesão E, Vidan J, Pereira J, et al. (2004). "Onset of X-linked sideroblastic anemia in the fourth decade". Haematologica. 89 (10): 1261–3. PMID 15477213.
May BK, Bhasker CR, Bawden MJ, Cox TC (1990). "Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis". Mol. Biol. Med. 7 (5): 405–21. PMID 2095458.
Dwyer BE, Smith MA, Richardson SL, et al. (2009). "Down-Regulation of Aminolevulinate Synthase, the Rate-Limiting Enzyme for Heme Biosynthesis in Alzheimer's Disease". Neurosci. Lett. 460 (2): 180–4. doi:10.1016/j.neulet.2009.05.058. PMC 2743886. PMID 19477221.
Furuyama K, Sassa S (2002). "Multiple mechanisms for hereditary sideroblastic anemia". Cell. Mol. Biol. (Noisy-le-grand). 48 (1): 5–10. PMID 11929048.
Guberman AS, Scassa ME, Cánepa ET (2005). "Repression of 5-aminolevulinate synthase gene by the potent tumor promoter, TPA, involves multiple signal transduction pathways". Arch. Biochem. Biophys. 436 (2): 285–96. doi:10.1016/j.abb.2005.02.011. hdl:11336/99172. PMID 15797241.
Roberts AG, Elder GH (2001). "Alternative splicing and tissue-specific transcription of human and rodent ubiquitous 5-aminolevulinate synthase (ALAS1) genes". Biochim. Biophys. Acta. 1518 (1–2): 95–105. doi:10.1016/s0167-4781(01)00187-7. PMID 11267664.
Szafranski K, Schindler S, Taudien S, et al. (2007). "Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns". Genome Biol. 8 (8): R154. doi:10.1186/gb-2007-8-8-r154. PMC 2374985. PMID 17672918.
Scassa ME, Guberman AS, Ceruti JM, Cánepa ET (2004). "Hepatic nuclear factor 3 and nuclear factor 1 regulate 5-aminolevulinate synthase gene expression and are involved in insulin repression". J. Biol. Chem. 279 (27): 28082–92. doi:10.1074/jbc.M401792200. hdl:20.500.12110/paper_00219258_v279_n27_p28082_Scassa. PMID 15123725.
Imabayashi H, Mori T, Gojo S, et al. (2003). "Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis". Exp. Cell Res. 288 (1): 35–50. doi:10.1016/S0014-4827(03)00130-7. PMID 12878157.
Fujii H, Takahashi T, Matsumi M, et al. (2004). "Increased heme oxygenase-1 and decreased delta-aminolevulinate synthase expression in the liver of patients with acute liver failure". Int. J. Mol. Med. 14 (6): 1001–5. doi:10.3892/ijmm.14.6.1001. PMID 15547665.
Zheng J, Shan Y, Lambrecht RW, et al. (2008). "Differential regulation of human ALAS1 mRNA and protein levels by heme and cobalt protoporphyrin". Mol. Cell. Biochem. 319 (1–2): 153–61. doi:10.1007/s11010-008-9888-0. PMID 18719978. S2CID 33770538.
Roberts AG, Redding SJ, Llewellyn DH (2005). "An alternatively-spliced exon in the 5'-UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem-mediated decay". FEBS Lett. 579 (5): 1061–6. doi:10.1016/j.febslet.2004.12.080. PMID 15710391. S2CID 32462861.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Jung M, Ohl F, Stephan C, et al. (2007). "[Quantifying gene expression in prostate carcinoma. Which endogenous reference genes are suitable?]". Urologe A. 46 (9): 1083–4. doi:10.1007/s00120-007-1436-0. PMID 17628775. S2CID 11640176.
Guberman AS, Scassa ME, Giono LE, et al. (2003). "Inhibitory effect of AP-1 complex on 5-aminolevulinate synthase gene expression through sequestration of cAMP-response element protein (CRE)-binding protein (CBP) coactivator". J. Biol. Chem. 278 (4): 2317–26. doi:10.1074/jbc.M205057200. hdl:20.500.12110/paper_00219258_v278_n4_p2317_Guberman. PMID 12433930.
Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ferreira GC, Cheltsov AV (2002). "Circular permutation of 5-aminolevulinate synthase as a tool to evaluate folding, structure and function". Cell. Mol. Biol. (Noisy-le-grand). 48 (1): 11–6. PMID 11929042.
Tsang HT, Connell JW, Brown SE, et al. (2006). "A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex". Genomics. 88 (3): 333–46. doi:10.1016/j.ygeno.2006.04.003. PMID 16730941.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Enzymes involved in the metabolism of heme and porphyrin

Porphyrin biosynthesis

early mitochondrial:	Aminolevulinic acid synthase ALAS1 ALAS2
cytosolic:	Porphobilinogen synthase Porphobilinogen deaminase Uroporphyrinogen III synthase Uroporphyrinogen III decarboxylase
late mitochondrial:	Coproporphyrinogen III oxidase Protoporphyrinogen oxidase Ferrochelatase

Heme degradation
to bile

spleen:	Heme oxygenase Biliverdin reductase
liver:	glucuronosyltransferase UGT1A1

References

External links

Further reading