5-aminolevulinate synthase, erythroid-specific, mitochondrial

Name5-aminolevulinate synthase, erythroid-specific, mitochondrial
Synonyms
  • 2.3.1.37
  • 5-aminolevulinic acid synthase 2
  • ALAS-E
  • ALASE
  • ASB
  • Delta-ALA synthase 2
  • Delta-aminolevulinate synthase 2
Gene NameALAS2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001789|5-aminolevulinate synthase, erythroid-specific, mitochondrial
MVTAAMLLQCCPVLARGPTSLLGKVVKTHQFLFGIGRCPILATQGPNCSQIHLKATKAGG
DSPSWAKGHCPFMLSELQDGKSKIVQKAAPEVQEDVKAFKTDLPSSLVSVSLRKPFSGPQ
EQEQISGKVTHLIQNNMPGNYVFSYDQFFRDKIMEKKQDHTYRVFKTVNRWADAYPFAQH
FSEASVASKDVSVWCSNDYLGMSRHPQVLQATQETLQRHGAGAGGTRNISGTSKFHVELE
QELAELHQKDSALLFSSCFVANDSTLFTLAKILPGCEIYSDAGNHASMIQGIRNSGAAKF
VFRHNDPDHLKKLLEKSNPKIPKIVAFETVHSMDGAICPLEELCDVSHQYGALTFVDEVH
AVGLYGSRGAGIGERDGIMHKIDIISGTLGKAFGCVGGYIASTRDLVDMVRSYAAGFIFT
TSLPPMVLSGALESVRLLKGEEGQALRRAHQRNVKHMRQLLMDRGLPVIPCPSHIIPIRV
GNAALNSKLCDLLLSKHGIYVQAINYPTVPRGEELLRLAPSPHHSPQMMEDFVEKLLLAW
TAVGLPLQDVSVAACNFCRRPVHFELMSEWERSYFGNMGPQYVTTYA
Number of residues587
Molecular Weight64632.86
Theoretical pI8.19
GO Classification
Functions
  • coenzyme binding
  • pyridoxal phosphate binding
  • 5-aminolevulinate synthase activity
  • glycine binding
Processes
  • oxygen homeostasis
  • erythrocyte differentiation
  • hemoglobin biosynthetic process
  • small molecule metabolic process
  • response to hypoxia
  • heme biosynthetic process
  • porphyrin-containing compound metabolic process
  • protoporphyrinogen IX biosynthetic process
  • cellular iron ion homeostasis
Components
  • mitochondrion
  • mitochondrial inner membrane
  • mitochondrial matrix
General FunctionPyridoxal phosphate binding
Specific FunctionNot Available
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID28586
UniProtKB IDP22557
UniProtKB Entry NameHEM0_HUMAN
Cellular LocationMitochondrion matrix
Gene sequence
>lcl|BSEQ0016244|5-aminolevulinate synthase, erythroid-specific, mitochondrial (ALAS2)
ATGGTGACTGCAGCCATGCTGCTACAGTGCTGCCCAGTGCTTGCCCGGGGCCCCACAAGC
CTCCTAGGCAAGGTGGTTAAGACTCACCAGTTCCTGTTTGGTATTGGACGCTGTCCCATC
CTGGCTACCCAAGGACCAAACTGTTCTCAAATCCACCTTAAGGCAACAAAGGCTGGAGGA
GATTCTCCATCTTGGGCGAAGGGCCACTGTCCCTTCATGCTGTCGGAACTCCAGGATGGG
AAGAGCAAGATTGTGCAGAAGGCAGCCCCAGAAGTCCAGGAAGATGTGAAGGCTTTCAAG
ACAGATCTGCCTAGCTCCCTGGTCTCAGTCAGCCTAAGGAAGCCATTTTCCGGTCCCCAG
GAGCAGGAGCAGATCTCTGGGAAGGTCACACACCTGATTCAGAACAATATGCCTGGAAAC
TATGTCTTCAGTTATGACCAGTTTTTCAGGGACAAGATCATGGAGAAGAAACAGGATCAC
ACCTACCGTGTGTTCAAGACTGTGAACCGCTGGGCTGATGCATATCCCTTTGCCCAACAT
TTCTCTGAGGCATCTGTGGCCTCAAAGGATGTGTCCGTCTGGTGTAGTAATGATTACCTG
GGCATGAGCCGACACCCTCAGGTCTTGCAAGCCACACAGGAGACCCTGCAGCGTCATGGT
GCTGGAGCTGGTGGCACCCGCAACATCTCAGGCACCAGTAAGTTTCATGTGGAGCTTGAG
CAGGAGCTGGCTGAGCTGCACCAGAAGGACTCAGCCCTGCTCTTCTCCTCCTGCTTTGTT
GCCAATGACTCTACTCTCTTCACCTTGGCCAAGATCCTGCCAGGGTGCGAGATTTACTCA
GACGCAGGCAACCATGCTTCCATGATCCAAGGTATCCGTAACAGTGGAGCAGCCAAGTTT
GTCTTCAGGCACAATGACCCTGACCACCTAAAGAAACTTCTAGAGAAGTCTAACCCTAAG
ATACCCAAAATTGTGGCCTTTGAGACTGTCCACTCCATGGATGGTGCCATCTGTCCCCTC
GAGGAGTTGTGTGATGTGTCCCACCAGTATGGGGCCCTGACCTTCGTGGATGAGGTCCAT
GCTGTAGGACTGTATGGGTCCCGGGGCGCTGGGATTGGGGAGCGTGATGGAATTATGCAT
AAGATTGACATCATCTCTGGAACTCTTGGCAAGGCCTTTGGCTGTGTGGGCGGCTACATT
GCCAGCACCCGTGACTTGGTGGACATGGTGCGCTCCTATGCTGCAGGCTTCATCTTTACC
ACTTCTCTGCCCCCCATGGTGCTCTCTGGAGCTCTAGAATCTGTGCGGCTGCTCAAGGGA
GAGGAGGGCCAAGCCCTGAGGCGAGCCCACCAGCGCAATGTCAAGCACATGCGCCAGCTA
CTCATGGACAGGGGCCTTCCTGTCATCCCCTGCCCCAGCCACATCATCCCCATCCGGGTG
GGCAATGCAGCACTCAACAGCAAGCTCTGTGATCTCCTGCTCTCCAAGCATGGCATCTAT
GTGCAGGCCATCAACTACCCAACTGTCCCCCGGGGTGAAGAGCTCCTGCGCTTGGCACCC
TCCCCCCACCACAGCCCTCAGATGATGGAAGATTTTGTGGAGAAGCTGCTGCTGGCTTGG
ACTGCGGTGGGGCTGCCCCTCCAGGATGTGTCTGTGGCTGCCTGCAATTTCTGTCGCCGT
CCTGTACACTTTGAGCTCATGAGTGAGTGGGAACGTTCCTACTTCGGGAACATGGGGCCC
CAGTATGTCACCACCTATGCCTGA
GenBank Gene IDX56352
GeneCard IDNot Available
GenAtlas IDALAS2
HGNC IDHGNC:397
Chromosome LocationX
LocusXp11.21
References
  1. Bishop DF: Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes. Nucleic Acids Res. 1990 Dec 11;18(23):7187-8. 2263504
  2. Cox TC, Bawden MJ, Martin A, May BK: Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA. EMBO J. 1991 Jul;10(7):1891-902. 2050125
  3. Surinya KH, Cox TC, May BK: Identification and characterization of a conserved erythroid-specific enhancer located in intron 8 of the human 5-aminolevulinate synthase 2 gene. J Biol Chem. 1998 Jul 3;273(27):16798-809. 9642238
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  5. Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glockner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, McLaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Muller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, Bentley DR: The DNA sequence of the human X chromosome. Nature. 2005 Mar 17;434(7031):325-37. 15772651
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Cox TC, Sadlon TJ, Schwarz QP, Matthews CS, Wise PD, Cox LL, Bottomley SS, May BK: The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis. Int J Biochem Cell Biol. 2004 Feb;36(2):281-95. 14643893
  8. Cox TC, Bottomley SS, Wiley JS, Bawden MJ, Matthews CS, May BK: X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser substitution in erythroid 5-aminolevulinate synthase. N Engl J Med. 1994 Mar 10;330(10):675-9. 8107717
  9. Cotter PD, Baumann M, Bishop DF: Enzymatic defect in "X-linked" sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4028-32. 1570328
  10. Furuyama K, Uno R, Urabe A, Hayashi N, Fujita H, Kondo M, Sassa S, Yamamoto M: R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity. Br J Haematol. 1998 Dec;103(3):839-41. 9858242
  11. Harigae H, Furuyama K, Kudo K, Hayashi N, Yamamoto M, Sassa S, Sasaki T: A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia. Am J Hematol. 1999 Oct;62(2):112-4. 10577279
  12. Cotter PD, May A, Li L, Al-Sabah AI, Fitzsimons EJ, Cazzola M, Bishop DF: Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis. Blood. 1999 Mar 1;93(5):1757-69. 10029606
  13. Cazzola M, May A, Bergamaschi G, Cerani P, Ferrillo S, Bishop DF: Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation. Blood. 2002 Dec 1;100(12):4236-8. Epub 2002 Aug 8. 12393718
  14. Hurford MT, Marshall-Taylor C, Vicki SL, Zhou JZ, Silverman LM, Rezuke WN, Altman A, Tsongalis GJ: A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia. Clin Chim Acta. 2002 Jul;321(1-2):49-53. 12031592
  15. Whatley SD, Ducamp S, Gouya L, Grandchamp B, Beaumont C, Badminton MN, Elder GH, Holme SA, Anstey AV, Parker M, Corrigall AV, Meissner PN, Hift RJ, Marsden JT, Ma Y, Mieli-Vergani G, Deybach JC, Puy H: C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. Am J Hum Genet. 2008 Sep;83(3):408-14. doi: 10.1016/j.ajhg.2008.08.003. Epub 2008 Sep 4. 18760763
  16. Bergmann AK, Campagna DR, McLoughlin EM, Agarwal S, Fleming MD, Bottomley SS, Neufeld EJ: Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations. Pediatr Blood Cancer. 2010 Feb;54(2):273-8. doi: 10.1002/pbc.22244. 19731322
  17. Kucerova J, Horvathova M, Mojzikova R, Belohlavkova P, Cermak J, Divoky V: New mutation in erythroid-specific delta-aminolevulinate synthase as the cause of X-linked sideroblastic anemia responsive to pyridoxine. Acta Haematol. 2011;125(4):193-7. doi: 10.1159/000322870. Epub 2011 Jan 20. 21252495
  18. To-Figueras J, Ducamp S, Clayton J, Badenas C, Delaby C, Ged C, Lyoumi S, Gouya L, de Verneuil H, Beaumont C, Ferreira GC, Deybach JC, Herrero C, Puy H: ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria. Blood. 2011 Aug 11;118(6):1443-51. doi: 10.1182/blood-2011-03-342873. Epub 2011 Jun 7. 21653323
  19. Ducamp S, Kannengiesser C, Touati M, Garcon L, Guerci-Bresler A, Guichard JF, Vermylen C, Dochir J, Poirel HA, Fouyssac F, Mansuy L, Leroux G, Tertian G, Girot R, Heimpel H, Matthes T, Talbi N, Deybach JC, Beaumont C, Puy H, Grandchamp B: Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations. Hum Mutat. 2011 Jun;32(6):590-7. doi: 10.1002/humu.21455. Epub 2011 Feb 24. 21309041