HEM0_HUMAN
ID HEM0_HUMAN Reviewed; 587 AA.
AC P22557; A8K3F0; A8K6C4; Q13735; Q5JZF5; Q8N6H3;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=5-aminolevulinate synthase, erythroid-specific, mitochondrial;
DE Short=ALAS-E;
DE EC=2.3.1.37 {ECO:0000269|PubMed:14643893, ECO:0000269|PubMed:21252495, ECO:0000269|PubMed:21309041, ECO:0000269|PubMed:21653323, ECO:0000269|PubMed:32499479};
DE AltName: Full=5-aminolevulinic acid synthase 2;
DE AltName: Full=Delta-ALA synthase 2;
DE AltName: Full=Delta-aminolevulinate synthase 2;
DE Flags: Precursor;
GN Name=ALAS2; Synonyms=ALASE, ASB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=2263504; DOI=10.1093/nar/18.23.7187;
RA Bishop D.F.;
RT "Two different genes encode delta-aminolevulinate synthase in humans:
RT nucleotide sequences of cDNAs for the housekeeping and erythroid genes.";
RL Nucleic Acids Res. 18:7187-7188(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=2050125; DOI=10.1002/j.1460-2075.1991.tb07715.x;
RA Cox T.C., Bawden M.J., Martin A., May B.K.;
RT "Human erythroid 5-aminolevulinate synthase: promoter analysis and
RT identification of an iron-responsive element in the mRNA.";
RL EMBO J. 10:1891-1902(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9642238; DOI=10.1074/jbc.273.27.16798;
RA Surinya K.H., Cox T.C., May B.K.;
RT "Identification and characterization of a conserved erythroid-specific
RT enhancer located in intron 8 of the human 5-aminolevulinate synthase 2
RT gene.";
RL J. Biol. Chem. 273:16798-16809(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, Placenta, and Umbilical cord blood;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3 AND 4), SUBCELLULAR LOCATION,
RP CATALYTIC ACTIVITY, TRANSIT PEPTIDE CLEAVAGE SITE, INTERACTION WITH SUCLA2,
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14643893; DOI=10.1016/s1357-2725(03)00246-2;
RA Cox T.C., Sadlon T.J., Schwarz Q.P., Matthews C.S., Wise P.D., Cox L.L.,
RA Bottomley S.S., May B.K.;
RT "The major splice variant of human 5-aminolevulinate synthase-2 contributes
RT significantly to erythroid heme biosynthesis.";
RL Int. J. Biochem. Cell Biol. 36:281-295(2004).
RN [9] {ECO:0007744|PDB:6HRH}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 143-578, CATALYTIC ACTIVITY,
RP FUNCTION, INTERACTION WITH SUCLA2, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP COFACTOR, AND MUTAGENESIS OF ARG-511.
RX PubMed=32499479; DOI=10.1038/s41467-020-16586-x;
RA Bailey H.J., Bezerra G.A., Marcero J.R., Padhi S., Foster W.R., Rembeza E.,
RA Roy A., Bishop D.F., Desnick R.J., Bulusu G., Dailey H.A. Jr., Yue W.W.;
RT "Human aminolevulinate synthase structure reveals a eukaryotic-specific
RT autoinhibitory loop regulating substrate binding and product release.";
RL Nat. Commun. 11:2813-2813(2020).
RN [10]
RP VARIANT SIDBA1 SER-388.
RX PubMed=8107717; DOI=10.1056/nejm199403103301004;
RA Cox T.C., Bottomley S.S., Wiley J.S., Bawden M.J., Matthews C.S., May B.K.;
RT "X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser
RT substitution in erythroid 5-aminolevulinate synthase.";
RL N. Engl. J. Med. 330:675-679(1994).
RN [11]
RP VARIANT SIDBA1 ASN-476.
RX PubMed=1570328; DOI=10.1073/pnas.89.9.4028;
RA Cotter P.D., Baumann M., Bishop D.F.;
RT "Enzymatic defect in 'X-linked' sideroblastic anemia: molecular evidence
RT for erythroid delta-aminolevulinate synthase deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:4028-4032(1992).
RN [12]
RP VARIANT SIDBA1 CYS-411.
RX PubMed=9858242; DOI=10.1046/j.1365-2141.1998.01050.x;
RA Furuyama K., Uno R., Urabe A., Hayashi N., Fujita H., Kondo M., Sassa S.,
RA Yamamoto M.;
RT "R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme
RT with low activity.";
RL Br. J. Haematol. 103:839-841(1998).
RN [13]
RP VARIANT SIDBA1 GLN-204.
RX PubMed=10577279;
RX DOI=10.1002/(sici)1096-8652(199910)62:2<112::aid-ajh9>3.0.co;2-l;
RA Harigae H., Furuyama K., Kudo K., Hayashi N., Yamamoto M., Sassa S.,
RA Sasaki T.;
RT "A novel mutation of the erythroid-specific gamma-aminolevulinate synthase
RT gene in a patient with non-inherited pyridoxine-responsive sideroblastic
RT anemia.";
RL Am. J. Hematol. 62:112-114(1999).
RN [14]
RP VARIANTS SIDBA1 HIS-199; CYS-411; GLN-448 AND CYS-452.
RX PubMed=10029606;
RA Cotter P.D., May A., Li L., Al-Sabah A.I., Fitzsimons E.J., Cazzola M.,
RA Bishop D.F.;
RT "Four new mutations in the erythroid-specific 5-aminolevulinate synthase
RT (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine
RT responsiveness after removal of iron overload by phlebotomy and
RT coinheritance of hereditary hemochromatosis.";
RL Blood 93:1757-1769(1999).
RN [15]
RP VARIANT SIDBA1 HIS-560.
RX PubMed=12393718; DOI=10.1182/blood-2002-03-0685;
RA Cazzola M., May A., Bergamaschi G., Cerani P., Ferrillo S., Bishop D.F.;
RT "Absent phenotypic expression of X-linked sideroblastic anemia in one of 2
RT brothers with a novel ALAS2 mutation.";
RL Blood 100:4236-4238(2002).
RN [16]
RP VARIANT SIDBA1 TYR-159.
RX PubMed=12031592; DOI=10.1016/s0009-8981(02)00095-5;
RA Hurford M.T., Marshall-Taylor C., Vicki S.L., Zhou J.Z., Silverman L.M.,
RA Rezuke W.N., Altman A., Tsongalis G.J.;
RT "A novel mutation in exon 5 of the ALAS2 gene results in X-linked
RT sideroblastic anemia.";
RL Clin. Chim. Acta 321:49-53(2002).
RN [17]
RP VARIANTS SIDBA1 LEU-520 AND HIS-560.
RX PubMed=16446107; DOI=10.1016/j.bcmd.2005.12.004;
RA Lee P.L., Barton J.C., Rao S.V., Acton R.T., Adler B.K., Beutler E.;
RT "Three kinships with ALAS2 P520L (c. 1559 C --> T) mutation, two in
RT association with severe iron overload, and one with sideroblastic anemia
RT and severe iron overload.";
RL Blood Cells Mol. Dis. 36:292-297(2006).
RN [18]
RP INVOLVEMENT IN XLDPT.
RX PubMed=18760763; DOI=10.1016/j.ajhg.2008.08.003;
RA Whatley S.D., Ducamp S., Gouya L., Grandchamp B., Beaumont C.,
RA Badminton M.N., Elder G.H., Holme S.A., Anstey A.V., Parker M.,
RA Corrigall A.V., Meissner P.N., Hift R.J., Marsden J.T., Ma Y.,
RA Mieli-Vergani G., Deybach J.C., Puy H.;
RT "C-terminal deletions in the ALAS2 gene lead to gain of function and cause
RT X-linked dominant protoporphyria without anemia or iron overload.";
RL Am. J. Hum. Genet. 83:408-414(2008).
RN [19]
RP VARIANTS SIDBA1 LEU-165; CYS-170; ALA-301; CYS-411; GLY-452; GLY-517 AND
RP LEU-520.
RX PubMed=19731322; DOI=10.1002/pbc.22244;
RA Bergmann A.K., Campagna D.R., McLoughlin E.M., Agarwal S., Fleming M.D.,
RA Bottomley S.S., Neufeld E.J.;
RT "Systematic molecular genetic analysis of congenital sideroblastic anemia:
RT evidence for genetic heterogeneity and identification of novel mutations.";
RL Pediatr. Blood Cancer 54:273-278(2010).
RN [20]
RP VARIANTS SIDBA1 GLU-156; CYS-452 AND HIS-452, CHARACTERIZATION OF VARIANT
RP SIDBA1 GLU-156, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21252495; DOI=10.1159/000322870;
RA Kucerova J., Horvathova M., Mojzikova R., Belohlavkova P., Cermak J.,
RA Divoky V.;
RT "New mutation in erythroid-specific delta-aminolevulinate synthase as the
RT cause of X-linked sideroblastic anemia responsive to pyridoxine.";
RL Acta Haematol. 125:193-197(2011).
RN [21]
RP VARIANT PHE-586, CHARACTERIZATION OF VARIANT PHE-586, POSSIBLE ROLE AS
RP MODIFIER GENE IN ERYTHROPOIETIC DISORDERS, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=21653323; DOI=10.1182/blood-2011-03-342873;
RA To-Figueras J., Ducamp S., Clayton J., Badenas C., Delaby C., Ged C.,
RA Lyoumi S., Gouya L., de Verneuil H., Beaumont C., Ferreira G.C.,
RA Deybach J.C., Herrero C., Puy H.;
RT "ALAS2 acts as a modifier gene in patients with congenital erythropoietic
RT porphyria.";
RL Blood 118:1443-1451(2011).
RN [22]
RP VARIANTS SIDBA1 HIS-170; HIS-218; LYS-242; ASN-263; LEU-339; CYS-375;
RP HIS-411; GLY-452 AND HIS-572, VARIANT LEU-520, CHARACTERIZATION OF VARIANTS
RP SIDBA1 HIS-170; HIS-218; LYS-242; ASN-263; LEU-339; CYS-375; HIS-411;
RP GLY-452 AND HIS-572, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21309041; DOI=10.1002/humu.21455;
RA Ducamp S., Kannengiesser C., Touati M., Garcon L., Guerci-Bresler A.,
RA Guichard J.F., Vermylen C., Dochir J., Poirel H.A., Fouyssac F., Mansuy L.,
RA Leroux G., Tertian G., Girot R., Heimpel H., Matthes T., Talbi N.,
RA Deybach J.C., Beaumont C., Puy H., Grandchamp B.;
RT "Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of
RT 29 probands and functional studies of 10 missense mutations.";
RL Hum. Mutat. 32:590-597(2011).
CC -!- FUNCTION: Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent
CC condensation of succinyl-CoA and glycine to form aminolevulinic acid
CC (ALA), with CoA and CO2 as by-products (PubMed:14643893,
CC PubMed:32499479, PubMed:21252495, PubMed:21653323, PubMed:21309041).
CC Contributes significantly to heme formation during erythropoiesis
CC (PubMed:2050125). {ECO:0000269|PubMed:14643893,
CC ECO:0000269|PubMed:21252495, ECO:0000269|PubMed:21309041,
CC ECO:0000269|PubMed:21653323, ECO:0000269|PubMed:32499479,
CC ECO:0000303|PubMed:2050125}.
CC -!- FUNCTION: [Isoform 3]: Catalyzes the pyridoxal 5'-phosphate (PLP)-
CC dependent condensation of succinyl-CoA and glycine to form
CC aminolevulinic acid (ALA), with CoA and CO2 as by-products
CC (PubMed:14643893). Catalytic activity is 75-85% of isoform 1 activity
CC (PubMed:14643893). {ECO:0000269|PubMed:14643893}.
CC -!- FUNCTION: [Isoform 4]: Catalyzes the pyridoxal 5'-phosphate (PLP)-
CC dependent condensation of succinyl-CoA and glycine to form
CC aminolevulinic acid (ALA), with CoA and CO2 as by-products
CC (PubMed:14643893). Catalytic activity is 65-75% of isoform 1 activity
CC (PubMed:14643893). {ECO:0000269|PubMed:14643893}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycine + H(+) + succinyl-CoA = 5-aminolevulinate + CO2 + CoA;
CC Xref=Rhea:RHEA:12921, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:356416; EC=2.3.1.37;
CC Evidence={ECO:0000269|PubMed:14643893, ECO:0000269|PubMed:21252495,
CC ECO:0000269|PubMed:21309041, ECO:0000269|PubMed:21653323,
CC ECO:0000269|PubMed:32499479};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC Evidence={ECO:0000305|PubMed:14643893, ECO:0000305|PubMed:32499479};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=glycine + H(+) + succinyl-CoA = 5-aminolevulinate + CO2 + CoA;
CC Xref=Rhea:RHEA:12921, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:356416; EC=2.3.1.37;
CC Evidence={ECO:0000269|PubMed:14643893};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC Evidence={ECO:0000305|PubMed:14643893};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=glycine + H(+) + succinyl-CoA = 5-aminolevulinate + CO2 + CoA;
CC Xref=Rhea:RHEA:12921, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:356416; EC=2.3.1.37;
CC Evidence={ECO:0000269|PubMed:14643893};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC Evidence={ECO:0000305|PubMed:14643893};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=glycine + H(+) + succinyl-CoA = 5-aminolevulinate + CO2 + CoA;
CC Xref=Rhea:RHEA:12921, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:356416; EC=2.3.1.37;
CC Evidence={ECO:0000269|PubMed:14643893};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12922;
CC Evidence={ECO:0000305|PubMed:14643893};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:32499479};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=31 uM for succinyl-CoA {ECO:0000269|PubMed:32499479};
CC KM=11.8 uM for glycine {ECO:0000269|PubMed:32499479};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; 5-aminolevulinate from glycine: step 1/1.
CC {ECO:0000305|PubMed:32499479}.
CC -!- SUBUNIT: Homodimer (PubMed:32499479). Interacts with SUCLA2
CC (PubMed:14643893, PubMed:32499479). {ECO:0000269|PubMed:14643893,
CC ECO:0000269|PubMed:32499479}.
CC -!- SUBUNIT: [Isoform 4]: Interacts with SUCLA2.
CC {ECO:0000269|PubMed:14643893}.
CC -!- INTERACTION:
CC P22557; Q8N9N5: BANP; NbExp=3; IntAct=EBI-2115743, EBI-744695;
CC P22557-2; Q8N9N5-2: BANP; NbExp=6; IntAct=EBI-12257000, EBI-11524452;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:14643893}; Peripheral membrane protein
CC {ECO:0000305}. Note=Localizes to the matrix side of the mitochondrion
CC inner membrane. {ECO:0000269|PubMed:14643893}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:14643893}; Peripheral membrane protein
CC {ECO:0000305}. Note=Localizes to the matrix side of the mitochondrion
CC inner membrane. {ECO:0000269|PubMed:14643893}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P22557-1; Sequence=Displayed;
CC Name=2; Synonyms=Delta4;
CC IsoId=P22557-2; Sequence=VSP_042852;
CC Name=3; Synonyms=F143M;
CC IsoId=P22557-3; Sequence=VSP_042851, VSP_042853;
CC Name=4;
CC IsoId=P22557-4; Sequence=VSP_047330, VSP_042852;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Erythroid-specific.
CC {ECO:0000269|PubMed:14643893, ECO:0000269|PubMed:2050125}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Erythroid-specific.
CC {ECO:0000269|PubMed:14643893}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Erythroid-specific.
CC {ECO:0000269|PubMed:14643893}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Erythroid-specific.
CC {ECO:0000269|PubMed:14643893}.
CC -!- DOMAIN: C-terminus is a mobile self-inhibitory loop which interferes
CC directly with active site. {ECO:0000269|PubMed:32499479}.
CC -!- DISEASE: Anemia, sideroblastic, 1 (SIDBA1) [MIM:300751]: A form of
CC sideroblastic anemia that shows a variable hematologic response to
CC pharmacologic doses of pyridoxine. Sideroblastic anemia is
CC characterized by anemia of varying severity, hypochromic peripheral
CC erythrocytes, systemic iron overload secondary to chronic ineffective
CC erythropoiesis, and the presence of bone marrow ringed sideroblasts.
CC Sideroblasts are characterized by iron-loaded mitochondria clustered
CC around the nucleus. {ECO:0000269|PubMed:10029606,
CC ECO:0000269|PubMed:10577279, ECO:0000269|PubMed:12031592,
CC ECO:0000269|PubMed:12393718, ECO:0000269|PubMed:1570328,
CC ECO:0000269|PubMed:16446107, ECO:0000269|PubMed:19731322,
CC ECO:0000269|PubMed:21252495, ECO:0000269|PubMed:21309041,
CC ECO:0000269|PubMed:8107717, ECO:0000269|PubMed:9858242}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Erythropoietic protoporphyria, X-linked dominant (XLDPT)
CC [MIM:300752]: A form of porphyria. Porphyrias are inherited defects in
CC the biosynthesis of heme, resulting in the accumulation and increased
CC excretion of porphyrins or porphyrin precursors. They are classified as
CC erythropoietic or hepatic, depending on whether the enzyme deficiency
CC occurs in red blood cells or in the liver. XLDPT is characterized
CC biochemically by a high proportion of zinc-protoporphyrin in
CC erythrocytes, in which a mismatch between protoporphyrin production and
CC the heme requirement of differentiating erythroid cells leads to
CC overproduction of protoporphyrin in amounts sufficient to cause
CC photosensitivity and liver disease. {ECO:0000269|PubMed:18760763}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry. Gain of function mutations in ALS2 are responsible for
CC XLDPT, but they can also be a possible aggravating factor in congenital
CC erythropoietic porphyria and other erythropoietic disorders caused by
CC mutations in other genes (PubMed:21309041).
CC {ECO:0000269|PubMed:21309041}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA39795.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; X56352; CAA39795.1; ALT_INIT; mRNA.
DR EMBL; X60364; CAA42916.1; -; mRNA.
DR EMBL; AF068624; AAC39838.1; -; Genomic_DNA.
DR EMBL; AK290565; BAF83254.1; -; mRNA.
DR EMBL; AK291589; BAF84278.1; -; mRNA.
DR EMBL; AK313118; BAG35939.1; -; mRNA.
DR EMBL; Z83821; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL020991; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471154; EAW93211.1; -; Genomic_DNA.
DR EMBL; CH471154; EAW93213.1; -; Genomic_DNA.
DR EMBL; BC030230; AAH30230.2; -; mRNA.
DR CCDS; CCDS14366.1; -. [P22557-1]
DR CCDS; CCDS35303.1; -. [P22557-2]
DR CCDS; CCDS43960.1; -. [P22557-4]
DR PIR; S16347; SYHUAE.
DR RefSeq; NP_000023.2; NM_000032.4. [P22557-1]
DR RefSeq; NP_001033056.1; NM_001037967.3. [P22557-2]
DR RefSeq; NP_001033057.1; NM_001037968.3. [P22557-4]
DR PDB; 5QQQ; X-ray; 1.93 A; A/B=143-578.
DR PDB; 5QQR; X-ray; 1.46 A; A/B=143-578.
DR PDB; 5QQS; X-ray; 1.85 A; A/B=143-578.
DR PDB; 5QQT; X-ray; 1.67 A; A/B=143-578.
DR PDB; 5QQU; X-ray; 1.55 A; A/B=143-578.
DR PDB; 5QQV; X-ray; 1.52 A; A/B=143-578.
DR PDB; 5QQW; X-ray; 1.56 A; A/B=143-578.
DR PDB; 5QQX; X-ray; 1.50 A; A/B=143-578.
DR PDB; 5QQY; X-ray; 1.49 A; A/B=143-578.
DR PDB; 5QQZ; X-ray; 1.55 A; A/B=143-578.
DR PDB; 5QR0; X-ray; 1.65 A; A/B=143-578.
DR PDB; 5QR1; X-ray; 1.44 A; A/B=143-578.
DR PDB; 5QR2; X-ray; 1.66 A; A/B=143-578.
DR PDB; 5QR3; X-ray; 1.71 A; A/B=143-578.
DR PDB; 5QR4; X-ray; 1.57 A; A/B=143-578.
DR PDB; 5QR5; X-ray; 1.49 A; A/B=143-578.
DR PDB; 5QR6; X-ray; 1.52 A; A/B=143-578.
DR PDB; 5QR7; X-ray; 1.74 A; A/B=143-578.
DR PDB; 5QR8; X-ray; 1.85 A; A/B=143-578.
DR PDB; 5QR9; X-ray; 1.62 A; A/B=143-578.
DR PDB; 5QRA; X-ray; 1.72 A; A/B=143-578.
DR PDB; 5QRB; X-ray; 1.72 A; A/B=143-578.
DR PDB; 5QRC; X-ray; 1.82 A; A/B=143-578.
DR PDB; 5QRD; X-ray; 1.76 A; A/B=143-578.
DR PDB; 5QRE; X-ray; 1.67 A; A/B=143-578.
DR PDB; 5QT3; X-ray; 1.95 A; A/B=143-578.
DR PDB; 6HRH; X-ray; 2.30 A; A/B=143-587.
DR PDBsum; 5QQQ; -.
DR PDBsum; 5QQR; -.
DR PDBsum; 5QQS; -.
DR PDBsum; 5QQT; -.
DR PDBsum; 5QQU; -.
DR PDBsum; 5QQV; -.
DR PDBsum; 5QQW; -.
DR PDBsum; 5QQX; -.
DR PDBsum; 5QQY; -.
DR PDBsum; 5QQZ; -.
DR PDBsum; 5QR0; -.
DR PDBsum; 5QR1; -.
DR PDBsum; 5QR2; -.
DR PDBsum; 5QR3; -.
DR PDBsum; 5QR4; -.
DR PDBsum; 5QR5; -.
DR PDBsum; 5QR6; -.
DR PDBsum; 5QR7; -.
DR PDBsum; 5QR8; -.
DR PDBsum; 5QR9; -.
DR PDBsum; 5QRA; -.
DR PDBsum; 5QRB; -.
DR PDBsum; 5QRC; -.
DR PDBsum; 5QRD; -.
DR PDBsum; 5QRE; -.
DR PDBsum; 5QT3; -.
DR PDBsum; 6HRH; -.
DR AlphaFoldDB; P22557; -.
DR SMR; P22557; -.
DR BioGRID; 106714; 3.
DR IntAct; P22557; 2.
DR STRING; 9606.ENSP00000332369; -.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR iPTMnet; P22557; -.
DR PhosphoSitePlus; P22557; -.
DR BioMuta; ALAS2; -.
DR DMDM; 20141346; -.
DR jPOST; P22557; -.
DR MassIVE; P22557; -.
DR MaxQB; P22557; -.
DR PaxDb; P22557; -.
DR PeptideAtlas; P22557; -.
DR PRIDE; P22557; -.
DR ProteomicsDB; 54000; -. [P22557-1]
DR ProteomicsDB; 54001; -. [P22557-2]
DR ProteomicsDB; 54002; -. [P22557-3]
DR ProteomicsDB; 63531; -.
DR ABCD; P22557; 1 sequenced antibody.
DR Antibodypedia; 457; 311 antibodies from 31 providers.
DR DNASU; 212; -.
DR Ensembl; ENST00000335854.8; ENSP00000337131.4; ENSG00000158578.21. [P22557-2]
DR Ensembl; ENST00000396198.7; ENSP00000379501.3; ENSG00000158578.21. [P22557-4]
DR Ensembl; ENST00000650242.1; ENSP00000497236.1; ENSG00000158578.21. [P22557-1]
DR GeneID; 212; -.
DR KEGG; hsa:212; -.
DR MANE-Select; ENST00000650242.1; ENSP00000497236.1; NM_000032.5; NP_000023.2.
DR UCSC; uc004dua.4; human. [P22557-1]
DR CTD; 212; -.
DR DisGeNET; 212; -.
DR GeneCards; ALAS2; -.
DR GeneReviews; ALAS2; -.
DR HGNC; HGNC:397; ALAS2.
DR HPA; ENSG00000158578; Tissue enriched (bone).
DR MalaCards; ALAS2; -.
DR MIM; 300751; phenotype.
DR MIM; 300752; phenotype.
DR MIM; 301300; gene.
DR neXtProt; NX_P22557; -.
DR OpenTargets; ENSG00000158578; -.
DR Orphanet; 443197; X-linked erythropoietic protoporphyria.
DR Orphanet; 75563; X-linked sideroblastic anemia.
DR PharmGKB; PA24689; -.
DR VEuPathDB; HostDB:ENSG00000158578; -.
DR eggNOG; KOG1360; Eukaryota.
DR GeneTree; ENSGT00940000159912; -.
DR HOGENOM; CLU_015846_6_1_1; -.
DR InParanoid; P22557; -.
DR OMA; NHASMIV; -.
DR OrthoDB; 930001at2759; -.
DR PhylomeDB; P22557; -.
DR TreeFam; TF300724; -.
DR BioCyc; MetaCyc:HS08311-MON; -.
DR BRENDA; 2.3.1.37; 2681.
DR PathwayCommons; P22557; -.
DR Reactome; R-HSA-189451; Heme biosynthesis.
DR SignaLink; P22557; -.
DR SIGNOR; P22557; -.
DR UniPathway; UPA00251; UER00375.
DR BioGRID-ORCS; 212; 19 hits in 711 CRISPR screens.
DR ChiTaRS; ALAS2; human.
DR GeneWiki; ALAS2; -.
DR GenomeRNAi; 212; -.
DR Pharos; P22557; Tbio.
DR PRO; PR:P22557; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P22557; protein.
DR Bgee; ENSG00000158578; Expressed in trabecular bone tissue and 109 other tissues.
DR ExpressionAtlas; P22557; baseline and differential.
DR Genevisible; P22557; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0003870; F:5-aminolevulinate synthase activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISS:UniProtKB.
DR GO; GO:0048821; P:erythrocyte development; IBA:GO_Central.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0006783; P:heme biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042541; P:hemoglobin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0032364; P:oxygen homeostasis; NAS:UniProtKB.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR010961; 4pyrrol_synth_NH2levulA_synth.
DR InterPro; IPR015118; 5aminolev_synth_preseq.
DR InterPro; IPR001917; Aminotrans_II_pyridoxalP_BS.
DR InterPro; IPR004839; Aminotransferase_I/II.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR Pfam; PF00155; Aminotran_1_2; 1.
DR Pfam; PF09029; Preseq_ALAS; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR01821; 5aminolev_synth; 1.
DR PROSITE; PS00599; AA_TRANSFER_CLASS_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Alternative splicing; Disease variant;
KW Heme biosynthesis; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..49
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:14643893"
FT CHAIN 50..587
FT /note="5-aminolevulinate synthase, erythroid-specific,
FT mitochondrial"
FT /id="PRO_0000001223"
FT ACT_SITE 391
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 163
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 258
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:32499479"
FT BINDING 259
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:32499479"
FT BINDING 280
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 299
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 332
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT BINDING 360
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:32499479"
FT BINDING 388
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:32499479"
FT BINDING 420
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:32499479"
FT BINDING 421
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:32499479"
FT BINDING 508
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P18079"
FT MOD_RES 391
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:32499479"
FT VAR_SEQ 1..142
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14643893, ECO:0000305"
FT /id="VSP_042851"
FT VAR_SEQ 1
FT /note="M -> MRGGEVALGWNKKKRLFCEDFRFKM (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_047330"
FT VAR_SEQ 102..138
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14643893,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_042852"
FT VAR_SEQ 143
FT /note="F -> M (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14643893, ECO:0000305"
FT /id="VSP_042853"
FT VARIANT 156
FT /note="K -> E (in SIDBA1; significantly reduced activity)"
FT /evidence="ECO:0000269|PubMed:21252495"
FT /id="VAR_066232"
FT VARIANT 159
FT /note="D -> Y (in SIDBA1; dbSNP:rs137852308)"
FT /evidence="ECO:0000269|PubMed:12031592"
FT /id="VAR_018604"
FT VARIANT 165
FT /note="F -> L (in SIDBA1; dbSNP:rs137852301)"
FT /evidence="ECO:0000269|PubMed:19731322"
FT /id="VAR_072328"
FT VARIANT 170
FT /note="R -> C (in SIDBA1)"
FT /evidence="ECO:0000269|PubMed:19731322"
FT /id="VAR_072329"
FT VARIANT 170
FT /note="R -> H (in SIDBA1; significantly increased
FT thermosensitivity)"
FT /evidence="ECO:0000269|PubMed:21309041"
FT /id="VAR_066233"
FT VARIANT 199
FT /note="Y -> H (in SIDBA1; dbSNP:rs137852310)"
FT /evidence="ECO:0000269|PubMed:10029606"
FT /id="VAR_012334"
FT VARIANT 204
FT /note="R -> Q (in SIDBA1; 15% to 35% activity of wild-type;
FT dbSNP:rs1338391423)"
FT /evidence="ECO:0000269|PubMed:10577279"
FT /id="VAR_012335"
FT VARIANT 218
FT /note="R -> H (in SIDBA1; significantly increased
FT thermosensitivity; dbSNP:rs185504937)"
FT /evidence="ECO:0000269|PubMed:21309041"
FT /id="VAR_066234"
FT VARIANT 242
FT /note="E -> K (in SIDBA1; significantly reduced activity)"
FT /evidence="ECO:0000269|PubMed:21309041"
FT /id="VAR_066235"
FT VARIANT 263
FT /note="D -> N (in SIDBA1; significantly reduced activity)"
FT /evidence="ECO:0000269|PubMed:21309041"
FT /id="VAR_066236"
FT VARIANT 301
FT /note="V -> A (in SIDBA1)"
FT /evidence="ECO:0000269|PubMed:19731322"
FT /id="VAR_072330"
FT VARIANT 339
FT /note="P -> L (in SIDBA1; significantly reduced activity)"
FT /evidence="ECO:0000269|PubMed:21309041"
FT /id="VAR_066237"
FT VARIANT 375
FT /note="R -> C (in SIDBA1; significantly reduced activity)"
FT /evidence="ECO:0000269|PubMed:21309041"
FT /id="VAR_066238"
FT VARIANT 388
FT /note="T -> S (in SIDBA1; dbSNP:rs137852300)"
FT /evidence="ECO:0000269|PubMed:8107717"
FT /id="VAR_000562"
FT VARIANT 411
FT /note="R -> C (in SIDBA1; 12% to 25% activity of wild-type;
FT dbSNP:rs137852305)"
FT /evidence="ECO:0000269|PubMed:10029606,
FT ECO:0000269|PubMed:19731322, ECO:0000269|PubMed:9858242"
FT /id="VAR_000563"
FT VARIANT 411
FT /note="R -> H (in SIDBA1; significantly reduced activity)"
FT /evidence="ECO:0000269|PubMed:21309041"
FT /id="VAR_066239"
FT VARIANT 448
FT /note="R -> Q (in SIDBA1)"
FT /evidence="ECO:0000269|PubMed:10029606"
FT /id="VAR_012336"
FT VARIANT 452
FT /note="R -> C (in SIDBA1; dbSNP:rs137852311)"
FT /evidence="ECO:0000269|PubMed:10029606,
FT ECO:0000269|PubMed:21252495"
FT /id="VAR_012337"
FT VARIANT 452
FT /note="R -> G (in SIDBA1; does not affect activity)"
FT /evidence="ECO:0000269|PubMed:19731322,
FT ECO:0000269|PubMed:21309041"
FT /id="VAR_066240"
FT VARIANT 452
FT /note="R -> H (in SIDBA1; dbSNP:rs863223904)"
FT /evidence="ECO:0000269|PubMed:21252495"
FT /id="VAR_066241"
FT VARIANT 476
FT /note="I -> N (in SIDBA1; dbSNP:rs137852299)"
FT /evidence="ECO:0000269|PubMed:1570328"
FT /id="VAR_000564"
FT VARIANT 517
FT /note="R -> G (in SIDBA1)"
FT /evidence="ECO:0000269|PubMed:19731322"
FT /id="VAR_072331"
FT VARIANT 520
FT /note="P -> L (in SIDBA1; likely benign variant; associated
FT in cis with H-560 in a patient; dbSNP:rs201062903)"
FT /evidence="ECO:0000269|PubMed:16446107,
FT ECO:0000269|PubMed:19731322, ECO:0000269|PubMed:21309041"
FT /id="VAR_066242"
FT VARIANT 560
FT /note="R -> H (in SIDBA1; associated in cis with L-520 in a
FT patient; dbSNP:rs892041887)"
FT /evidence="ECO:0000269|PubMed:12393718,
FT ECO:0000269|PubMed:16446107"
FT /id="VAR_018605"
FT VARIANT 572
FT /note="R -> H (in SIDBA1; does not affect activity)"
FT /evidence="ECO:0000269|PubMed:21309041"
FT /id="VAR_066243"
FT VARIANT 586
FT /note="Y -> F (rare variant found in a congenital
FT erythropoietic porphyria patient that also carries UROS
FT mutations R-73 and Q-248; increased enzyme activity;
FT dbSNP:rs139596860)"
FT /evidence="ECO:0000269|PubMed:21653323"
FT /id="VAR_066244"
FT MUTAGEN 511
FT /note="R->E: 2-fold increased enzyme activity with a lower
FT specificity for glycine and higher for succinyl-CoA."
FT /evidence="ECO:0000269|PubMed:32499479"
FT CONFLICT 182
FT /note="S -> F (in Ref. 1; CAA39795)"
FT /evidence="ECO:0000305"
FT CONFLICT 221
FT /note="A -> V (in Ref. 7; AAH30230)"
FT /evidence="ECO:0000305"
FT HELIX 145..158
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 206..219
FT /evidence="ECO:0007829|PDB:5QR1"
FT TURN 227..230
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 234..246
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 250..256
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 258..272
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 286..295
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 307..315
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 323..330
FT /evidence="ECO:0007829|PDB:5QR1"
FT TURN 332..334
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 340..349
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 353..357
FT /evidence="ECO:0007829|PDB:5QR1"
FT TURN 359..364
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 372..375
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 383..391
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 398..402
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 404..413
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 415..418
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 425..439
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 441..463
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 472..474
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 483..497
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 498..500
FT /evidence="ECO:0007829|PDB:5QR1"
FT TURN 506..508
FT /evidence="ECO:0007829|PDB:5QR1"
FT STRAND 515..518
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 526..542
FT /evidence="ECO:0007829|PDB:5QR1"
FT HELIX 569..575
FT /evidence="ECO:0007829|PDB:5QR1"
SQ SEQUENCE 587 AA; 64633 MW; FD821BE245C440B5 CRC64;
MVTAAMLLQC CPVLARGPTS LLGKVVKTHQ FLFGIGRCPI LATQGPNCSQ IHLKATKAGG
DSPSWAKGHC PFMLSELQDG KSKIVQKAAP EVQEDVKAFK TDLPSSLVSV SLRKPFSGPQ
EQEQISGKVT HLIQNNMPGN YVFSYDQFFR DKIMEKKQDH TYRVFKTVNR WADAYPFAQH
FSEASVASKD VSVWCSNDYL GMSRHPQVLQ ATQETLQRHG AGAGGTRNIS GTSKFHVELE
QELAELHQKD SALLFSSCFV ANDSTLFTLA KILPGCEIYS DAGNHASMIQ GIRNSGAAKF
VFRHNDPDHL KKLLEKSNPK IPKIVAFETV HSMDGAICPL EELCDVSHQY GALTFVDEVH
AVGLYGSRGA GIGERDGIMH KIDIISGTLG KAFGCVGGYI ASTRDLVDMV RSYAAGFIFT
TSLPPMVLSG ALESVRLLKG EEGQALRRAH QRNVKHMRQL LMDRGLPVIP CPSHIIPIRV
GNAALNSKLC DLLLSKHGIY VQAINYPTVP RGEELLRLAP SPHHSPQMME DFVEKLLLAW
TAVGLPLQDV SVAACNFCRR PVHFELMSEW ERSYFGNMGP QYVTTYA
