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P22557 (HEM0_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
5-aminolevulinate synthase, erythroid-specific, mitochondrial

Short name=ALAS-E
EC=2.3.1.37
Alternative name(s):
5-aminolevulinic acid synthase 2
Delta-ALA synthase 2
Delta-aminolevulinate synthase 2
Gene names
Name:ALAS2
Synonyms:ALASE, ASB
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length587 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

Succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2. Ref.8

Cofactor

Pyridoxal phosphate.

Pathway

Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; 5-aminolevulinate from glycine: step 1/1.

Subunit structure

Homodimer. Interacts with SUCLA2. Ref.8

Subcellular location

Mitochondrion matrix Ref.8.

Tissue specificity

Erythroid specific.

Involvement in disease

Anemia, sideroblastic, X-linked (XLSA) [MIM:300751]: A form of sideroblastic anemia that shows a variable hematologic response to pharmacologic doses of pyridoxine. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.19

Erythropoietic protoporphyria, X-linked dominant (XLDPT) [MIM:300752]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. XLDPT is characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Gain of function mutations in ALS2 are responsible for XLDPT, but they can also be a possible aggravating factor in congenital erythropoietic porphyria and other erythropoietic disorders caused by mutations in other genes (Ref.19). Ref.16

Miscellaneous

There are two delta-ALA synthases in vertebrates: an erythroid- specific form and one (housekeeping) which is expressed in all tissues.

Sequence similarities

Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.

Sequence caution

The sequence CAA39795.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processHeme biosynthesis
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainTransit peptide
   LigandPyridoxal phosphate
   Molecular functionAcyltransferase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular iron ion homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

erythrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

heme biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

hemoglobin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

oxygen homeostasis

Non-traceable author statement PubMed 16234850. Source: UniProtKB

porphyrin-containing compound metabolic process

Traceable author statement. Source: Reactome

protoporphyrinogen IX biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

response to hypoxia

Inferred from direct assay PubMed 16234850. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrial inner membrane

Inferred from direct assay Ref.8. Source: UniProtKB

mitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay PubMed 10727444. Source: UniProtKB

   Molecular_function5-aminolevulinate synthase activity

Inferred from direct assay Ref.8. Source: UniProtKB

coenzyme binding

Inferred from sequence or structural similarity. Source: UniProtKB

glycine binding

Inferred from sequence or structural similarity. Source: UniProtKB

pyridoxal phosphate binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P22557-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P22557-2)

Also known as: Delta4;

The sequence of this isoform differs from the canonical sequence as follows:
     102-138: Missing.
Note: Constitutes 35-45% of erythrocytes ALAS2 mRNAs. Catalytic activity is 70% of isoform 1 activity.
Isoform 3 (identifier: P22557-3)

Also known as: F143M;

The sequence of this isoform differs from the canonical sequence as follows:
     1-142: Missing.
     143-143: F → M
Note: Catalytic activity is 80% of isoform 1 activity.
Isoform 4 (identifier: P22557-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRGGEVALGWNKKKRLFCEDFRFKM
     102-138: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4949Mitochondrion
Chain50 – 5875385-aminolevulinate synthase, erythroid-specific, mitochondrial
PRO_0000001223

Sites

Active site3911 By similarity
Binding site1631Substrate By similarity
Binding site2801Substrate By similarity
Binding site2991Substrate By similarity
Binding site3321Pyridoxal phosphate By similarity
Binding site3601Pyridoxal phosphate By similarity
Binding site3881Pyridoxal phosphate By similarity
Binding site4201Pyridoxal phosphate By similarity
Binding site4211Pyridoxal phosphate By similarity
Binding site5081Substrate By similarity

Amino acid modifications

Modified residue3911N6-(pyridoxal phosphate)lysine Probable

Natural variations

Alternative sequence1 – 142142Missing in isoform 3.
VSP_042851
Alternative sequence11M → MRGGEVALGWNKKKRLFCED FRFKM in isoform 4.
VSP_047330
Alternative sequence102 – 13837Missing in isoform 2 and isoform 4.
VSP_042852
Alternative sequence1431F → M in isoform 3.
VSP_042853
Natural variant1561K → E in XLSA; significantly reduced activity. Ref.17
VAR_066232
Natural variant1591D → Y in XLSA. Ref.15
VAR_018604
Natural variant1701R → H in XLSA; significantly increased thermosensitivity. Ref.19
VAR_066233
Natural variant1991Y → H in XLSA. Ref.13
VAR_012334
Natural variant2041R → Q in XLSA; 15% to 35% activity of wild-type. Ref.12
VAR_012335
Natural variant2181R → H in XLSA; significantly increased thermosensitivity. Ref.19
Corresponds to variant rs185504937 [ dbSNP | Ensembl ].
VAR_066234
Natural variant2421E → K in XLSA; significantly reduced activity. Ref.19
VAR_066235
Natural variant2631D → N in XLSA; significantly reduced activity. Ref.19
VAR_066236
Natural variant3391P → L in XLSA; significantly reduced activity. Ref.19
VAR_066237
Natural variant3751R → C in XLSA; significantly reduced activity. Ref.19
VAR_066238
Natural variant3881T → S in XLSA. Ref.9
VAR_000562
Natural variant4111R → C in XLSA; 12% to 25% activity of wild-type. Ref.11 Ref.13
VAR_000563
Natural variant4111R → H in XLSA; significantly reduced activity. Ref.19
VAR_066239
Natural variant4481R → Q in XLSA. Ref.13
VAR_012336
Natural variant4521R → C in XLSA. Ref.13 Ref.17
VAR_012337
Natural variant4521R → G in XLSA; does not affect activity. Ref.19
VAR_066240
Natural variant4521R → H in XLSA. Ref.17
VAR_066241
Natural variant4761I → N in XLSA. Ref.10
VAR_000564
Natural variant5201P → L. Ref.19
Corresponds to variant rs201062903 [ dbSNP | Ensembl ].
VAR_066242
Natural variant5601R → H in XLSA. Ref.14
VAR_018605
Natural variant5721R → H in XLSA; does not affect activity. Ref.19
VAR_066243
Natural variant5861Y → F Rare variant found in a congenital erythropoietic porphyria patient that also carries UROS mutations R-73R and Q-248; increased enzyme activity. Ref.18
Corresponds to variant rs139596860 [ dbSNP | Ensembl ].
VAR_066244

Experimental info

Sequence conflict1821S → F in CAA39795. Ref.1
Sequence conflict2211A → V in AAH30230. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2002. Version 2.
Checksum: FD821BE245C440B5

FASTA58764,633
        10         20         30         40         50         60 
MVTAAMLLQC CPVLARGPTS LLGKVVKTHQ FLFGIGRCPI LATQGPNCSQ IHLKATKAGG 

        70         80         90        100        110        120 
DSPSWAKGHC PFMLSELQDG KSKIVQKAAP EVQEDVKAFK TDLPSSLVSV SLRKPFSGPQ 

       130        140        150        160        170        180 
EQEQISGKVT HLIQNNMPGN YVFSYDQFFR DKIMEKKQDH TYRVFKTVNR WADAYPFAQH 

       190        200        210        220        230        240 
FSEASVASKD VSVWCSNDYL GMSRHPQVLQ ATQETLQRHG AGAGGTRNIS GTSKFHVELE 

       250        260        270        280        290        300 
QELAELHQKD SALLFSSCFV ANDSTLFTLA KILPGCEIYS DAGNHASMIQ GIRNSGAAKF 

       310        320        330        340        350        360 
VFRHNDPDHL KKLLEKSNPK IPKIVAFETV HSMDGAICPL EELCDVSHQY GALTFVDEVH 

       370        380        390        400        410        420 
AVGLYGSRGA GIGERDGIMH KIDIISGTLG KAFGCVGGYI ASTRDLVDMV RSYAAGFIFT 

       430        440        450        460        470        480 
TSLPPMVLSG ALESVRLLKG EEGQALRRAH QRNVKHMRQL LMDRGLPVIP CPSHIIPIRV 

       490        500        510        520        530        540 
GNAALNSKLC DLLLSKHGIY VQAINYPTVP RGEELLRLAP SPHHSPQMME DFVEKLLLAW 

       550        560        570        580 
TAVGLPLQDV SVAACNFCRR PVHFELMSEW ERSYFGNMGP QYVTTYA 

« Hide

Isoform 2 (Delta4) [UniParc].

Checksum: BB28A593D343264F
Show »

FASTA55060,589
Isoform 3 (F143M) [UniParc].

Checksum: 3304747E4DE0CC2E
Show »

FASTA44549,395
Isoform 4 [UniParc].

Checksum: 7F5E13D5F36738CD
Show »

FASTA57463,487

References

« Hide 'large scale' references
[1]"Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes."
Bishop D.F.
Nucleic Acids Res. 18:7187-7188(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[2]"Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA."
Cox T.C., Bawden M.J., Martin A., May B.K.
EMBO J. 10:1891-1902(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[3]"Identification and characterization of a conserved erythroid-specific enhancer located in intron 8 of the human 5-aminolevulinate synthase 2 gene."
Surinya K.H., Cox T.C., May B.K.
J. Biol. Chem. 273:16798-16809(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
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. expand/collapse author list , 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 T.-O., 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Lung, Placenta and Umbilical cord blood.
[5]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., 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 K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Pancreas.
[8]"The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis."
Cox T.C., Sadlon T.J., Schwarz Q.P., Matthews C.S., Wise P.D., Cox L.L., Bottomley S.S., May B.K.
Int. J. Biochem. Cell Biol. 36:281-295(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, TRANSIT PEPTIDE CLEAVAGE SITE, INTERACTION WITH SUCLA2.
[9]"X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser substitution in erythroid 5-aminolevulinate synthase."
Cox T.C., Bottomley S.S., Wiley J.S., Bawden M.J., Matthews C.S., May B.K.
N. Engl. J. Med. 330:675-679(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT XLSA SER-388.
[10]"Enzymatic defect in 'X-linked' sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency."
Cotter P.D., Baumann M., Bishop D.F.
Proc. Natl. Acad. Sci. U.S.A. 89:4028-4032(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT XLSA ASN-476.
[11]"R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity."
Furuyama K., Uno R., Urabe A., Hayashi N., Fujita H., Kondo M., Sassa S., Yamamoto M.
Br. J. Haematol. 103:839-841(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT XLSA CYS-411.
[12]"A novel mutation of the erythroid-specific gamma-aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia."
Harigae H., Furuyama K., Kudo K., Hayashi N., Yamamoto M., Sassa S., Sasaki T.
Am. J. Hematol. 62:112-114(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT XLSA GLN-204.
[13]"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."
Cotter P.D., May A., Li L., Al-Sabah A.I., Fitzsimons E.J., Cazzola M., Bishop D.F.
Blood 93:1757-1769(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS XLSA HIS-199; CYS-411; GLN-448 AND CYS-452.
[14]"Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation."
Cazzola M., May A., Bergamaschi G., Cerani P., Ferrillo S., Bishop D.F.
Blood 100:4236-4238(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT XLSA HIS-560.
[15]"A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia."
Hurford M.T., Marshall-Taylor C., Vicki S.L., Zhou J.Z., Silverman L.M., Rezuke W.N., Altman A., Tsongalis G.J.
Clin. Chim. Acta 321:49-53(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT XLSA TYR-159.
[16]"C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload."
Whatley S.D., Ducamp S., Gouya L., Grandchamp B., Beaumont C., Badminton M.N., Elder G.H., Holme S.A., Anstey A.V., Parker M., Corrigall A.V., Meissner P.N., Hift R.J., Marsden J.T., Ma Y., Mieli-Vergani G., Deybach J.C., Puy H.
Am. J. Hum. Genet. 83:408-414(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN XLDPT.
[17]"New mutation in erythroid-specific delta-aminolevulinate synthase as the cause of X-linked sideroblastic anemia responsive to pyridoxine."
Kucerova J., Horvathova M., Mojzikova R., Belohlavkova P., Cermak J., Divoky V.
Acta Haematol. 125:193-197(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS XLSA GLU-156; CYS-452 AND HIS-452, CHARACTERIZATION OF VARIANT XLSA GLU-156.
[18]"ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria."
To-Figueras J., Ducamp S., Clayton J., Badenas C., Delaby C., Ged C., Lyoumi S., Gouya L., de Verneuil H., Beaumont C., Ferreira G.C., Deybach J.C., Herrero C., Puy H.
Blood 118:1443-1451(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHE-586, CHARACTERIZATION OF VARIANT PHE-586, POSSIBLE ROLE AS MODIFIER GENE IN ERYTHROPOIETIC DISORDERS.
[19]"Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations."
Ducamp S., Kannengiesser C., Touati M., Garcon L., Guerci-Bresler A., Guichard J.F., Vermylen C., Dochir J., Poirel H.A., Fouyssac F., Mansuy L., Leroux G., Tertian G., Girot R., Heimpel H., Matthes T., Talbi N., Deybach J.C. expand/collapse author list , Beaumont C., Puy H., Grandchamp B.
Hum. Mutat. 32:590-597(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS XLSA HIS-170; HIS-218; LYS-242; ASN-263; LEU-339; CYS-375; HIS-411; GLY-452 AND HIS-572, VARIANT LEU-520, CHARACTERIZATION OF VARIANTS XLSA HIS-170; HIS-218; LYS-242; ASN-263; LEU-339; CYS-375; HIS-411; GLY-452 AND HIS-572.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X56352 mRNA. Translation: CAA39795.1. Different initiation.
X60364 mRNA. Translation: CAA42916.1.
AF068624 Genomic DNA. Translation: AAC39838.1.
AK290565 mRNA. Translation: BAF83254.1.
AK291589 mRNA. Translation: BAF84278.1.
AK313118 mRNA. Translation: BAG35939.1.
Z83821 Genomic DNA. No translation available.
AL020991 Genomic DNA. Translation: CAA15886.1.
AL020991 Genomic DNA. Translation: CAX15017.1.
CH471154 Genomic DNA. Translation: EAW93211.1.
CH471154 Genomic DNA. Translation: EAW93213.1.
BC030230 mRNA. Translation: AAH30230.2.
PIRSYHUAE. S16347.
RefSeqNP_000023.2. NM_000032.4.
NP_001033056.1. NM_001037967.3.
NP_001033057.1. NM_001037968.3.
UniGeneHs.522666.
Hs.555936.

3D structure databases

ProteinModelPortalP22557.
SMRP22557. Positions 1-49, 151-540.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106714. 2 interactions.
IntActP22557. 1 interaction.
STRING9606.ENSP00000332369.

Chemistry

DrugBankDB00145. Glycine.

PTM databases

PhosphoSiteP22557.

Polymorphism databases

DMDM20141346.

Proteomic databases

PaxDbP22557.
PRIDEP22557.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330807; ENSP00000332369; ENSG00000158578. [P22557-1]
ENST00000335854; ENSP00000337131; ENSG00000158578. [P22557-2]
ENST00000396198; ENSP00000379501; ENSG00000158578. [P22557-4]
GeneID212.
KEGGhsa:212.
UCSCuc004dua.4. human. [P22557-1]
uc004dud.4. human. [P22557-2]

Organism-specific databases

CTD212.
GeneCardsGC0XM055053.
HGNCHGNC:397. ALAS2.
HPAHPA001638.
MIM300751. phenotype.
300752. phenotype.
301300. gene.
neXtProtNX_P22557.
Orphanet79278. Erythropoietic protoporphyria.
75563. X-linked sideroblastic anemia.
PharmGKBPA24689.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0156.
HOGENOMHOG000221020.
HOVERGENHBG005954.
InParanoidP22557.
KOK00643.
OMARAEKYIY.
PhylomeDBP22557.
TreeFamTF300724.

Enzyme and pathway databases

BioCycMetaCyc:HS08311-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00251; UER00375.

Gene expression databases

ArrayExpressP22557.
BgeeP22557.
CleanExHS_ALAS2.
GenevestigatorP22557.

Family and domain databases

Gene3D3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProIPR010961. 4pyrrol_synth_NH2levulA_synth.
IPR015118. 5aminolev_synth_preseq.
IPR001917. Aminotrans_II_pyridoxalP_BS.
IPR004839. Aminotransferase_I/II.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR015422. PyrdxlP-dep_Trfase_major_sub2.
[Graphical view]
PfamPF00155. Aminotran_1_2. 1 hit.
PF09029. Preseq_ALAS. 1 hit.
[Graphical view]
SUPFAMSSF53383. SSF53383. 1 hit.
TIGRFAMsTIGR01821. 5aminolev_synth. 1 hit.
PROSITEPS00599. AA_TRANSFER_CLASS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSALAS2. human.
GeneWikiALAS2.
GenomeRNAi212.
NextBio852.
PROP22557.
SOURCESearch...

Entry information

Entry nameHEM0_HUMAN
AccessionPrimary (citable) accession number: P22557
Secondary accession number(s): A8K3F0 expand/collapse secondary AC list , A8K6C4, Q13735, Q5JZF5, Q8N6H3
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 23, 2002
Last modified: April 16, 2014
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM