P08680 (HEM0_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	587 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	Succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2.
Cofactor	Pyridoxal phosphate.
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; 5-aminolevulinate from glycine: step 1/1.
Subunit structure	Interacts with SUCLA2 By similarity. Homodimer.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Erythroid specific.
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 AAA37207.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Heme biosynthesis
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	Pyridoxal phosphate
Molecular function	Acyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular iron ion homeostasis Inferred from mutant phenotype PubMed 10562540. Source: MGI erythrocyte differentiation Inferred from mutant phenotype PubMed 9446639. Source: UniProtKB heme biosynthetic process Inferred from mutant phenotype PubMed 9446639. Source: UniProtKB hemoglobin biosynthetic process Inferred from mutant phenotype PubMed 9446639. Source: UniProtKB protoporphyrinogen IX biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway response to hypoxia Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrial inner membrane Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	5-aminolevulinate synthase activity Inferred from sequence or structural similarity. Source: UniProtKB pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 49

49

Mitochondrion

Chain

50 – 587

538

5-aminolevulinate synthase, erythroid-specific, mitochondrial

PRO_0000001224

Sites

Active site

391

1

By similarity

Binding site

163

1

Substrate By similarity

Binding site

280

1

Substrate By similarity

Binding site

299

1

Substrate By similarity

Binding site

332

1

Pyridoxal phosphate By similarity

Binding site

360

1

Pyridoxal phosphate By similarity

Binding site

388

1

Pyridoxal phosphate By similarity

Binding site

420

1

Pyridoxal phosphate By similarity

Binding site

421

1

Pyridoxal phosphate By similarity

Binding site

508

1

Substrate By similarity

Amino acid modifications

Modified residue

391

1

N6-(pyridoxal phosphate)lysine

Experimental info

Mutagenesis

391

1

K → A or H: Abolishes enzyme activity.

Sequence conflict

61 – 75

15

Missing in AAA37207. Ref.1

Sequence conflict

66

1

A → R in BAB22254. Ref.3

Sequence conflict

171

1

W → R in AAA91866. Ref.2

Sequence conflict

338

1

C → V in AAA91866. Ref.2

Sequence conflict

368 – 372

5

RGAGI → GVQVS in AAA91866. Ref.2

Sequence conflict

427

1

V → M in AAA37207. Ref.1

Sequence conflict

479

1

R → W in AAA91866. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

587

Helix Strand Turn

Details...

Turn

5 – 8

4

Beta strand

14 – 16

3

Turn

23 – 27

5

Helix

28 – 32

5

Sequences

	Sequence		Length	Mass (Da)
	P08680 [UniParc]. Last modified January 23, 2002. Version 3. Checksum: A878D79FAD5B9856	FASTA	587	64,753
	10 20 30 40 50 60 MVAAAMLLRS CPVLSQGPTG LLGKVAKTYQ FLFSIGRCPI LATQGPTCSQ IHLKATKAGG 70 80 90 100 110 120 DSPSWAKSHC PFMLSELQDR KSKIVQRAAP EVQEDVKTFK TDLLSTMDST TRSHSFPSFQ 130 140 150 160 170 180 EPEQTEGAVP HLIQNNMTGS QAFGYDQFFR DKIMEKKQDH TYRVFKTVNR WANAYPFAQH 190 200 210 220 230 240 FSEASMASKD VSVWCSNDYL GISRHPRVLQ AIEETLKNHG AGAGGTRNIS GTSKFHVELE 250 260 270 280 290 300 QELAELHQKD SALLFSSCFV ANDSTLFTLA KLLPGCEIYS DAGNHASMIQ GIRNSGAAKF 310 320 330 340 350 360 VFRHNDPGHL KKLLEKSDPK TPKIVAFETV HSMDGAICPL EELCDVAHQY GALTFVDEVH 370 380 390 400 410 420 AVGLYGARGA GIGERDGIMH KLDIISGTLG KAFGCVGGYI ASTRDLVDMV RSYAAGFIFT 430 440 450 460 470 480 TSLPPMVLSG ALESVRLLKG EEGQALRRAH QRNVKHMRQL LMDRGFPVIP CPSHIIPIRV 490 500 510 520 530 540 GNAALNSKIC DLLLSKHSIY VQAINYPTVP RGEELLRLAP SPHHSPQMME NFVEKLLLAW 550 560 570 580 TEVGLPLQDV SVAACNFCHR PVHFELMSEW ERSYFGNMGP QYVTTYA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of mouse 5-aminolevulinic acid synthase cDNA and expression of its gene in hepatic and erythroid tissues." Schoenhaut D.S., Curtis P.J. Gene 48:55-63(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Two genes encode Ala synthase in DBA/2 mouse: housekeeping and erythroid-specific." Young E.G., Dierks P.M. Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: DBA/2. Tissue: Erythroleukemia.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Kidney.
[4]	"Heme biosynthesis in mammalian systems: evidence of a Schiff base linkage between the pyridoxal 5'-phosphate cofactor and a lysine residue in 5-aminolevulinate synthase." Ferreira G.C., Neame P.J., Dailey H.A. Protein Sci. 2:1959-1965(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PYRIDOXAL PHOSPHATE AT LYS-391.
[5]	"The solution structure and heme binding of the presequence of murine 5-aminolevulinate synthase." Goodfellow B.J., Dias J.S., Ferreira G.C., Henklein P., Wray V., Macedo A.L. FEBS Lett. 505:325-331(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-49, TRANSIT PEPTIDE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M15268 mRNA. Translation: AAA37207.1. Different initiation.
M63244 mRNA. Translation: AAA91866.1.
AK002642 mRNA. Translation: BAB22254.1.
AK077610 mRNA. Translation: BAC36898.1.

IPI

IPI00135065.

PIR

SYMSAL. A29040.

RefSeq

NP_001095916.1. NM_001102446.1.
NP_033783.1. NM_009653.3.

UniGene

Mm.302724.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H7D	NMR	-	A	1-49	[»]
1H7J	NMR	-	A	1-26	[»]

ProteinModelPortal

P08680.

SMR

P08680. Positions 1-49, 151-540.

ModBase

Search...

PTM databases

PhosphoSite

P08680.

Proteomic databases

PaxDb

P08680.

PRIDE

P08680.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000066337; ENSMUSP00000066040; ENSMUSG00000025270.

GeneID

11656.

KEGG

mmu:11656.

Organism-specific databases

CTD

212.

MGI

MGI:87990. Alas2.

Phylogenomic databases

eggNOG

COG0156.

GeneTree

ENSGT00530000063111.

HOGENOM

HOG000221020.

HOVERGEN

HBG005954.

InParanoid

P08680.

KO

K00643.

OrthoDB

EOG4H19VB.

Enzyme and pathway databases

UniPathway

UPA00251; UER00375.

Gene expression databases

ArrayExpress

P08680.

Bgee

P08680.

CleanEx

MM_ALAS2.

Genevestigator

P08680.

GermOnline

ENSMUSG00000025270. Mus musculus.

Family and domain databases

Gene3D

3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.

InterPro

IPR010961. 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]

Pfam

PF00155. Aminotran_1_2. 1 hit.
PF09029. Preseq_ALAS. 1 hit.
[Graphical view]

SUPFAM

SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.

TIGRFAMs

TIGR01821. 5aminolev_synth. 1 hit.

PROSITE

PS00599. AA_TRANSFER_CLASS_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P08680.

NextBio

279269.

SOURCE

Search...

Entry information

Entry name

HEM0_MOUSE

Accession

Primary (citable) accession number: P08680
Secondary accession number(s): Q64452, Q9DCN0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 23, 2002
Last modified:	May 1, 2013
This is version 132 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program