P05373 (HEM2_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Delta-aminolevulinic acid dehydratase
Short name=ALADH
EC=4.2.1.24

Alternative name(s):
Porphobilinogen synthase

Gene names

Name:	HEM2
Ordered Locus Names:	YGL040C

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	342 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
Catalytic activity	2 5-aminolevulinate = porphobilinogen + 2 H2O.
Cofactor	Binds 1 zinc ion per monomer. Ref.9
Enzyme regulation	Inhibited by divalent lead ions. Ref.8
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
Subunit structure	Homooctamer. Ref.8 Ref.12
Miscellaneous	Present with 11600 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the ALADH family.

Ontologies

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	heme biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB protoporphyrinogen IX biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	cytoplasm Inferred from direct assay PubMed 14562095. Source: SGD nucleus Inferred from direct assay PubMed 14562095. Source: SGD
Molecular_function	lead ion binding Inferred from sequence or structural similarity. Source: UniProtKB porphobilinogen synthase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-8239,EBI-8239
SRP1	Q02821	1	EBI-8239,EBI-1797
TEM1	P38987	1	EBI-8239,EBI-19113

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 342

342

Delta-aminolevulinic acid dehydratase

PRO_0000140534

Sites

Active site

210

1

Schiff-base intermediate with substrate Ref.8 Ref.9 Ref.11 Ref.12

Active site

263

1

Schiff-base intermediate with substrate Ref.8 Ref.9 Ref.11 Ref.12

Metal binding

133

1

Zinc; catalytic

Metal binding

135

1

Zinc; catalytic

Metal binding

143

1

Zinc; catalytic

Binding site

220

1

Substrate 1

Binding site

232

1

Substrate 1

Binding site

290

1

Substrate 2

Binding site

329

1

Substrate 2

Amino acid modifications

Modified residue

254

1

Phosphoserine Ref.7

Experimental info

Sequence conflict

291

1

G → D in AAA34669. Ref.1

Secondary structure

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342

Helix Strand Turn

Details...

Helix

14 – 16

3

Helix

19 – 21

3

Beta strand

22 – 24

3

Helix

25 – 30

6

Beta strand

32 – 34

3

Helix

38 – 40

3

Beta strand

41 – 50

10

Beta strand

54 – 56

3

Beta strand

58 – 60

3

Beta strand

64 – 66

3

Helix

68 – 80

13

Beta strand

85 – 91

7

Helix

103 – 106

4

Helix

111 – 122

12

Beta strand

126 – 132

7

Turn

135 – 137

3

Beta strand

138 – 140

3

Beta strand

142 – 144

3

Beta strand

150 – 152

3

Helix

154 – 171

18

Beta strand

174 – 178

5

Helix

185 – 195

11

Turn

199 – 201

3

Beta strand

203 – 211

9

Beta strand

213 – 215

3

Helix

217 – 223

7

Beta strand

228 – 230

3

Turn

233 – 235

3

Helix

242 – 254

13

Beta strand

258 – 265

8

Helix

266 – 268

3

Helix

269 – 278

10

Turn

279 – 281

3

Beta strand

284 – 288

5

Helix

290 – 301

12

Helix

307 – 320

14

Beta strand

324 – 328

5

Helix

331 – 337

7

Sequences

	Sequence		Length	Mass (Da)
	P05373 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 72F6EB11008BDF52	FASTA	342	37,740
	10 20 30 40 50 60 MHTAEFLETE PTEISSVLAG GYNHPLLRQW QSERQLTKNM LIFPLFISDN PDDFTEIDSL 70 80 90 100 110 120 PNINRIGVNR LKDYLKPLVA KGLRSVILFG VPLIPGTKDP VGTAADDPAG PVIQGIKFIR 130 140 150 160 170 180 EYFPELYIIC DVCLCEYTSH GHCGVLYDDG TINRERSVSR LAAVAVNYAK AGAHCVAPSD 190 200 210 220 230 240 MIDGRIRDIK RGLINANLAH KTFVLSYAAK FSGNLYGPFR DAACSAPSNG DRKCYQLPPA 250 260 270 280 290 300 GRGLARRALE RDMSEGADGI IVKPSTFYLD IMRDASEICK DLPICAYHVS GEYAMLHAAA 310 320 330 340 EKGVVDLKTI AFESHQGFLR AGARLIITYL APEFLDWLDE EN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the yeast HEM2 gene and transcriptional regulation of COX5 and COR1 by heme." Myers A.M., Crivellone M.D., Koerner T.J., Tzagoloff A. J. Biol. Chem. 262:16822-16829(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome VII." Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., Coblenz A., Coglievina M., Coissac E. , Defoor E., Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., Zollner A., Kleine K. Nature 387:81-84(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	"The characterization of two new clusters of duplicated genes suggests a 'Lego' organization of the yeast Saccharomyces cerevisiae chromosomes." Feuermann M., de Montigny J., Potier S., Souciet J.-L. Yeast 13:861-869(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-41. Strain: ATCC 204508 / S288c.
[6]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[7]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-254, MASS SPECTROMETRY.
[8]	"X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase." Erskine P.T., Senior N., Awan S., Lambert R., Lewis G., Tickle I.J., Sarwar M., Spencer P., Thomas P., Warren M.J., Shoolingin-Jordan P.M., Wood S.P., Cooper J.B. Nat. Struct. Biol. 4:1025-1031(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH LEAD IONS, SUBUNIT, ENZYME REGULATION, ACTIVE SITE.
[9]	"The Schiff base complex of yeast 5-aminolaevulinic acid dehydratase with laevulinic acid." Erskine P.T., Newbold R., Roper J., Coker A., Warren M.J., Shoolingin-Jordan P.M., Wood S.P., Cooper J.B. Protein Sci. 8:1250-1256(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH LAEVULINIC ACID AND ZINC IONS, COFACTOR, ACTIVE SITE.
[10]	"MAD analyses of yeast 5-aminolaevulinate dehydratase: their use in structure determination and in defining the metal-binding sites." Erskine P.T., Duke E.M., Tickle I.J., Senior N.M., Warren M.J., Cooper J.B. Acta Crystallogr. D 56:421-430(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH MERCURY IONS.
[11]	"The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with two diacid inhibitors." Erskine P.T., Coates L., Newbold R., Brindley A.A., Stauffer F., Wood S.P., Warren M.J., Cooper J.B., Shoolingin-Jordan P.M., Neier R. FEBS Lett. 503:196-200(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEXES WITH ZINC IONS; 4-OXOSEBACIC ACID AND 4,7-DIOXOSEBACIC ACID, ACTIVE SITE.
[12]	"The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with substrate and three inhibitors." Erskine P.T., Newbold R., Brindley A.A., Wood S.P., Shoolingin-Jordan P.M., Warren M.J., Cooper J.B. J. Mol. Biol. 312:133-141(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEXES WITH ZINC IONS; 5-AMINOLAEVULINIC ACID AND SUBSTRATE ANALOGS, ACTIVE SITE, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J03493 Genomic DNA. Translation: AAA34669.1.
Z72562 Genomic DNA. Translation: CAA96742.1.
AY692744 Genomic DNA. Translation: AAT92763.1.
BK006941 Genomic DNA. Translation: DAA08060.1.

PIR

S64042.

RefSeq

NP_011475.1. NM_001180905.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AW5	X-ray	2.30	A	1-340	[»]
1EB3	X-ray	1.75	A	1-340	[»]
1GJP	X-ray	1.80	A	1-340	[»]
1H7N	X-ray	1.60	A	1-342	[»]
1H7O	X-ray	1.75	A	1-341	[»]
1H7P	X-ray	1.64	A	1-342	[»]
1H7R	X-ray	2.00	A	1-342	[»]
1OHL	X-ray	1.60	A	1-342	[»]
1QML	X-ray	3.00	A	1-342	[»]
1QNV	X-ray	2.50	A	1-342	[»]
1W31	X-ray	1.90	A	1-342	[»]
1YLV	X-ray	2.15	A	1-342	[»]

ProteinModelPortal

P05373.

SMR

P05373. Positions 1-340.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-4311N.

IntAct

P05373. 4 interactions.

MINT

MINT-476599.

STRING

4932.YGL040C.

Proteomic databases

PaxDb

P05373.

PeptideAtlas

P05373.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YGL040C; YGL040C; YGL040C.

GeneID

852842.

KEGG

sce:YGL040C.

Organism-specific databases

CYGD

YGL040c.

SGD

S000003008. HEM2.

Phylogenomic databases

eggNOG

COG0113.

GeneTree

ENSGT00390000006998.

HOGENOM

HOG000020323.

KO

K01698.

OMA

MIISYHA.

OrthoDB

EOG454D75.

Enzyme and pathway databases

UniPathway

UPA00251; UER00318.

Gene expression databases

Genevestigator

P05373.

GermOnline

YGL040C. Saccharomyces cerevisiae.

Family and domain databases

Gene3D

3.20.20.70. 1 hit.

InterPro

IPR013785. Aldolase_TIM.
IPR001731. Porphobilinogen_synth.
[Graphical view]

PANTHER

PTHR11458. PTHR11458. 1 hit.

Pfam

PF00490. ALAD. 1 hit.
[Graphical view]

PIRSF

PIRSF001415. Porphbilin_synth. 1 hit.

PRINTS

PR00144. DALDHYDRTASE.

SMART

SM01004. ALAD. 1 hit.
[Graphical view]

PROSITE

PS00169. D_ALA_DEHYDRATASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P05373.

NextBio

972420.

Entry information

Entry name

HEM2_YEAST

Accession

Primary (citable) accession number: P05373
Secondary accession number(s): D6VU99

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 140 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program