P10518 (HEM2_MOUSE) 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:	Alad
Synonyms:	Lv

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	330 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 By similarity.
Catalytic activity	2 5-aminolevulinate = porphobilinogen + 2 H2O.
Cofactor	Binds 8 zinc ions per octamer. Only four zinc ions per octamer are required for full catalytic activity. Only four zinc ions per octamer are tightly bound. Can bind 2 zinc ions per subunit. The first zinc ion is important for catalysis By similarity.
Enzyme regulation	Can alternate between a fully active homooctamer and a low-activity homohexamer. A bound magnesium ion may promote the assembly of the fully active homooctamer. The magnesium-binding site is absent in the low-activity homohexamer. Inhibited by compounds that favor the hexameric state. Inhibited by divalent lead ions. The lead ions partially displace the zinc cofactor By similarity.
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
Subunit structure	Homooctamer; active form. Homohexamer; low activity form By similarity.
Sequence similarities	Belongs to the ALADH family.

Ontologies

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Ligand	Metal-binding Zinc
Molecular function	Lyase
Technical term	3D-structure Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to interleukin-4 Inferred from direct assay PubMed 9798653. Source: MGI heme biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB protein homooligomerization Inferred from electronic annotation. Source: Compara protoporphyrinogen IX biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
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...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 330

330

Delta-aminolevulinic acid dehydratase

PRO_0000140528

Sites

Active site

199

1

Schiff-base intermediate with substrate By similarity

Active site

252

1

Schiff-base intermediate with substrate By similarity

Metal binding

122

1

Zinc 1; catalytic By similarity

Metal binding

124

1

Zinc 1; catalytic By similarity

Metal binding

131

1

Zinc 2 By similarity

Metal binding

132

1

Zinc 1; catalytic By similarity

Metal binding

223

1

Zinc 2 By similarity

Binding site

209

1

Substrate 1 By similarity

Binding site

221

1

Substrate 1 By similarity

Binding site

279

1

Substrate 2 By similarity

Binding site

318

1

Substrate 2 By similarity

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

330

Helix Strand Turn

Details...

Helix

8 – 10

3

Helix

14 – 20

7

Helix

28 – 30

3

Beta strand

31 – 42

12

Beta strand

44 – 46

3

Beta strand

48 – 50

3

Beta strand

54 – 57

4

Helix

58 – 60

3

Helix

61 – 64

4

Helix

66 – 69

4

Turn

70 – 72

3

Beta strand

75 – 81

7

Helix

100 – 111

12

Beta strand

113 – 119

7

Helix

144 – 160

17

Beta strand

163 – 165

3

Helix

174 – 183

10

Turn

185 – 188

4

Beta strand

192 – 194

3

Helix

206 – 211

6

Helix

231 – 241

11

Helix

242 – 244

3

Beta strand

247 – 254

8

Helix

255 – 257

3

Helix

258 – 267

10

Beta strand

273 – 276

4

Helix

279 – 290

12

Helix

296 – 309

14

Beta strand

313 – 316

4

Helix

320 – 326

7

Sequences

	Sequence		Length	Mass (Da)
	P10518 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 84052DC911C153EB	FASTA	330	36,024
	10 20 30 40 50 60 MHHQSVLHSG YFHPLLRSWQ TAASTVSASN LIYPIFVTDV PDDVQPIASL PGVARYGVNQ 70 80 90 100 110 120 LEEMLRPLVE AGLRCVLIFG VPSRVPKDEQ GSAADSEDSP TIEAVRLLRK TFPSLLVACD 130 140 150 160 170 180 VCLCPYTSHG HCGLLSENGA FLAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKA 190 200 210 220 230 240 ALLKHGLGNR VSVMSYSAKF ASCFYGPFRD AAQSSPAFGD RRCYQLPPGA RGLALRAVAR 250 260 270 280 290 300 DIQEGADMLM VKPGLPYLDM VREVKDKHPE LPLAVYQVSG EFAMLWHGAQ AGAFDLRTAV 310 320 330 LETMTAFRRA GADIIITYFA PQLLKWLKEE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence of mouse erythroid delta-aminolevulinate dehydratase cDNA." Bishop T.R., Hodes Z.I., Frelin L.P., Boyer S.H. Nucleic Acids Res. 17:1775-1775(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"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: BALB/c, C57BL/6J and DBA/2. Tissue: Placenta.
[3]	"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]. Strain: FVB/N. Tissue: Colon.
[4]	"Crystal structure of 5-aminolevulinic acid dehydratase (ALAD) from Mus musculus." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X13752 mRNA. Translation: CAA32015.1.
AK032908 mRNA. Translation: BAC28080.1.
AK167673 mRNA. Translation: BAE39722.1.
AK168119 mRNA. Translation: BAE40090.1.
AK168132 mRNA. Translation: BAE40101.1.
BC055930 mRNA. Translation: AAH55930.1.

IPI

IPI00112719.

PIR

S03187.

RefSeq

NP_001263375.1. NM_001276446.1.
NP_032551.3. NM_008525.4.

UniGene

Mm.6988.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Z0I	X-ray	3.20	A/B	1-330	[»]
2Z1B	X-ray	3.30	A/B/C/D	1-330	[»]

ProteinModelPortal

P10518.

SMR

P10518. Positions 5-328.

ModBase

Search...

Protein-protein interaction databases

IntAct

P10518. 1 interaction.

PTM databases

PhosphoSite

P10518.

2D gel databases

REPRODUCTION-2DPAGE

P10518.

SWISS-2DPAGE

P10518.

Proteomic databases

PaxDb

P10518.

PRIDE

P10518.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000030090; ENSMUSP00000030090; ENSMUSG00000028393.
ENSMUST00000107444; ENSMUSP00000103068; ENSMUSG00000028393.

GeneID

17025.

KEGG

mmu:17025.

UCSC

uc008tez.1. mouse.

Organism-specific databases

CTD

210.

MGI

MGI:96853. Alad.

Phylogenomic databases

eggNOG

COG0113.

GeneTree

ENSGT00390000006998.

HOGENOM

HOG000020323.

HOVERGEN

HBG001222.

InParanoid

P10518.

KO

K01698.

OMA

AVMEAMT.

OrthoDB

EOG4BRWM1.

Enzyme and pathway databases

UniPathway

UPA00251; UER00318.

Gene expression databases

ArrayExpress

P10518.

Bgee

P10518.

CleanEx

MM_ALAD.

Genevestigator

P10518.

GermOnline

ENSMUSG00000028393. Mus musculus.

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

P10518.

NextBio

291138.

SOURCE

Search...

Entry information

Entry name

HEM2_MOUSE

Accession

Primary (citable) accession number: P10518
Secondary accession number(s): Q3THV6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program