P13716 (HEM2_HUMAN) 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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. Ref.10 Ref.11
Catalytic activity	2 5-aminolevulinate = porphobilinogen + 2 H2O. Ref.10 Ref.11 Ref.14
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. Ref.10
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. Ref.10 Ref.11 Ref.14
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
Subunit structure	Homooctamer; active form. Homohexamer; low activity form. Ref.11 Ref.14
Polymorphism	There are two common alleles of ALAD. Individuals heterozygous or homozygous for ALAD*2 Asn-59 have significantly higher blood lead levels than do ALAD*1 Lys-59 homozygotes when exposed to environmental lead.
Involvement in disease	Acute hepatic porphyria (AHEPP) [MIM:612740]: 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. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralysesand peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.16 Ref.17 Ref.19 Ref.21
Sequence similarities	Belongs to the ALADH family.
Biophysicochemical properties	Kinetic parameters: KM=0.09 mM for 5-aminolevulinate at pH 7 Ref.10 Vmax=43 µmol/h/mg enzyme at pH 7 pH dependence: Optimum pH is 6.8-7.3.
Sequence caution	The sequence AAH00977.3 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	Metal-binding Zinc
Molecular function	Lyase
Technical term	3D-structure Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	heme biosynthetic process Inferred from direct assay Ref.10. Source: UniProtKB protein homooligomerization Inferred from physical interaction Ref.10. Source: UniProtKB protoporphyrinogen IX biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	lead ion binding Inferred from direct assay Ref.10. Source: UniProtKB porphobilinogen synthase activity Inferred from direct assay Ref.10. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P13716-1)

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: P13716-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MQPQSVLHSG...SNLIYPIFVT → MPPTSSTPSL...QSISHPRSCR

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 330

330

Delta-aminolevulinic acid dehydratase

PRO_0000140526

Sites

Active site

199

1

Schiff-base intermediate with substrate Ref.9

Active site

252

1

Schiff-base intermediate with substrate Ref.9

Metal binding

122

1

Zinc 1; catalytic

Metal binding

124

1

Zinc 1; catalytic

Metal binding

131

1

Zinc 2

Metal binding

132

1

Zinc 1; catalytic

Metal binding

223

1

Zinc 2

Binding site

209

1

Substrate 1

Binding site

221

1

Substrate 1

Binding site

279

1

Substrate 2

Binding site

318

1

Substrate 2

Natural variations

Alternative sequence

1 – 38

38

MQPQS…PIFVT → MPPTSSTPSLSRPGLGQAGK PDTGSHPPPTISTSIFLSCF PTIPLSRPRTTGPSHSYQSI SHPRSCR in isoform 2.

VSP_037866

Natural variant

12

1

F → L in an asymptomatic patient with ALAD deficiency; hexamer with almost no residual activity; also found in a hereditary coproporphyria patient carrying the R-279 mutation in CPOX. Ref.14 Ref.18 Ref.20 Ref.21

VAR_020973

Natural variant

59

1

K → N in allele ALAD*2; 10% of population; fully active octamer. Ref.5 Ref.15 Ref.21
Corresponds to variant rs1800435 [ dbSNP | Ensembl ].

VAR_003633

Natural variant

133

1

G → R in AHEPP; mixture of about 50% hexamer and 50% octamer; about 10% residual activity. Ref.16 Ref.21

VAR_003634

Natural variant

153

1

V → M in AHEPP; about 95% octamer; about 40% residual activity. Ref.19 Ref.21

VAR_020974

Natural variant

240

1

R → W in AHEPP; mixture of about 80% hexamer and 20% octamer; about 4% residual activity. Ref.3 Ref.17 Ref.21

VAR_003635

Natural variant

274

1

A → T in AHEPP; mixture of about 14% hexamer and 86% octamer; about 20% enzyme residual activity. Ref.3 Ref.17 Ref.21

VAR_003636

Natural variant

275

1

V → M in AHEPP; mainly octamer; reduced activity. Ref.16 Ref.21

VAR_003637

Experimental info

Mutagenesis

122

1

C → A: Reduces enzyme activity about 1000000-fold; when associated with A-124 and A-132. Ref.10

Mutagenesis

124

1

C → A: Reduces enzyme activity about 1000000-fold; when associated with A-122 and A-132. Ref.10

Mutagenesis

131

1

H → A: No effect on catalytic activity; when associated with A-223. Ref.10

Mutagenesis

132

1

C → A: Reduces enzyme activity about 1000000-fold; when associated with A-122 and A-124. Ref.10

Mutagenesis

223

1

C → A: No effect on catalytic activity; when associated with A-131. Ref.10

Secondary structure

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330

Helix Strand Turn

Details...

Helix

8 – 10

3

Helix

14 – 20

7

Turn

21 – 24

4

Helix

28 – 30

3

Beta strand

31 – 37

7

Beta strand

44 – 46

3

Beta strand

48 – 50

3

Beta strand

54 – 56

3

Helix

58 – 71

14

Beta strand

75 – 80

6

Beta strand

83 – 85

3

Beta strand

94 – 98

5

Helix

100 – 111

12

Beta strand

115 – 121

7

Beta strand

123 – 126

4

Helix

141 – 160

20

Beta strand

163 – 167

5

Helix

174 – 184

11

Turn

188 – 190

3

Beta strand

192 – 194

3

Beta strand

198 – 200

3

Helix

203 – 205

3

Helix

206 – 210

5

Helix

221 – 223

3

Helix

231 – 243

13

Beta strand

247 – 253

7

Helix

255 – 257

3

Helix

258 – 267

10

Beta strand

273 – 277

5

Helix

279 – 290

12

Helix

296 – 310

15

Beta strand

313 – 317

5

Helix

320 – 326

7

Turn

327 – 329

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: E005F3055F6D9403	FASTA	330	36,295
	10 20 30 40 50 60 MQPQSVLHSG YFHPLLRAWQ TATTTLNASN LIYPIFVTDV PDDIQPITSL PGVARYGVKR 70 80 90 100 110 120 LEEMLRPLVE EGLRCVLIFG VPSRVPKDER GSAADSEESP AIEAIHLLRK TFPNLLVACD 130 140 150 160 170 180 VCLCPYTSHG HCGLLSENGA FRAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKE 190 200 210 220 230 240 ALMAHGLGNR VSVMSYSAKF ASCFYGPFRD AAKSSPAFGD RRCYQLPPGA RGLALRAVDR 250 260 270 280 290 300 DVREGADMLM VKPGMPYLDI VREVKDKHPD LPLAVYHVSG EFAMLWHGAQ AGAFDLKAAV 310 320 330 LEAMTAFRRA GADIIITYYT PQLLQWLKEE
	Isoform 2 [UniParc]. Checksum: 4AD5F3B2570ACD81	FASTA	359	39,034
	10 20 30 40 50 60 MPPTSSTPSL SRPGLGQAGK PDTGSHPPPT ISTSIFLSCF PTIPLSRPRT TGPSHSYQSI 70 80 90 100 110 120 SHPRSCRDVP DDIQPITSLP GVARYGVKRL EEMLRPLVEE GLRCVLIFGV PSRVPKDERG 130 140 150 160 170 180 SAADSEESPA IEAIHLLRKT FPNLLVACDV CLCPYTSHGH CGLLSENGAF RAEESRQRLA 190 200 210 220 230 240 EVALAYAKAG CQVVAPSDMM DGRVEAIKEA LMAHGLGNRV SVMSYSAKFA SCFYGPFRDA 250 260 270 280 290 300 AKSSPAFGDR RCYQLPPGAR GLALRAVDRD VREGADMLMV KPGMPYLDIV REVKDKHPDL 310 320 330 340 350 PLAVYHVSGE FAMLWHGAQA GAFDLKAAVL EAMTAFRRAG ADIIITYYTP QLLQWLKEE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human delta-aminolevulinate dehydratase: nucleotide sequence of a full-length cDNA clone." Wetmur J.G., Bishop D.F., Cantelmo C., Desnick R.J. Proc. Natl. Acad. Sci. U.S.A. 83:7703-7707(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"RsaI polymorphism in the human delta-aminolevulinate dehydratase gene at 9q34." Wetmur J.G. Nucleic Acids Res. 19:4307-4307(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[3]	"Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria." Ishida N., Fujita H., Fukuda Y., Noguchi T., Doss M., Kappas A., Sassa S. J. Clin. Invest. 89:1431-1437(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS AHEPP TRP-240 AND THR-274.
[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. , 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: Brain and Tongue.
[5]	NIEHS SNPs program Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-59.
[6]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] 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 1). Tissue: Placenta.
[8]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-17. Tissue: Platelet.
[9]	"Identification of lysine at the active site of human 5-aminolevulinate dehydratase." Gibbs P.N.B., Jordan P.M. Biochem. J. 236:447-451(1986) [PubMed] [Europe PMC] [Abstract] Cited for: ACTIVE SITE.
[10]	"The molecular mechanism of lead inhibition of human porphobilinogen synthase." Jaffe E.K., Martins J., Li J., Kervinen J., Dunbrack R.L. Jr. J. Biol. Chem. 276:1531-1537(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, MASS SPECTROMETRY, MUTAGENESIS OF CYS-122; CYS-124; HIS-131; CYS-132 AND CYS-223.
[11]	"Allosteric inhibition of human porphobilinogen synthase." Lawrence S.H., Ramirez U.D., Selwood T., Stith L., Jaffe E.K. J. Biol. Chem. 284:35807-35817(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, ENZYME REGULATION.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"The crystal structure of human Ala-dehydratase." Mills-Davies N.L., Thompson D., Cooper J.B., Shoolingin-Jordan P.M. Submitted (OCT-1998) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.83 ANGSTROMS) IN COMPLEX WITH PORPHOBILINOGEN AND ZINC IONS.
[14]	"Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase." Breinig S., Kervinen J., Stith L., Wasson A.S., Fairman R., Wlodawer A., Zdanov A., Jaffe E.K. Nat. Struct. Biol. 10:757-763(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT LEU-12 IN COMPLEX WITH SUBSTRATE ANALOG, SUBUNIT, MASS SPECTROMETRY, CATALYTIC ACTIVITY, ENZYME REGULATION.
[15]	"Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning." Wetmur J.G., Kaya A.H., Plewinska M., Desnick R.J. Am. J. Hum. Genet. 49:757-763(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASN-59.
[16]	"Delta-aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote." Plewinska M., Thunell S., Holmberg L., Wetmur J.G., Desnick R.J. Am. J. Hum. Genet. 49:167-174(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS AHEPP ARG-133 AND MET-275.
[17]	"Cloning and expression of the defective genes in delta-aminolevulinate dehydratase porphyria: compound heterozygosity in this hereditary liver disease." Sassa S., Ishida N., Fujita H., Fukuda Y., Noguchi T., Doss M., Kappas A. Trans. Assoc. Am. Physicians 105:250-259(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS AHEPP TRP-240 AND THR-274, CHARACTERIZATION OF VARIANTS AHEPP TRP-240 AND THR-274.
[18]	"A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity." Akagi R., Yasui Y., Harper P., Sassa S. Br. J. Haematol. 106:931-937(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-12, CHARACTERIZATION OF VARIANT LEU-12.
[19]	"Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria." Akagi R., Shimizu R., Furuyama K., Doss M.O., Sassa S. Hepatology 31:704-708(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT AHEPP MET-153, CHARACTERIZATION OF VARIANT AHEPP MET-153.
[20]	"Dual gene defects involving delta-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient." Akagi R., Inoue R., Muranaka S., Tahara T., Taketani S., Anderson K.E., Phillips J.D., Sassa S. Br. J. Haematol. 132:237-243(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-12.
[21]	"ALAD porphyria is a conformational disease." Jaffe E.K., Stith L. Am. J. Hum. Genet. 80:329-337(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS AHEPP ARG-133; MET-153; TRP-240; THR-274 AND MET-275, CHARACTERIZATION OF VARIANTS LEU-12 AND ASN-59.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M13928 mRNA. Translation: AAA51687.1.
X64467 Genomic DNA. Translation: CAA45796.1.
S99468 mRNA. Translation: AAC60581.1.
S99471 mRNA. Translation: AAC60582.1.
AK290490 mRNA. Translation: BAF83179.1.
AK312552 mRNA. Translation: BAG35449.1.
AY319481 Genomic DNA. Translation: AAP72012.1.
AL137066 Genomic DNA. Translation: CAH70099.3.
BC000977 mRNA. Translation: AAH00977.3. Different initiation.

IPI

IPI00442121.
IPI00790373.

PIR

A26478.

RefSeq

NP_000022.3. NM_000031.5.

UniGene

Hs.1227.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E51	X-ray	2.83	A/B	1-330	[»]
1PV8	X-ray	2.20	A/B	1-330	[»]

ProteinModelPortal

P13716.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000386284.

PTM databases

PhosphoSite

P13716.

Polymorphism databases

DMDM

122833.

2D gel databases

OGP

P13716.

REPRODUCTION-2DPAGE

P13716.

SWISS-2DPAGE

P13716.

Proteomic databases

PaxDb

P13716.

PRIDE

P13716.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000409155; ENSP00000386284; ENSG00000148218.

GeneID

210.

KEGG

hsa:210.

UCSC

uc004bhl.4. human.
uc011lxf.2. human.

Organism-specific databases

CTD

210.

GeneCards

GC09M116148.

HGNC

HGNC:395. ALAD.

HPA

HPA021023.
HPA022124.

MIM

125270. gene.
612740. phenotype.

neXtProt

NX_P13716.

Orphanet

100924. Porphyria due to ALA dehydratase deficiency.

PharmGKB

PA24687.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0113.

HOGENOM

HOG000020323.

HOVERGEN

HBG001222.

KO

K01698.

OMA

AVMEAMT.

OrthoDB

EOG4BRWM1.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00251; UER00318.

Gene expression databases

ArrayExpress

P13716.

Bgee

P13716.

CleanEx

HS_ALAD.

Genevestigator

P13716.

GermOnline

ENSG00000148218. Homo sapiens.

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

ChEMBL

CHEMBL3126.

ChiTaRS

ALAD. human.

DrugBank

DB00855. Aminolevulinic acid.

EvolutionaryTrace

P13716.

GenomeRNAi

210.

NextBio

840.

SOURCE

Search...

Entry information

Entry name

HEM2_HUMAN

Accession

Primary (citable) accession number: P13716
Secondary accession number(s): A8K375 , B2R6F2, Q16870, Q16871, Q9BVQ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	May 1, 2013
This is version 150 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.