Porphobilinogen deaminase - Homo sapiens (Human)

Sequence length	361 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

Function	Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps.
Catalytic activity	4 porphobilinogen + H₂O = hydroxymethylbilane + 4 NH₃.
Cofactor	Binds 1 dipyrromethane group covalently.
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4.
Subcellular location	Cytoplasm Probable.
Tissue specificity	Isoform 1 is ubiquitously expressed. Isoform 2 is found only in erythroid cells.
Involvement in disease	Defects in HMBS are the cause of acute intermittent porphyria (AIP) [MIM:176000]. AIP is 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. AIP is an autosomal dominant form of hepatic porphyria characterized by acute attacks of neurological dysfunctions with abdominal pain, hypertension, tachycardia, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45
Miscellaneous	The porphobilinogen subunits are added to the dipyrromethane group By similarity.
Sequence similarities	Belongs to the HMBS family.

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Molecular function	Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	heme biosynthetic process Inferred by curator. Source: UniProtKB
Cellular component	mitochondrion Inferred from direct assay. Source: HPA
Molecular function	hydroxymethylbilane synthase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 361

361

Porphobilinogen deaminase

PRO_0000143034

Binding site

261

1

Pyrromethane cofactor (covalent) By similarity

Modified residue

15

1

Phosphoserine

Alternative sequence

1 – 17

17

Missing in isoform 2.

VSP_002067

Natural variant

18

1

M → I in AIP. Ref.40

VAR_025558

Natural variant

22

1

R → C in AIP. Ref.29 Ref.31

VAR_003638

Natural variant

24

1

G → S in AIP.

VAR_011001

Natural variant

26

1

R → C in AIP. Ref.31 Ref.33 Ref.41

VAR_011002

Natural variant

26

1

R → H in AIP. Ref.17 Ref.31 Ref.41 Ref.42

VAR_003639

Natural variant

28

1

S → N in AIP.

VAR_011003

Natural variant

31

1

A → P in AIP. Ref.31

VAR_011004

Natural variant

31

1

A → T in AIP. Ref.19

VAR_003640

Natural variant

34

1

Q → K in AIP. Ref.14

VAR_003641

Natural variant

34

1

Q → P in AIP; less than 3% of activity. Ref.30

VAR_011005

Natural variant

34

1

Q → R in AIP. Ref.43

VAR_025559

Natural variant

35

1

T → M in AIP. Ref.38

VAR_011006

Natural variant

42

1

L → S in AIP. Ref.31

VAR_011007

Natural variant

55

1

A → S in AIP. Ref.19

VAR_003642

Natural variant

61

1

D → N in AIP. Ref.31

VAR_011008

Natural variant

61

1

D → Y in AIP. Ref.42

VAR_025560

Natural variant

78

1

T → P in AIP. Ref.35

VAR_025561

Natural variant

80

1

E → G in AIP. Ref.35

VAR_025562

Natural variant

81

1

L → P in AIP. Ref.44

VAR_025563

Natural variant

85

1

L → R in AIP. Ref.31

VAR_011009

Natural variant

86

1

E → V in AIP. Ref.41

VAR_025564

Natural variant

90

1

V → G in AIP. Ref.31

VAR_011010

Natural variant

92

1

L → P in AIP. Ref.41

VAR_025565

Natural variant

93

1

V → F in AIP; loss of activity. Ref.23

VAR_003643

Natural variant

93

1

Missing in AIP.

VAR_025566

Natural variant

96

1

S → F in AIP. Ref.40

VAR_025567

Natural variant

98

1

K → R in AIP.

VAR_003644

Natural variant

99

1

D → G in AIP. Ref.41

VAR_025568

Natural variant

99

1

D → H in AIP. Ref.40

VAR_025569

Natural variant

99

1

D → N in AIP. Ref.38

VAR_025570

Natural variant

111

1

G → R in AIP. Ref.18 Ref.30 Ref.31 Ref.34 Ref.35 Ref.38 Ref.41 Ref.42 Ref.45

VAR_003645

Natural variant

113

1

I → T in AIP. Ref.41

VAR_025571

Natural variant

116

1

R → Q in AIP. Ref.21

VAR_003646

Natural variant

116

1

R → W in AIP; loss of activity. Ref.23 Ref.27 Ref.34 Ref.36

VAR_003647

Natural variant

119

1

P → L in AIP. Ref.25 Ref.27

VAR_003648

Natural variant

122

1

A → G in AIP. Ref.40

VAR_025572

Natural variant

124

1

V → D in AIP.

VAR_011011

Natural variant

149

1

R → L in AIP. Ref.19

VAR_003649

Natural variant

149

1

R → Q in AIP. Ref.12

VAR_003650

Natural variant

152

1

Missing in AIP.

VAR_009223

Natural variant

167

1

R → Q in AIP. Ref.11 Ref.14 Ref.27

VAR_003651

Natural variant

167

1

R → W in AIP. Ref.13 Ref.15 Ref.27 Ref.34

VAR_003652

Natural variant

173

1

R → Q in AIP; 0.6% of wild-type activity. Ref.11 Ref.15 Ref.31 Ref.41 Ref.42 Ref.45

VAR_003653

Natural variant

173

1

R → W in AIP. Ref.21 Ref.27 Ref.30 Ref.31 Ref.34 Ref.35

VAR_003654

Natural variant

177

1

L → R in AIP. Ref.14 Ref.21 Ref.31

VAR_003655

Natural variant

178

1

D → N in AIP. Ref.41

VAR_011012

Natural variant

195

1

R → C in AIP. dbSNP rs34413634.

VAR_003656

Natural variant

201

1

R → W in AIP; residual activity. Ref.20 Ref.23 Ref.27 Ref.30

VAR_003657

Natural variant

202

1

V → L in AIP. Ref.33

VAR_011013

Natural variant

209

1

E → K in AIP.

VAR_011014

Natural variant

212

1

M → V in AIP; <2% residual activity. Ref.34

VAR_025573

Natural variant

216

1

G → D in AIP. Ref.27

VAR_011015

Natural variant

217

1

Q → H in AIP.

VAR_011016

Natural variant

217

1

Q → L in AIP. Ref.37

VAR_011017

Natural variant

219

1

A → D in AIP. Ref.31

VAR_011018

Natural variant

222

1

V → M in AIP. Ref.28

VAR_003658

Natural variant

223

1

E → K in AIP. Ref.19

VAR_003659

Natural variant

225

1

R → G in AIP. Ref.41

VAR_003660

Natural variant

225

1

R → Q in AIP. Ref.41

VAR_025574

Natural variant

236

1

G → S in AIP. Ref.43

VAR_025575

Natural variant

238

1

L → R in AIP.

VAR_003661

Natural variant

244

1

L → P in AIP. Ref.43

VAR_025576

Natural variant

245

1

L → R in AIP. Ref.12

VAR_003662

Natural variant

247

1

C → F in AIP; residual activity. Ref.23

VAR_003663

Natural variant

247

1

C → R in AIP. Ref.16 Ref.31

VAR_003664

Natural variant

248

1

I → IETLLRCI in AIP.

VAR_011019

Natural variant

1

E → A in AIP. Ref.25

VAR_003665

Natural variant

1

E → K in AIP. Ref.19

VAR_003666

Natural variant

1

E → Q in AIP.

VAR_011020

Natural variant

1

E → V in AIP.

VAR_011021

Natural variant

252

1

A → T in AIP. Ref.16

VAR_003667

Natural variant

252

1

A → V in AIP. Ref.16

VAR_003668

Natural variant

254

1

L → P in AIP. Ref.40

VAR_025577

Natural variant

256

1

H → N in AIP. Ref.14

VAR_003669

Natural variant

256

1

H → Y in AIP. Ref.41

VAR_011022

Natural variant

260

1

G → D in AIP. Ref.41

VAR_025578

Natural variant

261

1

C → Y in AIP. Ref.40

VAR_025579

Natural variant

267

1

V → M in AIP.

VAR_011023

Natural variant

269

1

T → I in AIP. Ref.21 Ref.31

VAR_003670

Natural variant

270

1

A → D in AIP.

VAR_011024

Natural variant

270

1

A → G in AIP. Ref.36

VAR_011025

Natural variant

274

1

G → R in AIP. Ref.21

VAR_003671

Natural variant

278

1

L → P in AIP. Ref.28

VAR_003672

Natural variant

280

1

G → R in AIP.

VAR_003673

Natural variant

281

1

Missing in AIP.

VAR_011026

Natural variant

329 – 332

4

Missing in AIP.

VAR_011027

Natural variant

335

1

G → D in AIP. Ref.42

VAR_011028

Natural variant

335

1

G → S in AIP; less than 3% of activity. Ref.30

VAR_011029

Natural variant

343

1

L → P in AIP. Ref.41

VAR_025580

Sequence conflict

177

1

L → M in AAA60029. Ref.3

Sequence conflict

177

1

L → M in AAA60030. Ref.3

Sequence conflict

210

1

E → K in CAA28499. Ref.2

Sequence conflict

349

1

N → T in CAA27801. Ref.1

1

.

361

Helix Strand Turn

Details...

Sequence		Length	Mass (Da)
Isoform 1 (Non-erythropoietic) [UniParc]. Last modified November 1, 1995. Version 2. Checksum: 8F2F6F4150F1AD7E Show »	FASTA	361	39,330
10 20 30 40 50 60 MSGNGNAAAT AEENSPKMRV IRVGTRKSQL ARIQTDSVVA TLKASYPGLQ FEIIAMSTTG 70 80 90 100 110 120 DKILDTALSK IGEKSLFTKE LEHALEKNEV DLVVHSLKDL PTVLPPGFTI GAICKRENPH 130 140 150 160 170 180 DAVVFHPKFV GKTLETLPEK SVVGTSSLRR AAQLQRKFPH LEFRSIRGNL NTRLRKLDEQ 190 200 210 220 230 240 QEFSAIILAT AGLQRMGWHN RVGQILHPEE CMYAVGQGAL GVEVRAKDQD ILDLVGVLHD 250 260 270 280 290 300 PETLLRCIAE RAFLRHLEGG CSVPVAVHTA MKDGQLYLTG GVWSLDGSDS IQETMQATIH 310 320 330 340 350 360 VPAQHEDGPE DDPQLVGITA RNIPRGPQLA AQNLGISLAN LLLSKGAKNI LDVARQLNDA H « Hide
Isoform 2 (Erythrocyte). Checksum: 0A5138172DB6E96F Show »	FASTA	344	37,699
10 20 30 40 50 60 MRVIRVGTRK SQLARIQTDS VVATLKASYP GLQFEIIAMS TTGDKILDTA LSKIGEKSLF 70 80 90 100 110 120 TKELEHALEK NEVDLVVHSL KDLPTVLPPG FTIGAICKRE NPHDAVVFHP KFVGKTLETL 130 140 150 160 170 180 PEKSVVGTSS LRRAAQLQRK FPHLEFRSIR GNLNTRLRKL DEQQEFSAII LATAGLQRMG 190 200 210 220 230 240 WHNRVGQILH PEECMYAVGQ GALGVEVRAK DQDILDLVGV LHDPETLLRC IAERAFLRHL 250 260 270 280 290 300 EGGCSVPVAV HTAMKDGQLY LTGGVWSLDG SDSIQETMQA TIHVPAQHED GPEDDPQLVG 310 320 330 340 ITARNIPRGP QLAAQNLGIS LANLLLSKGA KNILDVARQL NDAH « Hide

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminase." Raich N., Romeo P.-H., Dubart A., Beaupain D., Cohen-Solal M., Goossens M. Nucleic Acids Res. 14:5955-5968(1986) [PubMed: 2875434] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Tissue-specific expression of porphobilinogen deaminase. Two isoenzymes from a single gene." Grandchamp B., de Verneuil H., Beaumont C., Chretien S., Walter O., Nordmann Y. Eur. J. Biochem. 162:105-110(1987) [PubMed: 3816774] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Hydroxymethylbilane synthase: complete genomic sequence and amplifiable polymorphisms in the human gene." Yoo H.-W., Warner C.A., Chen C.-H., Desnick R.J. Genomics 15:21-29(1993) [PubMed: 7916736] [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. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon.
[5]	Mural R.J., Istrail S., Sutton G.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. Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Lung.
[7]	"Alternative transcription and splicing of the human porphobilinogen deaminase gene result either in tissue-specific or in housekeeping expression." Chretien S., Dubart A., Beaupain D., Raich N., Grandchamp B., Rosa J., Goossens M., Romeo P.-H. Proc. Natl. Acad. Sci. U.S.A. 85:6-10(1988) [PubMed: 3422427] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11 (ISOFORM 1), TISSUE SPECIFICITY.
[8]	"Porphobilinogen deaminase in human erythrocytes: purification of two forms with apparent molecular weights of 40 kDa and 42 kDa." Lannfelt L., Wetterberg L., Lilius L., Thunell S., Joernvall H., Pavlu B., Wielburski A., Gellerfors P. Scand. J. Clin. Lab. Invest. 49:677-684(1989) [PubMed: 2609111] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-36 (ISOFORM 2).
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, MASS SPECTROMETRY.
[11]	"Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene are responsible for acute intermittent porphyria." Delfau M.H., Picat C., de Rooij F.W.M., Hamer K., Bogard M., Wilson J.H.P., Deybach J.-C., Nordmann Y., Grandchamp B. J. Clin. Invest. 86:1511-1516(1990) [PubMed: 2243128] [Abstract] Cited for: VARIANTS AIP GLN-167 AND GLN-173.
[12]	"Molecular heterogeneity of acute intermittent porphyria: identification of four additional mutations resulting in the CRIM-negative subtype of the disease." Delfau M.H., Picat C., de Rooij F.W.M., Voortman G., Deybach J.-C., Nordmann Y., Grandchamp B. Am. J. Hum. Genet. 49:421-428(1991) [PubMed: 1714233] [Abstract] Cited for: VARIANTS AIP GLN-149 AND ARG-245.
[13]	"High frequency of mutations in exon 10 of the porphobilinogen deaminase gene in patients with a CRIM-positive subtype of acute intermittent porphyria." Gu X.-F., de Rooij F.W.M., Voortman G., Te Velde K., Nordmann Y., Grandchamp B. Am. J. Hum. Genet. 51:660-665(1992) [PubMed: 1496994] [Abstract] Cited for: VARIANT AIP TRP-167.
[14]	"Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA." Mgone C.S., Lanyon W.G., Moore M.R., Connor J.M. Hum. Genet. 90:12-16(1992) [PubMed: 1427766] [Abstract] Cited for: VARIANTS AIP LYS-34; GLN-167; ARG-177 AND ASN-256.
[15]	"CRIM-positive mutations of acute intermittent porphyria in Finland." Kauppinen R., Peltonen L., Pihlaja H., Mustajoki P. Hum. Mutat. 1:392-396(1992) [PubMed: 1301948] [Abstract] Cited for: VARIANTS AIP TRP-167 AND GLN-173.
[16]	"Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria." Mgone C.S., Lanyon W.G., Moore M.R., Louie G.V., Connor J.M. Hum. Genet. 92:619-622(1993) [PubMed: 8262523] [Abstract] Cited for: VARIANTS AIP ARG-247; THR-252 AND VAL-252.
[17]	"Acute intermittent porphyria caused by an arginine to histidine substitution (R26H) in the cofactor-binding cleft of porphobilinogen deaminase." Llewellyn D.H., Whatley S.D., Elder G.H. Hum. Mol. Genet. 2:1315-1316(1993) [PubMed: 8401516] [Abstract] Cited for: VARIANT AIP HIS-26.
[18]	"Two novel mutations of the porphobilinogen deaminase gene in acute intermittent porphyria." Gu X.-F., de Rooij F.W.M., de Baar E., Bruyland M., Lissens W., Nordmann Y., Grandchamp B. Hum. Mol. Genet. 2:1735-1736(1993) [PubMed: 8268934] [Abstract] Cited for: VARIANT AIP ARG-111.
[19]	"Detection of eleven mutations causing acute intermittent porphyria using denaturing gradient gel electrophoresis." Gu X.-F., de Rooij F.W.M., Voortman G., Te Velde K., Deybach J.-C., Nordmann Y., Grandchamp B. Hum. Genet. 93:47-52(1994) [PubMed: 8270254] [Abstract] Cited for: VARIANTS AIP THR-31; SER-55; LEU-149; LYS-223 AND LYS-250.
[20]	"Two new mutations in the porphobilinogen deaminase gene and a screening method using PCR amplification of specific alleles." Lundin G., Wedell A., Thunell S., Anvret M. Hum. Genet. 93:59-62(1994) [PubMed: 8270256] [Abstract] Cited for: VARIANT AIP TRP-201.
[21]	"Identification of five novel mutations in the porphobilinogen deaminase gene." Mgone C.S., Lanyon W.G., Moore M.R., Louie G.V., Connor J.M. Hum. Mol. Genet. 3:809-811(1994) [PubMed: 8081367] [Abstract] Cited for: VARIANTS AIP GLN-116; TRP-173; ARG-177; ILE-269 AND ARG-274.
[22]	"Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene." Astrin K.N., Desnick R.J. Hum. Mutat. 4:243-252(1994) [PubMed: 7866402] [Abstract] Cited for: REVIEW ON AIP VARIANTS.
[23]	"Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes 'variant acute intermittent porphyria' with normal expression of the erythroid-specific enzyme." Chen C.-H., Astrin K.H., Lee G., Anderson K.E., Desnick R.J. J. Clin. Invest. 94:1927-1937(1994) [PubMed: 7962538] [Abstract] Cited for: VARIANTS AIP PHE-93; TRP-116; TRP-201 AND PHE-247.
[24]	"Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene." Kauppinen R., Mustajoki S., Pihlaja H., Peltonen L., Mustajoki P. Hum. Mol. Genet. 4:215-222(1995) [PubMed: 7757070] [Abstract] Cited for: VARIANTS AIP.
[25]	"Four mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria." Lundin G., Hashemi J., Floderus Y., Thunell S., Sagen E., Laegreid A., Wassif W., Peters T., Anvret M. J. Med. Genet. 32:979-981(1995) [PubMed: 8825929] [Abstract] Cited for: VARIANTS AIP LEU-119 AND ALA-250.
[26]	"Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria." Puy H., Deybach J.-C., Lamoril J., Robreau A.-M., Da Silva V., Gouya L., Grandchamp B., Nordmann Y. Am. J. Hum. Genet. 60:1373-1383(1997) [PubMed: 9199558] [Abstract] Cited for: VARIANTS AIP.
[27]	"Genetic investigation of the porphobilinogen deaminase gene in Swedish acute intermittent porphyria families." Lundin G., Lee J.-S., Thunell S., Anvret M. Hum. Genet. 100:63-66(1997) [PubMed: 9225970] [Abstract] Cited for: VARIANTS AIP TRP-116; LEU-119; GLN-167; TRP-167; TRP-173; TRP-201 AND ASP-216.
[28]	"Three splicing defects, an insertion, and two missense mutations responsible for acute intermittent porphyria." Mustajoki S., Pihlaja H., Ahola H., Petersen N.E., Mustajoki P., Kauppinen R. Hum. Genet. 102:541-548(1998) [PubMed: 9654202] [Abstract] Cited for: VARIANTS AIP MET-222 AND PRO-278.
[29]	"Identification of two novel mutations in the hydroxymethylbilane synthase gene in three patients from two unrelated families with acute intermittent porphyria." Ong P.M., Lanyon W.G., Hift R.J., Halkett J., Cramp C.E., Moore M.R., Connor J.M. Hum. Hered. 48:24-29(1998) [PubMed: 9463797] [Abstract] Cited for: VARIANT AIP CYS-22.
[30]	"Identification and characterization of hydroxymethylbilane synthase mutations causing acute intermittent porphyria: evidence for an ancestral founder of the common G111R mutation." De Siervi A., Rossetti M.V., Parera V.E., Astrin K.H., Aizencang G.I., Glass I.A., Batlle A.M.C., Desnick R.J. Am. J. Med. Genet. 86:366-375(1999) [PubMed: 10494093] [Abstract] Cited for: VARIANTS AIP PRO-34; ARG-111; TRP-173; TRP-201; 329-LEU--GLN-332 DEL AND SER-335.
[31]	"Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations." Whatley S.D., Woolf J.R., Elder G.H. Hum. Genet. 104:505-510(1999) [PubMed: 10453740] [Abstract] Cited for: VARIANTS AIP CYS-22; CYS-26; HIS-26; PRO-31; SER-42; ASN-61; ARG-85; GLY-90; ARG-111; GLN-173; TRP-173; ARG-177; CYS-195; ASP-219; ARG-247 AND ILE-269.
[32]	"Acute intermittent porphyria: characterization of two novel mutations in the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one splicing aceptor site mutation (IVS8-1G>T)." De Siervi A., Mendez M., Parera V.E., Varela L., Batlle A.M.C., Rossetti M.V. Hum. Mutat. 14:355-355(1999) [PubMed: 10502788] [Abstract] Cited for: VARIANT AIP ALA-152 DEL.
[33]	"New mutations of the hydroxymethylbilane synthase gene in German patients with acute intermittent porphyria." Gross U., Puy H., Doss M., Robreau A.-M., Nordmann Y., Doss M.O., Deybach J.-C. Mol. Cell. Probes 13:443-447(1999) [PubMed: 10657149] [Abstract] Cited for: VARIANTS AIP CYS-26 AND LEU-202.
[34]	"Identification and expression of mutations in the hydroxymethylbilane synthase gene causing acute intermittent porphyria (AIP)." Solis C., Lopez-Echaniz I., Sefarty-Graneda D., Astrin K.H., Desnick R.J. Mol. Med. 5:664-671(1999) [PubMed: 10602775] [Abstract] Cited for: VARIANTS AIP ARG-111; TRP-116; TRP-167; TRP-173 AND VAL-212, CHARACTERIZATION OF VARIANT AIP VAL-212.
[35]	"Acute intermittent porphyria: novel missense mutations in the human hydroxymethylbilane synthase gene." Ramdall R.B., Cunha L., Astrin K.H., Katz D.R., Anderson K.E., Glucksman M., Bottomley S.S., Desnick R.J. Genet. Med. 2:290-295(2000) [PubMed: 11399210] [Abstract] Cited for: VARIANTS AIP PRO-78; GLY-80; ARG-111 AND TRP-173.
[36]	"Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic groups: mutations causing acute intermittent porphyria and specific intragenic polymorphisms." Robreau-Fraolini A.M., Puy H., Aquaron C., Bogard C., Traore M., Nordmann Y., Aquaron R., Deybach J.-C. Hum. Genet. 107:150-159(2000) [PubMed: 11030413] [Abstract] Cited for: VARIANTS AIP TRP-116 AND GLY-270.
[37]	"Identification of a prevalent nonsense mutation (W283X) and two novel mutations in the porphobilinogen deaminase gene of Swiss patients with acute intermittent porphyria." Schneider-Yin X., Bogard C., Rufenacht U.B., Puy H., Nordmann Y., Minder E.I., Deybach J.-C. Hum. Hered. 50:247-250(2000) [PubMed: 10782018] [Abstract] Cited for: VARIANT AIP LEU-217.
[38]	"Identification and characterization of two novel mutations that produce acute intermittent porphyria: a 3-base deletion (841-843delGGA) and a missense mutation (T35M)." De Siervi A., Weiss Cadiz D.E., Parera V.E., Batlle A.M.C., Rossetti M.V. Hum. Mutat. 16:373-373(2000) [PubMed: 11013452] [Abstract] Cited for: VARIANTS AIP MET-35; ARG-111 AND GLY-281 DEL.
[39]	Martinez di Montemuros F., Di Pierro E., Fiorelli G., Cappellini M.D. Hum. Genet. 109:241-241(2001) Cited for: VARIANT AIP ASN-99.
[40]	"Molecular and biochemical studies of acute intermittent porphyria in 196 patients and their families." Kauppinen R., von und zu Fraunberg M. Clin. Chem. 48:1891-1900(2002) [PubMed: 12406973] [Abstract] Cited for: VARIANTS AIP ILE-18; PHE-96; HIS-99; GLY-122; PRO-254 AND TYR-261.
[41]	"Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene." Floderus Y., Shoolingin-Jordan P.M., Harper P. Clin. Genet. 62:288-297(2002) [PubMed: 12372055] [Abstract] Cited for: VARIANTS AIP CYS-26; HIS-26; VAL-86; PRO-92; GLY-99; ARG-111; THR-113; GLN-173; ASN-178; GLN-225; GLY-225; TYR-256; ASP-260 AND PRO-343.
[42]	"Molecular study of the hydroxymethylbilane synthase gene (HMBS) among Polish patients with acute intermittent porphyria." Gregor A., Schneider-Yin X., Szlendak U., Wettstein A., Lipniacka A., Ruefenacht U.B., Minder E.I. Hum. Mutat. 19:310-310(2002) [PubMed: 11857754] [Abstract] Cited for: VARIANTS AIP HIS-26; TYR-61; VAL-93 DEL; ARG-111; GLN-173 AND ASP-335.
[43]	"Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias." Gouya L., Puy H., Robreau A.-M., Lyoumi S., Lamoril J., Da Silva V., Grandchamp B., Deybach J.-C. Hum. Genet. 114:256-262(2004) [PubMed: 14669009] [Abstract] Cited for: VARIANTS AIP ARG-34; SER-236 AND PRO-244.
[44]	"Homozygous acute intermittent porphyria in a 7-year-old boy with massive excretions of porphyrins and porphyrin precursors." Hessels J., Voortman G., van der Wagen A., van der Elzen C., Scheffer H., Zuijderhoudt F.M.J. J. Inherit. Metab. Dis. 27:19-27(2004) [PubMed: 14970743] [Abstract] Cited for: VARIANT AIP PRO-81.
[45]	"Mutation hotspots in the human porphobilinogen deaminase gene: recurrent mutations G111R and R173Q occurring at CpG motifs." Schneider-Yin X., Hergersberg M., Schuurmans M.M., Gregor A., Minder E.I. J. Inherit. Metab. Dis. 27:625-631(2004) [PubMed: 15669678] [Abstract] Cited for: VARIANTS AIP ARG-111 AND GLN-173.
+	Additional computationally mapped references.

GeneReviews

X04217 mRNA. Translation: CAA27801.1.
X04808 mRNA. Translation: CAA28499.1.
M95623 Genomic DNA. Translation: AAA60029.1.
M95623 Genomic DNA. Translation: AAA60030.1.
AK290275 mRNA. Translation: BAF82964.1.
CH471065 Genomic DNA. Translation: EAW67447.1.
BC000520 mRNA. Translation: AAH00520.1.
BC008149 mRNA. Translation: AAH08149.1.
BC019323 mRNA. Translation: AAH19323.1.
X68018 Genomic DNA. Translation: CAA48156.1.
S60381 Genomic DNA. Translation: AAC60602.1.

IPI

IPI00028160.
IPI00219877.

PIR

IBHUN. A45012.

RefSeq

NP_000181.2.
NP_001019553.1.

UniGene

Hs.82609

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3ECR	X-ray	2.18	A/B	1-361	[»]
3EQ1	X-ray	2.80	A/B	1-361	[»]

ModBase

STRING

P08397.

PRIDE

P08397.

Ensembl

ENST00000278715; ENSP00000278715; ENSG00000149397; Homo sapiens. [Genome view]

GeneID

3145.

KEGG

hsa:3145.

NMPDR

fig|9606.3.peg.6725.

UCSC

uc001puz.1. human.
uc001pvb.1. human.

CTD

3145.

GeneCards

GC11P118460.

H-InvDB

HIX0010283.

HGNC

HGNC:4982. HMBS.

HPA

HPA006114.

MIM

176000. phenotype.
609806. gene.

Orphanet

79276. Porphyria, acute intermittent.

PharmGKB

PA29317.

GenAtlas

HOGENOM

P08397.

HOVERGEN

P08397.

OMA

AKIGDKG

OrthoDB

EOG918F7M

BRENDA

2.5.1.61. 247.

Reactome

REACT_9431. Metabolism of porphyrins.

ArrayExpress

P08397.

Bgee

P08397.

CleanEx

HS_HMBS.

Genevestigator

P08397.

GermOnline

ENSG00000149397. Homo sapiens.

InterPro

IPR000860. 4pyrrol_synth_OHMeBilane_synth.
[Graphical view]

Gene3D

G3DSA:3.30.160.40. Porphobil_deam. 1 hit.

PANTHER

PTHR11557. Porphobil_deam. 1 hit.

Pfam

PF01379. Porphobil_deam. 1 hit.
PF03900. Porphobil_deamC. 1 hit.
[Graphical view]

PIRSF

PIRSF001438. 4pyrrol_synth_OHMeBilane_synth. 1 hit.

PRINTS

PR00151. PORPHBDMNASE.

TIGRFAMs

TIGR00212. hemC. 1 hit.

PROSITE

PS00533. PORPHOBILINOGEN_DEAM. 1 hit.
[Graphical view]

ProtoNet

NextBio

12464.

SOURCE

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

Isoform 1 (identifier: P08397-1)

Also known as: Non-erythropoietic;

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: P08397-2)

Also known as: Erythrocyte;

The sequence of this isoform differs from the canonical sequence as follows:
1-17: Missing.

Entry name

HEM3_HUMAN

Accession

Primary (citable) accession number: P08397
Secondary accession number(s): A8K2L0, P08396, Q16012

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	November 1, 1995
Last modified:	November 24, 2009
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.