Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P08397 (HEM3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 173. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Porphobilinogen deaminase

Short name=PBG-D
EC=2.5.1.61
Alternative name(s):
Hydroxymethylbilane synthase
Short name=HMBS
Pre-uroporphyrinogen synthase
Gene names
Name:HMBS
Synonyms:PBGD, UPS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length361 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps. HAMAP-Rule MF_00260

Catalytic activity

4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3. HAMAP-Rule MF_00260

Cofactor

Binds 1 dipyrromethane group covalently.

Pathway

Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4. HAMAP-Rule MF_00260

Subcellular location

Cytoplasm Probable HAMAP-Rule MF_00260.

Tissue specificity

Isoform 1 is ubiquitously expressed. Isoform 2 is found only in erythroid cells. Ref.8

Involvement in disease

Acute intermittent porphyria (AIP) [MIM:176000]: 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 attacks of gastrointestinal disturbances, abdominal colic, with neurological dysfunctions, hypertension, tachycardia and 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.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50

Miscellaneous

The porphobilinogen subunits are added to the dipyrromethane group.

Sequence similarities

Belongs to the HMBS family.

Alternative products

This entry describes 4 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.
Isoform 3 (identifier: P08397-3)

The sequence of this isoform differs from the canonical sequence as follows:
     218-257: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: P08397-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: Missing.
     218-257: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10
Chain2 – 361360Porphobilinogen deaminase HAMAP-Rule MF_00260
PRO_0000143034

Amino acid modifications

Modified residue21N-acetylserine Ref.10 Ref.12 Ref.13
Modified residue741N6-acetyllysine By similarity
Modified residue2611S-(dipyrrolylmethanemethyl)cysteine HAMAP-Rule MF_00260

Natural variations

Alternative sequence1 – 1717Missing in isoform 2 and isoform 4.
VSP_002067
Alternative sequence218 – 25740Missing in isoform 3 and isoform 4.
VSP_047294
Natural variant181M → I in AIP. Ref.45
VAR_025558
Natural variant221R → C in AIP. Ref.34 Ref.36
VAR_003638
Natural variant241G → S in AIP.
VAR_011001
Natural variant261R → C in AIP. Ref.36 Ref.38 Ref.46
VAR_011002
Natural variant261R → H in AIP. Ref.22 Ref.36 Ref.46 Ref.47
VAR_003639
Natural variant281S → N in AIP.
VAR_011003
Natural variant311A → P in AIP. Ref.36
VAR_011004
Natural variant311A → T in AIP. Ref.24
VAR_003640
Natural variant341Q → K in AIP. Ref.19
VAR_003641
Natural variant341Q → P in AIP; less than 3% of activity. Ref.35
VAR_011005
Natural variant341Q → R in AIP. Ref.48
VAR_025559
Natural variant351T → M in AIP. Ref.43
VAR_011006
Natural variant421L → S in AIP. Ref.36
VAR_011007
Natural variant551A → S in AIP. Ref.24
VAR_003642
Natural variant611D → N in AIP. Ref.36
VAR_011008
Natural variant611D → Y in AIP. Ref.47
VAR_025560
Natural variant781T → P in AIP. Ref.40
VAR_025561
Natural variant801E → G in AIP. Ref.40
VAR_025562
Natural variant811L → P in AIP. Ref.49
VAR_025563
Natural variant851L → R in AIP. Ref.36
VAR_011009
Natural variant861E → V in AIP. Ref.46
VAR_025564
Natural variant901V → G in AIP. Ref.36
VAR_011010
Natural variant921L → P in AIP. Ref.46
VAR_025565
Natural variant931V → F in AIP; loss of activity. Ref.28
VAR_003643
Natural variant931Missing in AIP. Ref.47
VAR_025566
Natural variant961S → F in AIP. Ref.45
VAR_025567
Natural variant981K → R in AIP.
VAR_003644
Natural variant991D → G in AIP. Ref.46
VAR_025568
Natural variant991D → H in AIP. Ref.45
VAR_025569
Natural variant991D → N in AIP. Ref.44
VAR_025570
Natural variant1111G → R in AIP. Ref.23 Ref.35 Ref.36 Ref.39 Ref.40 Ref.43 Ref.46 Ref.47 Ref.50
VAR_003645
Natural variant1131I → T in AIP. Ref.46
VAR_025571
Natural variant1161R → Q in AIP. Ref.26
VAR_003646
Natural variant1161R → W in AIP; loss of activity. Ref.28 Ref.32 Ref.39 Ref.41
VAR_003647
Natural variant1191P → L in AIP. Ref.30 Ref.32
VAR_003648
Natural variant1221A → G in AIP. Ref.45
VAR_025572
Natural variant1241V → D in AIP.
VAR_011011
Natural variant1491R → L in AIP. Ref.24
VAR_003649
Natural variant1491R → Q in AIP. Ref.17
VAR_003650
Natural variant1521Missing in AIP. Ref.37
VAR_009223
Natural variant1671R → Q in AIP. Ref.16 Ref.19 Ref.32
VAR_003651
Natural variant1671R → W in AIP. Ref.18 Ref.20 Ref.32 Ref.39
VAR_003652
Natural variant1731R → Q in AIP; 0.6% of wild-type activity. Ref.16 Ref.20 Ref.36 Ref.46 Ref.47 Ref.50
VAR_003653
Natural variant1731R → W in AIP. Ref.26 Ref.32 Ref.35 Ref.36 Ref.39 Ref.40
VAR_003654
Natural variant1771L → R in AIP. Ref.19 Ref.26 Ref.36
VAR_003655
Natural variant1781D → N in AIP. Ref.46
VAR_011012
Natural variant1951R → C in AIP. Ref.36
Corresponds to variant rs34413634 [ dbSNP | Ensembl ].
VAR_003656
Natural variant2011R → W in AIP; residual activity. Ref.25 Ref.28 Ref.32 Ref.35
VAR_003657
Natural variant2021V → L in AIP. Ref.38
VAR_011013
Natural variant2091E → K in AIP.
VAR_011014
Natural variant2121M → V in AIP; <2% residual activity. Ref.39
VAR_025573
Natural variant2161G → D in AIP. Ref.32
VAR_011015
Natural variant2171Q → H in AIP.
VAR_011016
Natural variant2171Q → L in AIP. Ref.42
VAR_011017
Natural variant2191A → D in AIP. Ref.36
VAR_011018
Natural variant2221V → M in AIP. Ref.33
VAR_003658
Natural variant2231E → K in AIP. Ref.24
VAR_003659
Natural variant2251R → G in AIP. Ref.46
VAR_003660
Natural variant2251R → Q in AIP. Ref.46
VAR_025574
Natural variant2361G → S in AIP. Ref.48
VAR_025575
Natural variant2381L → R in AIP.
VAR_003661
Natural variant2441L → P in AIP. Ref.48
VAR_025576
Natural variant2451L → R in AIP. Ref.17
VAR_003662
Natural variant2471C → F in AIP; residual activity. Ref.28
VAR_003663
Natural variant2471C → R in AIP. Ref.21 Ref.36
VAR_003664
Natural variant2481I → IETLLRCI in AIP.
VAR_011019
Natural variant2501E → A in AIP. Ref.30
VAR_003665
Natural variant2501E → K in AIP. Ref.24
VAR_003666
Natural variant2501E → Q in AIP.
VAR_011020
Natural variant2501E → V in AIP.
VAR_011021
Natural variant2521A → T in AIP. Ref.21
VAR_003667
Natural variant2521A → V in AIP. Ref.21
VAR_003668
Natural variant2541L → P in AIP. Ref.45
VAR_025577
Natural variant2561H → N in AIP. Ref.19
VAR_003669
Natural variant2561H → Y in AIP. Ref.46
VAR_011022
Natural variant2601G → D in AIP. Ref.46
VAR_025578
Natural variant2611C → Y in AIP. Ref.45
VAR_025579
Natural variant2671V → M in AIP.
VAR_011023
Natural variant2691T → I in AIP. Ref.26 Ref.36
VAR_003670
Natural variant2701A → D in AIP.
VAR_011024
Natural variant2701A → G in AIP. Ref.41
VAR_011025
Natural variant2741G → R in AIP. Ref.26
VAR_003671
Natural variant2781L → P in AIP. Ref.33
VAR_003672
Natural variant2801G → R in AIP.
VAR_003673
Natural variant2811Missing in AIP. Ref.43
VAR_011026
Natural variant329 – 3324Missing in AIP.
VAR_011027
Natural variant3351G → D in AIP. Ref.47
VAR_011028
Natural variant3351G → S in AIP; less than 3% of activity. Ref.35
VAR_011029
Natural variant3431L → P in AIP. Ref.46
VAR_025580

Experimental info

Sequence conflict1771L → M in AAA60029. Ref.3
Sequence conflict1771L → M in AAA60030. Ref.3
Sequence conflict2101E → K in CAA28499. Ref.2
Sequence conflict3491N → T in CAA27801. Ref.1

Secondary structure

..................................................... 361
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Non-erythropoietic) [UniParc].

Last modified November 1, 1995. Version 2.
Checksum: 8F2F6F4150F1AD7E

FASTA36139,330
        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) [UniParc].

Checksum: 0A5138172DB6E96F
Show »

FASTA34437,699
Isoform 3 [UniParc].

Checksum: 5B2871947E3AF78A
Show »

FASTA32134,895
Isoform 4 [UniParc].

Checksum: 05357CAA1B7417CC
Show »

FASTA30433,264

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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; 3 AND 4).
Tissue: Colon.
[5]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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: Brain and Lung.
[8]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 30-53, TISSUE SPECIFICITY.
[9]"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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 18-36 (ISOFORM 2).
[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] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[11]"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].
[12]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria."
Gill R., Kolstoe S.E., Mohammed F., Al D-Bass A., Mosely J.E., Sarwar M., Cooper J.B., Wood S.P., Shoolingin-Jordan P.M.
Biochem. J. 420:17-25(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS).
[15]"Structural insight into acute intermittent porphyria."
Song G., Li Y., Cheng C., Zhao Y., Gao A., Zhang R., Joachimiak A., Shaw N., Liu Z.J.
FASEB J. 23:396-404(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS), S-(DIPYRROLYLMETHANEMETHYL)CYSTEINE AT CYS-261.
[16]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP GLN-167 AND GLN-173.
[17]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP GLN-149 AND ARG-245.
[18]"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] [Europe PMC] [Abstract]
Cited for: VARIANT AIP TRP-167.
[19]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP LYS-34; GLN-167; ARG-177 AND ASN-256.
[20]"CRIM-positive mutations of acute intermittent porphyria in Finland."
Kauppinen R., Peltonen L., Pihlaja H., Mustajoki P.
Hum. Mutat. 1:392-396(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP TRP-167 AND GLN-173.
[21]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP ARG-247; THR-252 AND VAL-252.
[22]"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] [Europe PMC] [Abstract]
Cited for: VARIANT AIP HIS-26.
[23]"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] [Europe PMC] [Abstract]
Cited for: VARIANT AIP ARG-111.
[24]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP THR-31; SER-55; LEU-149; LYS-223 AND LYS-250.
[25]"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] [Europe PMC] [Abstract]
Cited for: VARIANT AIP TRP-201.
[26]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP GLN-116; TRP-173; ARG-177; ILE-269 AND ARG-274.
[27]"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] [Europe PMC] [Abstract]
Cited for: REVIEW ON AIP VARIANTS.
[28]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP PHE-93; TRP-116; TRP-201 AND PHE-247.
[29]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP.
[30]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP LEU-119 AND ALA-250.
[31]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP.
[32]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP TRP-116; LEU-119; GLN-167; TRP-167; TRP-173; TRP-201 AND ASP-216.
[33]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP MET-222 AND PRO-278.
[34]"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] [Europe PMC] [Abstract]
Cited for: VARIANT AIP CYS-22.
[35]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP PRO-34; ARG-111; TRP-173; TRP-201; 329-LEU--GLN-332 DEL AND SER-335.
[36]"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] [Europe PMC] [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.
[37]"Acute intermittent porphyria: characterization of two novel mutations in the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one splicing acceptor 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] [Europe PMC] [Abstract]
Cited for: VARIANT AIP ALA-152 DEL.
[38]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP CYS-26 AND LEU-202.
[39]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP ARG-111; TRP-116; TRP-167; TRP-173 AND VAL-212, CHARACTERIZATION OF VARIANT AIP VAL-212.
[40]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP PRO-78; GLY-80; ARG-111 AND TRP-173.
[41]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP TRP-116 AND GLY-270.
[42]"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] [Europe PMC] [Abstract]
Cited for: VARIANT AIP LEU-217.
[43]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP MET-35; ARG-111 AND GLY-281 DEL.
[44]Erratum
Martinez di Montemuros F., Di Pierro E., Fiorelli G., Cappellini M.D.
Hum. Genet. 109:241-241(2001)
Cited for: VARIANT AIP ASN-99.
[45]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP ILE-18; PHE-96; HIS-99; GLY-122; PRO-254 AND TYR-261.
[46]"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] [Europe PMC] [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.
[47]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP HIS-26; TYR-61; VAL-93 DEL; ARG-111; GLN-173 AND ASP-335.
[48]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP ARG-34; SER-236 AND PRO-244.
[49]"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] [Europe PMC] [Abstract]
Cited for: VARIANT AIP PRO-81.
[50]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS AIP ARG-111 AND GLN-173.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X04217 mRNA. Translation: CAA27801.1.
X04808 mRNA. Translation: CAA28499.1.
M95623 Genomic DNA. Translation: AAA60029.1.
M95623 Genomic DNA. Translation: AAA60030.1.
AK000628 mRNA. No translation available.
AK131072 mRNA. No translation available.
AK290275 mRNA. Translation: BAF82964.1.
AP003391 Genomic DNA. No translation available.
AP003392 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67447.1.
CH471065 Genomic DNA. Translation: EAW67449.1.
CH471065 Genomic DNA. Translation: EAW67450.1.
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.
PIRIBHUN. A45012.
RefSeqNP_000181.2. NM_000190.3.
NP_001019553.1. NM_001024382.1.
NP_001245137.1. NM_001258208.1.
NP_001245138.1. NM_001258209.1.
XP_005271588.1. XM_005271531.1.
XP_005271589.1. XM_005271532.1.
UniGeneHs.82609.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3ECRX-ray2.18A/B1-361[»]
3EQ1X-ray2.80A/B1-361[»]
ProteinModelPortalP08397.
SMRP08397. Positions 18-356.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109388. 2 interactions.
STRING9606.ENSP00000278715.

PTM databases

PhosphoSiteP08397.

Polymorphism databases

DMDM1170217.

Proteomic databases

PaxDbP08397.
PRIDEP08397.

Protocols and materials databases

DNASU3145.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000278715; ENSP00000278715; ENSG00000256269. [P08397-1]
ENST00000392841; ENSP00000376584; ENSG00000256269. [P08397-2]
ENST00000442944; ENSP00000392041; ENSG00000256269. [P08397-2]
ENST00000537841; ENSP00000444730; ENSG00000256269. [P08397-2]
ENST00000542729; ENSP00000443058; ENSG00000256269. [P08397-4]
ENST00000544387; ENSP00000438424; ENSG00000256269. [P08397-3]
ENST00000570821; ENSP00000458163; ENSG00000261883. [P08397-1]
ENST00000571030; ENSP00000461361; ENSG00000261883. [P08397-3]
ENST00000571563; ENSP00000458765; ENSG00000261883. [P08397-2]
ENST00000574152; ENSP00000458891; ENSG00000261883. [P08397-2]
ENST00000575587; ENSP00000460754; ENSG00000261883. [P08397-2]
ENST00000575888; ENSP00000461906; ENSG00000261883. [P08397-4]
GeneID3145.
KEGGhsa:3145.
UCSCuc001puz.1. human. [P08397-1]
uc001pve.2. human.

Organism-specific databases

CTD3145.
GeneCardsGC11P118955.
HGNCHGNC:4982. HMBS.
HPAHPA006114.
HPA050659.
MIM176000. phenotype.
609806. gene.
neXtProtNX_P08397.
Orphanet79276. Acute intermittent porphyria.
PharmGKBPA29317.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0181.
HOGENOMHOG000228587.
HOVERGENHBG000967.
InParanoidP08397.
KOK01749.
OMAPLRGNAN.
PhylomeDBP08397.
TreeFamTF105389.

Enzyme and pathway databases

BioCycMetaCyc:HS07607-MONOMER.
BRENDA2.5.1.61. 2681.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00251; UER00319.

Gene expression databases

ArrayExpressP08397.
BgeeP08397.
CleanExHS_HMBS.
GenevestigatorP08397.

Family and domain databases

Gene3D3.30.160.40. 1 hit.
HAMAPMF_00260. Porphobil_deam.
InterProIPR000860. 4pyrrol_synth_OHMeBilane_synth.
IPR022419. Porphobilin_deaminase_cofac_BS.
IPR022417. Porphobilin_deaminase_N.
IPR022418. Porphobilinogen_deaminase_C.
[Graphical view]
PANTHERPTHR11557. PTHR11557. 1 hit.
PfamPF01379. Porphobil_deam. 1 hit.
PF03900. Porphobil_deamC. 1 hit.
[Graphical view]
PIRSFPIRSF001438. 4pyrrol_synth_OHMeBilane_synth. 1 hit.
PRINTSPR00151. PORPHBDMNASE.
SUPFAMSSF54782. SSF54782. 2 hits.
TIGRFAMsTIGR00212. hemC. 1 hit.
PROSITEPS00533. PORPHOBILINOGEN_DEAM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP08397.
GeneWikiPorphobilinogen_deaminase.
GenomeRNAi3145.
NextBio12464.
PROP08397.
SOURCESearch...

Entry information

Entry nameHEM3_HUMAN
AccessionPrimary (citable) accession number: P08397
Secondary accession number(s): A8K2L0 expand/collapse secondary AC list , G3V1P4, G5EA58, P08396, Q16012
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 173 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM