P10746 · HEM4_HUMAN

  • Protein
    Uroporphyrinogen-III synthase
  • Gene
    UROS
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the branch point for the various sub-pathways leading to the wide diversity of porphyrins (PubMed:11689424, PubMed:18004775).
Porphyrins act as cofactors for a multitude of enzymes that perform a variety of processes within the cell such as methionine synthesis (vitamin B12) or oxygen transport (heme)

Catalytic activity

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
0.15 μMhydroxymethylbilane

pH Dependence

Optimum pH is 8.2.

Pathway

Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 3/4.

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentmitochondrion
Molecular Functionfolic acid binding
Molecular Functionuroporphyrinogen-III synthase activity
Biological Processcellular response to amine stimulus
Biological Processcellular response to arsenic-containing substance
Biological Processheme A biosynthetic process
Biological Processheme B biosynthetic process
Biological Processheme biosynthetic process
Biological Processheme O biosynthetic process
Biological Processprotoporphyrinogen IX biosynthetic process
Biological Processresponse to platinum ion
Biological Processuroporphyrinogen III biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Uroporphyrinogen-III synthase
  • EC number
  • Short names
    UROIIIS; UROS
  • Alternative names
    • Hydroxymethylbilane hydrolyase [cyclizing]
    • Uroporphyrinogen-III cosynthase

Gene names

    • Name
      UROS

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P10746
  • Secondary accessions
    • B2RC13
    • D3DRF7
    • Q9H2T1

Proteomes

Organism-specific databases

Subcellular Location

Disease & Variants

Involvement in disease

Congenital erythropoietic porphyria (CEP)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    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. The manifestations of CEP are heterogeneous, ranging from nonimmune hydrops fetalis due to severe hemolytic anemia in utero to milder, later onset forms, which have only skin lesions due to cutaneous photosensitivity in adult life. The deficiency in UROS activity results in the non-enzymatic conversion of hydroxymethylbilane (HMB) into the uroporphyrinogen-I isomer.
  • See also
    MIM:263700
Natural variants in CEP
Variant IDPosition(s)ChangeDescription
VAR_0216153V>Fin CEP; no residual activity; dbSNP:rs773301339
VAR_0036744L>Fin CEP; dbSNP:rs121908015
VAR_00367519Y>Cin CEP
VAR_02161647S>Pin CEP; severe cutaneous lesions; less than 3% wild-type activity; dbSNP:rs397515527
VAR_00367653P>Lin CEP; severe phenotype; no detectable activity; dbSNP:rs121908013
VAR_00367762T>Ain CEP; the effect on catalytic activity is controversial; dbSNP:rs28941775
VAR_00367866A>Vin CEP; mild phenotype; strong decrease in enzymatic activity, when tested in vitro; may affect thermal stability; dbSNP:rs28941774
VAR_02161769A>Tin CEP; less than 2% wild-type activity
VAR_00367973C>Rin CEP; frequent mutation in Western countries; severe phenotype; loss of enzymatic activity, when tested in vitro; dbSNP:rs121908012
VAR_00368082V>Fin CEP; mild phenotype; high residual activity; dbSNP:rs121908016
VAR_00368199V>Ain CEP
VAR_003682104A>Vin CEP; residual activity; dbSNP:rs397515528
VAR_021618129I>Tin CEP; no residual activity
VAR_013558188G>Rin CEP; less than 5% wild-type activity; dbSNP:rs121908017
VAR_021619188G>Win CEP; mild phenotype; less than 2% wild-type activity; dbSNP:rs121908017
VAR_021620210-211EL>HIQSQAQSQAQDNin CEP
VAR_003683212S>Pin CEP; no residual activity; dbSNP:rs139388833
VAR_021621219I>Sin CEP; moderately-severe phenotype; less than 2% wild-type activity; dbSNP:rs767029901
VAR_003684225G>Sin CEP; dbSNP:rs121908020
VAR_003685228T>Min CEP; loss of enzymatic activity, when tested in vitro; dbSNP:rs121908014
VAR_067318237L>Pin CEP; dbSNP:rs777433697
VAR_066247248P>Qin CEP; dbSNP:rs121908021

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_0216153in CEP; no residual activity; dbSNP:rs773301339
Natural variantVAR_0036744in CEP; dbSNP:rs121908015
Natural variantVAR_00367519in CEP
Natural variantVAR_02161647in CEP; severe cutaneous lesions; less than 3% wild-type activity; dbSNP:rs397515527
Natural variantVAR_00367653in CEP; severe phenotype; no detectable activity; dbSNP:rs121908013
Natural variantVAR_00367762in CEP; the effect on catalytic activity is controversial; dbSNP:rs28941775
Mutagenesis63Does not affect enzymatic activity.
Mutagenesis65Slightly affects enzymatic activity.
Natural variantVAR_00367866in CEP; mild phenotype; strong decrease in enzymatic activity, when tested in vitro; may affect thermal stability; dbSNP:rs28941774
Natural variantVAR_02161769in CEP; less than 2% wild-type activity
Natural variantVAR_00367973in CEP; frequent mutation in Western countries; severe phenotype; loss of enzymatic activity, when tested in vitro; dbSNP:rs121908012
Natural variantVAR_00368082in CEP; mild phenotype; high residual activity; dbSNP:rs121908016
Natural variantVAR_00368199in CEP
Mutagenesis103Slightly affects enzymatic activity.
Natural variantVAR_003682104in CEP; residual activity; dbSNP:rs397515528
Natural variantVAR_049345124in dbSNP:rs17153561
Mutagenesis127Does not affect enzymatic activity.
Natural variantVAR_021618129in CEP; no residual activity
Mutagenesis168Impairs enzymatic activity.
Natural variantVAR_049346171in dbSNP:rs17173752
Natural variantVAR_013558188in CEP; less than 5% wild-type activity; dbSNP:rs121908017
Natural variantVAR_021619188in CEP; mild phenotype; less than 2% wild-type activity; dbSNP:rs121908017
Mutagenesis197Does not affect enzymatic activity.
Natural variantVAR_021620210-211in CEP
Natural variantVAR_003683212in CEP; no residual activity; dbSNP:rs139388833
Natural variantVAR_021621219in CEP; moderately-severe phenotype; less than 2% wild-type activity; dbSNP:rs767029901
Mutagenesis220Does not affect enzymatic activity.
Natural variantVAR_003684225in CEP; dbSNP:rs121908020
Mutagenesis227Does not affect enzymatic activity.
Natural variantVAR_003685228in CEP; loss of enzymatic activity, when tested in vitro; dbSNP:rs121908014
Mutagenesis228Impairs enzymatic activity.
Natural variantVAR_067318237in CEP; dbSNP:rs777433697
Natural variantVAR_066247248in CEP; dbSNP:rs121908021

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 327 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
ChainPRO_00001352511-265UniProtUroporphyrinogen-III synthase
Modified residue (large scale data)245PRIDEPhosphoserine

Proteomic databases

PTM databases

Expression

Tissue specificity

Ubiquitous.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Monomer.

Protein-protein interaction databases

Miscellaneous

Family & Domains

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    265
  • Mass (Da)
    28,628
  • Last updated
    1989-07-01 v1
  • Checksum
    CEF171401361F61E
MKVLLLKDAKEDDCGQDPYIRELGLYGLEATLIPVLSFEFLSLPSFSEKLSHPEDYGGLIFTSPRAVEAAELCLEQNNKTEVWERSLKEKWNAKSVYVVGNATASLVSKIGLDTEGETCGNAEKLAEYICSRESSALPLLFPCGNLKREILPKALKDKGIAMESITVYQTVAHPGIQGNLNSYYSQQGVPASITFFSPSGLTYSLKHIQELSGDNIDQIKFAAIGPTTARALAAQGLPVSCTAESPTPQALATGIRKALQPHGCC

Computationally mapped potential isoform sequences

There are 14 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
Q5T3L7Q5T3L7_HUMANUROS133
Q5T3L8Q5T3L8_HUMANUROS139
Q5T3L9Q5T3L9_HUMANUROS185
A0A3B3IS33A0A3B3IS33_HUMANUROS78
A0A3B3IS76A0A3B3IS76_HUMANUROS151
A0A3B3ISL9A0A3B3ISL9_HUMANUROS160
A0A3B3ISM6A0A3B3ISM6_HUMANUROS292
A0A3B3ISX6A0A3B3ISX6_HUMANUROS137
A0A3B3ITJ2A0A3B3ITJ2_HUMANUROS265
A0A3B3IUC8A0A3B3IUC8_HUMANUROS111
A0A3B3IU75A0A3B3IU75_HUMANUROS74
A0A087X021A0A087X021_HUMANUROS122
A0A087WUV7A0A087WUV7_HUMANUROS110
A0A087WZB7A0A087WZB7_HUMANUROS68

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
J03824
EMBL· GenBank· DDBJ
AAA60273.1
EMBL· GenBank· DDBJ
mRNA
AF230665
EMBL· GenBank· DDBJ
AAG36795.1
EMBL· GenBank· DDBJ
mRNA
AH010036
EMBL· GenBank· DDBJ
AAG36794.1
EMBL· GenBank· DDBJ
Genomic DNA
AK314896
EMBL· GenBank· DDBJ
BAG37410.1
EMBL· GenBank· DDBJ
mRNA
AL360176
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471066
EMBL· GenBank· DDBJ
EAW49221.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471066
EMBL· GenBank· DDBJ
EAW49222.1
EMBL· GenBank· DDBJ
Genomic DNA
BC002573
EMBL· GenBank· DDBJ
AAH02573.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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