P10746 · HEM4_HUMAN
- ProteinUroporphyrinogen-III synthase
- GeneUROS
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids265 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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)
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
- hydroxymethylbilane = H2O + uroporphyrinogen III
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.15 μM | hydroxymethylbilane |
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
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | mitochondrion | |
Molecular Function | folic acid binding | |
Molecular Function | uroporphyrinogen-III synthase activity | |
Biological Process | cellular response to amine stimulus | |
Biological Process | cellular response to arsenic-containing substance | |
Biological Process | heme A biosynthetic process | |
Biological Process | heme B biosynthetic process | |
Biological Process | heme biosynthetic process | |
Biological Process | heme O biosynthetic process | |
Biological Process | protoporphyrinogen IX biosynthetic process | |
Biological Process | response to platinum ion | |
Biological Process | uroporphyrinogen III biosynthetic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameUroporphyrinogen-III synthase
- EC number
- Short namesUROIIIS; UROS
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP10746
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Involvement in disease
Congenital erythropoietic porphyria (CEP)
- Note
- DescriptionPorphyrias 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 alsoMIM:263700
Natural variants in CEP
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_021615 | 3 | V>F | in CEP; no residual activity; dbSNP:rs773301339 | |
VAR_003674 | 4 | L>F | in CEP; dbSNP:rs121908015 | |
VAR_003675 | 19 | Y>C | in CEP | |
VAR_021616 | 47 | S>P | in CEP; severe cutaneous lesions; less than 3% wild-type activity; dbSNP:rs397515527 | |
VAR_003676 | 53 | P>L | in CEP; severe phenotype; no detectable activity; dbSNP:rs121908013 | |
VAR_003677 | 62 | T>A | in CEP; the effect on catalytic activity is controversial; dbSNP:rs28941775 | |
VAR_003678 | 66 | A>V | in CEP; mild phenotype; strong decrease in enzymatic activity, when tested in vitro; may affect thermal stability; dbSNP:rs28941774 | |
VAR_021617 | 69 | A>T | in CEP; less than 2% wild-type activity | |
VAR_003679 | 73 | C>R | in CEP; frequent mutation in Western countries; severe phenotype; loss of enzymatic activity, when tested in vitro; dbSNP:rs121908012 | |
VAR_003680 | 82 | V>F | in CEP; mild phenotype; high residual activity; dbSNP:rs121908016 | |
VAR_003681 | 99 | V>A | in CEP | |
VAR_003682 | 104 | A>V | in CEP; residual activity; dbSNP:rs397515528 | |
VAR_021618 | 129 | I>T | in CEP; no residual activity | |
VAR_013558 | 188 | G>R | in CEP; less than 5% wild-type activity; dbSNP:rs121908017 | |
VAR_021619 | 188 | G>W | in CEP; mild phenotype; less than 2% wild-type activity; dbSNP:rs121908017 | |
VAR_021620 | 210-211 | EL>HIQSQAQSQAQDN | in CEP | |
VAR_003683 | 212 | S>P | in CEP; no residual activity; dbSNP:rs139388833 | |
VAR_021621 | 219 | I>S | in CEP; moderately-severe phenotype; less than 2% wild-type activity; dbSNP:rs767029901 | |
VAR_003684 | 225 | G>S | in CEP; dbSNP:rs121908020 | |
VAR_003685 | 228 | T>M | in CEP; loss of enzymatic activity, when tested in vitro; dbSNP:rs121908014 | |
VAR_067318 | 237 | L>P | in CEP; dbSNP:rs777433697 | |
VAR_066247 | 248 | P>Q | in CEP; dbSNP:rs121908021 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_021615 | 3 | in CEP; no residual activity; dbSNP:rs773301339 | |||
Sequence: V → F | ||||||
Natural variant | VAR_003674 | 4 | in CEP; dbSNP:rs121908015 | |||
Sequence: L → F | ||||||
Natural variant | VAR_003675 | 19 | in CEP | |||
Sequence: Y → C | ||||||
Natural variant | VAR_021616 | 47 | in CEP; severe cutaneous lesions; less than 3% wild-type activity; dbSNP:rs397515527 | |||
Sequence: S → P | ||||||
Natural variant | VAR_003676 | 53 | in CEP; severe phenotype; no detectable activity; dbSNP:rs121908013 | |||
Sequence: P → L | ||||||
Natural variant | VAR_003677 | 62 | in CEP; the effect on catalytic activity is controversial; dbSNP:rs28941775 | |||
Sequence: T → A | ||||||
Mutagenesis | 63 | Does not affect enzymatic activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 65 | Slightly affects enzymatic activity. | ||||
Sequence: R → A | ||||||
Natural variant | VAR_003678 | 66 | in CEP; mild phenotype; strong decrease in enzymatic activity, when tested in vitro; may affect thermal stability; dbSNP:rs28941774 | |||
Sequence: A → V | ||||||
Natural variant | VAR_021617 | 69 | in CEP; less than 2% wild-type activity | |||
Sequence: A → T | ||||||
Natural variant | VAR_003679 | 73 | in CEP; frequent mutation in Western countries; severe phenotype; loss of enzymatic activity, when tested in vitro; dbSNP:rs121908012 | |||
Sequence: C → R | ||||||
Natural variant | VAR_003680 | 82 | in CEP; mild phenotype; high residual activity; dbSNP:rs121908016 | |||
Sequence: V → F | ||||||
Natural variant | VAR_003681 | 99 | in CEP | |||
Sequence: V → A | ||||||
Mutagenesis | 103 | Slightly affects enzymatic activity. | ||||
Sequence: T → A | ||||||
Natural variant | VAR_003682 | 104 | in CEP; residual activity; dbSNP:rs397515528 | |||
Sequence: A → V | ||||||
Natural variant | VAR_049345 | 124 | in dbSNP:rs17153561 | |||
Sequence: K → R | ||||||
Mutagenesis | 127 | Does not affect enzymatic activity. | ||||
Sequence: E → A | ||||||
Natural variant | VAR_021618 | 129 | in CEP; no residual activity | |||
Sequence: I → T | ||||||
Mutagenesis | 168 | Impairs enzymatic activity. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_049346 | 171 | in dbSNP:rs17173752 | |||
Sequence: V → G | ||||||
Natural variant | VAR_013558 | 188 | in CEP; less than 5% wild-type activity; dbSNP:rs121908017 | |||
Sequence: G → R | ||||||
Natural variant | VAR_021619 | 188 | in CEP; mild phenotype; less than 2% wild-type activity; dbSNP:rs121908017 | |||
Sequence: G → W | ||||||
Mutagenesis | 197 | Does not affect enzymatic activity. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_021620 | 210-211 | in CEP | |||
Sequence: EL → HIQSQAQSQAQDN | ||||||
Natural variant | VAR_003683 | 212 | in CEP; no residual activity; dbSNP:rs139388833 | |||
Sequence: S → P | ||||||
Natural variant | VAR_021621 | 219 | in CEP; moderately-severe phenotype; less than 2% wild-type activity; dbSNP:rs767029901 | |||
Sequence: I → S | ||||||
Mutagenesis | 220 | Does not affect enzymatic activity. | ||||
Sequence: K → A | ||||||
Natural variant | VAR_003684 | 225 | in CEP; dbSNP:rs121908020 | |||
Sequence: G → S | ||||||
Mutagenesis | 227 | Does not affect enzymatic activity. | ||||
Sequence: T → A | ||||||
Natural variant | VAR_003685 | 228 | in CEP; loss of enzymatic activity, when tested in vitro; dbSNP:rs121908014 | |||
Sequence: T → M | ||||||
Mutagenesis | 228 | Impairs enzymatic activity. | ||||
Sequence: T → A | ||||||
Natural variant | VAR_067318 | 237 | in CEP; dbSNP:rs777433697 | |||
Sequence: L → P | ||||||
Natural variant | VAR_066247 | 248 | in CEP; dbSNP:rs121908021 | |||
Sequence: P → Q |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000135251 | 1-265 | UniProt | Uroporphyrinogen-III synthase | |||
Sequence: MKVLLLKDAKEDDCGQDPYIRELGLYGLEATLIPVLSFEFLSLPSFSEKLSHPEDYGGLIFTSPRAVEAAELCLEQNNKTEVWERSLKEKWNAKSVYVVGNATASLVSKIGLDTEGETCGNAEKLAEYICSRESSALPLLFPCGNLKREILPKALKDKGIAMESITVYQTVAHPGIQGNLNSYYSQQGVPASITFFSPSGLTYSLKHIQELSGDNIDQIKFAAIGPTTARALAAQGLPVSCTAESPTPQALATGIRKALQPHGCC | |||||||
Modified residue (large scale data) | 245 | PRIDE | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitous.
Gene expression databases
Organism-specific databases
Structure
Sequence
- Sequence statusComplete
- Length265
- Mass (Da)28,628
- Last updated1989-07-01 v1
- ChecksumCEF171401361F61E
Computationally mapped potential isoform sequences
There are 14 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q5T3L7 | Q5T3L7_HUMAN | UROS | 133 | ||
Q5T3L8 | Q5T3L8_HUMAN | UROS | 139 | ||
Q5T3L9 | Q5T3L9_HUMAN | UROS | 185 | ||
A0A3B3IS33 | A0A3B3IS33_HUMAN | UROS | 78 | ||
A0A3B3IS76 | A0A3B3IS76_HUMAN | UROS | 151 | ||
A0A3B3ISL9 | A0A3B3ISL9_HUMAN | UROS | 160 | ||
A0A3B3ISM6 | A0A3B3ISM6_HUMAN | UROS | 292 | ||
A0A3B3ISX6 | A0A3B3ISX6_HUMAN | UROS | 137 | ||
A0A3B3ITJ2 | A0A3B3ITJ2_HUMAN | UROS | 265 | ||
A0A3B3IUC8 | A0A3B3IUC8_HUMAN | UROS | 111 | ||
A0A3B3IU75 | A0A3B3IU75_HUMAN | UROS | 74 | ||
A0A087X021 | A0A087X021_HUMAN | UROS | 122 | ||
A0A087WUV7 | A0A087WUV7_HUMAN | UROS | 110 | ||
A0A087WZB7 | A0A087WZB7_HUMAN | UROS | 68 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |