HEM4_HUMAN
Source:
PM19886704
PM23856902
Marked as 'Non-membrane protein'
Confidence:
low (only semi-automatic identification from reviews)
Search PubMed for
(RBC AND this entry)
Gene names:
UROS
Protein names and data:
HEM4_HUMAN
, Uroporphyrinogen-III synthase; UROIIIS; UROS; 4.2.1.75
, Hydroxymethylbilane hydrolyase [cyclizing]; Uroporphyrinogen-III cosynthase
Lenght: 265 a.a.
Mass: 28628 Da
fasta formatted sequence
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. 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 = uroporphyrinogen III + H(2)O.
Pathway:
Porphyrin-containing compound metabolism; protoporphyrin- IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 3/4.
Disease:
( OMIM:
263700
606938
)
Congenital erythropoietic porphyria (CEP) [MIM:263700]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry. Note=Severe congenital erythropoietic porphyria is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non- immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders.
Tissue specificity:
Ubiquitous.
Genetic variants
3 - 3
V -> F (in CEP; no residual activity). VAR_021615
4 - 4
L -> F (in CEP). VAR_003674
19 - 19
Y -> C (in CEP). VAR_003675
47 - 47
S -> P (in CEP; less than 3% wild-type activity; severe cutaneous lesions). VAR_021616
53 - 53
P -> L (in CEP; no detectable activity; severe phenotype). VAR_003676
62 - 62
T -> A (in CEP; no detectable activity according to PubMed:1737856, while it does not affect enzymatic activity according to PubMed:11689424; dbSNP:rs28941775). VAR_003677
28941775
66 - 66
A -> V (in CEP; residual activity; mild phenotype; dbSNP:rs28941774). VAR_003678
28941774
69 - 69
A -> T (in CEP; less than 2% wild-type activity; moderately-severe phenotype). VAR_021617
73 - 73
C -> R (in CEP; frequent mutation in Western countries; no detectable activity; severe phenotype). VAR_003679
82 - 82
V -> F (in CEP; high residual activity; mild phenotype; dbSNP:rs121908016). VAR_003680
121908016
99 - 99
V -> A (in CEP). VAR_003681
104 - 104
A -> V (in CEP; residual activity). VAR_003682
124 - 124
K -> R (in dbSNP:rs17153561). VAR_049345
17153561
129 - 129
I -> T (in CEP; no residual activity). VAR_021618
171 - 171
V -> G (in dbSNP:rs17173752). VAR_049346
17173752
188 - 188
G -> R (in CEP; less than 5% wild-type activity). VAR_013558
188 - 188
G -> W (in CEP; less than 2% wild-type activity; mild phenotype). VAR_021619
210 - 211
EL -> HIQSQAQSQAQDN (in CEP). VAR_021620
212 - 212
S -> P (in CEP; no residual activity). VAR_003683
219 - 219
I -> S (in CEP; less than 2% wild-type activity; moderately-severe phenotype). VAR_021621
225 - 225
G -> S (in CEP). VAR_003684
228 - 228
T -> M (in CEP; no detectable activity). VAR_003685
237 - 237
L -> P (in CEP). VAR_067318
248 - 248
P -> Q (in CEP). VAR_066247
Database cross-references
UniProt:
P10746
Ensembl:
ENST00000368786
Ensembl:
ENST00000368797
MIM:
263700
MIM:
606938
neXtProt:
NX_P10746
Antibodypedia:
P10746
(may not find the protein thus also not any antibody)
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