Cytosolic 5'-nucleotidase 3A (NT5C3A)

The protein contains 336 amino acids for an estimated molecular weight of 37948 Da.

 

Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP) (PubMed:24603684). CMP seems to be the preferred substrate (PubMed:15968458). (updated: Jan. 31, 2018)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 89%
Model score: 91

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VariantDescription
P5ND
P5ND; reduced catalytic activity in vitro; reduced protein stability in vivo, probably through increased proteasomal degradation
P5ND
P5ND
P5ND
P5ND; reduced catalytic activity especially towards UMP
P5ND; reduced catalytic activity especially towards UMP
P5ND

The reference OMIM entry for this protein is 266120

Uridine 5-prime monophosphate hydrolase deficiency, hemolytic anemia due to
Hemolytic anemia due to umph1 deficiency
Pyrimidine 5-prime nucleotidase deficiency, hemolytic anemia due to
Hemolytic anemia due to p5n deficiency
P5n deficiency
U

A number sign (#) is used with this entry because hemolytic anemia due to uridine 5-prime monophosphate hydrolase deficiency is caused by homozygous or compound heterozygous mutation in the NT5C3A gene (606224) on chromosome 7p14.

DESCRIPTION

Deficiency of pyrimidine 5-prime nucleotidase, also called uridine 5-prime monophosphate hydrolase, causes an autosomal recessive hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. The enzyme is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties. Hirono et al. (1988) suggested that this deficiency is the third most common RBC enzymopathy--after G6PD (300908) and pyruvate kinase (see 266200) deficiencies--causing hemolysis (summary by Marinaki et al., 2001).

CLINICAL FEATURES

Valentine et al. (1974) showed deficiency of this enzyme in 4 subjects with hereditary hemolytic anemia. Ribosephosphate pyrophosphokinase was severely reduced, probably as an epiphenomenon resulting from inhibition of its synthesis by high concentrations of pyrimidine. Hansen et al. (1983) reported 2 affected Norwegian sibs, the first cases in Scandinavia. The parents were distantly related. The 2 children showed intravascular hemolysis with hemoglobinuria and loss of iron in the urine necessitating iron medication. Ericson et al. (1983) reported 2 affected Norwegian children, a brother and sister, and noted that one of the first families of Valentine et al. (1974) was of Norwegian origin. The disease has, however, been described in many parts of the world. Disturbed synthesis of red cell membrane phospholipids was suggested as being partly responsible for intravascular hemolysis. Energy production was thought to be adequate. Although not separable electrophoretically, 2 P5N isozymes with different substrate specificities are demonstrable by the fact that UMPH1 is lacking in patients with hemolytic anemia, whereas normal UMPH2 activity is retained in these patients; see 191720 (Swallow et al., 1983; Paglia et al., 1984). Hirono et al. (1987) separated the 2 isozymes of P5N chromatographically and studied their biochemical properties from 5 patients with P5N deficiency. They found that P5N-II had normal activity and other normal enzymologic properties, whereas P5N-I from these patients had abnormal properties including reduced activity. They suggested that the main cause of P5N deficiency may be an abnormality of P5N-I, probably arising from a structural gene mutation. De Korte et al. (1989) concluded that analysis of ribonucleotide patterns, in combination with determination of P5N activity, improves the accuracy of diagnosis of heterozygosity. David et al. (1991) demonstrated inhibition of the hexose monophosphate shunt in young erythrocytes by pyrimidine nucleotides.

MOLECULAR GENETICS

In patients with hemolytic anemia due to deficiency of P5N, Marinaki et al. (2001) identified mutations in the UMPH1 gene (606224.0001-606224.0003). In Turkish patients with pyrimidine 5-prime nucleotidase deficiency (266120), Balta et al. (2003) identified homozygous mutations in the UMPH1 gene (606224.0004-606224.0005). ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for NT5C3A

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 266120 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed