Diphosphoinositol polyphosphate phosphohydrolase 2 (NUDT4)

The protein contains 180 amino acids for an estimated molecular weight of 20306 Da.

 

Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis of dinucleoside oligophosphate Ap6A, but not Ap5A. The major reaction products are ADP and p4a from Ap6A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA. (updated: March 4, 2015)

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.

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 96%
Model score: 84
MODL_MODELLER-9.18

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No binding partner found

The reference OMIM entry for this protein is 609229

Nucleoside diphosphate-linked moiety x motif 4; nudt4
Nudix motif 4
Diphosphoinositol polyphosphate phosphohydrolase 2; dipp2
Kiaa0487

DESCRIPTION

Members of the DIPP subfamily of Nudix proteins, such as NUDT4, hydrolyze specific diphosphoinositol polyphosphates and diadenosine polyphosphates (Caffrey et al., 2000).

CLONING

By searching an EST database for sequences similar to NUDT3 (609228), followed by PCR of heart and fetal kidney cDNA libraries, Caffrey et al. (2000) obtained cDNA clones encoding 2 splice variants of NUDT4, which they designated DIPP2-alpha and DIPP2-beta. The DIPP2 transcripts use several alternate polyadenylation signals. The 5-prime UTRs have a high GC content, and the longer 3-prime UTRs contain Alu repeats. DIPP2-alpha and DIPP2-beta encode proteins of 180 and 181 amino acids, respectively; an additional CAG codon in the DIPP2-beta transcript results in an insertion of gln86. Both proteins contain a central Nudix motif, followed by a gly-rich extension (GxxGxxxxxxG) characteristic of DIPP-type hydrolases. Northern blot analysis detected transcripts of 1.5 and 1.8 kb in skeletal muscle, kidney, placenta, and pancreas. A 4.2-kb transcript was detected in heart, skeletal muscle, kidney, and pancreas, with weaker expression in brain, placenta, lung, and liver. By PCR analysis, Caffrey and Shears (2001) found that both DIPP2-alpha and DIPP2-beta were expressed in a human leukemia cell line and in an adenocarcinoma cell line. They determined that the 2 transcripts result from alternative splicing at an AGCAG pentamer that offers adjacent, alternate intronic 3-prime borders.

GENE FUNCTION

Caffrey et al. (2000) determined that purified recombinant DIPP2-alpha hydrolyzed the beta phosphate from diphosphoinositol pentakisphosphate (PP-InsP5) and PP-tetrakisphosphate (PP-InsP4). DIPP2-alpha showed high affinity for PP-InsP5. Recombinant DIPP2-beta was 5-fold less active against PP-InsP5 and 2.5-fold less active against PP-InsP4 than DIPP2-alpha. Both enzymes also hydrolyzed diadenosine hexaphosphate. DIPP2-beta showed activity against diadenosine pentaphosphate, but DIPP2-alpha did not.

GENE STRUCTURE

Caffrey and Shears (2001) determined that the NUDT4 gene contains 4 exons.

MAPPING

By Southern blot analysis, radiation hybrid analysis, and FISH, Caffrey and Shears (2001) mapped the NUDT4 gene to chromosome 12q21. They identified 2 intronless NUDT4 pseudogenes on chromosome 1. ... More on the omim web site

Subscribe to this protein entry history

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 16, 2016: Protein entry updated
Automatic update: OMIM entry 609229 was added.