Multiple inositol polyphosphate phosphatase 1 (MINPP1)

The protein contains 487 amino acids for an estimated molecular weight of 55051 Da.

 

Acts as a phosphoinositide 5- and phosphoinositide 6-phosphatase and regulates cellular levels of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). Also acts as a 2,3-bisphosphoglycerate 3-phosphatase, by mediating the dephosphorylation of 2,3-bisphosphoglycerate (2,3-BPG) to produce phospho-D-glycerate without formation of 3-phosphoglycerate. May play a role in bone development (endochondral ossification). May play a role in the transition of chondrocytes from proliferation to hypertrophy (By similarity). (updated: Nov. 22, 2017)

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. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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: 0%
Model score: 0
No model available.

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VariantDescription
NMTC2
NMTC2

The reference OMIM entry for this protein is 605391

Multiple inositol polyphosphate phosphatase 1; minpp1
Mipp, rat, homolog of
Hiper1, chicken, homolog of

DESCRIPTION

MINPP1 hydrolyzes the abundant metabolites inositol pentakisphosphate and inositol hexakisphosphate and, like PTEN (601728), has the ability to remove 3-phosphate from inositol phosphate substrates.

CLONING

In addition to inositol triphosphate, an important second messenger in eukaryotic cells, there are a number of inositol polyphosphates, as well as enzymes that affect their metabolism, that play a role in signaling activity. The rat enzyme Mipp removes polyphosphate groups from a number of inositol polyphosphates that contain at least 4 phosphates. The chick gene HiPER1 (histidine phosphatase of the endoplasmic reticulum), a homolog of Mipp, is expressed strongly in growth plate chondrocytes transiting from proliferation to hypertrophy. By searching an EST database with rat Mipp as the probe, Caffrey et al. (1999) identified a cDNA encoding human MINPP1, which they called MIPP. Sequence analysis predicted that the 487-amino acid MINPP1 protein is 84% identical to rat Mipp and about 53% identical to chick HiPER1. The N terminus of MINPP1 contains an ER-targeting domain consisting of a relatively long net-positive-charge (n) region, a hydrophobic core region, and a recognition site for signal peptidases. Because of the 13-amino-acid-long n region, Caffrey et al. (1999) suggested that translocation of MINPP1 to the ER may not require TRAM (605190), which is needed for proteins with short (5 residues or less) n regions. MINPP1 catalytic activity appears to require sequences in the C terminus. Western blot analysis demonstrated that MINPP1 is expressed as an approximately 51-kD protein. Northern blot analysis detected a 2.5-kb MINPP1 transcript in all tissues tested except for peripheral blood leukocytes; highest expression was detected in kidney, liver, and placenta. In situ hybridization analysis showed that Minpp1 is expressed much more intensely in hypertrophic than in proliferating or resting rat chondrocytes. By RT-PCR, RACE, and library screening, Chi et al. (1999) identified a cDNA encoding MINPP1. Northern blot analysis detected a 2.6-kb MINPP1 transcript in HeLa cells and human chondrocytes. The authors noted that the C-terminal ER-retention signal is conserved between chick, rat, and human MINPP1 sequences. Functional analysis showed that mouse Minpp1 converts inositol tetrakisphosphate to inositol triphosphate.

MAPPING

Using FISH, radiation hybrid analysis, and YAC screening, Chi et al. (1999) mapped the MINPP1 gene to 10q23, proximal to the tumor suppressor PTEN (601728), in a region that is frequently mutated in cancer. By radiation hybrid analysis, Chi et al. (1999) mapped the mouse Minpp1 gene to chromosome 19, also in proximity to Pten.

ANIMAL MODEL

Chi et al. (2000) used homologous recombination to generate Minpp1-deficient mice. They observed that these mice were fertile, lacked obvious defects, and had normal chondrocyte differentiation. An increase in levels of cytosolic inositol polyphosphates was reversible by the introduction of Minpp1 to the ER, showing that ER-based Minpp1 plays a role in the maintenance of steady-state levels of these polyphosphates. In contrast, introduction into the cytosol of truncated Minpp1 lacking the ER-targeting domain reduced the polyphosphates to below their natural levels and was accompanied by slowed cellular proliferation.

MOLECULAR GENETICS

Germline mutations in the tumor suppressor gene PTEN, which encodes a dual-s ... 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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605391 was added.