Disease relevance of MINPP1

• Somatic mutation and germline variants of MINPP1, a phosphatase gene located in proximity to PTEN on 10q23.3, in follicular thyroid carcinomas [1].
• We show here that the ATDC5 chondrocyte progenitor cell line can recapitulate developmentally specific changes in MINPP expression previously only seen in longitudinal bone growth plates-both an initial 2-3-fold increase and a subsequent decrease back to initial levels during transition to hypertrophy [2].

High impact information on MINPP1

• We have determined the order of human BAC clones at the hPTEN locus and that the locus contains hPAPSS2 and hMINPP1 genes oriented as are their Fugu orthologs [3].
• Because of this overlapping function with PTEN and the physical location of MINPP1 to a region with frequent LOH in follicular thyroid tumors, we considered it to be an excellent candidate gene that could contribute to the pathogenesis of follicular thyroid tumors [1].
• These results suggest a role for MINPP1 in the pathogenesis of at least a subset of malignant follicular thyroid tumors, and MINPP1 might act as a low penetrance predisposition allele for FTC [1].
• We analyzed DNA from tumor and corresponding normal tissue from 23 patients with FA and 15 patients with FTC for LOH and mutations at the MINPP1 locus [1].
• Because functional anatomic pattern of encoding and retrieval activation that defines the HIPER model was unprecedented and unexpected, it is difficult to relate the model to what is already known or thought about functional neuroanatomy of episodic memory in the hippocampal regions [4].

Biological context of MINPP1

• The latter observation provides a context for proposing that MIPP may aid bone mineralization and salvage the inositol moiety prior to apoptosis [5].
• The amino acid sequences of the murine and human MINPP proteins share >80% identity with the rat enzyme and >56% identity with HiPER1, with conservation of the C-terminal consensus sequence that retains proteins in the endoplasmic reticulum [6].
• We demonstrate that the rate of hydrolysis of InsP(6) by recombinant avian MINPP (0.7mumol/mg protein/min) defines it as by far the most active phytase found to date in any animal cell (the corresponding activity of recombinant mammalian MINPP is only 0.006mumol/mg protein/min) [7].
• Although avian MINPP has less than 20% sequence identity with microbial phytases, we create a homology model of MINPP in which it is predicted that the structure of the phytase active site is well-conserved [7].

Anatomical context of MINPP1

• In a model chicken cell line, we overexpressed a mutant form of MINPP that is secretion-competent [7].

Associations of MINPP1 with chemical compounds

• 3. MINPP1 has the ability to remove 3-phosphate from inositol phosphate substrates, a function that overlaps that of PTEN [1].
• Sequence analysis of plant and fruit fly MINPP homologs supports the hypothesis that the MINPP enzymes constitute a distinct evolutionary group within the histidine phosphatase family [6].

Analytical, diagnostic and therapeutic context of MINPP1

• This model is validated by site-directed mutagenesis and by use of a substrate analogue, scyllo-InsP(6), which we demonstrate is only a weak MINPP substrate [7].

References