Multiple Inositol Polyphosphate Phosphatase: Evolution as a Distinct Group within the Histidine Phosphatase Family and Chromosomal Localization of the Human and Mouse Genes to Chromosomes 10q23 and 19

Chi, Hongbo; Tiller, George E.; Dasouki, Majed; Romano, P. R.; Wang, Jun; O’Keefe, Regis J.; Puzas, J. Edward; Rosier, Randy N.; Reynolds, Paul

doi:10.1006/geno.1998.5736

Cited by 44 publications

(54 citation statements)

References 57 publications

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“…37,38 Since Htr1a is a G-protein-coupled receptor, it is of interest that a G-protein b subunit is one of the few human protein for which a regulatory role of N-linked phosphorylation has been described. [39][40][41][42][43] LHPP does not share meaningful sequence homology with either of the identified human phosphoamidases, 44,45 although these also are not homologous to each other. Among human proteins, Lhpp shares close sequence homology only with Hdhd2, also of undetermined function (Supplementary Figure S1).…”

Section: Discussionmentioning

confidence: 99%

Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

et al. 2008

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The HTR1A À1019C > G genotype was associated with major depression in the Utah population. Linkage analysis on Utah pedigrees with strong family histories of major depression including only cases with the HTR1A À1019G allele revealed a linkage peak on chromosome 10 (maximum HLOD = 4.4). Sequencing of all known genes in the linkage region revealed disease-segregating single-nucleotide polymorphisms (SNPs) in LHPP. LHPP SNPs were also associated with major depression in both Utah and Ashkenazi populations. Consistent with the linkage evidence, LHPP associations depended on HTR1A genotype. Lhpp or a product of a collinear brain-specific transcript, therefore, may interact with Htr1a in the pathogenesis of major depression.

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Section: Discussionmentioning

confidence: 99%

Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

et al. 2008

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“…First, two of the predicted avian MINPP active site residues (H69, H332, Fig. 2) are conserved in mammalian MINPPs; earlier studies showed that these residues are catalytically essential (Chi et al, 1999;Caffrey et al, 1999). Second, studies with phytases (Kostrewa et al, 1997) have shown the importance to catalysis of three other residues that are conserved in the MINPP active site (R68, R72, R156; Fig.…”

Section: Verification Of the Homology Modelmentioning

confidence: 98%

“…It is difficult to obtain high yields of pure recombinant MINPP by heterologous expression in either E. coli (Chi et al, 1999;Caffrey et al, 1999) or in insect cells (data not shown); this has previously hindered detailed MINPP studies. We have now expressed avian MINPP (Romano et al, 1998) in the methylotrophic yeast, P. pastoris, with the addition of a C-terminal poly [His] epitope tag (Fig.…”

Section: Expression and Characterization Of Recombinant Avian Minppmentioning

confidence: 99%

“…Animal cells do contain InsP 6 (Shears, 2001), and an InsP 6 -phosphatase, namely, the multiple inositol polyphosphate phosphatase, or MINPP (Craxton et al, 1997;Chi et al, 1999). However, mammalian MINPP has very weak activity against InsP 6 .…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, phytases from a range of micro-organisms have between 10 3 -fold and 10 4 -fold higher specific activities (Wyss et al, 1999a;Mullaney et al, 2002). Furthermore, phylogenetic analysis (Chi et al, 1999) has indicated that MINPP is not a close relative of genuine phytases. Thus, there is a consensus in the recent literature that animal cells do not contain enzymes that are physiologically active and specific phytases (Lei and Porres, 2003;Mullaney and Ullah, 2003;Simon and Igbasan, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Avian multiple inositol polyphosphate phosphatase is an active phytase that can be engineered to help ameliorate the planet's “phosphate crisis”

Cho

Choi

Darden

et al. 2006

Journal of Biotechnology

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Contemporary phytase research is primarily concerned with ameliorating the problem of inadequate digestion of inositol hexakisphosphate (phytate; InsP 6 ) in monogastric farm animal feed, so as to reduce the pollution that results from the high phosphate content of the manure. In the current study we pursue a new, safe and cost-effective solution. We demonstrate that the rate of hydrolysis of InsP 6 by recombinant avian MINPP (0.7 μmol/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 0.006 μmol/mg protein/min). 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. 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. In a model chicken cell line, we overexpressed a mutant form of MINPP that is secretion-competent. This version of the enzyme was actively secreted without affecting either cell viability or the cellular levels of any inositol phosphates. Our studies offer a genetic strategy for greatly improving dietary InsP 6 digestion in poultry.

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Fine‐structure deletion mapping of 10q22–24 identifies regions of loss of heterozygosity and suggests that sporadic follicular thyroid adenomas and follicular thyroid carcinomas develop along distinct neoplastic pathways

Yeh

Marsh

Zedenius

et al. 1999

Genes Chromosomes & Cancer

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Previous studies have demonstrated frequent loss of heterozygosity (LOH) of markers on chromosome arm 10q in both follicular thyroid carcinomas (FTCs) and follicular thyroid adenomas (FAs). A novel tumor suppressor gene, PTEN, has been mapped to 10q23.3 and is the susceptibility gene for Cowden syndrome, an autosomal dominant disorder characterized by multiple hamartomas and a risk of benign and malignant tumors of the breast and thyroid. Studies examining the relationship of somatic PTEN status and follicular thyroid neoplasms have only demonstrated a variable subset of tumors that have somatic monoallelic deletions of PTEN, suggesting that other tumor suppressor genes may be present in this region. We therefore sought to conduct a detailed examination of LOH of 20 polymorphic markers in a 19‐cM region spanning 10q22–24, including PTEN, in 44 FAs and 17 FTCs. Using this fine‐structure somatic mapping approach, we defined at least two novel regions of LOH in follicular adenomas and follicular carcinomas, suggesting the presence of at least two distinct tumor suppressor genes that may play a role in thyroid neoplasia. Furthermore, the difference in patterns of LOH in adenomas versus carcinomas lends additional support to the hypothesis that adenomas and carcinomas can develop along two separate, nonserial pathways. Genes Chromosomes Cancer 26:322–328, 1999. © 1999 Wiley‐Liss, Inc.

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Multiple Inositol Polyphosphate Phosphatase: Evolution as a Distinct Group within the Histidine Phosphatase Family and Chromosomal Localization of the Human and Mouse Genes to Chromosomes 10q23 and 19

Cited by 44 publications

References 57 publications

Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

Avian multiple inositol polyphosphate phosphatase is an active phytase that can be engineered to help ameliorate the planet's “phosphate crisis”

Fine‐structure deletion mapping of 10q22–24 identifies regions of loss of heterozygosity and suggests that sporadic follicular thyroid adenomas and follicular thyroid carcinomas develop along distinct neoplastic pathways

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