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Gene Review

PNN  -  pinin, desmosome associated protein

Homo sapiens

Synonyms: 140 kDa nuclear and cell adhesion-related phosphoprotein, DRS, DRS protein, DRSP, Desmosome-associated protein, ...
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Disease relevance of PNN


Psychiatry related information on PNN

  • No associations were found between the psychometric data and measures of PIP and MEMA leakage from REM into NREM [4].
  • Correlations with psychometric test data showed PIP rate in REM to be related to the psychoticism scale of the Minnesota Multiphasic Personality Inventory and MEMA rate in REM to be inversely related to the Barron Ego Strength scale [4].
  • In this study, we evaluated the correlation of patients' scores on Mattis' Dementia Rating Scale (DRS; total and subscale scores) with scores on the Medication Management Ability Assessment (MMAA), a performance-based measure of medication management [5].
  • Older adults with epilepsy who were receiving antiepileptic drug (AED) polytherapy (n=11) displayed worse performance on the attention, initiation/perseveration, and memory subscales of the DRS and Logical Memory delayed recall score compared with those older adults with epilepsy receiving monotherapy (n=14) [6].
  • The Dementia Rating Scale (DRS; Mattis, 1976, 1988) is commonly used in the assessment of dementia, although little is known about the relationship of performance on this test to specific cognitive deficits in Alzheimer's disease (AD) [7].

High impact information on PNN

  • We have identified a protein named pinin that is associated with the mature desmosomes of the epithelia (Ouyang, P., and S.P. Sugrue. 1992. J. Cell Biol. 118:1477-1488) [8].
  • Expression of the full-length cDNA clones in human 293 cells and monkey COS-7 cells demonstrated that a 140-kD immunoreactive species on Western blots corresponded to pinin [8].
  • Therefore, pinin may play a significant role in reinforcing the intermediate filament-desmosome complex. cDNA clones coding for pinin were identified, using degenerative oligonucleotide probes that were based on the internal amino acid sequence of pinin for the screening of a cDNA library [8].
  • Immunofluorescence staining revealed that the expressed pinin protein was assembled to the lateral boundaries of the cells in contact, which is consistent with the staining pattern of pinin in epithelial cells [8].
  • We suggest that the function of pinin is to pin intermediate filaments to the desmosome [8].

Chemical compound and disease context of PNN

  • The probability of hyperplasia was 0.060 (95% CI, 0.043-0.078) for the E(2) monotherapy group, 0.007 for the 2-mg DRSP/E(2) group, and nonsignificant for the remaining drospirenone/estradiol groups.Endometrial bleeding decreased in all treatment groups over time [9].
  • DRSP also prevented hypertension and fetal growth retardation in pregnant rats after L-NAME, an inhibitor of nitric oxide synthase [10].
  • My last three trials were a trial of photocoagulation in diabetic retinopathy (DRS), a six-country trial of the antiarrhythmic drug mexiletine (IMPACT), and a study involving two diagnostic procedures for pulmonary embolism (PIOPED) [11].
  • A similar improvement in skin condition (acne, seborrhea) was observed in women receiving EE/DRSP or ethinylestradiol 35microg/cyproterone acetate 2mg in a randomized, double-blind trial [12].
  • A significant and consistent weight loss was seen with DRSP/EE compared to a reference preparation containing desogestrel [13].

Biological context of PNN


Anatomical context of PNN


Associations of PNN with chemical compounds

  • From our results we conclude that this nuclear protein, characterized by a domain exceptionally rich in serine residues and hence termed DRS-protein, occurs in at least two genetically different forms in a diffusible state as well as in special ribonucleoprotein-particles, "speckles" [6], and is a widespread if not ubiquitous nuclear protein [21].
  • In this study, a collection of quinolone and quinoline derivatives' carcinogenicity is determined by qualitatively predicting their genotoxicity potential with predictive PNN (probabilistic neural network) classification models [22].
  • DFT calculations (B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d,p)) are used to evaluate the bonding, ground-state structures, and energy landscape for the different isomers of 3: the thermodynamics and kinetics of the successive elimination of chlorotrimethylsilane (TMS-Cl) resulting in the formation of covalent azide analogues such as TMS-PNN or TMS-NNP [23].
  • The solution NMR spectroscopic and X-ray crystallographic studies are indicative of a trigonal bipyramidal geometry for these aluminium complexes in which the amino nitrogen atom is trans to the phosphorus donor of the [PNN](-) ligand [24].
  • Electron-rich, bulky PNN-type ruthenium complexes: synthesis, characterization and catalysis of alcohol dehydrogenation [25].

Physical interactions of PNN

  • Nuclear Pnn/DRS protein binds to spliced mRNPs and participates in mRNA processing and export via interaction with RNPS1 [26].
  • The SR-like trans-acting splicing factor Htra2-beta1 was shown to interact with this ESE and to restore full-length SMN2 expression in vivo in a concentration-dependent manner [27].

Other interactions of PNN

  • Here we identify that SR-cyp, a Moca family of nuclear cyclophilin, interacts and colocalizes with nuclear pinin (pnn), a SR-related protein involving in pre-mRNA splicing [28].
  • The alignment of the pinin gene with STS markers localized the gene to the previously identified TS locus D14S75-D14S288 [1].
  • memA/DRS, a putative mediator of multiprotein complexes, is overexpressed in the metastasizing human melanoma cell lines BLM and MV3 [2].
  • MEMA is also homologous to pinin, a 140 kDa protein associated with the desmosome-intermediate filament complex, and to a 32 kDa porcine neutrophilic protein that was copurified with components of the NADPH-oxidase enzyme complex [2].
  • The SR-like splicing factor Htra2-beta1 facilitates correct splicing of SMN2 exon 7 through direct interaction with an exonic splicing enhancer within exon 7 [29].

Analytical, diagnostic and therapeutic context of PNN

  • Immunofluorescence analysis, using the antifusion protein antibody, demonstrated pinin at lateral epithelial boundaries, which is consistent with desmosomal localization [8].
  • Dissection of protein linkage between keratins and pinin, a protein with dual location at desmosome-intermediate filament complex and in the nucleus [15].
  • This protein, referred to as pNO40 based on its molecular weight on SDS-PAGE, was identified through yeast two hybrid interaction screen of a human kidney cDNA library using pinin (pnn) protein as the bait [30].
  • Expression of memA mRNA is elevated in the highly metastasizing human melanoma cell lines and derived xenografts, as compared with the non-metastasizing ones [2].
  • Sequence analysis revealed that the MEMA protein is identical with a 160 kDa nuclear 'domain rich in serines' (DRS) protein occurring free in the nucleoplasm and in U2-ribonucleoprotein structures [2].


  1. Characterization of the gene encoding pinin/DRS/memA and evidence for its potential tumor suppressor function. Shi, Y., Ouyang, P., Sugrue, S.P. Oncogene (2000) [Pubmed]
  2. memA/DRS, a putative mediator of multiprotein complexes, is overexpressed in the metastasizing human melanoma cell lines BLM and MV3. Degen, W.G., Agterbos, M.A., Muyrers, J.P., Bloemers, H.P., Swart, G.W. Biochim. Biophys. Acta (1999) [Pubmed]
  3. The pathogenic effect of IgG4 autoantibodies in endemic pemphigus foliaceus (fogo selvagem). Rock, B., Martins, C.R., Theofilopoulos, A.N., Balderas, R.S., Anhalt, G.J., Labib, R.S., Futamura, S., Rivitti, E.A., Diaz, L.A. N. Engl. J. Med. (1989) [Pubmed]
  4. Phasic events of REM sleep: phenomenology of middle ear muscle activity and periorbital integrated potentials in the same normal population. Benson, K., Zarcone, V.P. Sleep. (1979) [Pubmed]
  5. Cognitive predictors of medication adherence among middle-aged and older outpatients with schizophrenia. Jeste, S.D., Patterson, T.L., Palmer, B.W., Dolder, C.R., Goldman, S., Jeste, D.V. Schizophr. Res. (2003) [Pubmed]
  6. Cognitive functioning in community dwelling older adults with chronic partial epilepsy. Martin, R.C., Griffith, H.R., Faught, E., Gilliam, F., Mackey, M., Vogtle, L. Epilepsia (2005) [Pubmed]
  7. Association between Dementia Rating Scale performance and neurocognitive domains in Alzheimer's disease. Knox, M.R., Lacritz, L.H., Chandler, M.J., Munro Cullum, C. The Clinical neuropsychologist. (2003) [Pubmed]
  8. Characterization of pinin, a novel protein associated with the desmosome-intermediate filament complex. Ouyang, P., Sugrue, S.P. J. Cell Biol. (1996) [Pubmed]
  9. Long-term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind, multicenter trial. Archer, D.F., Thorneycroft, I.H., Foegh, M., Hanes, V., Glant, M.D., Bitterman, P., Kempson, R.L. Menopause (New York, N.Y.) (2005) [Pubmed]
  10. Conception and pharmacodynamic profile of drospirenone. Elger, W., Beier, S., Pollow, K., Garfield, R., Shi, S.Q., Hillisch, A. Steroids (2003) [Pubmed]
  11. Varied acceptance of clinical trial results. Klimt, C.R. Controlled clinical trials. (1989) [Pubmed]
  12. Ethinylestradiol/drospirenone: a review of its use as an oral contraceptive. Keam, S.J., Wagstaff, A.J. Treatments in endocrinology. (2003) [Pubmed]
  13. Yasmin: the reason why. Thorneycroft, I.H. The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception. (2002) [Pubmed]
  14. Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. Alpatov, R., Munguba, G.C., Caton, P., Joo, J.H., Shi, Y., Shi, Y., Hunt, M.E., Sugrue, S.P. Mol. Cell. Biol. (2004) [Pubmed]
  15. Dissection of protein linkage between keratins and pinin, a protein with dual location at desmosome-intermediate filament complex and in the nucleus. Shi, J., Sugrue, S.P. J. Biol. Chem. (2000) [Pubmed]
  16. Desmosome signaling. Inhibition of p38MAPK prevents pemphigus vulgaris IgG-induced cytoskeleton reorganization. Berkowitz, P., Hu, P., Liu, Z., Diaz, L.A., Enghild, J.J., Chua, M.P., Rubenstein, D.S. J. Biol. Chem. (2005) [Pubmed]
  17. Modulation of alternative pre-mRNA splicing in vivo by pinin. Wang, P., Lou, P.J., Leu, S., Ouyang, P. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  18. Reduction of Pnn by RNAi induces loss of cell-cell adhesion between human corneal epithelial cells. Joo, J.H., Alpatov, R., Munguba, G.C., Jackson, M.R., Hunt, M.E., Sugrue, S.P. Mol. Vis. (2005) [Pubmed]
  19. Tyrosine-phosphorylated plakoglobin is associated with desmogleins but not desmoplakin after epidermal growth factor receptor activation. Gaudry, C.A., Palka, H.L., Dusek, R.L., Huen, A.C., Khandekar, M.J., Hudson, L.G., Green, K.J. J. Biol. Chem. (2001) [Pubmed]
  20. Antibodies differentiate desmosome-form and nucleus-form pinin: evidence that pinin is a moonlighting protein with dual location at the desmosome and within the nucleus. Ouyang, P. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  21. Evidence that "pinin", reportedly a differentiation-specific desmosomal protein, is actually a widespread nuclear protein. Brandner, J.M., Reidenbach, S., Franke, W.W. Differentiation (1997) [Pubmed]
  22. Probabilistic neural network multiple classifier system for predicting the genotoxicity of quinolone and quinoline derivatives. He, L., Jurs, P.C., Kreatsoulas, C., Custer, L.L., Durham, S.K., Pearl, G.M. Chem. Res. Toxicol. (2005) [Pubmed]
  23. Mono-, di-, and tricoordinated phosphorus attached to a N-N unit: an experimental and theoretical study. Fischer, G., Herler, S., Mayer, P., Schulz, A., Villinger, A., Weigand, J.J. Inorganic chemistry. (2005) [Pubmed]
  24. Organoaluminium complexes incorporating an amido phosphine chelate with a pendant amine arm. Lee, W.Y., Liang, L.C. Dalton transactions (Cambridge, England : 2003) (2005) [Pubmed]
  25. Electron-rich, bulky PNN-type ruthenium complexes: synthesis, characterization and catalysis of alcohol dehydrogenation. Zhang, J., Gandelman, M., Shimon, L.J., Milstein, D. Dalton transactions (Cambridge, England : 2003) (2007) [Pubmed]
  26. Nuclear Pnn/DRS protein binds to spliced mRNPs and participates in mRNA processing and export via interaction with RNPS1. Li, C., Lin, R.I., Lai, M.C., Ouyang, P., Tarn, W.Y. Mol. Cell. Biol. (2003) [Pubmed]
  27. Exclusion of Htra2-beta1, an up-regulator of full-length SMN2 transcript, as a modifying gene for spinal muscular atrophy. Helmken, C., Wirth, B. Hum. Genet. (2000) [Pubmed]
  28. Over-expression of SR-cyclophilin, an interaction partner of nuclear pinin, releases SR family splicing factors from nuclear speckles. Lin, C.L., Leu, S., Lu, M.C., Ouyang, P. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  29. Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-beta1. Helmken, C., Hofmann, Y., Schoenen, F., Oprea, G., Raschke, H., Rudnik-Schöneborn, S., Zerres, K., Wirth, B. Hum. Genet. (2003) [Pubmed]
  30. Molecular characterization of a novel nucleolar protein, pNO40. Chang, W.L., Lee, D.C., Leu, S., Huang, Y.M., Lu, M.C., Ouyang, P. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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