Disease relevance of C20orf42

• Transcriptional analysis shows that only URP1 is significantly differentially regulated, being over-expressed in 70% of the colon carcinomas and 60% of the lung carcinomas tested [1].
• Recurrent mutations in kindlin-1, a novel keratinocyte focal contact protein, in the autosomal recessive skin fragility and photosensitivity disorder, Kindler syndrome [2].
• SETTING: The pediatric ICU at Kind Edward VIII Hospital, Durban, South Africa. PATIENTS: HIV-positive cases were classified as "acquired immunodeficiency syndrome," "symptomatic HIV," and "HIV-unrelated diseases." Controls were matched for age, race, gender, severity of disease, and admitting diagnosis [3].
• The heat-stable (70degrees C) acid phosphatase test performed by the method of Kind and King is a simple method for differentiating Mycobacterium kansasii, M. marinum, M. gastri, M. nonchromogenicum, and M. triviale from other slowly growing mycobacteria, and M. fortuitum from other rapidly growing acid-fast bacilli [4].
• In kindlin-1-deficient skin, basal keratinocytes show multiple abnormalities: cell polarity is lost, proliferation is strongly reduced, and several cells undergo apoptosis [5].

Psychiatry related information on C20orf42

• MEASUREMENTS AND MAIN RESULTS: Kind and amount of sedatives and analgesics, duration of administration, and occurrence of withdrawal symptoms [6].
• The projectives reviewed include The Rorschach, The Hand Test, The Thematic Apperception Test (TAT), the Kinetic Family Drawings, Human Figure Drawings, Draw Your Favorite Kind of Day, The Rosebush: A Visualization Strategy, and The House-Tree-Person [7].

High impact information on C20orf42

• Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome [8].
• Kindlerin might be involved in the bidirectional signaling between integrin molecules in the membrane and the cytoskeleton, and could be involved in cell adhesion processes via integrin signaling [9].
• We were unable to identify a mutation in kindlerin in a fifth consanguineous family from Algeria with a similar phenotype and in which the patient was homozygous for the markers in the 20p12.3 interval [9].
• We report the localization to chromosome 20p12.3 by homozygosity mapping and the identification of a new gene, which we propose to name kindlerin [9].
• The kindlerin protein contains several domains which are shared by a diverse group of peripheral membrane proteins that function as membrane-cytoskeleton linkers: two regions homologous to band 4.1 domain of which one includes a FERM domain with a NPKY sequence motif, and a third region with a PH or pleckstrin homology domain [9].

Biological context of C20orf42

• Finally, we have shown that the genomic structure for all three genes is nearly identical with all encoded by 15 exons although URP1 gene localized to chromosome 20p13, URP2 to 11q12 and MIG-2 to 14q22 [1].
• Quantification of URP1 expression by qRT-PCR showed up-regulation of the gene by 60-fold in lung tumors and up to nearly 6-fold in colon tumors [1].
• The presence of multiple FERM domains characteristic of cytoplasmic plasma membrane to cytoskeleton linkers and a PH domain typical of membrane-anchored proteins involved in signal transduction suggest an important role for URP1 in tumorigenesis [1].
• Due to the strong sequence homology to the C. elegans UNC-112 we call this gene URP1, for UNC-112 related protein [1].
• This mutation deletes exons 10 and 11 from the KIND1 mRNA leading to a truncated kindlin-1 [10].

Anatomical context of C20orf42

• Kindlin-1 is considered to be a component in the linkage of the actin cytoskeleton to the extracellular matrix and as such is proposed to have both structural and cell-signalling functions [11].
• Consistent with these biochemical findings, kindlerin is present at focal adhesions, sites of integrin-rich, membrane-substratum adhesion [12].
• The Kindlin-1 (URP1) gene is mutated in Kindler syndrome, the first skin blistering disease affecting actin attachment in basal keratinocytes [13].
• In situ hybridizations showed that Kindlin-1 is preferentially expressed in epithelia, and Kindlin-2 in striated and smooth muscle cells [13].
• Novel KIND1 Gene Mutation in Kindler Syndrome With Severe Gastrointestinal Tract Involvement [14].

Associations of C20orf42 with chemical compounds

• SNP analysis of URP1 reveals that it is highly polymorphic, containing seven sites, four of which are in the coding region and one position that results in the interchangeable substitution of glutamic acid and lysine [1].
• Ribena Tooth Kind [15].
• The theme of Pulling Together included the subthemes of Perpetual Vigilance and Returning to Normalcy, and the third theme of Moving Beyond included the subtheme of An Optimal Unfolding of a New Kind of Consciousness [16].
• This is the contention of Daniel Callahan, who, in his new book, What Kind of Life: The Limits of Medical Progress, calls for a revolution of sorts-a change in the nation's psychological and political foundations [17].
• The results showed that Kind had a slight color change delta E* = -1.72, Trim demonstrated the most color change delta E* = -13.84, while the remaining resins demonstrated a noticeable change in color due to in vitro aging [18].

Physical interactions of C20orf42

• The critical residues in the talin FERM domain that mediate integrin binding show a high degree of conservation in kindlerin [12].

Regulatory relationships of C20orf42

• Immunofluorescence, gene expression and cell biology studies have shown that kindlin-1 is expressed mainly in basal keratinocytes and plays a role in the attachment of the actin cytoskeleton via focal contacts to the extracellular matrix [19].

Other interactions of C20orf42

• Two additional kindlin proteins, kindlin-2 and kindlin-3, have also been described [11].
• URP1: a member of a novel family of PH and FERM domain-containing membrane-associated proteins is significantly over-expressed in lung and colon carcinomas [1].
• One gene up-regulated by TGF-beta was recently named kindlerin (Jobard, F., Bouadjar, B., Caux, F., Hadj-Rabia, S., Has, C., Matsuda, F., Weissenbach, J., Lathrop, M., Prud'homme, J. F., and Fischer, J. (2003) Hum. Mol. Genet. 12, 925-935) [12].
• Furthermore, kindlerin is recruited into a molecular complex with the beta1A and beta3 integrin cytoplasmic domains [12].
• While both localize to integrin-mediated adhesion sites in cultured keratinocytes Kindlin-2, but not Kindlin-1, colocalizes with E-cadherin to cell-cell contacts in differentiated keratinocytes [13].

Analytical, diagnostic and therapeutic context of C20orf42

• Northern blot analysis of URP1 indicates that normal expression is restricted to neuromuscular tissues [1].
• TGF-beta stimulation of HMEC resulted in a marked induction of kindlerin RNA, and Western blotting demonstrated a corresponding increase in protein abundance [12].
• Dr. Bass felt that his "Right Kind" method of oral hygiene was not well received by the dental profession [20].
• The recent finding of KIND1 mutations in Kindler syndrome facilitates early diagnosis, prophylactic measures and more precise definition of the phenotype [21].
• Report on the international workshop of the Kind Philipp Foundation on late effects after bone marrow transplantation in childhood malignancies [22].

References