The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

GCA  -  grancalcin, EF-hand calcium binding protein

Homo sapiens

Synonyms: GCL, Grancalcin
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GCA

  • The aims of the present study were: a) to assess whether plasma AM levels are abnormal in patients with polymyalgia rheumatica and giant cell arteritis (PMR and GCA) and b) to investigate if this parameter is related to clinical and biochemical indicators of disease activity in these patients [1].
  • CONCLUSION: Plasma levels of AM are elevated in patients with active GCA and correlate with parameters that reflect the acute phase response [1].
  • In contrast, we propose that the domain for selecting the corner of the tRNA L shape diverged early, after the separation between E. coli and yeast, while that for selecting the GCA-containing anticodon loop diverged late, after the separation between yeast and human [2].
  • Giant cell (temporal, cranial) arteritis (GCA) is usually confirmed in patients presenting with classic features [3].
  • We describe herein 2 patients with biopsy-proven GCA who presented with severe anemia and significant weight loss, which corrected after corticosteroid therapy [3].

High impact information on GCA

  • One substitution was in codon 191, ACA (threonine) rather than GCA (alanine), and the other was in codon 283, TTT (phenylalanine) instead of TTG (leucine) [4].
  • Six different flanking codons starting with G (GCG, GCU, GCC, GCA, GAU and GGA) strongly augmented selection of AUG#1 when compared with matched mRNAs that had A or C instead of G in position +4 [5].
  • In separate studies, we have also established that the GCA triplet does not form bimolecular (GCA)2 motifs but instead promotes the formation of hairpins containing a GCA-turn motif in which the loop contains a single cytidine closed by a sheared G.A pair [6].
  • The GCA hairpin loop consists of a single cytidine residue closed by a sheared G.A pair and this structure is discussed in the context of triplet expansions in triplet-repeat diseases [7].
  • A transition at the last nucleotide of exon 9 (1269GCG --> GCA) was found in a Japanese PK variant, PK 'Kamata.' The mutation did not alter the amino acid sequence, but caused skipping of the ninth exonic sequence in the R-PK transcripts [8].

Chemical compound and disease context of GCA

  • In cell-free protein synthesis studies with RNA from phage MS2 as template, normal Escherichia coli tRNASer3 promotes two base translocation at GCA alanine codons with a resultant shift of ribosomes to the minus one reading frame [9].
  • OBJECTIVE: To assess the risk of lymphoma associated with steroid treatment of GCA/PMR [10].
  • A codon 146 mutation substituting threonine (ACA) for alanine (GCA) was detected in the tumor tissue of a patient with colon cancer and was not detected in the normal tissue of the same patient [11].
  • E. coli tRNA(Ala) has a VGC anticodon (V is 5-oxyacetic acid uridine) while tRNA(Cys) has the complementary GCA anticodon with a modified adenine on the 3' side, namely 2-methylthio N6-isopentenyl adenine (mS2i6A37) in E [12].
  • The three laboratory investigations were, therefore, of limited value in confirming relapses of PMR/GCA during prednisolone treatment, but alpha 1-ACT may be useful as an indicator of underlying disease activity and hence as a guide to the speed that the prednisolone dosage should be reduced [13].

Biological context of GCA

  • Subsequently five further genotypes with additional GCA- and GCG-trinucleotides were identified in single OPMD patients [14].
  • Within the PMR/GCA group with active disease, AM plasma levels were positively correlated with ESR (r = 0.6, p = 0.02), and negatively with hematocrit (r = -0.57, p = 0.03) and hemoglobin (r = -0.55, p = 0.04) [1].
  • A novel EF-hand Ca(2+)-binding protein we have called grancalcin has been identified and characterized [15].
  • Analysis of the DNA sequences upstream from CRY1 revealed the presence of three sequences, HOMOL1 (consensus, A/TACATCC/TG/ATA/GCA), RPG (consensus, ACCCA/GTACATT/CT/A), and a thymine-rich sequence, found upstream of more than 20 other cloned yeast genes encoding components of the translational apparatus [16].
  • Here we report studies of the binding site selectivity of I-BABP for glycocholic (GCA) and glycochenodeoxycholic (GCDA) acids using isotope-enriched bile salts along with two-dimensional heteronuclear NMR methods [17].

Anatomical context of GCA


Associations of GCA with chemical compounds

  • Systematic testing of the heterodimerization abilities of the PEF proteins using the yeast two-hybrid and glutathione S-transferase pull-down assays revealed the new finding that grancalcin interacts strongly with sorcin [19].
  • Twelve patients (9 PMR and 3 GCA) were studied when they had active disease before any steroid therapy and the remaining 5 patients (2 PMR and 3 GCA) were in complete clinical remission and no longer receiving steroid treatment [1].
  • Here, the structure of a truncated form of grancalcin, which is lacking 52 N-terminal residues, in the presence and absence of Ca(2+) is presented [21].
  • These corresponded to two previously identified polymorphisms [Gly971 --> Arg (GGG --> AGG) and Ala804 (GCA --> GCG)] as well as five novel polymorphisms [Pro190 --> Arg (CCC --> CGC), Met209 --> Thr (ATG --> ACG), Ser809 --> Phe (TCT --> TTT), Leu142 (CTT --> CTC), and Gly625 (GGC --> GGT)] [22].
  • Translation of the UGA codon by tRNA sub GCA sup Cys necessitates a G:A mispairing in the first anticodon position [20].

Physical interactions of GCA

  • Our recent finding that grancalcin interacts with L-plastin, a protein known to have actin bundling activity, suggests that grancalcin may play a role in regulation of adherence and migration of neutrophils [23].
  • Thus, GCA resembles galectin-3 in its binding characteristics but is likewise related to galectin-1 by sequence homology of its primary structure and by the molecular mass of its subunits [24].

Other interactions of GCA

  • This was substantiated by co-immunoprecipitation of grancalcin by anti-L-plastin antibodies and vice versa [18].
  • We found that both native and recombinant grancalcin always exists as a homodimer, regardless of the Ca(2+) load [18].
  • The PEF family proteins sorcin and grancalcin interact in vivo and in vitro [19].
  • This observation supports the hypothesis, formulated on the basis of the structure of a homologous protein ALG-2 which shows significant differences in the orientation of EF4 and EF5 compared with grancalcin, that calcium is a necessary factor but not sufficient alone for inducing a significant conformational change in PEF proteins [21].
  • Isolation and characterization of grancalcin, a novel 28 kDa EF-hand calcium-binding protein from human neutrophils [25].

Analytical, diagnostic and therapeutic context of GCA

  • By affinity chromatography of solubilized human neutrophils on immobilized grancalcin, L-plastin, a leukocyte-specific actin-bundling protein, was found to interact with grancalcin in a negative Ca(2+)-dependent manner [18].
  • RESULTS: Plasma AM concentration was significantly higher in patients with active GCA compared to the control group (p < 0.05) and with patients with isolated PMR (p < 0.05) [1].
  • We therefore suggest that GCA should be included in the list of differential diagnosis of an ovarian or breast tumor in an elderly woman, particularly when systemic symptoms and parameters of inflammation are present [26].
  • The sequence analyses in terms of base doublets or triplets confirm the preference of MX for alternating pyrimidine-purine sites, the most significant triplet sequences being (5' to 3') CTA, GCA, TAC, ACT, CAC and TTA [27].
  • The performance characteristics of 5 scintillation cameras were compared: Searle 19, Searle 37, Ohio Nuclear, Picker 2C and Toshiba GCA 202 [28].


  1. Plasma adrenomedullin levels in patients with polymyalgia rheumatica and giant cell arteritis. Garcia-Unzueta, M.T., Martínez-Taboada, V.M., Amado-Señarís, J.A., Rodríguez-Valverde, V. Clin. Exp. Rheumatol. (2006) [Pubmed]
  2. Aminoacylation of tRNA in the evolution of an aminoacyl-tRNA synthetase. Lipman, R.S., Hou, Y.M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Severe anemia as the presenting manifestation of giant cell arteritis. Weiss, L.M., Gonzalez, E., Miller, S.B., Agudelo, C.A. Arthritis Rheum. (1995) [Pubmed]
  4. Sequence of the variant thyroxine-binding globulin of Australian aborigines. Only one of two amino acid replacements is responsible for its altered properties. Takeda, K., Mori, Y., Sobieszczyk, S., Seo, H., Dick, M., Watson, F., Flink, I.L., Seino, S., Bell, G.I., Refetoff, S. J. Clin. Invest. (1989) [Pubmed]
  5. Recognition of AUG and alternative initiator codons is augmented by G in position +4 but is not generally affected by the nucleotides in positions +5 and +6. Kozak, M. EMBO J. (1997) [Pubmed]
  6. A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins. Zhu, L., Chou, S.H., Reid, B.R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. Structure of a single-cytidine hairpin loop formed by the DNA triplet GCA. Zhu, L., Chou, S.H., Xu, J., Reid, B.R. Nat. Struct. Biol. (1995) [Pubmed]
  8. Frame shift mutation, exon skipping, and a two-codon deletion caused by splice site mutations account for pyruvate kinase deficiency. Kanno, H., Fujii, H., Wei, D.C., Chan, L.C., Hirono, A., Tsukimoto, I., Miwa, S. Blood (1997) [Pubmed]
  9. Characterization of ribosomal frameshift events by protein sequence analysis. Dayhuff, T.J., Atkins, J.F., Gesteland, R.F. J. Biol. Chem. (1986) [Pubmed]
  10. Do steroids increase lymphoma risk? A case-control study of lymphoma risk in polymyalgia rheumatica/giant cell arteritis. Askling, J., Klareskog, L., Hjalgrim, H., Baecklund, E., Björkholm, M., Ekbom, A. Ann. Rheum. Dis. (2005) [Pubmed]
  11. A novel point mutation at codon 146 of the K-ras gene in a human colorectal cancer identified by the polymerase chain reaction. Orita, S., Higashi, T., Kawasaki, Y., Harada, A., Igarashi, H., Monden, T., Morimoto, H., Shimano, T., Mori, T., Miyoshi, J. Virus Genes (1991) [Pubmed]
  12. Temperature jump relaxation studies on the interactions between transfer RNAs with complementary anticodons. The effect of modified bases adjacent to the anticodon triplet. Houssier, C., Grosjean, H. J. Biomol. Struct. Dyn. (1985) [Pubmed]
  13. Alpha 1-antichymotrypsin, C-reactive protein and erythrocyte sedimentation rate in polymyalgia rheumatica and giant cell arteritis. Pountain, G.D., Calvin, J., Hazleman, B.L. Br. J. Rheumatol. (1994) [Pubmed]
  14. Genetic heterogeneity in 30 German patients with oculopharyngeal muscular dystrophy. Müller, T., Deschauer, M., Kolbe-Fehr, F., Zierz, S. J. Neurol. (2006) [Pubmed]
  15. Molecular cloning and characterization of grancalcin, a novel EF-hand calcium-binding protein abundant in neutrophils and monocytes. Boyhan, A., Casimir, C.M., French, J.K., Teahan, C.G., Segal, A.W. J. Biol. Chem. (1992) [Pubmed]
  16. Structure and expression of the Saccharomyces cerevisiae CRY1 gene: a highly conserved ribosomal protein gene. Larkin, J.C., Thompson, J.R., Woolford, J.L. Mol. Cell. Biol. (1987) [Pubmed]
  17. A single hydroxyl group governs ligand site selectivity in human ileal bile acid binding protein. Tochtrop, G.P., DeKoster, G.T., Covey, D.F., Cistola, D.P. J. Am. Chem. Soc. (2004) [Pubmed]
  18. Biochemical characterization of the penta-EF-hand protein grancalcin and identification of L-plastin as a binding partner. Lollike, K., Johnsen, A.H., Durussel, I., Borregaard, N., Cox, J.A. J. Biol. Chem. (2001) [Pubmed]
  19. The PEF family proteins sorcin and grancalcin interact in vivo and in vitro. Hansen, C., Tarabykina, S., la Cour, J.M., Lollike, K., Berchtold, M.W. FEBS Lett. (2003) [Pubmed]
  20. The hypotrichous ciliate Euplotes octocarinatus has only one type of tRNACys with GCA anticodon encoded on a single macronuclear DNA molecule. Grimm, M., Brünen-Nieweler, C., Junker, V., Heckmann, K., Beier, H. Nucleic Acids Res. (1998) [Pubmed]
  21. Structure of Ca(2+)-loaded human grancalcin. Jia, J., Borregaard, N., Lollike, K., Cygler, M. Acta Crystallogr. D Biol. Crystallogr. (2001) [Pubmed]
  22. Molecular scanning of the insulin receptor substrate-1 (IRS-1) gene in Japanese patients with NIDDM: identification of five novel polymorphisms. Ura, S., Araki, E., Kishikawa, H., Shirotani, T., Todaka, M., Isami, S., Shimoda, S., Yoshimura, R., Matsuda, K., Motoyoshi, S., Miyamura, N., Kahn, C.R., Shichiri, M. Diabetologia (1996) [Pubmed]
  23. Crystal structure of human grancalcin, a member of the penta-EF-hand protein family. Jia, J., Han, Q., Borregaard, N., Lollike, K., Cygler, M. J. Mol. Biol. (2000) [Pubmed]
  24. Forssman disaccharide is the specific ligand of a galectin from the sponge Geodia cydonium but does not mediate its binding to nuclear protein np56. Hanisch, F.G., Baldus, S.E., Kümmel, T.A. Glycobiology (1996) [Pubmed]
  25. Isolation and characterization of grancalcin, a novel 28 kDa EF-hand calcium-binding protein from human neutrophils. Teahan, C.G., Totty, N.F., Segal, A.W. Biochem. J. (1992) [Pubmed]
  26. Systemic vasculitis presenting as a tumorlike lesion. Four case reports and an analysis of 79 reported cases. Kariv, R., Sidi, Y., Gur, H. Medicine (Baltimore) (2000) [Pubmed]
  27. Aza-bioisosteres of 9, 10-anthracenedione: a modulation of DNA sequence specificity. Sissi, C., Capranico, G., Menta, E., Palumbo, M. Mol. Pharmacol. (1996) [Pubmed]
  28. Comparative assessment of scintillation camera performance. Moretti, J.L., Mensch, B., Guey, A., Desgrez, A. Radiology. (1976) [Pubmed]
WikiGenes - Universities