CALCIUM

General Function:

Voltage-gated calcium channel activity

Specific Function:

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.

Gene Name:

CACNA1C

Uniprot ID:

Q13936

Molecular Weight:

248974.1 Da

References

1. Boda D, Giri J, Henderson D, Eisenberg B, Gillespie D: Analyzing the components of the free-energy landscape in a calcium selective ion channel by Widom's particle insertion method. J Chem Phys. 2011 Feb 7;134(5):055102. doi: 10.1063/1.3532937. [21303162 ]

General Function:

Signal transducer activity

Specific Function:

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.

Gene Name:

ATP2C1

Uniprot ID:

P98194

Molecular Weight:

100576.42 Da

References

1. Bonza MC, Martin H, Kang M, Lewis G, Greiner T, Giacometti S, Van Etten JL, De Michelis MI, Thiel G, Moroni A: A functional calcium-transporting ATPase encoded by chlorella viruses. J Gen Virol. 2010 Oct;91(Pt 10):2620-9. doi: 10.1099/vir.0.021873-0. Epub 2010 Jun 23. [20573858 ]

General Function:

Calcium ion binding

Specific Function:

Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.

Gene Name:

TNNC2

Uniprot ID:

P02585

Molecular Weight:

18121.895 Da

References

1. Dweck D, Reynaldo DP, Pinto JR, Potter JD: A dilated cardiomyopathy troponin C mutation lowers contractile force by reducing strong myosin-actin binding. J Biol Chem. 2010 Jun 4;285(23):17371-9. doi: 10.1074/jbc.M109.064105. Epub 2010 Apr 6. [20371872 ]

General Function:

Troponin t binding

Specific Function:

Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.

Gene Name:

TNNC1

Uniprot ID:

P63316

Molecular Weight:

18402.36 Da

References

1. Baylor SM, Hollingworth S: Calcium indicators and calcium signalling in skeletal muscle fibres during excitation-contraction coupling. Prog Biophys Mol Biol. 2011 May;105(3):162-79. doi: 10.1016/j.pbiomolbio.2010.06.001. Epub 2010 Jun 25. [20599552 ]

General Function:

Structural constituent of cytoskeleton

Specific Function:

Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.

Gene Name:

SPTBN1

Uniprot ID:

Q01082

Molecular Weight:

274606.995 Da

References

1. Wallis CJ, Wenegieme EF, Babitch JA: Characterization of calcium binding to brain spectrin. J Biol Chem. 1992 Mar 5;267(7):4333-7. [1537825 ]

General Function:

Zinc ion binding

Specific Function:

Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization. May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity.

Gene Name:

S100B

Uniprot ID:

P04271

Molecular Weight:

10712.985 Da

References

1. Friel LA, Romero R, Edwin S, Nien JK, Gomez R, Chaiworapongsa T, Kusanovic JP, Tolosa JE, Hassan SS, Espinoza J: The calcium binding protein, S100B, is increased in the amniotic fluid of women with intra-amniotic infection/inflammation and preterm labor with intact or ruptured membranes. J Perinat Med. 2007;35(5):385-93. [17624933 ]

General Function:

Poly(a) rna binding

Specific Function:

Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue.

Gene Name:

CAST

Uniprot ID:

P20810

Molecular Weight:

76572.035 Da

References

1. De Tullio R, Averna M, Stifanese R, Parr T, Bardsley RG, Pontremoli S, Melloni E: Multiple rat brain calpastatin forms are produced by distinct starting points and alternative splicing of the N-terminal exons. Arch Biochem Biophys. 2007 Sep 1;465(1):148-56. Epub 2007 May 30. [17570336 ]

General Function:

Protease binding

Specific Function:

May play a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin. Can mediate the interaction of chondrocytes with the cartilage extracellular matrix through interaction with cell surface integrin receptors. Could play a role in the pathogenesis of osteoarthritis. Potent suppressor of apoptosis in both primary chondrocytes and transformed cells. Suppresses apoptosis by blocking the activation of caspase-3 and by inducing the IAP family of survival proteins (BIRC3, BIRC2, BIRC5 and XIAP). Essential for maintaining a vascular smooth muscle cells (VSMCs) contractile/differentiated phenotype under physiological and pathological stimuli. Maintains this phenotype of VSMCs by interacting with ITGA7 (By similarity).

Gene Name:

COMP

Uniprot ID:

P49747

Molecular Weight:

82859.88 Da

References

1. Chen FH, Herndon ME, Patel N, Hecht JT, Tuan RS, Lawler J: Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan. J Biol Chem. 2007 Aug 24;282(34):24591-8. Epub 2007 Jun 22. [17588949 ]

General Function:

Titin binding

Specific Function:

Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis.

Gene Name:

CALM1

Uniprot ID:

P0DP23

Molecular Weight:

16837.47 Da

General Function:

Zinc ion binding

Specific Function:

Catalyzes the degradation of compounds such as putrescine, histamine, spermine, and spermidine, substances involved in allergic and immune responses, cell proliferation, tissue differentiation, tumor formation, and possibly apoptosis. Placental DAO is thought to play a role in the regulation of the female reproductive function.

Gene Name:

AOC1

Uniprot ID:

P19801

Molecular Weight:

85377.1 Da

General Function:

Zinc ion binding

Specific Function:

Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does not interfere with calcium binding. Required for the copper-dependent stress-induced export of IL1A and FGF1. The calcium-free protein binds to lipid vesicles containing phosphatidylserine, but not to vesicles containing phosphatidylcholine (By similarity).

Gene Name:

S100A13

Uniprot ID:

Q99584

Molecular Weight:

11471.095 Da

General Function:

Zinc ion binding

Gene Name:

ALPP

Uniprot ID:

P05187

Molecular Weight:

57953.31 Da

References

1. Llinas P, Masella M, Stigbrand T, Menez A, Stura EA, Le Du MH: Structural studies of human alkaline phosphatase in complex with strontium: implication for its secondary effect in bones. Protein Sci. 2006 Jul;15(7):1691-700. [16815919 ]

General Function:

S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. The iNOS-S100A8/A9 transnitrosylase complex directs selective inflammatory stimulus-dependent S-nitrosylation of GAPDH and probably multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity.

Specific Function:

Arachidonic acid binding

Gene Name:

S100A8

Uniprot ID:

P05109

Molecular Weight:

10834.43 Da

General Function:

S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. Has transnitrosylase activity; in oxidatively-modified low-densitity lipoprotein (LDL(ox))-induced S-nitrosylation of GAPDH on 'Cys-247' proposed to transfer the NO moiety from NOS2/iNOS to GAPDH via its own S-nitrosylated Cys-3. The iNOS-S100A8/A9 transnitrosylase complex is proposed to also direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif.

Specific Function:

Antioxidant activity

Gene Name:

S100A9

Uniprot ID:

P06702

Molecular Weight:

13241.955 Da

General Function:

Identical protein binding

Specific Function:

May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes. May also play a role in suppressing tumor cell growth.

Gene Name:

S100A2

Uniprot ID:

P29034

Molecular Weight:

11116.695 Da

References

1. Koch M, Bhattacharya S, Kehl T, Gimona M, Vasak M, Chazin W, Heizmann CW, Kroneck PM, Fritz G: Implications on zinc binding to S100A2. Biochim Biophys Acta. 2007 Mar;1773(3):457-70. Epub 2006 Dec 19. [17239974 ]

General Function:

Ferroxidase activity

Specific Function:

Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. May also play a role in fetal lung development or pulmonary antioxidant defense (By similarity).

Gene Name:

CP

Uniprot ID:

P00450

Molecular Weight:

122204.45 Da

References

1. Bento I, Peixoto C, Zaitsev VN, Lindley PF: Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites. Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):240-8. Epub 2007 Jan 16. [17242517 ]

General Function:

Induces cartilage and bone formation. Also act in mesoderm induction, tooth development, limb formation and fracture repair. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity).

Specific Function:

Bmp receptor binding

Gene Name:

BMP4

Uniprot ID:

P12644

Molecular Weight:

46554.545 Da

General Function:

Structural constituent of bone

Specific Function:

Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation.

Gene Name:

MGP

Uniprot ID:

P08493

Molecular Weight:

12353.06 Da

References

1. Yao Y, Shahbazian A, Bostrom KI: Proline and gamma-carboxylated glutamate residues in matrix Gla protein are critical for binding of bone morphogenetic protein-4. Circ Res. 2008 May 9;102(9):1065-74. doi: 10.1161/CIRCRESAHA.107.166124. Epub 2008 Mar 27. [18369157 ]

General Function:

Calcium ion binding

Specific Function:

Potential calcium-dependent cell-adhesion protein.

Gene Name:

PCDH19

Uniprot ID:

Q8TAB3

Molecular Weight:

126251.425 Da

References

1. Dibbens LM, Tarpey PS, Hynes K, Bayly MA, Scheffer IE, Smith R, Bomar J, Sutton E, Vandeleur L, Shoubridge C, Edkins S, Turner SJ, Stevens C, O'Meara S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Jones D, Lee R, Madison M, Mironenko T, Varian J, West S, Widaa S, Wray P, Teague J, Dicks E, Butler A, Menzies A, Jenkinson A, Shepherd R, Gusella JF, Afawi Z, Mazarib A, Neufeld MY, Kivity S, Lev D, Lerman-Sagie T, Korczyn AD, Derry CP, Sutherland GR, Friend K, Shaw M, Corbett M, Kim HG, Geschwind DH, Thomas P, Haan E, Ryan S, McKee S, Berkovic SF, Futreal PA, Stratton MR, Mulley JC, Gecz J: X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat Genet. 2008 Jun;40(6):776-81. doi: 10.1038/ng.149. Epub 2008 May 11. [18469813 ]

General Function:

Protein dimerization activity

Specific Function:

Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca(2+)-regulated signals along the death pathway (By similarity). Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity. May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphoprylation of the Akt signaling pathway. Seems to play a role in the regulation of the distribution and function of MCOLN1 in the endosomal pathway. Isoform 2 has a lower Ca(2+) affinity than isoform 1. Isoform 1 and, to a lesser extend, isoform 2, can stabilize SHISA5.

Gene Name:

PDCD6

Uniprot ID:

O75340

Molecular Weight:

21868.32 Da

References

1. Suzuki H, Kawasaki M, Kakiuchi T, Shibata H, Wakatsuki S, Maki M: Crystallization and X-ray diffraction analysis of N-terminally truncated human ALG-2. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Nov 1;64(Pt 11):974-7. doi: 10.1107/S1744309108030297. Epub 2008 Oct 31. [18997320 ]