Protein no.* Swiss-Prot/ TrEMBL Accession no. Protein name Subcellular location Biological process Molecular function Function** HepG2 LC01* Q13148 TAR DNA-binding protein 43 Nucleus 3'-UTR-mediated mrna stabilization RNA splicing Cell death Mrna processing Mitosis Negative regulation by host of viral transcription Transcription from RNA polymerase II promotor Double-stranded DNA binding Mrna 3'-UTR binding Microtubule binding Nucleotide binding Transcription factor activity DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. LC02* P13693 Translationally-controlled tumor protein Cytoplasm Anti-apoptosis Calcium ion Transport Cellular calcium ion homeostasis Response to virus Calcium ion binding Protein binding Involved in calcium binding and microtubule stabilization. LC03* P81605 Dermcidin Secreted Defense response to bacterium Defense response to fungus Killing of cells of another organism Protein binding DCD-1 displays antimicrobial activity thereby limiting skin infection by potential pathogens in the first few hours after bacterial colonization. Highly effective against E.coli, E.faecalis, S.aureus and C.albicans. Optimal pH and salt concentration resemble the conditions in sweat.                                                                                                       Survival-promoting peptide promotes survival of neurons and displays phosphatase activity. It may bind IgG. LC04 Q9C0H9 p130Cas-associated protein Cytoplasm Exocytosis Protein binding Delays the onset of cell spreading in the early stages of cell adhesion to fibronectin. Also involved in calcium-dependent exocytosis from PC12 cells LC05 P98160 Basement membrane-specific heparan sulfate proteoglycan core protein Secreted Cell adhesion Angiogenesis Protein C-terminus binding Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development. Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6. The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity. Mcf-7 BC01* P25054 Adenomatous polyposis coli protein Cell junction Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane Microtubule Wnt signaling pathway Microtubule plus-end binding Protein kinase regulator activity Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization. BC02* Q16644 MAP kinase-activated protein kinase 3 Nucleus Cytoplasm. Myd88-dependent toll-like receptor signaling pathway Ras protein signal transduction TRIF-dependent toll-like receptor signaling pathway Toll signaling pathway Innate immune response Macropinocytosis Nerve growth factor receptor signaling pathway Peptidyl-serine phosphorylation Response to lipopolysaccharide Stress-activated MAPK cascade Toll-like receptor 1 signaling pathway Toll-like receptor 2 signaling pathway Toll-like receptor 3 signaling pathway Toll-like receptor 4 signaling pathway Kinase Serine/threonine-protein kinase Transferase Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. BC03* Q04721 Neurogenic locus notch homolog protein 2 Cell membrane Membrane Nucleus Differentiation Notch signaling pathway Transcription Transcription regulation Calcium ion binding Receptor activity Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs .Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. BC04* P42345 Serine /threonine-protein kinase mTOR Cytoplasm Endoplasmic reticulum Golgi apparatus Lysosome Membrane Mitochondrion Mitochondrion outer membrane Nucleus T cell costimulation TOR signaling cascade Cell growth Cellular response to hypoxia Cellular response to nutrient levels Epidermal growth factor receptor signaling pathway Fibroblast growth factor receptor signaling pathway Germ cell development Insulin receptor signaling pathway Negative regulation of NFAT protein import into nucleus Negative regulation of autophagy Negative regulation of cell size Negative regulation of macroautophagy Nerve growth factor receptor signaling pathway Peptidyl-serine phosphorylation Peptidyl-threonine phosphorylation Phosphatidylinositol-mediated signaling Positive regulation of actin filament polymerization Positive regulation of endothelial cell proliferation Positive regulation of lamellipodium assembly Positive regulation of lipid biosynthetic process Positive regulation of myotube differentiation Positive regulation of peptidyl-tyrosine phosphorylation Positive regulation of protein kinase B signaling cascade Positive regulation of protein phosphorylation Positive regulation of stress fiber assembly Positive regulation of transcription from RNA polymerase III promoter Positive regulation of translation Protein autophosphorylation Protein catabolic process Regulation of Racgtpase activity Regulation of actin cytoskeleton organization Regulation of carbohydrate utilization Regulation of fatty acid beta-oxidation Regulation of glycogen biosynthetic process Regulation of protein kinase activity Regulation of response to food Response to amino acid stimulus Response to nutrient Ruffle organization Kinase Serine/threonine-protein kinase Transferase Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'. BC05* P08047 Transcription factor Sp1 Nucleus Cytoplasm. Host-virus interaction Transcription Transcription regulation RNA polymerase II core promoter proximal region sequence-specific DNA binding RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription RNA polymerase II core promoter sequence-specific DNA binding RNA polymerase II repressing transcription factor binding Bhlh transcription factor binding Double-stranded DNA binding Enhancer binding Protein homodimerization activity Sequence-specific DNA binding transcription factor activity Zinc ion binding Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Ht-29 CC01* Q9UKL3 CASP8-associated protein 2 Cytoplasm Mitochondrion Nucleus Apoptosis Cell cycle Transcription Transcription regulation DNA binding SUMO polymer binding Cysteine-type endopeptidase activator activity involved in apoptotic process Death receptor binding Transcription corepressor activity Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation. Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis. Required for histone gene transcription and progression through S phase. CC02* P49792 E3 SUMO-protein ligase RanBP2 Membrane Nuclear pore complex Nucleus Protein transport Translocation Transport Ubl conjugation pathway Mrna transport Isomerase Ligase Rotamase E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Could also have isomerase or chaperone activity and may bind RNA or DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1. Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB. CC03* P13639 Elongation factor 2 Cytoplasm. Protein biosynthesis Elongation factor Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylatedtRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. CC04* Q8WX93 Palladin Cell junction Cell projection Cytoplasm Cytoskeleton Cytoskeleton organization Muscle alpha-actinin binding Cytoskeletal protein required for organization of normal actin cytoskeleton. Roles in establishing cell morphology, motility, cell adhesion and cell-extracellular matrix interactions in a variety of cell types. May function as a scaffolding molecule with the potential to influence both actin polymerization and the assembly of existing actin filaments into higher-order arrays. Binds to proteins that bind to either monomeric or filamentous actin. Localizes at sites where active actin remodeling takes place, such as lamellipodia and membrane ruffles. Different isoforms may have functional differences. Involved in the control of morphological and cytoskeletal changes associated with dendritic cell maturation. Involved in targeting ACTN to specific subcellular foci. CC05 Q8NF91 Nesprin-1 Cytoplasm Cytoskeleton Membrane Nucleus Golgi organization Cell death Cytoskeletal anchoring at nuclear membrane Muscle cell differentiation Nuclear matrix anchoring at nuclear membrane Actin binding Protein homodimerization activity Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. May be involved in the maintenance of nuclear organization and structural integrity. Connects nuclei to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm. May be required for centrosome migration to the apical cell surface during early ciliogenesis. CC06 Q9BWX5 Transcription factor GATA-5 Nucleus Transcription Transcription regulation Activator Binds to the functionally important CEF-1 nuclear protein binding site in the cardiac-specific slow/cardiac troponin C transcriptional enhancer. May play an important role in the transcriptional program(s) that underlies smooth muscle cell diversity *The proteins were involved in the PI3K/AKT/mTOR pathway. **The protein functions in Table 2 were reproduced from the UniProtKB web site.

Table 2: Subcellular location and protein function of 16 proteins with higher confidence levels identified in cancer.

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