Chain A, 14-3-3 protein sigma
Protein Classification
14-3-3 family protein( domain architecture ID 10178211)
14-3-3 family protein belongs to a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells that play important roles in many biological processes which are regulated by phosphorylation, including cell cycle regulation, cell proliferation, protein trafficking, metabolic regulation and apoptosis
List of domain hits
| Name | Accession | Description | Interval | E-value | |||||
| 14-3-3_sigma | cd10019 | 14-3-3 sigma, an isoform of 14-3-3 protein; 14-3-3 protein sigma isoform, also known as ... |
1-242 | 3.38e-178 | |||||
14-3-3 sigma, an isoform of 14-3-3 protein; 14-3-3 protein sigma isoform, also known as stratifin or human mammary epithelial marker (HME) 1, has been most directly linked to tumor development. In humans, it is expressed by the SFN gene, strictly in stratified squamous epithelial cells in response to DNA damage where it is transcriptionally induced in a p53-dependent manner, subsequently causing cell-cycle arrest at the G2/M checkpoint. Up-regulation and down-regulation of 14-3-3 sigma expression have both been described in tumors. For example, in human breast cancer, 14-3-3 sigma is predominantly down-regulated by CpG methylation, acting as both a tumor suppressor and a prognostic indicator, while in human scirrhous-type gastric carcinoma (SGC), it is up-regulated and may play an important role in SGC carcinogenesis and progression. Loss of 14-3-3 sigma expression sensitizes tumor cells to treatment with conventional cytostatic drugs, making this protein an attractive therapeutic target. 14-3-3 domains are an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. : Pssm-ID: 206756 [Multi-domain] Cd Length: 242 Bit Score: 489.16 E-value: 3.38e-178
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| Name | Accession | Description | Interval | E-value | |||||
| 14-3-3_sigma | cd10019 | 14-3-3 sigma, an isoform of 14-3-3 protein; 14-3-3 protein sigma isoform, also known as ... |
1-242 | 3.38e-178 | |||||
14-3-3 sigma, an isoform of 14-3-3 protein; 14-3-3 protein sigma isoform, also known as stratifin or human mammary epithelial marker (HME) 1, has been most directly linked to tumor development. In humans, it is expressed by the SFN gene, strictly in stratified squamous epithelial cells in response to DNA damage where it is transcriptionally induced in a p53-dependent manner, subsequently causing cell-cycle arrest at the G2/M checkpoint. Up-regulation and down-regulation of 14-3-3 sigma expression have both been described in tumors. For example, in human breast cancer, 14-3-3 sigma is predominantly down-regulated by CpG methylation, acting as both a tumor suppressor and a prognostic indicator, while in human scirrhous-type gastric carcinoma (SGC), it is up-regulated and may play an important role in SGC carcinogenesis and progression. Loss of 14-3-3 sigma expression sensitizes tumor cells to treatment with conventional cytostatic drugs, making this protein an attractive therapeutic target. 14-3-3 domains are an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. Pssm-ID: 206756 [Multi-domain] Cd Length: 242 Bit Score: 489.16 E-value: 3.38e-178
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| 14-3-3 | pfam00244 | 14-3-3 protein; |
9-230 | 1.32e-139 | |||||
14-3-3 protein; Pssm-ID: 459729 Cd Length: 221 Bit Score: 390.73 E-value: 1.32e-139
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| BMH1 | COG5040 | 14-3-3 family protein [Signal transduction mechanisms]; |
3-247 | 1.11e-111 | |||||
14-3-3 family protein [Signal transduction mechanisms]; Pssm-ID: 227373 Cd Length: 268 Bit Score: 321.90 E-value: 1.11e-111
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| 14_3_3 | smart00101 | 14-3-3 homologues; 14-3-3 homologues mediates signal transduction by binding to ... |
3-241 | 5.18e-107 | |||||
14-3-3 homologues; 14-3-3 homologues mediates signal transduction by binding to phosphoserine-containing proteins. They are involved in growth factor signalling and also interact with MEK kinases. Pssm-ID: 128412 Cd Length: 244 Bit Score: 309.15 E-value: 5.18e-107
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| Name | Accession | Description | Interval | E-value | |||||
| 14-3-3_sigma | cd10019 | 14-3-3 sigma, an isoform of 14-3-3 protein; 14-3-3 protein sigma isoform, also known as ... |
1-242 | 3.38e-178 | |||||
14-3-3 sigma, an isoform of 14-3-3 protein; 14-3-3 protein sigma isoform, also known as stratifin or human mammary epithelial marker (HME) 1, has been most directly linked to tumor development. In humans, it is expressed by the SFN gene, strictly in stratified squamous epithelial cells in response to DNA damage where it is transcriptionally induced in a p53-dependent manner, subsequently causing cell-cycle arrest at the G2/M checkpoint. Up-regulation and down-regulation of 14-3-3 sigma expression have both been described in tumors. For example, in human breast cancer, 14-3-3 sigma is predominantly down-regulated by CpG methylation, acting as both a tumor suppressor and a prognostic indicator, while in human scirrhous-type gastric carcinoma (SGC), it is up-regulated and may play an important role in SGC carcinogenesis and progression. Loss of 14-3-3 sigma expression sensitizes tumor cells to treatment with conventional cytostatic drugs, making this protein an attractive therapeutic target. 14-3-3 domains are an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. Pssm-ID: 206756 [Multi-domain] Cd Length: 242 Bit Score: 489.16 E-value: 3.38e-178
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| 14-3-3 | pfam00244 | 14-3-3 protein; |
9-230 | 1.32e-139 | |||||
14-3-3 protein; Pssm-ID: 459729 Cd Length: 221 Bit Score: 390.73 E-value: 1.32e-139
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| 14-3-3_beta_zeta | cd10022 | 14-3-3 beta and zeta isoforms of 14-3-3 protein; 14-3-3 protein beta and zeta isoform (also ... |
2-232 | 3.10e-128 | |||||
14-3-3 beta and zeta isoforms of 14-3-3 protein; 14-3-3 protein beta and zeta isoform (also known as tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta and zeta polypeptide) are encoded by the YWHAB gene and YWHAZ gene in humans. They have been linked to mitogenic signaling and the cell cycle machinery, and to cancer initiation and progression, respectively. The beta isoform has been shown to interact with RAF1 and CDC25 phosphatases and its overexpression is associated with invasion, migration, metastasis and proliferation of tumor cells and its elevated levels are correlated with tumor size, the number of lymph node metastases and a reduced survival rate. It is significantly overexpressed in lung cancer tissues, mutated chronic lymphocytic leukemia (M-CLL), gastric cancer tissues, aflatoxin B1-induced rat hepatocellular carcinoma K1 and K2 cells, as well as renal cell carcinoma cysts, and can potentially be used as a diagnostic and prognostic biomarker in the cancer. Numerous proteins involved in anti-apoptosis and tumor progression were also found to be differentially expressed in gastric cancer cells where 14-3-3 beta is overexpressed. 14-3-3 beta also interacts with human Dapper1 (hDpr1), a key negative regulator of Wnt signaling, via hDpr1 phosphorylation by protein kinase A, thus attenuating the ability of hDpr1 to promote Dishevelled (Dvl) degradation, and subsequently enhancing Wnt signaling. The zeta isoform is ubiquitously expressed and localized to most subcellular regions, including the cytoplasm, plasma membrane, mitochondria, and nucleus. Its overexpression and gene amplification in multiple cancers are correlated with poor prognosis and chemoresistance in cancer patients. 14-3-3 zeta has been identified as a biomarker with high sensitivity and specificity for diagnosis and prognosis in multiple tumor types, including hepatocellular carcinoma, head and neck cancer, indicating a potential clinical application for using 14-3-3 zeta in selecting treatment options and predicting cancer outcome. It also interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. 14-3-3 domains are an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. Pssm-ID: 206758 Cd Length: 229 Bit Score: 362.08 E-value: 3.10e-128
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| 14-3-3_theta | cd10023 | 14-3-3 theta/tau (theta in mice, tau in human), an isoform of 14-3-3 protein; 14-3-3 tau/theta ... |
1-236 | 3.55e-128 | |||||
14-3-3 theta/tau (theta in mice, tau in human), an isoform of 14-3-3 protein; 14-3-3 tau/theta (tau in humans, theta in mice) isoform (also known as tyrosine 3-monooxygenase/ tryptophan 5-monooxygenase activation protein, theta polypeptide) is encoded by the YWHAQ gene in humans and plays an important role in controlling apoptosis through interactions with ASK1, c-jun NH-terminal kinase, and p38 mitogen-activated protein kinase (MAPK). Its interaction with CDC25c regulates entry into the cell cycle and subsequent interaction with Bad prevents apoptosis. 14-3-3 theta protein expression is induced in patients with amyotrophic lateral sclerosis. 14-3-3 tau is often overexpressed in breast cancer, which is associated with the downregulation of p21, a p53 target gene, and thus leads to tamoxifen resistance in MCF7 breast cancer cells and shorter patient survival. Therefore, 14-3-3 tau may be a potential therapeutic target in breast cancer. Additionally, 14-3-3 theta mediates nucleocytoplasmic shuttling of the coronavirus nucleocapsid protein which causes severe acute respiratory syndrome. 14-3-3 domain is an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. Pssm-ID: 206759 Cd Length: 234 Bit Score: 362.46 E-value: 3.55e-128
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| 14-3-3 | cd08774 | 14-3-3 domain; 14-3-3 domain is an essential part of 14-3-3 proteins, a ubiquitous class of ... |
6-228 | 1.09e-125 | |||||
14-3-3 domain; 14-3-3 domain is an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. 14-3-3 proteins play important roles in many biological processes that are regulated by phosphorylation, including cell cycle regulation, cell proliferation, protein trafficking, metabolic regulation and apoptosis. More than 300 binding partners of the 14-3-3 domain have been identified in all subcellular compartments and include transcription factors, signaling molecules, tumor suppressors, biosynthetic enzymes, cytoskeletal proteins and apoptosis factors. 14-3-3 binding can alter the conformation, localization, stability, phosphorylation state, activity as well as molecular interactions of a target protein. They function only as dimers, some preferring strictly homodimeric interaction, while others form heterodimers. Binding of the 14-3-3 domain to its target occurs in a phosphospecific manner where it binds to one of two consensus sequences of their target proteins; RSXpSXP (mode-1) and RXXXpSXP (mode-2). In some instances, 14-3-3 domain containing proteins are involved in regulation and signaling of a number of cellular processes in phosphorylation-independent manner. Many organisms express multiple isoforms: there are seven mammalian 14-3-3 family members (beta, gamma, eta, theta, epsilon, sigma, zeta), each encoded by a distinct gene, while plants contain up to 13 isoforms. The flexible C-terminal segment of 14-3-3 isoforms shows the highest sequence variability and may significantly contribute to individual isoform uniqueness by playing an important regulatory role by occupying the ligand binding groove and blocking the binding of inappropriate ligands in a distinct manner. Elevated amounts of 14-3-3 proteins are found in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. In protozoa, like Plasmodium or Cryptosporidium parvum 14-3-3 proteins play an important role in key steps of parasite development. Pssm-ID: 206755 Cd Length: 225 Bit Score: 355.35 E-value: 1.09e-125
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| 14-3-3_1 | cd11310 | 14-3-3 protein domain; This 14-3-3 domain family includes proteins in Caenorhabditis elegans, ... |
2-233 | 3.55e-122 | |||||
14-3-3 protein domain; This 14-3-3 domain family includes proteins in Caenorhabditis elegans, the silkworm (Bombyx mori) as well as barley (Hordeum vulgare). In C. elegans, 14-3-3 proteins are SIR-2.1 binding partners which induce transcriptional activation of DAF-16 during stress and are required for the life-span extension conferred by extra copies of sir-2.1. In B. mori, the 14-3-3 proteins are expressed widely in larval and adult tissues, including the brain, fat body, Malpighian tube, silk gland, midgut, testis, ovary, antenna, and pheromone gland, and interact with the N-terminal fragment of Hsp60, suggesting that 14-3-3 (a molecular adaptor) and Hsp60 (a molecular chaperone) work together to achieve a wide range of cellular functions in B. mori. In barley aleurone cells, 14-3-3 proteins and members of the ABF transcription factor family have a regulatory function in the gibberellic acid (GA) pathway since the balance of GA and abscisic acid (ABA) is a determining factor during transition of embryogenesis and seed germination. 14-3-3 is an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. Pssm-ID: 206764 Cd Length: 230 Bit Score: 347.07 E-value: 3.55e-122
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| BMH1 | COG5040 | 14-3-3 family protein [Signal transduction mechanisms]; |
3-247 | 1.11e-111 | |||||
14-3-3 family protein [Signal transduction mechanisms]; Pssm-ID: 227373 Cd Length: 268 Bit Score: 321.90 E-value: 1.11e-111
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| 14-3-3_fungi | cd11309 | Fungal 14-3-3 protein domain; This family containing fungal 14-3-3 domains includes the yeasts ... |
3-233 | 8.08e-111 | |||||
Fungal 14-3-3 protein domain; This family containing fungal 14-3-3 domains includes the yeasts Saccharomyces cerevisiae (BMH1 and BMH2) and Schizosaccharomyces pombe (rad24 and rad25) isoforms. They possess distinctively variant C-terminal segments that differentiate them from the mammalian isoforms; the C-terminus is longer and BMH1/2 isoforms contain polyglutamine (polyQ) sequences of unknown function. The C-terminal segments of yeast 14-3-3 isoforms may thus behave in a different manner compared to the higher eukaryote isoforms. Yeast 14-3-3 proteins bind to numerous proteins involved in a variety of yeast cellular processes making them excellent model organisms for elucidating the function of the 14-3-3 protein family. BMH1 and BMH2 are positive regulators of rapamycin-sensitive signaling via TOR kinases while they play an inhibitory role in Rtg3p-dependent transcription involved in retrograde signaling. 14-3-3 domains are an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. Pssm-ID: 206763 Cd Length: 231 Bit Score: 318.09 E-value: 8.08e-111
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| 14-3-3_plant | cd10026 | Plant 14-3-3 protein domain; Plant 14-3-3 isoforms, similar to their highly conserved homologs ... |
3-233 | 1.34e-110 | |||||
Plant 14-3-3 protein domain; Plant 14-3-3 isoforms, similar to their highly conserved homologs in mammals, bind to phosphorylated target proteins to modulate their function. They have been implicated in a variety of physiological functions; in particular, abiotic and biotic stress responses, primary metabolism, as well as various aspects of plant growth and development. They function through the regulation of a diverse range of proteins including transcription factors, kinases, structural proteins, ion channels as well as pathogen defense-related proteins. The 14-3-3 proteins are affected transcriptionally as well as functionally by the environment of the plant, both intracellular and extracellular, thus playing a key role in the response to environmental stress, pathogens and light conditions. Plant 14-3-3 proteins have been divided into epsilon-like groups and non-epsilon groups based on phylogenetic clustering. They have a varying number of isoforms (for example, Arabidopsis has thirteen known protein isoforms, cotton has six) with variation in their affinity for specific binding partners, suggesting specific roles in specific processes. Pssm-ID: 206762 Cd Length: 237 Bit Score: 317.75 E-value: 1.34e-110
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| 14-3-3_epsilon | cd10020 | 14-3-3 epsilon, an isoform of 14-3-3 protein; 14-3-3 protein epsilon isoform (isoform (also ... |
3-232 | 4.51e-109 | |||||
14-3-3 epsilon, an isoform of 14-3-3 protein; 14-3-3 protein epsilon isoform (isoform (also known as tyrosine 3-monooxygenase/ tryptophan 5-monooxygenase activation protein, epsilon polypeptide) is encoded by the YWHAE gene in humans and is involved in cancer cell survival and growth. It interacts with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. Overexpression of 14-3-3 epsilon in primary hepatocellular carcinoma (HCC) tissues predicts a high risk of extrahepatic metastasis and worse survival, and is a potential therapeutic target. It has also been implicated in the pathogenesis of small cell lung cancer. 14-3-3 epsilon overexpression protects colorectal cancer and endothelial cells from oxidative stress-induced apoptosis, while its suppression by non-steroidal anti-inflammatory drugs induces cancer and endothelial cell death. Cellular levels of 14-3-3 epsilon could possibly serve as an important regulator of cell survival in response to oxidative stress and other death signals. 14-3-3 domains are an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. Pssm-ID: 206757 Cd Length: 230 Bit Score: 313.94 E-value: 4.51e-109
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| 14_3_3 | smart00101 | 14-3-3 homologues; 14-3-3 homologues mediates signal transduction by binding to ... |
3-241 | 5.18e-107 | |||||
14-3-3 homologues; 14-3-3 homologues mediates signal transduction by binding to phosphoserine-containing proteins. They are involved in growth factor signalling and also interact with MEK kinases. Pssm-ID: 128412 Cd Length: 244 Bit Score: 309.15 E-value: 5.18e-107
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| 14-3-3_gamma | cd10024 | 14-3-3 gamma, an isoform of 14-3-3 protein; 14-3-3 gamma isoform (also known as tyrosine ... |
1-242 | 2.38e-102 | |||||
14-3-3 gamma, an isoform of 14-3-3 protein; 14-3-3 gamma isoform (also known as tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide) is encoded by the YWHAG gene in humans and is induced by growth factors in human vascular smooth muscle cells. It is also highly expressed in skeletal and heart muscles, suggesting an important role in muscle tissue. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways. 14-3-3 gamma mediates Cdc25A proteolysis to block premature mitotic entry after DNA damage. 14-3-3 gamma mediates the interaction between Chk1 and Cdc25A; this complex has an essential function in Cdc25A phosphorylation and degradation to block premature mitotic entry after DNA damage. Increased expression of 14-3-3 gamma in lung cancer coincides with loss of functional p53, possibly in a cooperative manner promoting genomic instability. Also, during cell cycle, 14-3-3 gamma protects p21, a cyclin-dependent kinase inhibitor, from degradation mediated by the p53 suppressor MDMX, which may account for elevation of p21 levels independent of p53 and in response to DNA damage. Elevated expression of 14-3-3 gamma in human hepatocellular carcinoma predicts extrahepatic metastasis and worse survival, thus making this protein a candidate biomarker and a potential target for novel therapies against the disease. Pssm-ID: 206760 Cd Length: 246 Bit Score: 297.46 E-value: 2.38e-102
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| 14-3-3_eta | cd10025 | 14-3-3 eta, an isoform of 14-3-3 protein; 14-3-3 eta isoform (also known as tyrosine ... |
2-238 | 1.52e-95 | |||||
14-3-3 eta, an isoform of 14-3-3 protein; 14-3-3 eta isoform (also known as tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide) is expressed mainly in brain, and is involved in hypothalamic-pituitary-adrenocortical (HPA) axis regulation. In humans, it is encoded by the YWHAH gene, and is a positional and functional candidate for schizophrenia as well as bipolar disorder (BP). This gene contains a 7 bp repeat sequence in its 5' Untranslated Region (UTR), and early-onset schizophrenia has been associated with changes in the number of this repeat. 14-3-3 eta and gamma are found in the serum and synovial fluid of patients with joint inflammation. Specifically, 14-3-3 eta, which plays a regulatory role in chondrogenic differentiation, is significantly overexpressed in juvenile rheumatoid arthritis (JRA), a chronic inflammatory disease often associated with growth impairment. Overexpression of Gremlin 1, the bone morphogenetic protein antagonist, may play an oncogenic role in carcinomas of the uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma, since it functions by interaction with the 14-3-3 eta domain. Therefore, Gremlin 1 and its binding protein 14-3-3 eta could be appropriate targets for developing diagnostic and therapeutic strategies against human cancers. 14-3-3 domain is an essential part of 14-3-3 proteins, a ubiquitous class of regulatory, phosphoserine/threonine-binding proteins found in all eukaryotic cells, including yeast, protozoa and mammalian cells. Pssm-ID: 206761 Cd Length: 239 Bit Score: 279.69 E-value: 1.52e-95
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