DAP3

Last updated
DAP3
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases DAP3 , DAP-3, MRP-S29, MRPS29, bMRP-10, death associated protein 3, S29mt
External IDs OMIM: 602074 MGI: 1929538 HomoloGene: 3404 GeneCards: DAP3
Orthologs
SpeciesHumanMouse
Entrez

7818

65111

Ensembl

ENSG00000132676

ENSMUSG00000068921

UniProt

P51398

Q9ER88

RefSeq (mRNA)

NM_001199849
NM_001199850
NM_001199851
NM_004632
NM_033657

Contents

NM_001164533
NM_022994
NM_001368419

RefSeq (protein)

NP_001186778
NP_001186779
NP_001186780
NP_004623
NP_387506

NP_001158005
NP_075370
NP_001355348

Location (UCSC) Chr 1: 155.69 – 155.74 Mb Chr 3: 88.92 – 88.95 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

28S ribosomal protein S29, mitochondrial, also known as death-associated protein 3 (DAP3), is a protein that in humans is encoded by the DAP3 gene on chromosome 1. [5] [6] [7] [8] This gene encodes a 28S subunit protein of the mitochondrial ribosome (mitoribosome) and plays key roles in translation, cellular respiration, and apoptosis. [7] [8] [9] [10] Moreover, DAP3 is associated with cancer development, but has been observed to aid some cancers while suppressing others. [10] [11] [12]

Structure

The DAP3 gene encodes a 46 kDa protein located in the lower area of the small mitoribosomal subunit. [9] [12] [13] [14] This protein contains a P-loop motif that binds GTP and a highly conserved 17-residue targeting sequence responsible for its localization to the mitochondria. [9] [11] [12] [13] Of interest, many of the phosphorylation sites on this protein are highly conserved and clustered around GTP-binding motifs. [9]

Several splice variants were observed in human ESTs that differ largely in the 5’ UTR region. [7] [14] Pseudogenes for this gene are also found in chromosomes 1 and 2. [7]

Function

DAP3 is a 28S subunit protein of mitoribosomes and localizes to the mitochondrial matrix. [7] [8] [9] As part of the mitoribosome, DAP3 participates in the translation of the 13 ETC complex proteins encoded in the mitochondrial genome, and consequently, in the regulation of cellular respiration. [7] [8] [9] [10] As a member of the death-associated protein (DAP) family, DAP3 can also be found outside of the mitochondria to initiate the extrinsic apoptotic pathway through its interactions with apoptotic factors, such as tumor necrosis factor-alpha, Fas ligand, and gamma interferon. [7] [8] [11] [12] [13] Additionally, DAP3 interacts with the factor IPS-1 to activate caspases 3, 8, and 9, resulting in a type of extracellular apoptosis called anoikis. [12] [13] Moreover, DAP3 may contribute to apoptosis through its mediation of mitochondrial fragmentation, as this function extends to the mediation of the oxidative stress response, reactive oxygen species (ROS) production, and ultimately, mitochondrial homeostasis. [10] [11] [13] DAP3 is essential for life, and its deletion in embryos is lethal. [14] Nonetheless, DAP3 and its apoptotic activity can be inhibited by AKT phosphorylation. [12] [13]

Clinical significance

As aforementioned, death associated protein 3 (DAP3) has regulatory roles in cell respiration and apoptosis. Both opposites and cell respiration are important elements of cell death pathways and have underlying mechanistic roles in ischemia-reperfusion injury. [15] [16] [17]

During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response. [18] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.

DAP3 has been implicated in numerous cancers. Studies demonstrated that DAP3 expression tended to be low to nonexistent in the tumor cells of B-cell lymphoma, non-small cell lung cancer, head and neck cancer, breast cancer, gastric cancer, and colon cancer, possibly due to hypermethylation of the gene's promoter. [11] [12] Moreover, DAP3 expression has been positively correlated with improved cancer prognosis, indicating that the protein combats cancer progression through its proapoptotic function. [11] [12] As a result, DAP3 could serve as a potential biomarker to monitor the effectiveness of therapeutic treatments such as chemotherapy. [11] However, in other cancers, such as glioblastoma multiforme (GBM) and thymoma, DAP3 expression was found to be upregulated. [10] [14] Thus, the specific role of DAP3 in various cancers requires further study. [17]

Interactions

DAP3 has been shown to interact with:

Related Research Articles

Apoptosis Programmed cell death in multicellular organisms

Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between the ages of 8 and 14, approximately 20–30 billion cells die per day.

Fas ligand

Fas ligand is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.

Bcl-2-associated X protein

Apoptosis regulator BAX, also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. BAX is a member of the Bcl-2 gene family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis.

Fas receptor

The Fas receptor, also known as Fas, FasR, apoptosis antigen 1, cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the FAS gene. Fas was first identified using a monoclonal antibody generated by immunizing mice with the FS-7 cell line. Thus, the name Fas is derived from FS-7-associated surface antigen.

BH3 interacting-domain death agonist

The BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains, and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities.

Bcl-2-associated death promoter

The BCL2 associated agonist of cell death (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. BAD is a member of the BH3-only family, a subfamily of the Bcl-2 family. It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.

Caspase 8

Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs have been identified in numerous mammals for which complete genome data are available. These unique orthologs are also present in birds.

XIAP

X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3) and baculoviral IAP repeat-containing protein 4 (BIRC4), is a protein that stops apoptotic cell death. In humans, this protein (XIAP) is produced by a gene named XIAP gene located on the X chromosome.

BCL2-like 1

Bcl-2-like 1 or BCL2L1 is a human gene. Through alternative splicing, it encodes both of the human proteins Bcl-xL and Bcl-xS.

Death receptor 4

Death receptor 4 (DR4), also known as TRAIL receptor 1 (TRAILR1) and tumor necrosis factor receptor superfamily member 10A (TNFRSF10A), is a cell surface receptor of the TNF-receptor superfamily that binds TRAIL and mediates apoptosis.

BAG1

BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the BAG1 gene.

Caspase 10

Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene.

DAPK1

Death-associated protein kinase 1 is an enzyme that in humans is encoded by the DAPK1 gene.

BNIP3

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 is a protein that in humans is encoded by the BNIP3 gene.

Death receptor 5

Death receptor 5 (DR5), also known as TRAIL receptor 2 (TRAILR2) and tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), is a cell surface receptor of the TNF-receptor superfamily that binds TRAIL and mediates apoptosis.

Diablo homolog

Diablo homolog (DIABLO) is a mitochondrial protein that in humans is encoded by the DIABLO gene on chromosome 12. DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC. This protein binds inhibitor of apoptosis proteins (IAPs), thus freeing caspases to activate apoptosis. Due to its proapoptotic function, SMAC is implicated in a broad spectrum of tumors, and small molecule SMAC mimetics have been developed to enhance current cancer treatments.

DNA damage-inducible transcript 3

DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the DDIT3 gene. It is a member of the CCAAT/enhancer-binding protein (C/EBP) family of DNA-binding transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis, and has an important role in the cell's stress response.

HtrA serine peptidase 2

Serine protease HTRA2, mitochondrial is an enzyme that in humans is encoded by the HTRA2 gene. This protein is involved in caspase-dependent apoptosis and in Parkinson's disease.

SIVA1

Apoptosis regulatory protein Siva is a protein that in humans is encoded by the SIVA1 gene. This gene encodes a protein with an important role in the apoptotic pathway induced by the CD27 antigen, a member of the tumor necrosis factor receptor (TFNR) superfamily. The CD27 antigen cytoplasmic tail binds to the N-terminus of this protein. Two alternatively spliced transcript variants encoding distinct proteins have been described.

Mitochondrial ribosomal protein L41

39S ribosomal protein L41, mitochondrial is a protein that in humans is encoded by the MRPL41 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000132676 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000068921 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Kissil JL, Deiss LP, Bayewitch M, Raveh T, Khaspekov G, Kimchi A (Nov 1995). "Isolation of DAP3, a novel mediator of interferon-gamma-induced cell death". The Journal of Biological Chemistry. 270 (46): 27932–6. doi: 10.1074/jbc.270.46.27932 . PMID   7499268.
  6. ↑ Kissil JL, Kimchi A (September 1997). "Assignment of death associated protein 3 (DAP3) to human chromosome 1q21 by in situ hybridization". Cytogenetics and Cell Genetics. 77 (3–4): 252. doi:10.1159/000134587. PMID   9284927.
  7. 1 2 3 4 5 6 7 "Entrez Gene: DAP3 death associated protein 3".
  8. 1 2 3 4 5 6 Tang T, Zheng B, Chen SH, Murphy AN, Kudlicka K, Zhou H, Farquhar MG (Feb 2009). "hNOA1 interacts with complex I and DAP3 and regulates mitochondrial respiration and apoptosis". The Journal of Biological Chemistry. 284 (8): 5414–24. doi:10.1074/jbc.M807797200. PMC   2643507 . PMID   19103604.
  9. 1 2 3 4 5 6 Miller JL, Koc H, Koc EC (Feb 2008). "Identification of phosphorylation sites in mammalian mitochondrial ribosomal protein DAP3". Protein Science. 17 (2): 251–60. doi:10.1110/ps.073185608. PMC   2222727 . PMID   18227431.
  10. 1 2 3 4 5 Jacques C, Fontaine JF, Franc B, Mirebeau-Prunier D, Triau S, Savagner F, Malthiery Y (Jul 2009). "Death-associated protein 3 is overexpressed in human thyroid oncocytic tumours". British Journal of Cancer. 101 (1): 132–8. doi:10.1038/sj.bjc.6605111. PMC   2713694 . PMID   19536094.
  11. 1 2 3 4 5 6 7 Jia Y, Ye L, Ji K, Zhang L, Hargest R, Ji J, Jiang WG (Jan 2014). "Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy". British Journal of Cancer. 110 (2): 421–9. doi:10.1038/bjc.2013.712. PMC   3899757 . PMID   24300973.
  12. 1 2 3 4 5 6 7 8 9 10 11 Wazir U, Jiang WG, Sharma AK, Mokbel K (Feb 2012). "The mRNA expression of DAP3 in human breast cancer: correlation with clinicopathological parameters". Anticancer Research. 32 (2): 671–4. PMID   22287761.
  13. 1 2 3 4 5 6 Miyazaki T, Shen M, Fujikura D, Tosa N, Kim HR, Kon S, Uede T, Reed JC (Oct 2004). "Functional role of death-associated protein 3 (DAP3) in anoikis". The Journal of Biological Chemistry. 279 (43): 44667–72. doi: 10.1074/jbc.M408101200 . PMID   15302871.
  14. 1 2 3 4 5 6 7 Han MJ, Chiu DT, Koc EC (Apr 2010). "Regulation of mitochondrial ribosomal protein S29 (MRPS29) expression by a 5'-upstream open reading frame". Mitochondrion. 10 (3): 274–83. doi:10.1016/j.mito.2009.12.150. PMC   2844934 . PMID   20079882.
  15. ↑ Gracia-Sancho J, Casillas-Ramírez A, Peralta C (Aug 2015). "Molecular pathways in protecting the liver from ischaemia/reperfusion injury: a 2015 update". Clinical Science. 129 (4): 345–62. doi:10.1042/CS20150223. PMID   26014222.
  16. ↑ Ekert PG, Vaux DL (Dec 2005). "The mitochondrial death squad: hardened killers or innocent bystanders?". Current Opinion in Cell Biology. 17 (6): 626–30. doi:10.1016/j.ceb.2005.09.001. PMID   16219456.
  17. 1 2 Kissil JL, Kimchi A (Jun 1998). "Death-associated proteins: from gene identification to the analysis of their apoptotic and tumour suppressive functions". Molecular Medicine Today. 4 (6): 268–74. doi:10.1016/s1357-4310(98)01263-5. PMID   9679246.
  18. ↑ Kerr JF, Wyllie AH, Currie AR (Aug 1972). "Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics". British Journal of Cancer. 26 (4): 239–57. doi:10.1038/bjc.1972.33. PMC   2008650 . PMID   4561027.
  19. 1 2 Miyazaki T, Reed JC (Jun 2001). "A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins". Nature Immunology. 2 (6): 493–500. doi:10.1038/88684. PMID   11376335. S2CID   6923467.
  20. 1 2 Hulkko SM, Wakui H, Zilliacus J (Aug 2000). "The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the glucocorticoid receptor and affects the receptor function". The Biochemical Journal. 349 (3): 885–93. doi:10.1042/bj3490885. PMC   1221218 . PMID   10903152.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.