RMDN3

Last updated
RMDN3
Identifiers
Aliases RMDN3 , FAM82A2, FAM82C, RMD-3, RMD3, ptpip51, regulator of microtubule dynamics 3
External IDs OMIM: 611873 MGI: 1915059 HomoloGene: 34926 GeneCards: RMDN3
Orthologs
SpeciesHumanMouse
Entrez

55177

67809

Ensembl

ENSG00000137824

ENSMUSG00000070730

UniProt

Q96TC7

Q3UJU9

RefSeq (mRNA)

NM_001033136

RefSeq (protein)

NP_001028308

Location (UCSC) Chr 15: 40.74 – 40.76 Mb Chr 2: 118.97 – 118.99 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Regulator of microtubule dynamics protein 3 (RMDN3), more commonly known as Protein tyrosine phosphatase interacting protein 51 (PTPIP51), is a protein that in humans is encoded by the RMDN3 gene on chromosome 15. [5] [6] This protein contributes to multiple biological functions, including cellular differentiation, proliferation, motility, cytoskeleton formation, and apoptosis, and has been associated with numerous cancers. [7] [8] [9]

Contents

Structure

PTPIP51 contains two conserved domains, called conserved region 1 (CR1) and conserved region 2 (CR2), which serve as binding sites for 14-3-3 proteins. Close to these conserved domains are two tyrosine residues, tyrosine 53 and 158, which serve as phosphorylation sites for various kinases. [8] In addition, PTPIP51 has a mitochondrial targeting sequence at its N-terminal which is responsible for inducing apoptosis, though some splicing variants lack this sequence. [5] [10] It also contains a 33-residue coiled coil domain at positions 92 – 124. [5] Crystal structure of TPR domain of PTPIP51 was determined. [11]

Function

PTPIP51 is a member of the RMDN protein family and localizes to the outer mitochondrial membrane, cytoplasm, and nucleus. [5] This protein is involved in cellular differentiation, proliferation, motility, cytoskeleton formation, and apoptosis. [7] [8] These biological functions thus serve to facilitate mammalian development through processes such as placental villi formation and angiogenesis. [7] [10] In particular, it is expressed in differentiated cells and tissues, such as follicular and inter-follicular epidermis, epithelia, skeletal muscle, testis, and nervous tissue. [7] [10] PTPIP51 is also expressed differentially in neutrophils, but not other immune cells, and thus may partake in immune cell signaling and myeloid development by interacting with TCPTP and PTP1B. [10] Its interactions with PTP1B, along with the proteins 14-3-3β, Raf-1, c-Src, PKA, and DAGKα, determine the mechanisms by which it influences the mitogen-activated protein kinase (MAPK) pathway. [8] PTPIP51 has been observed to induce apoptosis by disrupting the mitochondrial membrane potential, resulting in the release of cytochrome c. [12] In vitro phospholipid binding and transfer functions has been reported [11]

Clinical significance

There is currently little known about the RMDN3 protein with respect to its clinical significance other than an apparent role in oncology. The main mechanism for the RMDN3 protein is its role as an apoptotic constituent. 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. [13] 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.

Both the protein and mRNA of PTPIP51 have been implicated in various carcinomas, including prostate carcinoma (PCa), keratinocyte carcinoma, basal cell carcinomas, and squamous cell carcinomas. [7] [9] [10] It is hypothesized that overexpression of PTPIP51 in PCa results from retrotransposon elements activated by CpG island hypomethylation, which has been observed in late prostate carcinogenesis. [7] Moreover, the protein has been observed to interact with PTP1B to influence the MAPK pathway in acute myeloid leukemia. [8] In addition to cancers, PTPIP51 has been associated with benign prostate hyperplasia (BPH) and, by extension, with BPH-related conditions, including aging and lower urinary tract dysfunction. [7]

Interactions

RMDN3 has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">HSPA8</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the HSPA8 gene on chromosome 11. As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, autophagy, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence, and aging.

<span class="mw-page-title-main">Apoptosis regulator BAX</span> Mammalian protein found in Homo sapiens

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.

<span class="mw-page-title-main">Bcl-2 homologous antagonist killer</span> Protein-coding gene in the species Homo sapiens

Bcl-2 homologous antagonist/killer is a protein that in humans is encoded by the BAK1 gene on chromosome 6. The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress.

<span class="mw-page-title-main">HSPA1A</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 1, also termed Hsp72, is a protein that in humans is encoded by the HSPA1A gene. As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. In addition, Hsp72 also facilitates DNA repair. Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and inflammatory diseases such as Diabetes mellitus type 2 and rheumatoid arthritis.

<span class="mw-page-title-main">Peptidylprolyl isomerase A</span> Protein-coding gene in the species Homo sapiens

Peptidylprolyl isomerase A (PPIA), also known as cyclophilin A (CypA) or rotamase A is an enzyme that in humans is encoded by the PPIA gene on chromosome 7. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the cis-trans isomerization of proline imidic peptide bonds, which allows it to regulate many biological processes, including intracellular signaling, transcription, inflammation, and apoptosis. Due to its various functions, PPIA has been implicated in a broad range of inflammatory diseases, including atherosclerosis and arthritis, and viral infections.

<span class="mw-page-title-main">ADAM15</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.

<span class="mw-page-title-main">DLC1</span> Protein-coding gene in the species Homo sapiens

Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.

<span class="mw-page-title-main">HSPA1L</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 1L is a protein that in humans is encoded by the HSPA1L gene on chromosome 6. As a member of the heat shock protein 70 (Hsp70) family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and Graft-versus-host disease.

<span class="mw-page-title-main">DAP3</span> Protein-coding gene in the species Homo sapiens

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. This gene encodes a 28S subunit protein of the mitochondrial ribosome (mitoribosome) and plays key roles in translation, cellular respiration, and apoptosis. Moreover, DAP3 is associated with cancer development, but has been observed to aid some cancers while suppressing others.

<span class="mw-page-title-main">BOK (gene)</span> Protein-coding gene in the species Homo sapiens

Bok is a protein-coding gene of the Bcl-2 family that is found in many invertebrates and vertebrates. It induces apoptosis, a special type of cell death. Currently, the precise function of Bok in this process is unknown.

<span class="mw-page-title-main">ENDOG</span> Protein-coding gene in the species Homo sapiens

Endonuclease G, mitochondrial is an enzyme that in humans is encoded by the ENDOG gene. This protein primarily participates in caspase-independent apoptosis via DNA degradation when translocating from the mitochondrion to nucleus under oxidative stress. As a result, EndoG has been implicated in cancer, aging, and neurodegenerative diseases such as Parkinson's disease (PD). Regulation of its expression levels thus holds potential to treat or ameliorate those conditions.

<span class="mw-page-title-main">ADP/ATP translocase 4</span> Protein-coding gene in the species Homo sapiens

ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4. This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential. In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival. Outside this role, the SLC25AC31 gene has not been implicated in any human disease.

<span class="mw-page-title-main">VDAC2</span> Protein-coding gene in the species Homo sapiens

Voltage-dependent anion-selective channel protein 2 is a protein that in humans is encoded by the VDAC2 gene on chromosome 10. This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms. VDACs are generally involved in the regulation of cell metabolism, mitochondrial apoptosis, and spermatogenesis. Additionally, VDAC2 participates in cardiac contractions and pulmonary circulation, which implicate it in cardiopulmonary diseases. VDAC2 also mediates immune response to infectious bursal disease (IBD).

<span class="mw-page-title-main">Necroptosis</span> Programmed form of necrosis, or inflammatory cell death

Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell death via apoptosis. The discovery of necroptosis showed that cells can execute necrosis in a programmed fashion and that apoptosis is not always the preferred form of cell death. Furthermore, the immunogenic nature of necroptosis favors its participation in certain circumstances, such as aiding in defence against pathogens by the immune system. Necroptosis is well defined as a viral defense mechanism, allowing the cell to undergo "cellular suicide" in a caspase-independent fashion in the presence of viral caspase inhibitors to restrict virus replication. In addition to being a response to disease, necroptosis has also been characterized as a component of inflammatory diseases such as Crohn's disease, pancreatitis, and myocardial infarction.

<span class="mw-page-title-main">ADP/ATP translocase 2</span> Protein-coding gene in humans

ADP/ATP translocase 2 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.

<span class="mw-page-title-main">BinCARD</span> Protein-coding gene in the species Homo sapiens

Bcl10-interacting CARD protein, also known as BinCARD, is a protein that in humans is encoded by the C9orf89 gene on chromosome 9. BinCARD is a member of the death-domain superfamily and contains a caspase recruitment domain (CARD). This protein regulates apoptosis and the immune response by inhibiting Bcl10, thus implicating it in diseases stemming from Bcl10 dysfunction.

<span class="mw-page-title-main">MUL1</span> Protein-coding gene in the species Homo sapiens

Mitochondrial E3 ubiquitin protein ligase 1 (MUL1) is an enzyme that in humans is encoded by the MUL1 gene on chromosome 1. This enzyme localizes to the outer mitochondrial membrane, where it regulates mitochondrial morphology and apoptosis through multiple pathways, including the Akt, JNK, and NF-κB. Its proapoptotic function thus implicates it in cancer and Parkinson's disease.

<span class="mw-page-title-main">FASTKD1</span> Protein-coding gene in the species Homo sapiens

FAST kinase domain-containing protein 1 is a protein that in humans is encoded by the FASTKD1 gene on chromosome 2. This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress. FASTKD1 is also an RNA-binding protein and has been associated with endometrial cancer.

<span class="mw-page-title-main">FASTKD2</span> Protein-coding gene in the species Homo sapiens

FAST kinase domain-containing protein 2 (FASTKD2) is a protein that in humans is encoded by the FASTKD2 gene on chromosome 2. This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress. FASTKD2 has been implicated in mitochondrial encephalomyopathy, breast cancer, and prostate cancer.

<span class="mw-page-title-main">FAM162A</span> Protein-coding gene in the species Homo sapiens

Human growth and transformation-dependent protein (HGTD-P), also called E2-induced gene 5 protein (E2IG5), is a protein that in humans is encoded by the FAM162A gene on chromosome 3. This protein promotes intrinsic apoptosis in response to hypoxia via interactions with hypoxia-inducible factor-1α (HIF-1α). As a result, it has been associated with cerebral ischemia, myocardial infarction, and various cancers.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000137824 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000070730 – 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. 1 2 3 4 "Q96TC7 - RMD3_HUMAN".
  6. ↑ "Entrez Gene: Regulator of microtubule dynamics protein 3".
  7. 1 2 3 4 5 6 7 8 9 10 Koch P, Petri M, Paradowska A, Stenzinger A, Sturm K, Steger K, Wimmer M (Dec 2009). "PTPIP51 mRNA and protein expression in tissue microarrays and promoter methylation of benign prostate hyperplasia and prostate carcinoma". The Prostate. 69 (16): 1751–62. doi:10.1002/pros.21025. PMID   19691131. S2CID   10018029.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 13 Brobeil A, Bobrich M, Tag C, Wimmer M (Jul 2012). "PTPIP51 in protein interactions: regulation and in situ interacting partners". Cell Biochemistry and Biophysics . 63 (3): 211–22. doi:10.1007/s12013-012-9357-y. PMID   22544307. S2CID   17085225.
  9. 1 2 Barop J, Sauer H, Steger K, Wimmer M (May 2009). "Differentiation-dependent PTPIP51 expression in human skeletal muscle cell culture". The Journal of Histochemistry and Cytochemistry. 57 (5): 425–35. doi:10.1369/jhc.2008.952846. PMC   2675071 . PMID   19124842.
  10. 1 2 3 4 5 Koch P, Stenzinger A, Viard M, Märker D, Mayser P, Nilles M, Schreiner D, Steger K, Wimmer M (Oct 2008). "The novel protein PTPIP51 is expressed in human keratinocyte carcinomas and their surrounding stroma". Journal of Cellular and Molecular Medicine. 12 (5B): 2083–95. doi:10.1111/j.1582-4934.2008.00198.x. PMC   4506173 . PMID   19012732.
  11. 1 2 Yeo HK, Park TH, Kim HY, Jang H, Lee J, Hwang GS, Ryu SE, Park SH, Song HK, Ban HS, Yoon HJ, Lee BI (Jun 2021). "Phospholipid transfer function of PTPIP51 at mitochondria-associated ER membranes". EMBO Reports. 22 (6): e51323. doi:10.15252/embr.202051323. PMC   8183395 . PMID   33938112.
  12. ↑ Lv BF, Yu CF, Chen YY, Lu Y, Guo JH, Song QS, Ma DL, Shi TP, Wang L (Sep 2006). "Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondria protein with an N-terminal mitochondrial targeting sequence and induces apoptosis". Apoptosis. 11 (9): 1489–501. doi:10.1007/s10495-006-8882-9. PMID   16820967. S2CID   25152476.
  13. ↑ 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.
  14. ↑ De Vos, KJ; Mórotz, GM; Stoica, R; Tudor, EL; Lau, KF; Ackerley, S; Warley, A; Shaw, CE; Miller, CC (15 March 2012). "VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis". Human Molecular Genetics. 21 (6): 1299–311. doi:10.1093/hmg/ddr559. PMC   3284118 . PMID   22131369.
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.