AP5M1

Last updated
AP5M1
Identifiers
Aliases AP5M1 , C14orf108, MUDENG, Mu5, MuD, adaptor related protein complex 5 mu 1 subunit, adaptor related protein complex 5 subunit mu 1
External IDs OMIM: 614368 MGI: 1921635 HomoloGene: 10081 GeneCards: AP5M1
Orthologs
SpeciesHumanMouse
Entrez

55745

74385

Ensembl

ENSG00000053770

n/a

UniProt

Q9H0R1

Q8BJ63

RefSeq (mRNA)

NM_018229

NM_144535
NM_001360070

RefSeq (protein)

NP_060699

NP_653118
NP_001346999

Location (UCSC) Chr 14: 57.27 – 57.3 Mb n/a
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse
The 3D structure of the protein AP5M1. The alpha fold structure was obtained from Uniprot (AF-Q9H0R1-F1) and modeled using ChimeraX. The three domains are emphasized with color. The first domain is yellow, the second domain is teal, and the third domain is pink. AP5M1 3D Protein Structure.png
The 3D structure of the protein AP5M1. The alpha fold structure was obtained from Uniprot (AF-Q9H0R1-F1) and modeled using ChimeraX. The three domains are emphasized with color. The first domain is yellow, the second domain is teal, and the third domain is pink.

AP-5 complex subunit mu (AP5M1), otherwise known as MUDENG (MuD), is a protein that is encoded by the AP5M1 gene. [4] The AP5M1 gene was originally discovered when screening for genes which helped to promote death in Fas-mediated apoptosis. [5] [6] It is a highly conserved gene. [5] [7] [6]

Contents

MuD is the medium-sized subunit of the AP5 adaptor complex. [8] MuD is expressed throughout the body and is located within both the mitochondria as well as the endoplasmic reticulum (ER) of cells. [5] [7] [6]

MuD has been shown to have the ability to induce apoptosis; however, there is evidence that it plays an anti-apoptotic role in apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). [5] [7] [6] [9] [10]

Structure

MuD consists of 490 amino acids that interact to form a tertiary structure with three domains. [11] [12]

The overall structure shares similarities with adaptor protein (AP) complexes that are related to clathrin-mediated endocytosis; amino acids 197 through 417 are a shared adaptin domain found in AP μ subunits. [13] [14]

Within the adaptin domain are two aspartic acids, D276 and D290, which serve as binding sites for caspase-3. [14]

Function

The overall function of MuD remains unclear. [15] It is known, however, that MuD regulates the expression of BAX, a pro-apoptotic member of the Bcl-2 family of proteins. [16] [15] Due to— and dependent upon— this relationship, MuD has been able to induce cell death in tumor cells. [17] [16] [15]

Additionally, MuD has been suggested to be involved in endosomal trafficking. [17] [16] [18] [15]

TRAIL and MuD

TRAIL, an apoptosis-inducing ligand, activates caspase-8 and caspase-3, which initiate the intrinsic pathway of apoptosis by cleaving BH3 interacting-domain death agonist (Bid) into tBid, another pro-apoptotic member of the Bl-2 protein family. [19] [20] [21] [22] MuD interferes with this process because D276 and D290 act as alternative binding sites for caspase-3, decreasing the amount of Bid that gets cleaved. [20] [19] [21] Tumor cells being treated with TRAIL are 32% more likely to survive when MuD is being expressed. [19]    

Related Research Articles

<span class="mw-page-title-main">Caspase</span> Family of cysteine proteases

Caspases are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions.

<span class="mw-page-title-main">Death effector domain</span> InterPro Domain

The death-effector domain (DED) is a protein interaction domain found only in eukaryotes that regulates a variety of cellular signalling pathways. The DED domain is found in inactive procaspases and proteins that regulate caspase activation in the apoptosis cascade such as FAS-associating death domain-containing protein (FADD). FADD recruits procaspase 8 and procaspase 10 into a death induced signaling complex (DISC). This recruitment is mediated by a homotypic interaction between the procaspase DED and a second DED that is death effector domain in an adaptor protein that is directly associated with activated TNF receptors. Complex formation allows proteolytic activation of procaspase into the active caspase form which results in the initiation of apoptosis. Structurally the DED domain are a subclass of protein motif known as the death fold and contains 6 alpha helices, that closely resemble the structure of the Death domain (DD).

<span class="mw-page-title-main">Fas receptor</span> Protein found in humans

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.

<span class="mw-page-title-main">Caspase 3</span> Protein-coding gene in the species Homo sapiens

Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.

<span class="mw-page-title-main">Caspase 7</span> Protein-coding gene in the species Homo sapiens

Caspase-7, apoptosis-related cysteine peptidase, also known as CASP7, is a human protein encoded by the CASP7 gene. CASP7 orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.

<span class="mw-page-title-main">Caspase 6</span> Protein-coding gene in the species Homo sapiens

Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene. CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis, early immune response and neurodegeneration in Huntington's and Alzheimer's disease.

<span class="mw-page-title-main">Brain-specific angiogenesis inhibitor 1</span> Protein-coding gene in the species Homo sapiens

Brain-specific angiogenesis inhibitor 1 is a protein that in humans is encoded by the BAI1 gene. It is a member of the adhesion-GPCR family of receptors.

<span class="mw-page-title-main">APAF1</span> Mammalian protein found in Homo sapiens

Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.

<span class="mw-page-title-main">DNA damage-inducible transcript 3</span> Human protein and coding gene

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.

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

Protein kinase C iota type is an enzyme that in humans is encoded by the PRKCI gene.

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

DNA fragmentation factor subunit alpha (DFFA), also known as Inhibitor of caspase-activated DNase (ICAD), is a protein that in humans is encoded by the DFFA gene.

<span class="mw-page-title-main">GADD45B</span> Protein-coding gene in the species Homo sapiens

Growth arrest and DNA-damage-inducible, beta, also known as GADD45B, is a protein which in humans is encoded by the GADD45B gene.

<span class="mw-page-title-main">N-alpha-acetyltransferase 10</span> Protein-coding gene in the species Homo sapiens

N-alpha-acetyltransferase 10 (NAA10) also known as NatA catalytic subunit Naa10 and arrest-defective protein 1 homolog A (ARD1A) is an enzyme subunit that in humans is encoded NAA10 gene. Together with its auxiliary subunit Naa15, Naa10 constitutes the NatA complex that specifically catalyzes the transfer of an acetyl group from acetyl-CoA to the N-terminal primary amino group of certain proteins. In higher eukaryotes, 5 other N-acetyltransferase (NAT) complexes, NatB-NatF, have been described that differ both in substrate specificity and subunit composition.

<span class="mw-page-title-main">Caspase 14</span> Protein-coding gene in the species Homo sapiens

Caspase 14 is an enzyme that in humans is encoded by the CASP14 gene.

<span class="mw-page-title-main">DNASE1L3</span> Protein-coding gene in the species Homo sapiens

Deoxyribonuclease gamma is an enzyme that in humans is encoded by the DNASE1L3 gene.

<span class="mw-page-title-main">IFI35</span> Protein-coding gene in the species Homo sapiens

Interferon-induced 35 kDa protein is a protein that in humans is encoded by the IFI35 gene.

<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">GADD45GIP1</span> Protein-coding gene in the species Homo sapiens

Growth arrest and DNA-damage-inducible proteins-interacting protein 1 is a protein that in humans is encoded by the GADD45GIP1 gene.

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

Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. It breaks up the DNA during apoptosis and promotes cell differentiation. It is usually an inactive monomer inhibited by ICAD. This is cleaved before dimerization.

Caspase-2 is an enzyme. This enzyme catalyses the following chemical reaction

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000053770 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ Hirst, Jennifer; Barlow, Lael D.; Francisco, Gabriel Casey; Sahlender, Daniela A.; Seaman, Matthew N. J.; Dacks, Joel B.; Robinson, Margaret S. (2011-10-11). "The fifth adaptor protein complex". PLOS Biology. 9 (10): e1001170. doi:10.1371/journal.pbio.1001170. ISSN   1545-7885. PMC   3191125 . PMID   22022230.
  5. 1 2 3 4 Lee, Mi-Rha; Shin, Jin Na; Moon, Ae Ran; Park, Sun-Young; Hong, Gilsun; Lee, Mi-Ja; Yun, Cheol-Won; Seol, Dai-Wu; Piya, Sujan; Bae, Jeehyeon; Oh, Jae-Wook; Kim, Tae-Hyoung (2008-06-06). "A novel protein, MUDENG, induces cell death in cytotoxic T cells". Biochemical and Biophysical Research Communications. 370 (3): 504–508. doi:10.1016/j.bbrc.2008.03.139. ISSN   1090-2104. PMID   18395520.
  6. 1 2 3 4 Choi, J.-H.; Lim, J.-B.; Wickramanayake, D. D.; Wagley, Y.; Kim, J.; Lee, H.-C.; Seo, H. G.; Kim, T.-H.; Oh, J.-W. (2016). "Characterization of MUDENG, a novel anti-apoptotic protein". Oncogenesis. 5 (5): e221. doi:10.1038/oncsis.2016.30. ISSN   2157-9024. PMC   4945747 . PMID   27136675.
  7. 1 2 3 Muthu, Manikandan; Chun, Sechul; Gopal, Judy; Park, Gyun-Seok; Nile, Arti; Shin, Jisoo; Shin, Juhyun; Kim, Tae-Hyoung; Oh, Jae-Wook (2020-08-04). "The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?". International Journal of Molecular Sciences. 21 (15): 5583. doi: 10.3390/ijms21155583 . ISSN   1422-0067. PMC   7432215 . PMID   32759789.
  8. ↑ Hirst, Jennifer; Irving, Carol; Borner, Georg H. H. (2012-11-21). "Adaptor protein complexes AP-4 and AP-5: new players in endosomal trafficking and progressive spastic paraplegia". Traffic. 14 (2): 153–164. doi: 10.1111/tra.12028 . ISSN   1600-0854. PMID   23167973. S2CID   13766991.
  9. ↑ Shin, Jin Na; Han, Ji Hye; Kim, Ji-Young; Moon, Ae-Ran; Kim, Ji Eun; Chang, Jeong Hwan; Bae, Jeehyeon; Oh, Jae Wook; Kim, Tae-Hyoung (2013-05-31). "MUDENG is cleaved by caspase-3 during TRAIL-induced cell death". Biochemical and Biophysical Research Communications. 435 (2): 234–238. doi:10.1016/j.bbrc.2013.04.075. ISSN   1090-2104. PMID   23665015.
  10. ↑ Won, Miae; Luo, Yongyang; Lee, Dong-Ho; Shin, Eunkyoung; Suh, Dae-Shik; Kim, Tae-Hyoung; Jin, Hanyong; Bae, Jeehyeon (2019-10-15). "BAX is an essential key mediator of AP5M1-induced apoptosis in cervical carcinoma cells". Biochemical and Biophysical Research Communications. 518 (2): 368–373. doi:10.1016/j.bbrc.2019.08.065. ISSN   1090-2104. PMID   31427081. S2CID   201095590.
  11. ↑ Muthu, Manikandan; Chun, Sechul; Gopal, Judy; Park, Gyun-Seok; Nile, Arti; Shin, Jisoo; Shin, Juhyun; Kim, Tae-Hyoung; Oh, Jae-Wook (2020-08-04). "The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?". International Journal of Molecular Sciences. 21 (15): 5583. doi: 10.3390/ijms21155583 . ISSN   1422-0067. PMC   7432215 . PMID   32759789.
  12. ↑ Choi, J.-H.; Lim, J.-B.; Wickramanayake, D. D.; Wagley, Y.; Kim, J.; Lee, H.-C.; Seo, H. G.; Kim, T.-H.; Oh, J.-W. (2016). "Characterization of MUDENG, a novel anti-apoptotic protein". Oncogenesis. 5 (5): e221. doi:10.1038/oncsis.2016.30. ISSN   2157-9024. PMC   4945747 . PMID   27136675.
  13. ↑ Lee, Mi-Rha; Shin, Jin Na; Moon, Ae Ran; Park, Sun-Young; Hong, Gilsun; Lee, Mi-Ja; Yun, Cheol-Won; Seol, Dai-Wu; Piya, Sujan; Bae, Jeehyeon; Oh, Jae-Wook; Kim, Tae-Hyoung (2008-06-06). "A novel protein, MUDENG, induces cell death in cytotoxic T cells". Biochemical and Biophysical Research Communications. 370 (3): 504–508. doi:10.1016/j.bbrc.2008.03.139. ISSN   1090-2104. PMID   18395520.
  14. 1 2 Shin, Jin Na; Han, Ji Hye; Kim, Ji-Young; Moon, Ae-Ran; Kim, Ji Eun; Chang, Jeong Hwan; Bae, Jeehyeon; Oh, Jae Wook; Kim, Tae-Hyoung (2013-05-31). "MUDENG is cleaved by caspase-3 during TRAIL-induced cell death". Biochemical and Biophysical Research Communications. 435 (2): 234–238. doi:10.1016/j.bbrc.2013.04.075. ISSN   1090-2104. PMID   23665015.
  15. 1 2 3 4 Won, Miae; Luo, Yongyang; Lee, Dong-Ho; Shin, Eunkyoung; Suh, Dae-Shik; Kim, Tae-Hyoung; Jin, Hanyong; Bae, Jeehyeon (2019-10-15). "BAX is an essential key mediator of AP5M1-induced apoptosis in cervical carcinoma cells". Biochemical and Biophysical Research Communications. 518 (2): 368–373. doi:10.1016/j.bbrc.2019.08.065. ISSN   1090-2104. PMID   31427081. S2CID   201095590.
  16. 1 2 3 Muthu, Manikandan; Chun, Sechul; Gopal, Judy; Park, Gyun-Seok; Nile, Arti; Shin, Jisoo; Shin, Juhyun; Kim, Tae-Hyoung; Oh, Jae-Wook (2020-08-04). "The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?". International Journal of Molecular Sciences. 21 (15): 5583. doi: 10.3390/ijms21155583 . ISSN   1422-0067. PMC   7432215 . PMID   32759789.
  17. 1 2 Lee, Mi-Rha; Shin, Jin Na; Moon, Ae Ran; Park, Sun-Young; Hong, Gilsun; Lee, Mi-Ja; Yun, Cheol-Won; Seol, Dai-Wu; Piya, Sujan; Bae, Jeehyeon; Oh, Jae-Wook; Kim, Tae-Hyoung (2008-06-06). "A novel protein, MUDENG, induces cell death in cytotoxic T cells". Biochemical and Biophysical Research Communications. 370 (3): 504–508. doi:10.1016/j.bbrc.2008.03.139. ISSN   1090-2104. PMID   18395520.
  18. ↑ Hirst, Jennifer; Irving, Carol; Borner, Georg H. H. (2012-11-21). "Adaptor protein complexes AP-4 and AP-5: new players in endosomal trafficking and progressive spastic paraplegia". Traffic. 14 (2): 153–164. doi: 10.1111/tra.12028 . ISSN   1600-0854. PMID   23167973. S2CID   13766991.
  19. 1 2 3 Choi, J.-H.; Lim, J.-B.; Wickramanayake, D. D.; Wagley, Y.; Kim, J.; Lee, H.-C.; Seo, H. G.; Kim, T.-H.; Oh, J.-W. (2016). "Characterization of MUDENG, a novel anti-apoptotic protein". Oncogenesis. 5 (5): e221. doi:10.1038/oncsis.2016.30. ISSN   2157-9024. PMC   4945747 . PMID   27136675.
  20. 1 2 Muthu, Manikandan; Chun, Sechul; Gopal, Judy; Park, Gyun-Seok; Nile, Arti; Shin, Jisoo; Shin, Juhyun; Kim, Tae-Hyoung; Oh, Jae-Wook (2020-08-04). "The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?". International Journal of Molecular Sciences. 21 (15): 5583. doi: 10.3390/ijms21155583 . ISSN   1422-0067. PMC   7432215 . PMID   32759789.
  21. 1 2 Shin, Jin Na; Han, Ji Hye; Kim, Ji-Young; Moon, Ae-Ran; Kim, Ji Eun; Chang, Jeong Hwan; Bae, Jeehyeon; Oh, Jae Wook; Kim, Tae-Hyoung (2013-05-31). "MUDENG is cleaved by caspase-3 during TRAIL-induced cell death". Biochemical and Biophysical Research Communications. 435 (2): 234–238. doi:10.1016/j.bbrc.2013.04.075. ISSN   1090-2104. PMID   23665015.
  22. ↑ Dimberg, L. Y.; Anderson, C. K.; Camidge, R.; Behbakht, K.; Thorburn, A.; Ford, H. L. (2013-03-14). "On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics". Oncogene. 32 (11): 1341–1350. doi:10.1038/onc.2012.164. ISSN   1476-5594. PMC   4502956 . PMID   22580613.


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