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== Function ==
== Function ==
Matrix metalloproteinase 28, also known as Epilysin, belongs to a family of proteins known as matrix metalloproteinases which are common to tissue regulation. Matrix metalloproteinases are commonly known to degrade the extracellular matrix, alongside regulating cell surface receptors MMP-28 releases growth factors and adhesion molecules to modulate inflammation. MMP-28 is unique in that it can be found in many regular tissues, denoting a potential role in maintaining the healthy structure and function of most tissue. MMPs commonly modulate their expression via negative and positive feedback loops as a result of releasing and responding to growth hormones.
Matrix metalloproteinase 28, also known as Epilysin, belongs to a family of proteins known as matrix metalloproteinases which are common to tissue regulation. Matrix metalloproteinases are commonly known to degrade the extracellular matrix, alongside regulating cell surface receptors MMP-28 releases growth factors and adhesion molecules to modulate inflammation<ref>{{Cite journal |last=Illman |first=Sara A. |last2=Lohi |first2=Jouko |last3=Keski-Oja |first3=Jorma |date=2008-11 |title=Epilysin (MMP-28) - structure, expression and potential functions |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2008.00782.x |journal=Experimental Dermatology |language=en |volume=17 |issue=11 |pages=897–907 |doi=10.1111/j.1600-0625.2008.00782.x}}</ref>. MMP-28 is unique in that it can be found in many regular tissues, denoting a potential role in maintaining the healthy structure and function of most tissue. MMPs commonly modulate their expression via negative and positive feedback loops as a result of releasing and responding to growth hormones.

MMP-28 is less frequently found in tissues such as the brain, colon, heart, and lungs<ref>{{Cite journal |last=Lohi |first=Jouko |last2=Wilson |first2=Carole L. |last3=Roby |first3=Jill D. |last4=Parks |first4=William C. |date=2001-03 |title=Epilysin, a Novel Human Matrix Metalloproteinase (MMP-28) Expressed in Testis and Keratinocytes and in Response to Injury |url=https://linkinghub.elsevier.com/retrieve/pii/S0021925819342838 |journal=Journal of Biological Chemistry |language=en |volume=276 |issue=13 |pages=10134–10144 |doi=10.1074/jbc.M001599200}}</ref>. However, MMP-28 is expressed heavily in organs such as the testes. Epilysin is also found in high concentration in basal keratinocytes in injured skin, even at some distance away from the wound, showing a role in repairing damaged tissue. MMP-28 also can alter the cell membrane to become more adhesive, and not allowing the cell to migrate.<ref>{{Cite journal |last=Rodgers |first=Ursula R. |last2=Kevorkian |first2=Lara |last3=Surridge |first3=Alison K. |last4=Waters |first4=Jasmine G. |last5=Swingler |first5=Tracey E. |last6=Culley |first6=Kirsty |last7=Illman |first7=Sara |last8=Lohi |first8=Jouko |last9=Parker |first9=Andrew E. |last10=Clark |first10=Ian M. |date=2009-06 |title=Expression and function of matrix metalloproteinase (MMP)-28 |url=https://linkinghub.elsevier.com/retrieve/pii/S0945053X09000377 |journal=Matrix Biology |language=en |volume=28 |issue=5 |pages=263–272 |doi=10.1016/j.matbio.2009.04.006 |pmc=PMC2724077 |pmid=19375502}}</ref>

== Structure ==
MMP-28 is a 520 amino acid long protein. The estimated signal peptide sequence appears as a long tail of random coil coming off of the protein that helps to guide the protein to excretion with the sequence PRCGVTD<ref name=":1">{{Cite journal |last=Lohi |first=Jouko |last2=Wilson |first2=Carole L. |last3=Roby |first3=Jill D. |last4=Parks |first4=William C. |date=2001-03 |title=Epilysin, a Novel Human Matrix Metalloproteinase (MMP-28) Expressed in Testis and Keratinocytes and in Response to Injury |url=http://dx.doi.org/10.1074/jbc.m001599200 |journal=Journal of Biological Chemistry |volume=276 |issue=13 |pages=10134–10144 |doi=10.1074/jbc.m001599200 |issn=0021-9258}}</ref>.
[[File:Alphafold Predicted Structure.png|left|thumb|354x354px|Predicted Alphafold 3d Structure<ref>{{Cite journal |last=Varadi |first=Mihaly |last2=Anyango |first2=Stephen |last3=Deshpande |first3=Mandar |last4=Nair |first4=Sreenath |last5=Natassia |first5=Cindy |last6=Yordanova |first6=Galabina |last7=Yuan |first7=David |last8=Stroe |first8=Oana |last9=Wood |first9=Gemma |last10=Laydon |first10=Agata |last11=Žídek |first11=Augustin |date=2022-01-07 |title=AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models |url=https://academic.oup.com/nar/article/50/D1/D439/6430488 |journal=Nucleic Acids Research |language=en |volume=50 |issue=D1 |pages=D439–D444 |doi=10.1093/nar/gkab1061 |issn=0305-1048 |pmc=PMC8728224 |pmid=34791371}}</ref><ref>{{Cite web |title=AlphaFold Database |url=https://www.uniprot.org/uniprotkb/Q9H239 |access-date=05/09/2022 |website=Uniprot}}</ref><ref>{{Cite journal |last=Jumper |first=John |last2=Evans |first2=Richard |last3=Pritzel |first3=Alexander |last4=Green |first4=Tim |last5=Figurnov |first5=Michael |last6=Ronneberger |first6=Olaf |last7=Tunyasuvunakool |first7=Kathryn |last8=Bates |first8=Russ |last9=Žídek |first9=Augustin |last10=Potapenko |first10=Anna |last11=Bridgland |first11=Alex |date=2021-08-26 |title=Highly accurate protein structure prediction with AlphaFold |url=https://www.nature.com/articles/s41586-021-03819-2 |journal=Nature |language=en |volume=596 |issue=7873 |pages=583–589 |doi=10.1038/s41586-021-03819-2 |issn=0028-0836 |pmc=PMC8371605 |pmid=34265844}}</ref>]]
The zinc binding catalytic site is tucked within an alpha helix within the center of the protein with a HEIGHTLGLTH sequence at positions 240-250 with a hemopexin-like domain. Epilysin contains 8 exons, 5 of which are splice sites unique to MMP-28 and not used by any other metalloproteinase in the MMP family.

Epilysin contains 8 exons, 5 of which are splice sites unique to MMP-28 and not used by any other metalloproteinase in the MMP family.

The full amino acid sequence is listed on uniprot<ref>{{Cite web |title=Uniprot |url=https://www.uniprot.org/uniprotkb/Q9H239/entry |archive-url=https://www.uniprot.org/uniprotkb/Q9H239/entry |access-date=05/09/2022 |website=Uniprot}}</ref>.

[[File:Chimera_Active_Site.pdf|center|thumb|506x506px|Chimera protein structure with highlighted active site]]


[[File:Predicted_Peptide_Location.pdf|left|thumb|626x626px|Predicted signal peptide sequence location]]

== Clinical Implications ==
The overexpression of MMP-28 is linked to the metastasis of tumors in cancer<ref>{{Cite journal |last=Zhang |first=Jizhen |last2=Pan |first2=Qi |last3=Yan |first3=Wenhui |last4=Wang |first4=Yiru |last5=He |first5=Xujun |last6=Zhao |first6=Zhongsheng |date=2018-03-22 |title=Overexpression of MMP21 and MMP28 is associated with gastric cancer progression and poor prognosis |url=http://dx.doi.org/10.3892/ol.2018.8328 |journal=Oncology Letters |doi=10.3892/ol.2018.8328 |issn=1792-1074}}</ref>. Expression of MMP-28 can be linked to tumor diameter, depth of invasion, and stage of metastasis. In patients with positive overexpression of MMP-28, survival may be significantly less likely compared to negative expression of this protein, making it a potentially important marker for proactive prognosis of some forms of cancer.

MMP-28 may also play an important role in the breakdown of myelin<ref>{{Cite journal |last=Werner |first=Sean R |last2=Dotzlaf |first2=Joseph E |last3=Smith |first3=Rosamund C |date=2008-09-09 |title=MMP-28 as a regulator of myelination |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551619/ |journal=BMC Neuroscience |volume=9 |pages=83 |doi=10.1186/1471-2202-9-83 |issn=1471-2202 |pmc=2551619 |pmid=18778487}}</ref>, an important component of nervous system functionality. Demyelization may interrupt nerve signaling or even halt it completely, which can create severe neurological effects such as multiple sclerosis transverse myelitis and neuromyelitis optica<ref>{{Cite web |title=Find out more about demylinating disease like multiple sclerosis |url=https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/expert-answers/demyelinating-disease/faq-20058521 |access-date=2022-04-24 |website=Mayo Clinic |language=en}}</ref>.


MMP-28 is less frequently found in tissues such as the brain, colon, heart, and lungs. However, MMP-28 is expressed heavily in organs such as the testes. Epilysin is also found in high concentration in basal keratinocytes in injured skin, even at some distance away from the wound, showing a role in repairing damaged tissue. MMP-28 also can alter the cell membrane to become more adhesive, and not allowing the cell to migrate.


== References ==
== References ==

Revision as of 08:22, 9 May 2022

MMP28
Identifiers
AliasesMMP28, EPILYSIN, MM28, MMP-25, MMP-28, MMP25, matrix metallopeptidase 28
External IDsOMIM: 608417; MGI: 2153062; HomoloGene: 41559; GeneCards: MMP28; OMA:MMP28 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

79148

118453

Ensembl

ENSG00000278843
ENSG00000271447

ENSMUSG00000020682

UniProt

Q9H239

n/a

RefSeq (mRNA)

NM_001032278
NM_024302
NM_032950

NM_080453
NM_172797
NM_001320300

RefSeq (protein)

NP_001027449
NP_077278
NP_116568
NP_116568.1

n/a

Location (UCSC)Chr 17: 35.76 – 35.8 MbChr 11: 83.33 – 83.35 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Matrix metalloproteinase 28 also known as epilysin is an enzyme that in humans is encoded by the MMP28 gene.[5][6][7]

Function

Matrix metalloproteinase 28, also known as Epilysin, belongs to a family of proteins known as matrix metalloproteinases which are common to tissue regulation. Matrix metalloproteinases are commonly known to degrade the extracellular matrix, alongside regulating cell surface receptors MMP-28 releases growth factors and adhesion molecules to modulate inflammation[8]. MMP-28 is unique in that it can be found in many regular tissues, denoting a potential role in maintaining the healthy structure and function of most tissue. MMPs commonly modulate their expression via negative and positive feedback loops as a result of releasing and responding to growth hormones.

MMP-28 is less frequently found in tissues such as the brain, colon, heart, and lungs[9]. However, MMP-28 is expressed heavily in organs such as the testes. Epilysin is also found in high concentration in basal keratinocytes in injured skin, even at some distance away from the wound, showing a role in repairing damaged tissue. MMP-28 also can alter the cell membrane to become more adhesive, and not allowing the cell to migrate.[10]

Structure

MMP-28 is a 520 amino acid long protein. The estimated signal peptide sequence appears as a long tail of random coil coming off of the protein that helps to guide the protein to excretion with the sequence PRCGVTD[11].

File:Alphafold Predicted Structure.png
Predicted Alphafold 3d Structure[12][13][14]

The zinc binding catalytic site is tucked within an alpha helix within the center of the protein with a HEIGHTLGLTH sequence at positions 240-250 with a hemopexin-like domain. Epilysin contains 8 exons, 5 of which are splice sites unique to MMP-28 and not used by any other metalloproteinase in the MMP family.

Epilysin contains 8 exons, 5 of which are splice sites unique to MMP-28 and not used by any other metalloproteinase in the MMP family.

The full amino acid sequence is listed on uniprot[15].

File:Chimera Active Site.pdf
Chimera protein structure with highlighted active site


File:Predicted Peptide Location.pdf
Predicted signal peptide sequence location

Clinical Implications

The overexpression of MMP-28 is linked to the metastasis of tumors in cancer[16]. Expression of MMP-28 can be linked to tumor diameter, depth of invasion, and stage of metastasis. In patients with positive overexpression of MMP-28, survival may be significantly less likely compared to negative expression of this protein, making it a potentially important marker for proactive prognosis of some forms of cancer.

MMP-28 may also play an important role in the breakdown of myelin[17], an important component of nervous system functionality. Demyelization may interrupt nerve signaling or even halt it completely, which can create severe neurological effects such as multiple sclerosis transverse myelitis and neuromyelitis optica[18].


References

  1. ^ a b c ENSG00000271447 GRCh38: Ensembl release 89: ENSG00000278843, ENSG00000271447 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020682 – 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. ^ Lohi J, Wilson CL, Roby JD, Parks WC (Mar 2001). "Epilysin, a novel human matrix metalloproteinase (MMP-28) expressed in testis and keratinocytes and in response to injury". J Biol Chem. 276 (13): 10134–44. doi:10.1074/jbc.M001599200. PMID 11121398.
  6. ^ Marchenko GN, Strongin AY (Mar 2001). "MMP-28, a new human matrix metalloproteinase with an unusual cysteine-switch sequence is widely expressed in tumors". Gene. 265 (1–2): 87–93. doi:10.1016/S0378-1119(01)00360-2. PMID 11255011.
  7. ^ "Entrez Gene: MMP28 matrix metallopeptidase 28".
  8. ^ Illman, Sara A.; Lohi, Jouko; Keski-Oja, Jorma (2008-11). "Epilysin (MMP-28) - structure, expression and potential functions". Experimental Dermatology. 17 (11): 897–907. doi:10.1111/j.1600-0625.2008.00782.x. {{cite journal}}: Check date values in: |date= (help)
  9. ^ Lohi, Jouko; Wilson, Carole L.; Roby, Jill D.; Parks, William C. (2001-03). "Epilysin, a Novel Human Matrix Metalloproteinase (MMP-28) Expressed in Testis and Keratinocytes and in Response to Injury". Journal of Biological Chemistry. 276 (13): 10134–10144. doi:10.1074/jbc.M001599200. {{cite journal}}: Check date values in: |date= (help)CS1 maint: unflagged free DOI (link)
  10. ^ Rodgers, Ursula R.; Kevorkian, Lara; Surridge, Alison K.; Waters, Jasmine G.; Swingler, Tracey E.; Culley, Kirsty; Illman, Sara; Lohi, Jouko; Parker, Andrew E.; Clark, Ian M. (2009-06). "Expression and function of matrix metalloproteinase (MMP)-28". Matrix Biology. 28 (5): 263–272. doi:10.1016/j.matbio.2009.04.006. PMC 2724077. PMID 19375502. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  11. ^ Lohi, Jouko; Wilson, Carole L.; Roby, Jill D.; Parks, William C. (2001-03). "Epilysin, a Novel Human Matrix Metalloproteinase (MMP-28) Expressed in Testis and Keratinocytes and in Response to Injury". Journal of Biological Chemistry. 276 (13): 10134–10144. doi:10.1074/jbc.m001599200. ISSN 0021-9258. {{cite journal}}: Check date values in: |date= (help)CS1 maint: unflagged free DOI (link)
  12. ^ Varadi, Mihaly; Anyango, Stephen; Deshpande, Mandar; Nair, Sreenath; Natassia, Cindy; Yordanova, Galabina; Yuan, David; Stroe, Oana; Wood, Gemma; Laydon, Agata; Žídek, Augustin (2022-01-07). "AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models". Nucleic Acids Research. 50 (D1): D439–D444. doi:10.1093/nar/gkab1061. ISSN 0305-1048. PMC 8728224. PMID 34791371.{{cite journal}}: CS1 maint: PMC format (link)
  13. ^ "AlphaFold Database". Uniprot. Retrieved 05/09/2022. {{cite web}}: Check date values in: |access-date= (help)
  14. ^ Jumper, John; Evans, Richard; Pritzel, Alexander; Green, Tim; Figurnov, Michael; Ronneberger, Olaf; Tunyasuvunakool, Kathryn; Bates, Russ; Žídek, Augustin; Potapenko, Anna; Bridgland, Alex (2021-08-26). "Highly accurate protein structure prediction with AlphaFold". Nature. 596 (7873): 583–589. doi:10.1038/s41586-021-03819-2. ISSN 0028-0836. PMC 8371605. PMID 34265844.{{cite journal}}: CS1 maint: PMC format (link)
  15. ^ "Uniprot". Uniprot. Retrieved 05/09/2022. {{cite web}}: Check |archive-url= value (help); Check date values in: |access-date= (help)
  16. ^ Zhang, Jizhen; Pan, Qi; Yan, Wenhui; Wang, Yiru; He, Xujun; Zhao, Zhongsheng (2018-03-22). "Overexpression of MMP21 and MMP28 is associated with gastric cancer progression and poor prognosis". Oncology Letters. doi:10.3892/ol.2018.8328. ISSN 1792-1074.
  17. ^ Werner, Sean R; Dotzlaf, Joseph E; Smith, Rosamund C (2008-09-09). "MMP-28 as a regulator of myelination". BMC Neuroscience. 9: 83. doi:10.1186/1471-2202-9-83. ISSN 1471-2202. PMC 2551619. PMID 18778487.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  18. ^ "Find out more about demylinating disease like multiple sclerosis". Mayo Clinic. Retrieved 2022-04-24.

Further reading

External links

  • The MEROPS online database for peptidases and their inhibitors: M10.030


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