Fascin: Difference between revisions

Latest revision as of 09:14, 8 June 2025

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Human fascin complex with anti-metastatic inhibitor (PDB id 6i0z).

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Function

Fascin (FASC) is an actin microfilament cross-linking and bundling protein in mammalian cells. At least 3 fascins are known. FASC 1 is expressed in multiple cells while FASC 2 is found mostly in retina and FASC 3 in testis^[1].

Disease

There is a direct relation between FASC expression in breast cancer patients and metastasis and shorter disease-free survival^[2].

Relevance

FASC is overexpresed in inflammatory bowel disease^[3].

Structural highlights

FASC 3D structure shows it to contain 4 β-trefoil domains. A complex between FASC and an anti-metastatic agent shows the inhibitor binding to domains 1 and 2 ^[4]. The anti-metastatic agent is situated in deep pocket.

↑ Gungor-Ordueri NE, Cheng CY. Fascin - An actin binding and bundling protein in the testis and its role in ectoplasmic specialization dynamics. Spermatogenesis. 2015 Feb 23;5(1):e1002733. doi: 10.1080/21565562.2014.1002733., eCollection 2015 Jan-Apr. PMID:26413410 doi:https://dx.doi.org/10.1080/21565562.2014.1002733
↑ Al-Alwan M, Olabi S, Ghebeh H, Barhoush E, Tulbah A, Al-Tweigeri T, Ajarim D, Adra C. Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. PLoS One. 2011;6(11):e27339. doi: 10.1371/journal.pone.0027339. Epub 2011 Nov 4. PMID:22076152 doi:https://dx.doi.org/10.1371/journal.pone.0027339
↑ Qualtrough D, Smallwood K, Littlejohns D, Pignatelli M. The actin-bundling protein fascin is overexpressed in inflammatory bowel disease and may be important in tissue repair. BMC Gastroenterol. 2011 Feb 23;11:14. doi: 10.1186/1471-230X-11-14. PMID:21345224 doi:https://dx.doi.org/10.1186/1471-230X-11-14
↑ Francis S, Croft D, Schuttelkopf AW, Parry C, Pugliese A, Cameron K, Claydon S, Drysdale M, Gardner C, Gohlke A, Goodwin G, Gray CH, Konczal J, McDonald L, Mezna M, Pannifer A, Paul NR, Machesky L, McKinnon H, Bower J. Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents. Bioorg Med Chem Lett. 2019 Jan 30. pii: S0960-894X(19)30056-3. doi:, 10.1016/j.bmcl.2019.01.035. PMID:30773430 doi:https://dx.doi.org/10.1016/j.bmcl.2019.01.035

3D structures of fascin

1dfc, 3llp, 3p53 - hFASC 1 - human
4gov, 4goy, 4gp0, 4gp3 - hFASC 1 (mutant)
6i0z, 6i17, 6i16, 6i18, 6i11, 6i10, 6i13, 6i12, 6i15, 6i14 - hFASC + anti-metastatic inhibitor
6b0t - hFASC + inhibitor
8vo6, 8vo7, 8vo8, 8vo9, 8voa – hFASC + actin – Cryo EM
7zau – hFASC + nanobody

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] Gungor-Ordueri NE, Cheng CY. Fascin - An actin binding and bundling protein in the testis and its role in ectoplasmic specialization dynamics. Spermatogenesis. 2015 Feb 23;5(1):e1002733. doi: 10.1080/21565562.2014.1002733., eCollection 2015 Jan-Apr. PMID:26413410 doi:https://dx.doi.org/10.1080/21565562.2014.1002733

[2] Al-Alwan M, Olabi S, Ghebeh H, Barhoush E, Tulbah A, Al-Tweigeri T, Ajarim D, Adra C. Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. PLoS One. 2011;6(11):e27339. doi: 10.1371/journal.pone.0027339. Epub 2011 Nov 4. PMID:22076152 doi:https://dx.doi.org/10.1371/journal.pone.0027339

[3] Qualtrough D, Smallwood K, Littlejohns D, Pignatelli M. The actin-bundling protein fascin is overexpressed in inflammatory bowel disease and may be important in tissue repair. BMC Gastroenterol. 2011 Feb 23;11:14. doi: 10.1186/1471-230X-11-14. PMID:21345224 doi:https://dx.doi.org/10.1186/1471-230X-11-14

[4] Francis S, Croft D, Schuttelkopf AW, Parry C, Pugliese A, Cameron K, Claydon S, Drysdale M, Gardner C, Gohlke A, Goodwin G, Gray CH, Konczal J, McDonald L, Mezna M, Pannifer A, Paul NR, Machesky L, McKinnon H, Bower J. Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents. Bioorg Med Chem Lett. 2019 Jan 30. pii: S0960-894X(19)30056-3. doi:, 10.1016/j.bmcl.2019.01.035. PMID:30773430 doi:https://dx.doi.org/10.1016/j.bmcl.2019.01.035

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@@ Line 1: / Line 1: @@
+<StructureSection load='6i0z' size='400' side='right' caption='Human fascin complex with anti-metastatic inhibitor (PDB id [[6i0z]]).' scene='86/862889/Cv/1'>
-<StructureSection load='6i0z' size='340' side='right' caption='Human fascin complex with anti-metastatic inhibitor (PDB id [[6i0z]]).' scene=''>
 == Function ==
@@ Line 17: / Line 16: @@
 == Structural highlights ==
+FASC 3D structure shows it to contain <scene name='86/862889/Cv/2'>4 β-trefoil domains</scene>. A complex between FASC and an anti-metastatic agent shows the <scene name='86/862889/Cv/3'>inhibitor binding to domains 1 and 2</scene> <ref>PMID:30773430</ref>. <scene name='86/862889/Cv/4'>The anti-metastatic agent is situated in deep pocket</scene>.
 </StructureSection>
 == 3D structures of fascin ==
@@ Line 26: / Line 24: @@
 [[6i0z]], [[6i17]], [[6i16]], [[6i18]], [[6i11]], [[6i10]], [[6i13]], [[6i12]], [[6i15]], [[6i14]] - hFASC + anti-metastatic inhibitor<br />
 [[6b0t]] - hFASC + inhibitor<br />
+[[8vo6]], [[8vo7]], [[8vo8]], [[8vo9]], [[8voa]] – hFASC + actin – Cryo EM<br />
+[[7zau]] – hFASC + nanobody<br />
 == References ==
 <references/>
+[[Category:Topic Page]]

Fascin: Difference between revisions

Latest revision as of 09:14, 8 June 2025

Contents

Function

Disease

Relevance

Structural highlights

3D structures of fascin

References

Proteopedia Page Contributors and Editors (what is this?)

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