Serpin: Difference between revisions

Revision as of 15:53, 10 September 2019

Function

Serpin or serine protease inhibitor (Ser) are protease inhibitors.

Ser C1 is Antithrombin.
Ser A5 is protein C inhibitor.
Ser A6 is Corticosteroid-binding globulin.
Ser A8 is angiotensinogen.
Ser A7 is a thyroxine-binding globulin.
Ser B1 is leukocyte elastase inhibitor^[1].
Ser B3 is squamos cell carcinoma antigen 1^[2].
Ser B5 is Maspin^[3].
Ser crmA is cysteine and serine proteinase inhibitor^[4].
Ser I1 is neuroserpin.
Ser A10 is protein Z-related protease inhibitor.
Ser A1 is Alpha-1-antitrypsin.
Ser A3 is α 1-antichymotrypsin.
Ser E1 is Plasminogen activator inhibitor.

Disease

Mutation in Ser A7 causes partial thyroxine-binding globulin deficiency^[5]. Ser B3 may contribute to tumor cell resistance to anti-neoplastic drugs^[6]. Ser A3 promotes growth of endometrial cancer cells ^[7].

Structural highlights

Ser A7 - a thyrosine-binding globulin - ^[8]. Water molecules are shown as red spheres.

Structure of cleaved human serpin A7. Residues 32-380 (cyan), residues 381-415 (salmon) complex with thyroxine-fluoresein, ethylene glycol and Ca+2 ion (green) (PDB entry 2xn6)

Drag the structure with the mouse to rotate

3D structures of serpin3D structures of serpin

Updated on 10-September-2019

Serpin
- 5hgc – Ser – zebra finch
- 1mtp, 1sng – Ser – Thermobifida fusca
Serpin A1 see Alpha-1-antitrypsin
Serpin A3 (α 1-antichymotrypsin)
- 2ach, 1as4, 3caa – hSer-A3
- 4caa, 1qmn, 3dlw – hSer-A3 (mutant)
- 5om2, 5om3, 5om5, 5om6, 5om7, 5om8, 6ftp – hSer-A3 (mutant) + antibiotic
- 1yxa – mSer-A3N - mouse
Serpin A5
- 2ol2 – hSer-A5
- 3dy0 – hSer-A5 + heparin
Serpin A6 see Corticosteroid-binding globulin
Serpin A7 or thyroxine-binding globulin
- 2riv – hSer-A7
- 2riw, 4x30 – hSer-A7 + thyroxine
- 2xn3 – hSer-A7 + mefenamic acid
- 2xn5 – hSer-A7 + furosemide
- 2xn6, 2xn7 – hSer-A7 + thyroxine-fluoresein
- 4yia - hSer-A7 + indomethacin
Serpin A8 or angiotensin-II
- 2jp8 – hSer-A8 – NMR
- 2wxw, 5m3x, 5m3y – hSer-A8
- 2x0b – hSer-A8 + renin
- 5e2q – hSer-A8 + DPP
- 4fys – hSer-A8 + CD13
- 2wxx, 2wxy, 2wy0 – mSer-A8 – mouse
- 2wxz, 2wy1 – rSer-A8
Serpin A10 or protein Z-dependent protease inhibitor
- 4afx, 4aju – hSer-A10 (mutant)
- 3h5c, 3f1s – hSer-A10 + vitamin K-dependent protein Z
- 4ajt – mSer-A10
Serpin A12 (Vaspin)
- 4if8 – hSer-A12
- 4y3k, 4y40 – hSer-A12 (mutant)
- 5ei0 – Ser-A12 – Escherichia coli
Serpin A18
- 4r9i – Ser-A18 – bee
Serpin B1 (leukocyte elastase inhibitor)
- 1hle – Ser-B1 – horse
- 4ga7 – hSer-B1 (mutant)
Serpin B3
- 2zv6, 4zk3 – hSer-B3
Serpin B4
- 4zk0 – hSer-B4
Serpin B5 (Maspin)
- 1xqg, 1wz9, 1xu8 - hSer-B5
- 1xqj – hSer-B5 (mutant)
Serpin C1 see Antithrombin
Ser crmA (ice inhibitor)
- 1c8o, 1f0c, 1m93 – cvSer-crmA (mutant) – cowpox virus
Serpin E1 see Plasminogen activator inhibitor
Serpin E2 or Gila-derived nexin
- 4dy0 – hSer-E2 + heparin
- 4dy7 – hSer-E2 + thrombin
Serpin I1 (Neuroserpin)
- 3fgq, 2f02, 3f5n – hSer-I1
- 1jjo – mSer-I1
Serpin K
- 1sek – ThSer-K – Tobacco hornworm
Serpin 1
- 1k9o – ThSer-1 (mutant) + trypsin II
- 3le2 – Ser-1 – Arabidopsis thaliana
Serpin 2
- 1m93 – cvSer-2
- 3nda – Ser-2 – Sheep tick
- 3pzf – mmSer-2 – malaria mosquito
- 4ro9, 4roa, 4rob, 4rsq – mmSer-2 (mutant)
Serpin 4 (Serine protease inhibitor 4)
- 4p0f, 4p0o – Ser-4 – Drosophila melanogaster
Serpin 18
- 4r9i – Ser-18 - silkworm

ReferencesReferences

↑ El Ouaamari A, Dirice E, Gedeon N, Hu J, Zhou JY, Shirakawa J, Hou L, Goodman J, Karampelias C, Qiang G, Boucher J, Martinez R, Gritsenko MA, De Jesus DF, Kahraman S, Bhatt S, Smith RD, Beer HD, Jungtrakoon P, Gong Y, Goldfine AB, Liew CW, Doria A, Andersson O, Qian WJ, Remold-O'Donnell E, Kulkarni RN. SerpinB1 Promotes Pancreatic beta Cell Proliferation. Cell Metab. 2016 Jan 12;23(1):194-205. doi: 10.1016/j.cmet.2015.12.001. Epub 2015, Dec 15. PMID:26701651 doi:http://dx.doi.org/10.1016/j.cmet.2015.12.001
↑ Quarta S, Vidalino L, Turato C, Ruvoletto M, Calabrese F, Valente M, Cannito S, Fassina G, Parola M, Gatta A, Pontisso P. SERPINB3 induces epithelial-mesenchymal transition. J Pathol. 2010 Jul;221(3):343-56. doi: 10.1002/path.2708. PMID:20527027 doi:http://dx.doi.org/10.1002/path.2708
↑ Maass N, Hojo T, Ueding M, Luttges J, Kloppel G, Jonat W, Nagasaki K. Expression of the tumor suppressor gene Maspin in human pancreatic cancers. Clin Cancer Res. 2001 Apr;7(4):812-7. PMID:11309327
↑ Zhou Q, Snipas S, Orth K, Muzio M, Dixit VM, Salvesen GS. Target protease specificity of the viral serpin CrmA. Analysis of five caspases. J Biol Chem. 1997 Mar 21;272(12):7797-800. PMID:9065443
↑ Sklate RT, Olcese MC, Maccallini GC, Sarmiento RG, Targovnik HM, Rivolta CM. Novel mutation p.A64D in the Serpina7 gene as a cause of partial thyroxine-binding globulin deficiency associated with increases affinity in transthyretin by a known p.A109T mutation in the TTR gene. Horm Metab Res. 2014 Feb;46(2):100-8. doi: 10.1055/s-0033-1358741. Epub 2013 Dec , 19. PMID:24356794 doi:http://dx.doi.org/10.1055/s-0033-1358741
↑ Pontisso P. Role of SERPINB3 in hepatocellular carcinoma. Ann Hepatol. 2014 Nov-Dec;13(6):722-7. PMID:25332258
↑ Yang GD, Yang XM, Lu H, Ren Y, Ma MZ, Zhu LY, Wang JH, Song WW, Zhang WM, Zhang R, Zhang ZG. SERPINA3 promotes endometrial cancer cells growth by regulating G2/M cell cycle checkpoint and apoptosis. Int J Clin Exp Pathol. 2014 Mar 15;7(4):1348-58. eCollection 2014. PMID:24817931
↑ Qi X, Loiseau F, Chan WL, Yan Y, Wei Z, Milroy LG, Myers RM, Ley SV, Read RJ, Carrell RW, Zhou A. Allosteric modulation of hormone release from thyroxine and corticosteroid binding-globulins. J Biol Chem. 2011 Feb 16. PMID:21325280 doi:10.1074/jbc.M110.171082

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] El Ouaamari A, Dirice E, Gedeon N, Hu J, Zhou JY, Shirakawa J, Hou L, Goodman J, Karampelias C, Qiang G, Boucher J, Martinez R, Gritsenko MA, De Jesus DF, Kahraman S, Bhatt S, Smith RD, Beer HD, Jungtrakoon P, Gong Y, Goldfine AB, Liew CW, Doria A, Andersson O, Qian WJ, Remold-O'Donnell E, Kulkarni RN. SerpinB1 Promotes Pancreatic beta Cell Proliferation. Cell Metab. 2016 Jan 12;23(1):194-205. doi: 10.1016/j.cmet.2015.12.001. Epub 2015, Dec 15. PMID:26701651 doi:http://dx.doi.org/10.1016/j.cmet.2015.12.001

[2] Quarta S, Vidalino L, Turato C, Ruvoletto M, Calabrese F, Valente M, Cannito S, Fassina G, Parola M, Gatta A, Pontisso P. SERPINB3 induces epithelial-mesenchymal transition. J Pathol. 2010 Jul;221(3):343-56. doi: 10.1002/path.2708. PMID:20527027 doi:http://dx.doi.org/10.1002/path.2708

[3] Maass N, Hojo T, Ueding M, Luttges J, Kloppel G, Jonat W, Nagasaki K. Expression of the tumor suppressor gene Maspin in human pancreatic cancers. Clin Cancer Res. 2001 Apr;7(4):812-7. PMID:11309327

[4] Zhou Q, Snipas S, Orth K, Muzio M, Dixit VM, Salvesen GS. Target protease specificity of the viral serpin CrmA. Analysis of five caspases. J Biol Chem. 1997 Mar 21;272(12):7797-800. PMID:9065443

[5] Sklate RT, Olcese MC, Maccallini GC, Sarmiento RG, Targovnik HM, Rivolta CM. Novel mutation p.A64D in the Serpina7 gene as a cause of partial thyroxine-binding globulin deficiency associated with increases affinity in transthyretin by a known p.A109T mutation in the TTR gene. Horm Metab Res. 2014 Feb;46(2):100-8. doi: 10.1055/s-0033-1358741. Epub 2013 Dec , 19. PMID:24356794 doi:http://dx.doi.org/10.1055/s-0033-1358741

[6] Pontisso P. Role of SERPINB3 in hepatocellular carcinoma. Ann Hepatol. 2014 Nov-Dec;13(6):722-7. PMID:25332258

[7] Yang GD, Yang XM, Lu H, Ren Y, Ma MZ, Zhu LY, Wang JH, Song WW, Zhang WM, Zhang R, Zhang ZG. SERPINA3 promotes endometrial cancer cells growth by regulating G2/M cell cycle checkpoint and apoptosis. Int J Clin Exp Pathol. 2014 Mar 15;7(4):1348-58. eCollection 2014. PMID:24817931

[8] Qi X, Loiseau F, Chan WL, Yan Y, Wei Z, Milroy LG, Myers RM, Ley SV, Read RJ, Carrell RW, Zhou A. Allosteric modulation of hormone release from thyroxine and corticosteroid binding-globulins. J Biol Chem. 2011 Feb 16. PMID:21325280 doi:10.1074/jbc.M110.171082

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 ==Structural highlights ==
-Ser A7 - a thyrosine-binding globulin - <scene name='51/517379/Cv/3'>binding site contains thyroxin derivative</scene><ref>PMID:21325280</ref>. Water molecules are shown as red spheres. <scene name='51/517379/Bp/1'>TextToBeDisplayed</scene>
+Ser A7 - a thyrosine-binding globulin - <scene name='51/517379/Cv/3'>binding site contains thyroxin derivative</scene><ref>PMID:21325280</ref>. Water molecules are shown as red spheres.
 </StructureSection>