AMINO ACIDS – SUPPLEMENTARY FILE:

Computational analyses of the effect of novel amino acid clusters of human transglutaminase 2 on its structure and function

Kiruphagaran Thangaraju*, Róbert Király*, János András Mótyán*, Viktor Attila Ambrus#*, Mónika Fuxreiter #*†, László Fésüs*‡†

*Department of Biochemistry and Molecular Biology, #MTA-DE Momentum Laboratory of Protein Dynamics, ‡MTA-DE Stem cell, Apoptosis and Genomics Research Group of Hungarian Academy of Sciences, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;

To whom correspondence should be addressed: László Fésüs, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1., Debrecen, Hungary 4012. Phone: +36 52 416 432, Fax: +36 52 314 989, Email:

† These authors contributed equally to this study

Comparative sequence alignment of human and primate TGM2 proteins

HUMAN MAEELVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFS 60

PONAB MAEDLVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFS 60

NOMLE ---DLVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRYY-ASVYSLTFS 56

GORGO MAEELVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFS 60

PANTR MAEELVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFS 60

CALJA MAEELILERCDLELESNGRDHHTADLCQEKLVVRRGQPFRLTLHFEGRNYEASVDSLTFS 60

MACMU MAEDLVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFS 60

BABON MAEDLVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFS 60 GREEN MAEDLILERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFS 60

HUMAN VVTGPAPSQEAGTKARFPLRDAVEEGDWTATVVDQQDCTLSLQLTTPANAPIGLYRLSLE 120

PONAB VVTGPAPSQEAGTKARFPLRDAVEEGDWTATVVDQQDCTLSLQLTTPADAPIGLYRLSLE 120

NOMLE VVTGPAPSQEAGTKARFPLRDAVEEGDWTATVVDQQDRTLSLQLTTPANAPIGLYRLSLE 116

GORGO VVTGPAPSQEAGTKARFPLRDAVEEGDWTATVVDQQDCTLSLQLTTPANAPIGLYRLSLE 120

PANTR VVTGPAPSQEAGTKARFPLRDAVDEGDWTATVVDQQDCTLSLQLTTPANAPIGLYRLSLE 120

CALJA VVTGPAPSKEAGTKARFPLQDAVEEGGWTAAVVDQQDCALSLQLTAPADAPIGLYRLSLE 120

MACMU VVTGPAPSQEAGTKARFPLRDAVEEGDWTATVVDQQDCTLSLQLTTPANAPIGLYRLSLE 120

BABON VVTGPAPSQEAGTKARFPLRDAVEEGDWTATVVDQQDCTLSLQLTTPANAPIGLYRLSLE 120

GREEN VVTGPAPSQEAGTKARFPLRDAVEEGDWTATVVDQQDCTLSLQLTTPANAPIGLYRLSLE 120

HUMAN ASTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERQEYVLTQQGFIYQGSAKFIKNIPW 180

PONAB ASTGYQGSSFVLGHFILLFNSWCPADAVYLDSEEERQEYVLTQQGFIYQGSAKFIKNIPW 180

NOMLE ATTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERQEYILTQQGFIYQGSAKFIKNIPW 176

GORGO ASTGYQGSSFVLGHFILLFNAWCPADAVYLDLEEERQEYVLTQQGFIYQGSAKFIKNIPW 180

PANTR ASTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERQEYVLTQQGFIYQGSAKFIKNIPW 180

CALJA AATGYQGSSFVLGHFTLLFNAWCPVDAVYLDSEEERQEYILTQQGFIYQGSAKFIKSVPW 180

MACMU ASTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERREYVLTQQGFIYQGSAKFIKSIPW 180

BABON ASTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERQEYVLTQQGFIYQGSAKFIKSIPW 180

GREEN ASTGYQGSSFVLGHFILLFNAWCPADAVYLDLEEERQEYVLTQQGFIYQGSAKFIKSIPW 180

HUMAN NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGR 240

PONAB NFGQFEDGILDICLMLLDVNPKFLKNAGRDCSRRSSPIYVGRVVSGMVNCNDDQGVLLGR 240

NOMLE NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVRKKR 236

GORGO NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGR 240

PANTR NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGR 240

CALJA NFGQFEDGILDICLMLLDVNPKFVKDAGRDCSRRSSPIYIGRVVSGMVNCNDDQGVLLGR 240

MACMU NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGR 240

BABON NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGR 240

GREEN NFGQFEDGILDICLILLDVNPKFLKNAGRDSSRRSSPVYVGRVVSGMVNCNDDQGVLLGR 240

HUMAN WDNNYGDGVSPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN 300

PONAB WDNNYGDGISPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN 300

NOMLE WDNNYGDGISPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN 296

GORGO WDNNYGDGISPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN 300

PANTR WDNNYGDGVSPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN 300

CALJA WDNNYGDGVSPMFWIGSVDILRRWRNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN 300

MACMU WDNNYGDGVSPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN 300

BABON WDNNYGDGVNPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN 300

GREEN WDNNYGDGVSPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN 300

HUMAN YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT 360

PONAB YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT 360

NOMLE YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT 356

GORGO YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT 360

PANTR YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT 360

CALJA YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT 360

MACMU YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT 360

BABON YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT 360

GREEN YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT 360

HUMAN PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVHKSINRSL 420

PONAB PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVHKSINHSL 420

NOMLE PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVHKSINHSL 416

GORGO PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVHKSINRSL 420

PANTR PQEKSGGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVHKSINRSL 420

CALJA PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSMHKSVNRSL 420

MACMU PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVSKSINRSL 420

BABON PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVSKSINRSL 420

GREEN PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVSKSINRSL 420

HUMANIVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG 480

PONABIVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG 480

NOMLEIVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG 476

GORGOIVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG 480

PANTRIVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG 480

CALJAVVGMKISTKSVGCDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEEAGMAMRIRVG 480

MACMUTVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG 480

BABONTVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG 480

GREENTVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG 480

HUMAN QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKYLLNLNLEPFSEK 540

PONAB QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKYLLNLNLEPFSEK 540

NOMLE QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKYLLNLNLEPFSEK 536

GORGO QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKYLLNLNLEPFSEK 540

PANTR QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKYLLNLNLEPFSEK 540

CALJA QSMNMGSDFDVFAHITNNTTEEHACRLLLCARTVSYNGVLGPECGTKDLLNLTLEPFSEK 540

MACMU QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKHLLNLNLEPFSEK 540

BABON QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKHLLNLNLEPFSEK 540

GREEN QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKHLLNLNLEPFSEK 540

HUMAN SVPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK 600

PONAB SVPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK 600

NOMLE SIPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK 596

GORGO SIPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK 600

PANTR SVPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK 600

CALJA SIPLRILYEKYCDCLTESNLIKVRGLLVEPATNSYLLAERDLYLENPEIKIRILGEPKQK 600

MACMU SIPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK 600

BABON SIPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK 600

GREEN SIPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK 600

HUMAN RKLVAEVSLQNPLPVALEGCTFTVEGAGLTEEQKTVEIPDPVEAGEEVKVRMDLLPLHMG 660

PONAB RKLVAEVSLQNPLPVALEGCTFTVEGAGLTEEQKTVEIPDPVEAGEEVKVRIDLLPLHVG 660

NOMLE RKLVAEVSLRNPLPVALAGCTFTVEGAGLTEEQKRVEIPDPVESGEEVKVRMDLLPLHMG 656

GORGO RKLVAEVSLQNPLPVALEGCTFTVEGAGLTEEQKTVEIPDPVEAGEEVKVRMDLLPLHMG 660

PANTR RKLVAEVSLQNPLPVALEGCTFTVEGAGLTEEQKTVEIPDPVEAGEEVKVRMDLLPLHMG 660

CALJA RKLVAEVSLRNPLTVSLAGCIFTVEGAGLTEEQKTVEIQDPVEAGEEVKVRVALLPLHVG 660

MACMU RKLVAEVSLQNPLPVALEGCTFTVEGAGLTEEQKTVEIPDPVEAGEEVKVRMDLLPLHMG 660

BABON RKLVAEVSLQNPLPVALEGCTFTVEGAGLTEEQKTVEIPDPVEAGEEVKVRMDLLPLHMG 660

GREEN RKLVAEVSLQNPLPVALEGCTFTVEGAGLTEEQKTVEIPDPVEAGEEVKVRMDLLPLHMG 660

HUMAN LHKLVVNFESDKLKAVKGFRNVIIGPA 687

PONAB LHKLVVNFESDKLKAVKGFRNVIIGPA 687

NOMLE LHKLVVNFESDKLKAVKGFRNIIIGPA 683

GORGO LHKLVVNFESDKLKAVKGFRNVIIGPA 687

PANTR LHKLVVNFESDKLKAVKGFRNVIIGPA 687

CALJA RHKLVVNFESDKLKAVKGFRNVIIGPA 687

MACMU LHKLVVNFESDKLKAVKGFRNVIIGPA 687

BABONLHKLVVNFESDKLKAVKGFRNVIIGPA 687

GREEN LHKLVVNFESDKLKAVKGFRNVIIGPA 687

Fig. S1 Comparison was made by the UniProt ClustalO program. Sequences from UniProt were used. Lanes: 1. human, 2. sumatran orangutan (PONAB), 3. northern white-cheeked gibbon (NOMLE), 4. gorilla (GORGO), 5. chimpanzee (PANTR), 6. white-tufted-ear marmoset (CALJA), 7. rhesus macaque (MACMU), 8. olive baboon (BABON), 9. green monkey (GREEN). All the amino acid clusters are bolded and underlined. Residues different from human TGM2 are highlighted in yellow (grey background).

Novel amino acid clusters in members of the human transglutaminase family in comparison to the mouse sequence

F13A HUMANMSETSRTAFGGRRAVPPNNSNAAEDDLPTVELQGVVPRGVNLQEFLNVTSVHLFKERWDT60

F13A MOUSE MSDTPASTFGGRRAVPPNNSNAAEVDLPTEELQGLVPRGVNLKDYLNVTAVHLFKERWDS60

F13A HUMANTYILFNPWCEDDAVYLDNEKEREEYVLNDIGVIFYGEVNDIKTRSWSYGQFEDGILDTCL 240

F13A MOUSE TYILFNPWCEEDAVYLDDEKEREEYVLNDIGVIFYGDFKDIKSRSWSYGQFEDGILDTCL 240

F13A HUMAN EQASLHFFVTARINETRDVLAKQKSTVLTIPEIIIKVRGTQVVGSDMTVTVQFTNPLKET660

F13A MOUSE EQGFLHFFVTARINESRDVLAKQKSIILTIPKITIKVRGAAMVGSDMVVTVEFTNPLKET660

TGM1 HUMANADDDWGPEPSDSRGRGSSSGTRRPGSRGSDSRRPVSRGSGVNAAGDGTIREGMLVVNGVD 116

TGM1 MOUSEGDDDWGPEPSGSRSRGTSSRG----RDSRGGRRPESRGSGVNAAGDGTIREGMLVVTGVD 115

TGM3 HUMAN MAALGVQSINWQTAFNRQAHHTDKFSSQELILRRGQNFQVLMIMNKGLGSNERLEFIVST60

TGM3 MOUSE MSALQIQNVNWQVPMNRRAHHTDKFSSQDSIVRRGQPWEIILVCNRSLESGEDLNFIVST60

TGM3 HUMAN GPYPSESAMTKAVFPLSNGSSGGWSAVLQASNGNTLTISISSPASAPIGRYTMALQIFSQ 120

TGM3 MOUSE GPQPSESARTKAVFSISGRSTGGWNAALKANSGNNLAIAIASPVSAPIGLYTLSVEISSR 120

TGM3 HUMANSQGVFQCGPASVIGVREGDVQLNFDMPFIFAEVNADRITWLYDNTTGKQWKNSVNSHTIG420

TGM3 MOUSESQGVFQCGPASVNAIKAGDVDRNFDMIFIFAEVNADRITWIYNNRNNTQKQNSVDTHSIG420

TGM3 HUMAN RYISTKAVGSNARMDVTDKYKYPEGSDQERQVFQKALGKLKPNTPFAATSSMGLETEEQE480

TGM3 MOUSE KYISTKAVGSNSRMDVTDKYKYPEGSSEERQVHQKALDKLKPNASFGATSSRNPEGEDKE480

TGM3 HUMAN PSIIGKLKVAGMLAVGKEVNLVLLLKNLSRDTKTVTVNMTAWTIIYNGTLVHEVWKDSAT 540

TGM3 MOUSE PSISGKFKVTGILAVGKEVSLSLMLKNMTNDRKTVTMNMTAWTIVYNGTLVHEVWKDSAT 540

TGM3 HUMAN MSLDPEEEAEHPIKISYAQYEKYLKSDNMIRITAVCKVPDESEVVVERDIILDNPTLTLE600

TGM3 MOUSE ISLDPEEEIQYPVKIAYSQYERYLKADNMIRITAVCKVPDEAEVVVERDVILDNPALTLE600

TGM4 HUMAN MMDASKELQVLHIDFLNQDNAVSHHTWEFQTSSPVFRRGQVFHLRLVLNQPLQSYHQLKL 60

TGM4 MOUSE –MDSRNVLIIYAVNVERKLNAAAHHTSEYQTKKLVLRRGQIFTLKVILNRPLQPQDELKV 59

TGM4 HUMAN TAPYKWTGSAPILQQYYNTKQAVCFGQCWVFAGILTTVLRALGIPARSVTGFDSAHDTER 300

TGM4 MOUSE TAPYVWTSSVPILQQHYVTRMPVRYGQCWVFSGILTTALRAVGIPARSVTNFESAHDTEK 287

TGM4 HUMAN QLLVCNCIFKNTLAIPLTDVKFSLESLGISSLQTSDHGTVQPGETIQSQIKCTPIKTGPK 660

TGM4 MOUSE QPLVITSKFTNTLPIPLTNIKFSVESLGLANMKSWEQETVPPGKTITFQMECTPVKAGPQ 646

TGM5 HUMAN-----MAQGLEVALTDLQSSRNNVRHHTEEITVDHLLVRRGQAFNLTLYFRNRSFQPGLD 55

TGM5 MOUSEMAQGCPITGLEVALTDLQSSQNNVRHHTEEISVDRLVVRRGQAFSITLYFKNRGFQPGMD 60

TGM5 HUMAN NIIFVVETGPLPDLALGTRAVFSLARHHSPSPWIAWLETNGATSTEVSLCAPPTAAVGRY 115

TGM5 MOUSE SIMFVAETGPLPDLAKGTRAVFSFTGSGGPSPWIASLEANRANSLEVSLCAPPIAAVGRY 120

TGM5 HUMANLHQDTSSVGNFISTKSIQSDERDDITENYKYEEGSLQERQVFLKALQKLKARSFHGSQRG 475

TGM5 MOUSELHQDTATVGNFISTKSIQSDERDDITESYKYEEGSLQEREVFLKALQKLQATRSQGPHQA 480

TGM5 HUMAN AELQPSRPTSLSQDSPRSLHTPSLRPSDVVQVSLKFKLLDPPNMGQDICFVLLALNMSSQ 535

TGM5 MOUSE N-SNPFSSVPPRHNSARSPDSPSLQPSDVLQVSLKFELLDSPKMGQDINFVLLAVNMSPQ 539

TGM7 HUMAN EISQGQGHSVTYPLGTFILLFNPWSPEDDVYLPSEILLQEYIMRDYGFVYKGHERFITSW 180

TGM7 MOUSE EISQGQGPGVTYPLGNFILLFNPWSTEDDVYLPSETLLREYIMSDYGFIYKGQTNSITSR 86

TGM7 HUMAN DPTPQQTSSGLFCCGPASVKAIREGDVHLAYDTPFVYAEVNADEVIWLLGDGQAQEILAH420

TGM7 MOUSE DPTPQQTSSGLFCCGPASVKAIKEGDVQLPYDTPFVYAEVNADEVVWLFEGGQVQEILAH326

TGM7 HUMAN NTSSIGKEISTKMVGSDQRQSITSSYKYPEGSPEERAVFMKASRKMLGPQRASLPFLDLL 480

TGM7 MOUSE NTSYIGKAISTKMVGSDERLDITSSYKYPEGSSEERSAFIKASWKLLEPRRNASSLLDLL 386

TGM7 HUMAN ESGGLRDQPAQLQLHLARIPEWGQDLQLLLRIQRVPDSTHPRGPIGLVVRFCAQALLHGG540

TGM7 MOUSE GSENLKAKPVRLQLHLVRAPMWGQDLPLMLYVQRVPVRDHVQGSVGLTVRFCAQALLHGG446

TGM7 HUMAN GTQKPFWRHTVRMNLDFGKETQWPLLLPYSNYRNKLTDEKLIRVSGIAEVEETGRSMLVL600

TGM7 MOUSE GTRKPFWRHIVHLNVDFEKELQWPFLLPYSSYRDKLTDERLIRVAGIAEVEETGQFILVL506

Fig. S2Amino acid clusters in human transglutaminase family members F13A, TGM1, TGM3, TGM4, TGM5, and TGM7 compared to their mouse counterparts are presented using sequences from UniProt (shaded grey). Only sequences where the clusters appear are shown. In case of TGM4 due to the presence of many clusters only few examples are shown. TGM6 is not shown as it does not contain any cluster. TGM2 clusters are presented in the main text.

Influence of human amino acid clusters on stability of mouse TGM2

FigS3. Influence of human amino acid clusters on stability of mouse TGM2. The stability analysis was carried out by FoldX software using homology model structures of human TGM2.Mouse sequence was modified with human TGM2 amino acid clusters and then relative free energy or thermodynamic stability ΔΔG [kcal/mol] was calculated for each cluster.The amino acid cluster changes (mouse to human change) are indicated along with thethermodynamic stability ΔΔG [kcal/mol] values.ΔΔGmousehuman=ΔΔGhuman-ΔΔG mouse (human relative to mouse).Colour code for different domains of mouse TGM2: β-sandwich domain, 1-139 (red); Catalytic core, 140-465 (green);β-barrel 1, 466-583, (cyan);β-barrel 2, 584-686, (orange).