Macie Duran Week 6

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Macie M. Duran

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Purpose

The purpose of this project was to further explore the ACE2 receptor and SARS-CoV-2 spike protein by conducting research. Gaining knowledge on the interaction between ACE2 and SARS-CoV-2 allows us to further understand the viral entry mechanism, and potentially develop preventative measures and treatments for COVID-19.

Methods & Results

Coronavirus Research Project

  • I used NCBI GenBank and UniProt to find the ACE2 receptor amino acid sequences for rabbit, cat, ferret, mouse, rat, pig, civet, bat, chimpanzee, human, and opossum (outgroup). The sequences are below.
  • Rabbit:
>QHX39726.1 angiotensin I converting enzyme 2 [Oryctolagus cuniculus]
MSGSSWLLLSLVAVTAAQSTIEELAKTFLEKFNQEAEDLSYQSALASWDYNTNITEENVQKMNDAEAKWS
AFYEEQSKLAKTYPSQEVQNLTVKRQLQALQQSGSSALSADKSKQLNTILSTMSTIYSTGKVCNQSNPQE
CFLLEPGLDEIMAKSTDYNERLWAWEGWRSVVGKQLRPLYEEYVVLKNEMARANNYEDYGDYWRADYEAE
GADGYDYSRSQLIDDVERTFSEIKPLYEQLHAYVRTKLMDAYPSRISPTGCLPAHLLGDMWGRFWTNLYS
LTVPFGQKPNIDVTDTMVNQGWDAERIFKEAEKFFVSVGLPSMTHGFWENSMLPESGDGRKVVCHPTAWD
LGKRDFRIKMCTKVTMDNFLTAHHEMGHIQYDMAYATQPFLLRNGANEGFHEAVGEIMSLSAATPEHLKS
IGLLPYDFHEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKEQWMQKWWEMKREIVGVVEP
MPHDETYCDPAALFHVANDYSFIRYYTRTIYQFQFQEALCQAAQHEGPLHKCDISNSTEAGQKLLNMLRL
GRSEPWTLALENVVGAKNMDVRPLLNYFEPLFTWLKEQNRNSFVGWSTEWTPYADQSIKVRISLKTALGD
QAYEWNDSEMYLFRSSVAYAMRKYFSEVKNQTILFGEEDVRVSDLKPRISFNFFVTAPNNVNDIIPRNEV
EEAISMSRSRINDIFRLDDNSLEFVGIQPTLEPPYESPVPIWLVVFGVVMGMIVIGIVVLIFTGIKDRRK
QKQAKREENPYGFVDMSKGENNSGFQNSDDIQTSF
>sp|Q56H28|ACE2_FELCA Angiotensin-converting enzyme 2 OS=Felis catus OX=9685 GN=ACE2 PE=2 SV=1
MSGSFWLLLSFAALTAAQSTTEELAKTFLEKFNHEAEELSYQSSLASWNYNTNITDENVQ
KMNEAGAKWSAFYEEQSKLAKTYPLAEIHNTTVKRQLQALQQSGSSVLSADKSQRLNTIL
NAMSTIYSTGKACNPNNPQECLLLEPGLDDIMENSKDYNERLWAWEGWRAEVGKQLRPLY
EEYVALKNEMARANNYEDYGDYWRGDYEEEWTDGYNYSRSQLIKDVEHTFTQIKPLYQHL
HAYVRAKLMDTYPSRISPTGCLPAHLLGDMWGRFWTNLYPLTVPFGQKPNIDVTDAMVNQ
SWDARRIFKEAEKFFVSVGLPNMTQGFWENSMLTEPGDSRKVVCHPTAWDLGKGDFRIKM
CTKVTMDDFLTAHHEMGHIQYDMAYAVQPFLLRNGANEGFHEAVGEIMSLSAATPNHLKT
IGLLSPGFSEDSETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKEQWMQKWWEM
KREIVGVVEPVPHDETYCDPASLFHVANDYSFIRYYTRTIYQFQFQEALCRIAKHEGPLH
KCDISNSSEAGKKLLQMLTLGKSKPWTLALEHVVGEKKMNVTPLLKYFEPLFTWLKEQNR
NSFVGWNTDWRPYADQSIKVRISLKSALGDEAYEWNDNEMYLFRSSVAYAMREYFSKVKN
QTIPFVEDNVWVSNLKPRISFNFFVTASKNVSDVIPRSEVEEAIRMSRSRINDAFRLDDN
SLEFLGIQPTLSPPYQPPVTIWLIVFGVVMGVVVVGIVLLIVSGIRNRRKNNQARSEENP
YASVDLSKGENNPGFQHADDVQTSF
>BAE53380.1 angiotensin I converting enzyme 2 [Mustela putorius furo]
MLGSSWLLLSLAALTAAQSTTEDLAKTFLEKFNYEAEELSYQNSLASWNYNTNITDENIQKMNIAGAKWS
AFYEEESQHAKTYPLEEIQDPIIKRQLRALQQSGSSVLSADKRERLNTILNAMSTIYSTGKACNPNNPQE
CLLLEPGLDDIMENSKDYNERLWAWEGWRSEVGKQLRPLYEEYVALKNEMARANNYEDYGDYWRGDYEEE
WADGYSYSRNQLIEDVEHTFTQIKPLYEHLHAYVRAKLMDAYPSRISPTGCLPAHLLGDMWGRFWTNLYP
LMVPFRQKPNIDVTDAMVNQSWDARRIFEEAETFFVSVGLPNMTEGFWQNSMLTEPGDNRKVVCHPTAWD
LGKRDFRIKMCTKVTMDDFLTAHHEMGHIQYDMAYAEQPFLLRNGANEGFHEAVGEIMSLSAATPNHLKN
IGLLPPDFSEDSETDINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKEQWMQKWWEMKRDIVGVVEP
LPHDETYCDPAALFHVANDYSFIRYYTRTIYQFQFQEALCQIAKHEGPLYKCDISNSSEAGQKLHEMLSL
GRSKPWTFALERVVGAKTMDVRPLLNYFEPLFTWLKEQNRNSFVGWNTDWSPYADQSIKVRISLKSALGE
KAYEWNDNEMYFFQSSIAYAMREYFSKVKNQTIPFVGKDVRVSDLKPRISFNFIVTSPENMSDIIPRADV
EEAIRKSRGRINDAFRLDDNSLEFLGIQPTLEPPYQPPVTIWLIVFGVVMGVVVVGIFLLIFSGIRNRRK
NNQARSEENPYASVDLSKGENNPGFQNVDDVQTSF
>sp|Q8R0I0|ACE2_MOUSE Angiotensin-converting enzyme 2 OS=Mus musculus OX=10090 GN=Ace2 PE=1 SV=1
MSSSSWLLLSLVAVTTAQSLTEENAKTFLNNFNQEAEDLSYQSSLASWNYNTNITEENAQ
KMSEAAAKWSAFYEEQSKTAQSFSLQEIQTPIIKRQLQALQQSGSSALSADKNKQLNTIL
NTMSTIYSTGKVCNPKNPQECLLLEPGLDEIMATSTDYNSRLWAWEGWRAEVGKQLRPLY
EEYVVLKNEMARANNYNDYGDYWRGDYEAEGADGYNYNRNQLIEDVERTFAEIKPLYEHL
HAYVRRKLMDTYPSYISPTGCLPAHLLGDMWGRFWTNLYPLTVPFAQKPNIDVTDAMMNQ
GWDAERIFQEAEKFFVSVGLPHMTQGFWANSMLTEPADGRKVVCHPTAWDLGHGDFRIKM
CTKVTMDNFLTAHHEMGHIQYDMAYARQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS
IGLLPSDFQEDSETEINFLLKQALTIVGTLPFTYMLEKWRWMVFRGEIPKEQWMKKWWEM
KREIVGVVEPLPHDETYCDPASLFHVSNDYSFIRYYTRTIYQFQFQEALCQAAKYNGSLH
KCDISNSTEAGQKLLKMLSLGNSEPWTKALENVVGARNMDVKPLLNYFQPLFDWLKEQNR
NSFVGWNTEWSPYADQSIKVRISLKSALGANAYEWTNNEMFLFRSSVAYAMRKYFSIIKN
QTVPFLEEDVRVSDLKPRVSFYFFVTSPQNVSDVIPRSEVEDAIRMSRGRINDVFGLNDN
SLEFLGIHPTLEPPYQPPVTIWLIIFGVVMALVVVGIIILIVTGIKGRKKKNETKREENP
YDSMDIGKGESNAGFQNSDDAQTSF
>sp|Q5EGZ1|ACE2_RAT Angiotensin-converting enzyme 2 OS=Rattus norvegicus OX=10116 GN=Ace2 PE=1 SV=1
MSSSCWLLLSLVAVATAQSLIEEKAESFLNKFNQEAEDLSYQSSLASWNYNTNITEENAQ
KMNEAAAKWSAFYEEQSKIAQNFSLQEIQNATIKRQLKALQQSGSSALSPDKNKQLNTIL
NTMSTIYSTGKVCNSMNPQECFLLEPGLDEIMATSTDYNRRLWAWEGWRAEVGKQLRPLY
EEYVVLKNEMARANNYEDYGDYWRGDYEAEGVEGYNYNRNQLIEDVENTFKEIKPLYEQL
HAYVRTKLMEVYPSYISPTGCLPAHLLGDMWGRFWTNLYPLTTPFLQKPNIDVTDAMVNQ
SWDAERIFKEAEKFFVSVGLPQMTPGFWTNSMLTEPGDDRKVVCHPTAWDLGHGDFRIKM
CTKVTMDNFLTAHHEMGHIQYDMAYAKQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS
IGLLPSNFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFQDKIPREQWTKKWWEM
KREIVGVVEPLPHDETYCDPASLFHVSNDYSFIRYYTRTIYQFQFQEALCQAAKHDGPLH
KCDISNSTEAGQKLLNMLSLGNSGPWTLALENVVGSRNMDVKPLLNYFQPLFVWLKEQNR
NSTVGWSTDWSPYADQSIKVRISLKSALGKNAYEWTDNEMYLFRSSVAYAMREYFSREKN
QTVPFGEADVWVSDLKPRVSFNFFVTSPKNVSDIIPRSEVEEAIRMSRGRINDIFGLNDN
SLEFLGIYPTLKPPYEPPVTIWLIIFGVVMGTVVVGIVILIVTGIKGRKKKNETKREENP
YDSMDIGKGESNAGFQNSDDAQTSF
>tr|A0A220QT48|A0A220QT48_PIG Angiotensin-converting enzyme OS=Sus scrofa domesticus OX=9825 GN=ACE2 PE=2 SV=1
MSGSFWLLLSLIPVTAAQSTTEELAKTFLEKFNLEAEDLAYQSSLASWNYNTNITDENIQ
KMNDARAKWSAFYEEQSRIAKTYPLDEIQTLILKRQLQALQQSGTSGLSADKSKRLNTIL
NTMSTIYSSGKVLDPNNPQECLVLEPGLDEIMENSKDYSRRLWAWESWRAEVGKQLRPLY
EEYVVLENEMARANNYEDYGDYWRGDYEVTGTGDYDYSRNQLMEDVERTFAEIKPLYEHL
HAYVRAKLMDAYPSRISPTGCLPAHLLGDMWGRFWTNLYPLTVPFGEKPSIDVTEAMVNQ
SWDAIRIFEEAEKFFVSIGLPNMTQGFWNNSMLTEPGDGRKVVCHPTAWDLGKGDFRIKM
CTKVTMDDFLTAHHEMGHIQYDMAYAIQPYLLRNGANEGFHEAVGEIMSLSAATPHYLKA
LGLLPPDFYEDSETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKEQWMQKWWEM
KREIVGVVEPLPHDETYCDPACLFHVAEDYSFIRYYTRTIYQFQFHEALCRTAKHEGPLY
KCDISNSTEAGQKLLQMLSLGKSEPWTLALENIVGVKTMDVKPLLSYFEPLLTWLKAQNG
NSSVGWNTDWTPYADQSIKVRISLKSALGKEAYEWNDNEMYLFRSSIAYAMRNYFSSAKN
ETIPFGAEDVWVSDLKPRISFNFFVTSPANMSDIIPRSDVEKAISMSRSRINDAFRLDDN
TLEFLGIQPTLGPPDEPPVTVWLIIFGVVMGLVVVGIVVLIFTGIRDRRKKKQASSEENP
YGSMDLSKGESNSGFQNGDDIQTSF
>sp|Q56NL1|ACE2_PAGLA Angiotensin-converting enzyme 2 OS=Paguma larvata OX=9675 GN=ACE2 PE=1 SV=1
MSGSFWLLLSFAALTAAQSTTEELAKTFLETFNYEAQELSYQSSVASWNYNTNITDENAK
NMNEAGAKWSAYYEEQSKLAQTYPLAEIQDAKIKRQLQALQQSGSSVLSADKSQRLNTIL
NAMSTIYSTGKACNPNNPQECLLLEPGLDNIMENSKDYNERLWAWEGWRAEVGKQLRPLY
EEYVALKNEMARANNYEDYGDYWRGDYEEEWTGGYNYSRNQLIQDVEDTFEQIKPLYQHL
HAYVRAKLMDTYPSRISRTGCLPAHLLGDMWGRFWTNLYPLTVPFGQKPNIDVTDAMVNQ
NWDARRIFKEAEKFFVSVGLPNMTQGFWENSMLTEPGDGRKVVCHPTAWDLGKGDFRIKM
CTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPNHLKT
IGLLSPAFSEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGAIPKEQWMQKWWEM
KRNIVGVVEPVPHDETYCDPASLFHVANDYSFIRYYTRTIYQFQFQEALCQIAKHEGPLH
KCDISNSTEAGKKLLEMLSLGRSEPWTLALERVVGAKNMNVTPLLNYFEPLFTWLKEQNR
NSFVGWDTDWRPYSDQSIKVRISLKSALGEKAYEWNDNEMYLFRSSIAYAMREYFSKVKN
QTIPFVEDNVWVSDLKPRISFNFFVTFSNNVSDVIPRSEVEDAIRMSRSRINDAFRLDDN
SLEFLGIEPTLSPPYRPPVTIWLIVFGVVMGAIVVGIVLLIVSGIRNRRKNDQAGSEENP
YASVDLNKGENNPGFQHADDVQTSF
>tr|E2DHI2|E2DHI2_RHIFE Angiotensin-converting enzyme OS=Rhinolophus ferrumequinum OX=59479 GN=ACE2 PE=2 SV=1
MSGSSWFLLSLVAVTAAQSTTEDLAKKFLDDFNSEAENLSHQSSLASWEYNTNISDENVQ
KMDEAGAKWSDFYEKQSKLAKNFSLEEIHNDTVKLQLQILQQSGSPVLSEDKSKRLNSIL
NAMSTIYSTGKVCKPNNPQECLLLEPGLDNIMGTSKDYNERLWAWEGWRAEVGKQLRPLY
EEYVVLKNEMARGYHYEDYGDYWRRDYETEGSPDLEYSRDQLIKDVERIFAEIKPLYEQL
HAYVRTKLMDTYPFHISPTGCLPAHLLGDMWGRFWTNLYPLTVPFGQKPNIDVTDAMLNQ
NWDAKRIFKEAEKFLVSIGLPNMTEGFWNNSMLTDPGDGRKVVCHPTAWDLGKGDFRIKM
CTKVTMEDFLTAHHEMGHIQYDMAYASQPYLLRNGANEGFHEAVGEVMSLSVATPEHLKT
MGLLSSDFLEDNETEINFLFKQALNIVGTLPLTYMLEKWRWMVFKGEIPKEEWMKKWWEM
KRKIVGVVEPVPHDETYCDPASLFHVANDYSFIRYYTRTIFEFQFHEALCRIAKHDGPLH
KCGISNSTDAGEKLHQMLSVGKSQPWTSVLKDFVGSKNMDVGPLLRYFEPLYTWLTEQNR
KSFVGWNTDWSPYADQSIKVWISLKSALGEKAYEWNNNEMYLFRSSVAYAMREYFLKTKN
QTILFGEEDVWVSNLKPRISFNFYVTSPRNLSDIIPRPEVEGAIRMSRSRINDAFRLDDN
SLEFLGIQPTLGPPYQPPVTIWLIVFGVVMAVVVVGIVVLIITGIRDRRKKDQARSEENP
YSSVDLSKGENNPGFQNGNDVQTSF
>tr|A0A2J8KU96|A0A2J8KU96_PANTR Angiotensin-converting enzyme OS=Pan troglodytes OX=9598 GN=ACE2 PE=3 SV=1
MSGSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQ
NMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTIL
NTMSAIYSTGKVCNPNNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLY
EEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHL
HAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQ
AWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILM
CTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS
IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPEDQWMKKWWEM
KREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLH
KCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNK
NSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKN
QMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRKSRSRINDAFRLNDN
SLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARSEENP
YASVDTSKGENNPGFQNTDDVQTSF
>sp|Q9BYF1|ACE2_HUMAN Angiotensin-converting enzyme 2 OS=Homo sapiens OX=9606 GN=ACE2 PE=1 SV=2
MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQ
NMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTIL
NTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLY
EEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHL
HAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQ
AWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILM
CTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS
IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEM
KREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLH
KCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNK
NSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKN
QMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDN
SLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARSGENP
YASIDISKGENNPGFQNTDDVQTSF
>tr|F6WXR7|F6WXR7_MONDO Angiotensin-converting enzyme OS=Monodelphis domestica OX=13616 GN=ACE2 PE=3 SV=2
MLDPLWLFFSLLAVTAAQNSIEEDAKTFLDDYNAKAEELSHQSALASWEYNTNITNENVE
KMNEAAARWSSFYENQSSISRTYPLNEITNATVKLQLKSLQKKEGAVLSTEQSVRLNTIL
NTMSTLYSTGSVCNSETPQQCFLLEPGLDKIMDESTDYDERLWAWEGWRSKVGKEMRPLY
EEYVELKNELAKGNNYEDYGDYWRGDYEVEEPSEYVYSRPQLKKDVENTFKQIKSLYEHL
HAYVRRKMRNTYGSLISETGGLPAHLLGDMWGRFWTNLYSLTMPYREKPNIDVTSAMKKQ
NWSARRIFQEAEMFFASVGLPNMTEGFWKNSMLTEPNDGRKVVCHPTAWDLGKNDFRIKM
CTKVTMDDFLTAHHEMGHIQYDMAYAKQPFTLRNGANEGFHEAVGEIMSLSAATPKHLQA
LGLLPPTFQEDNETEINFLFKQALTIIGTMPFTYMLENWRWMVFEGKIPKEEWMKKWWEM
KREIVGVVEPLPHDETYCDPAALFHVANDYSFIRYYTRTIYQFQFHKALCKIAQPSAALH
KCDITNSTEAGTKLQNMLKMGKSEPWTKALESIVGNKMMDAGPLLEYFEPLFTWLKEQNK
DAYVGWNTDWSPYNAYKIKVRISLKTLGENAYTWNENEMYLFQSSIVFAMRQYFLIKKKQ
SIPFSNENVKMFDLKPRISFYFFVTFPPNGTSFVPREEVEAAISMSRDRINDAFRLNDNS
LEFVGISPTLAPPYEPPVTVWMIVFGVVMGIVVIGIVYLIYTGVRDRKKRAKTSSSNDEN
PYVDVDVAGGQHNPAFQSSEDAQTSF
  • Then I used Phylogeny.fr to create a multiple sequence alignment.
  • I scrolled to the section titled "Phylogeny Analysis" and selected "One Click."
  • I pasted the sequences above in FASTA format into the text box and clicked "Submit".
  • Of the numbered tabs at the top of the page, I selected 3. Alignment.
  • Under the section labeled Output, I selected Alignment in Clustal Format. The alignments are displayed in a text format with symbols indicating conservation between the sequences. "*" indicates invariant conservation, ":" indicates high conservation, "." indicates weak conservation, and a space indicates no conservation.
  • I have included the text alignment in clustal format below:
tr|F6WXR7|      MLDPLWLFFSLLAVTAAQNSIEEDAKTFLDDYNAKAEELSHQSALASWEYNTNITNENVE
tr|E2DHI2|      MSGSSWFLLSLVAVTAAQSTTEDLAKKFLDDFNSEAENLSHQSSLASWEYNTNISDENVQ
sp|Q8R0I0|      MSSSSWLLLSLVAVTTAQSLTEENAKTFLNNFNQEAEDLSYQSSLASWNYNTNITEENAQ
sp|Q5EGZ1|      MSSSCWLLLSLVAVATAQSLIEEKAESFLNKFNQEAEDLSYQSSLASWNYNTNITEENAQ
tr|A0A220Q      MSGSFWLLLSLIPVTAAQSTTEELAKTFLEKFNLEAEDLAYQSSLASWNYNTNITDENIQ
QHX39726.1      MSGSSWLLLSLVAVTAAQSTIEELAKTFLEKFNQEAEDLSYQSALASWDYNTNITEENVQ
tr|A0A2J8K      MSGSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQ
sp|Q9BYF1|      MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQ
BAE53380.1      MLGSSWLLLSLAALTAAQSTTEDLAKTFLEKFNYEAEELSYQNSLASWNYNTNITDENIQ
sp|Q56NL1|      MSGSFWLLLSFAALTAAQSTTEELAKTFLETFNYEAQELSYQSSVASWNYNTNITDENAK
sp|Q56H28|      MSGSFWLLLSFAALTAAQSTTEELAKTFLEKFNHEAEELSYQSSLASWNYNTNITDENVQ
                * .. *:::*: .:::**.  *: *:.**: :* :*::* :*.::***:*****::** :
tr|F6WXR7|      KMNEAAARWSSFYENQSSISRTYPLNEITNATVKLQLKSLQKKEGAVLSTEQSVRLNTIL
tr|E2DHI2|      KMDEAGAKWSDFYEKQSKLAKNFSLEEIHNDTVKLQLQILQQSGSPVLSEDKSKRLNSIL
sp|Q8R0I0|      KMSEAAAKWSAFYEEQSKTAQSFSLQEIQTPIIKRQLQALQQSGSSALSADKNKQLNTIL
sp|Q5EGZ1|      KMNEAAAKWSAFYEEQSKIAQNFSLQEIQNATIKRQLKALQQSGSSALSPDKNKQLNTIL
tr|A0A220Q      KMNDARAKWSAFYEEQSRIAKTYPLDEIQTLILKRQLQALQQSGTSGLSADKSKRLNTIL
QHX39726.1      KMNDAEAKWSAFYEEQSKLAKTYPSQEVQNLTVKRQLQALQQSGSSALSADKSKQLNTIL
tr|A0A2J8K      NMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTIL
sp|Q9BYF1|      NMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTIL
BAE53380.1      KMNIAGAKWSAFYEEESQHAKTYPLEEIQDPIIKRQLRALQQSGSSVLSADKRERLNTIL
sp|Q56NL1|      NMNEAGAKWSAYYEEQSKLAQTYPLAEIQDAKIKRQLQALQQSGSSVLSADKSQRLNTIL
sp|Q56H28|      KMNEAGAKWSAFYEEQSKLAKTYPLAEIHNTTVKRQLQALQQSGSSVLSADKSQRLNTIL
                :*. *  .** : :::*  :. :.  *:    :* **. **:.  . ** ::  .**:**
tr|F6WXR7|      NTMSTLYSTGSVCNSETPQQCFLLEPGLDKIMDESTDYDERLWAWEGWRSKVGKEMRPLY
tr|E2DHI2|      NAMSTIYSTGKVCKPNNPQECLLLEPGLDNIMGTSKDYNERLWAWEGWRAEVGKQLRPLY
sp|Q8R0I0|      NTMSTIYSTGKVCNPKNPQECLLLEPGLDEIMATSTDYNSRLWAWEGWRAEVGKQLRPLY
sp|Q5EGZ1|      NTMSTIYSTGKVCNSMNPQECFLLEPGLDEIMATSTDYNRRLWAWEGWRAEVGKQLRPLY
tr|A0A220Q      NTMSTIYSSGKVLDPNNPQECLVLEPGLDEIMENSKDYSRRLWAWESWRAEVGKQLRPLY
QHX39726.1      STMSTIYSTGKVCNQSNPQECFLLEPGLDEIMAKSTDYNERLWAWEGWRSVVGKQLRPLY
tr|A0A2J8K      NTMSAIYSTGKVCNPNNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLY
sp|Q9BYF1|      NTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLY
BAE53380.1      NAMSTIYSTGKACNPNNPQECLLLEPGLDDIMENSKDYNERLWAWEGWRSEVGKQLRPLY
sp|Q56NL1|      NAMSTIYSTGKACNPNNPQECLLLEPGLDNIMENSKDYNERLWAWEGWRAEVGKQLRPLY
sp|Q56H28|      NAMSTIYSTGKACNPNNPQECLLLEPGLDDIMENSKDYNERLWAWEGWRAEVGKQLRPLY
                .:**::**:*.. .  .**:*::*****:.**  * **. ******.**: ***::****
tr|F6WXR7|      EEYVELKNELAKGNNYEDYGDYWRGDYEVEEPSEYVYSRPQLKKDVENTFKQIKSLYEHL
tr|E2DHI2|      EEYVVLKNEMARGYHYEDYGDYWRRDYETEGSPDLEYSRDQLIKDVERIFAEIKPLYEQL
sp|Q8R0I0|      EEYVVLKNEMARANNYNDYGDYWRGDYEAEGADGYNYNRNQLIEDVERTFAEIKPLYEHL
sp|Q5EGZ1|      EEYVVLKNEMARANNYEDYGDYWRGDYEAEGVEGYNYNRNQLIEDVENTFKEIKPLYEQL
tr|A0A220Q      EEYVVLENEMARANNYEDYGDYWRGDYEVTGTGDYDYSRNQLMEDVERTFAEIKPLYEHL
QHX39726.1      EEYVVLKNEMARANNYEDYGDYWRADYEAEGADGYDYSRSQLIDDVERTFSEIKPLYEQL
tr|A0A2J8K      EEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHL
sp|Q9BYF1|      EEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHL
BAE53380.1      EEYVALKNEMARANNYEDYGDYWRGDYEEEWADGYSYSRNQLIEDVEHTFTQIKPLYEHL
sp|Q56NL1|      EEYVALKNEMARANNYEDYGDYWRGDYEEEWTGGYNYSRNQLIQDVEDTFEQIKPLYQHL
sp|Q56H28|      EEYVALKNEMARANNYEDYGDYWRGDYEEEWTDGYNYSRSQLIKDVEHTFTQIKPLYQHL
                **** *:**:*.. :*:******* ***        *.* ** .***  * :**.**::*
tr|F6WXR7|      HAYVRRKMRNTYGSLISETGGLPAHLLGDMWGRFWTNLYSLTMPYREKPNIDVTSAMKKQ
tr|E2DHI2|      HAYVRTKLMDTYPFHISPTGCLPAHLLGDMWGRFWTNLYPLTVPFGQKPNIDVTDAMLNQ
sp|Q8R0I0|      HAYVRRKLMDTYPSYISPTGCLPAHLLGDMWGRFWTNLYPLTVPFAQKPNIDVTDAMMNQ
sp|Q5EGZ1|      HAYVRTKLMEVYPSYISPTGCLPAHLLGDMWGRFWTNLYPLTTPFLQKPNIDVTDAMVNQ
tr|A0A220Q      HAYVRAKLMDAYPSRISPTGCLPAHLLGDMWGRFWTNLYPLTVPFGEKPSIDVTEAMVNQ
QHX39726.1      HAYVRTKLMDAYPSRISPTGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDTMVNQ
tr|A0A2J8K      HAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQ
sp|Q9BYF1|      HAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQ
BAE53380.1      HAYVRAKLMDAYPSRISPTGCLPAHLLGDMWGRFWTNLYPLMVPFRQKPNIDVTDAMVNQ
sp|Q56NL1|      HAYVRAKLMDTYPSRISRTGCLPAHLLGDMWGRFWTNLYPLTVPFGQKPNIDVTDAMVNQ
sp|Q56H28|      HAYVRAKLMDTYPSRISPTGCLPAHLLGDMWGRFWTNLYPLTVPFGQKPNIDVTDAMVNQ
                ***** *: :.*   **  * ******************.*  *: :**.****.:* .*
tr|F6WXR7|      NWSARRIFQEAEMFFASVGLPNMTEGFWKNSMLTEPNDGRKVVCHPTAWDLGKNDFRIKM
tr|E2DHI2|      NWDAKRIFKEAEKFLVSIGLPNMTEGFWNNSMLTDPGDGRKVVCHPTAWDLGKGDFRIKM
sp|Q8R0I0|      GWDAERIFQEAEKFFVSVGLPHMTQGFWANSMLTEPADGRKVVCHPTAWDLGHGDFRIKM
sp|Q5EGZ1|      SWDAERIFKEAEKFFVSVGLPQMTPGFWTNSMLTEPGDDRKVVCHPTAWDLGHGDFRIKM
tr|A0A220Q      SWDAIRIFEEAEKFFVSIGLPNMTQGFWNNSMLTEPGDGRKVVCHPTAWDLGKGDFRIKM
QHX39726.1      GWDAERIFKEAEKFFVSVGLPSMTHGFWENSMLPESGDGRKVVCHPTAWDLGKRDFRIKM
tr|A0A2J8K      AWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILM
sp|Q9BYF1|      AWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILM
BAE53380.1      SWDARRIFEEAETFFVSVGLPNMTEGFWQNSMLTEPGDNRKVVCHPTAWDLGKRDFRIKM
sp|Q56NL1|      NWDARRIFKEAEKFFVSVGLPNMTQGFWENSMLTEPGDGRKVVCHPTAWDLGKGDFRIKM
sp|Q56H28|      SWDARRIFKEAEKFFVSVGLPNMTQGFWENSMLTEPGDSRKVVCHPTAWDLGKGDFRIKM
                 *.* ***:*** *:.*:*** ** *** ****.:. : .*.**********: **** *
tr|F6WXR7|      CTKVTMDDFLTAHHEMGHIQYDMAYAKQPFTLRNGANEGFHEAVGEIMSLSAATPKHLQA
tr|E2DHI2|      CTKVTMEDFLTAHHEMGHIQYDMAYASQPYLLRNGANEGFHEAVGEVMSLSVATPEHLKT
sp|Q8R0I0|      CTKVTMDNFLTAHHEMGHIQYDMAYARQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS
sp|Q5EGZ1|      CTKVTMDNFLTAHHEMGHIQYDMAYAKQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS
tr|A0A220Q      CTKVTMDDFLTAHHEMGHIQYDMAYAIQPYLLRNGANEGFHEAVGEIMSLSAATPHYLKA
QHX39726.1      CTKVTMDNFLTAHHEMGHIQYDMAYATQPFLLRNGANEGFHEAVGEIMSLSAATPEHLKS
tr|A0A2J8K      CTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS
sp|Q9BYF1|      CTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS
BAE53380.1      CTKVTMDDFLTAHHEMGHIQYDMAYAEQPFLLRNGANEGFHEAVGEIMSLSAATPNHLKN
sp|Q56NL1|      CTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPNHLKT
sp|Q56H28|      CTKVTMDDFLTAHHEMGHIQYDMAYAVQPFLLRNGANEGFHEAVGEIMSLSAATPNHLKT
                ******::****************** **: ***************:****.*** :*: 
tr|F6WXR7|      LGLLPPTFQEDNETEINFLFKQALTIIGTMPFTYMLENWRWMVFEGKIPKEEWMKKWWEM
tr|E2DHI2|      MGLLSSDFLEDNETEINFLFKQALNIVGTLPLTYMLEKWRWMVFKGEIPKEEWMKKWWEM
sp|Q8R0I0|      IGLLPSDFQEDSETEINFLLKQALTIVGTLPFTYMLEKWRWMVFRGEIPKEQWMKKWWEM
sp|Q5EGZ1|      IGLLPSNFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFQDKIPREQWTKKWWEM
tr|A0A220Q      LGLLPPDFYEDSETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKEQWMQKWWEM
QHX39726.1      IGLLPYDFHEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKEQWMQKWWEM
tr|A0A2J8K      IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPEDQWMKKWWEM
sp|Q9BYF1|      IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEM
BAE53380.1      IGLLPPDFSEDSETDINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKEQWMQKWWEM
sp|Q56NL1|      IGLLSPAFSEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGAIPKEQWMQKWWEM
sp|Q56H28|      IGLLSPGFSEDSETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKEQWMQKWWEM
                :***.  * **.**:****:****.*:**:*:*****:****** . ** ::* :*****
tr|F6WXR7|      KREIVGVVEPLPHDETYCDPAALFHVANDYSFIRYYTRTIYQFQFHKALCKIAQPSAALH
tr|E2DHI2|      KRKIVGVVEPVPHDETYCDPASLFHVANDYSFIRYYTRTIFEFQFHEALCRIAKHDGPLH
sp|Q8R0I0|      KREIVGVVEPLPHDETYCDPASLFHVSNDYSFIRYYTRTIYQFQFQEALCQAAKYNGSLH
sp|Q5EGZ1|      KREIVGVVEPLPHDETYCDPASLFHVSNDYSFIRYYTRTIYQFQFQEALCQAAKHDGPLH
tr|A0A220Q      KREIVGVVEPLPHDETYCDPACLFHVAEDYSFIRYYTRTIYQFQFHEALCRTAKHEGPLY
QHX39726.1      KREIVGVVEPMPHDETYCDPAALFHVANDYSFIRYYTRTIYQFQFQEALCQAAQHEGPLH
tr|A0A2J8K      KREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLH
sp|Q9BYF1|      KREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLH
BAE53380.1      KRDIVGVVEPLPHDETYCDPAALFHVANDYSFIRYYTRTIYQFQFQEALCQIAKHEGPLY
sp|Q56NL1|      KRNIVGVVEPVPHDETYCDPASLFHVANDYSFIRYYTRTIYQFQFQEALCQIAKHEGPLH
sp|Q56H28|      KREIVGVVEPVPHDETYCDPASLFHVANDYSFIRYYTRTIYQFQFQEALCRIAKHEGPLH
                **.*******:**********.****::***********:::***::***. *: ...*:
tr|F6WXR7|      KCDITNSTEAGTKLQNMLKMGKSEPWTKALESIVGNKMMDAGPLLEYFEPLFTWLKEQNK
tr|E2DHI2|      KCGISNSTDAGEKLHQMLSVGKSQPWTSVLKDFVGSKNMDVGPLLRYFEPLYTWLTEQNR
sp|Q8R0I0|      KCDISNSTEAGQKLLKMLSLGNSEPWTKALENVVGARNMDVKPLLNYFQPLFDWLKEQNR
sp|Q5EGZ1|      KCDISNSTEAGQKLLNMLSLGNSGPWTLALENVVGSRNMDVKPLLNYFQPLFVWLKEQNR
tr|A0A220Q      KCDISNSTEAGQKLLQMLSLGKSEPWTLALENIVGVKTMDVKPLLSYFEPLLTWLKAQNG
QHX39726.1      KCDISNSTEAGQKLLNMLRLGRSEPWTLALENVVGAKNMDVRPLLNYFEPLFTWLKEQNR
tr|A0A2J8K      KCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNK
sp|Q9BYF1|      KCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNK
BAE53380.1      KCDISNSSEAGQKLHEMLSLGRSKPWTFALERVVGAKTMDVRPLLNYFEPLFTWLKEQNR
sp|Q56NL1|      KCDISNSTEAGKKLLEMLSLGRSEPWTLALERVVGAKNMNVTPLLNYFEPLFTWLKEQNR
sp|Q56H28|      KCDISNSSEAGKKLLQMLTLGKSKPWTLALEHVVGEKKMNVTPLLKYFEPLFTWLKEQNR
                **.*:**::** ** :** :*.* *** .*: .** . *:. *** **:**  **. ** 
tr|F6WXR7|      DAYVGWNTDWSPYNAYKIKVRISLKT-LGENAYTWNENEMYLFQSSIVFAMRQYFLIKKK
tr|E2DHI2|      KSFVGWNTDWSPYADQSIKVWISLKSALGEKAYEWNNNEMYLFRSSVAYAMREYFLKTKN
sp|Q8R0I0|      NSFVGWNTEWSPYADQSIKVRISLKSALGANAYEWTNNEMFLFRSSVAYAMRKYFSIIKN
sp|Q5EGZ1|      NSTVGWSTDWSPYADQSIKVRISLKSALGKNAYEWTDNEMYLFRSSVAYAMREYFSREKN
tr|A0A220Q      NSSVGWNTDWTPYADQSIKVRISLKSALGKEAYEWNDNEMYLFRSSIAYAMRNYFSSAKN
QHX39726.1      NSFVGWSTEWTPYADQSIKVRISLKTALGDQAYEWNDSEMYLFRSSVAYAMRKYFSEVKN
tr|A0A2J8K      NSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKN
sp|Q9BYF1|      NSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKN
BAE53380.1      NSFVGWNTDWSPYADQSIKVRISLKSALGEKAYEWNDNEMYFFQSSIAYAMREYFSKVKN
sp|Q56NL1|      NSFVGWDTDWRPYSDQSIKVRISLKSALGEKAYEWNDNEMYLFRSSIAYAMREYFSKVKN
sp|Q56H28|      NSFVGWNTDWRPYADQSIKVRISLKSALGDEAYEWNDNEMYLFRSSVAYAMREYFSKVKN
                .: ***.*:* **   .***.****: ** :** *.:.**::*.**:.:***:**   *:
tr|F6WXR7|      QSIPFSNENVKMFDLKPRISFYFFVTFPPNGTSFVPREEVEAAISMSRDRINDAFRLNDN
tr|E2DHI2|      QTILFGEEDVWVSNLKPRISFNFYVTSPRNLSDIIPRPEVEGAIRMSRSRINDAFRLDDN
sp|Q8R0I0|      QTVPFLEEDVRVSDLKPRVSFYFFVTSPQNVSDVIPRSEVEDAIRMSRGRINDVFGLNDN
sp|Q5EGZ1|      QTVPFGEADVWVSDLKPRVSFNFFVTSPKNVSDIIPRSEVEEAIRMSRGRINDIFGLNDN
tr|A0A220Q      ETIPFGAEDVWVSDLKPRISFNFFVTSPANMSDIIPRSDVEKAISMSRSRINDAFRLDDN
QHX39726.1      QTILFGEEDVRVSDLKPRISFNFFVTAPNNVNDIIPRNEVEEAISMSRSRINDIFRLDDN
tr|A0A2J8K      QMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRKSRSRINDAFRLNDN
sp|Q9BYF1|      QMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDN
BAE53380.1      QTIPFVGKDVRVSDLKPRISFNFIVTSPENMSDIIPRADVEEAIRKSRGRINDAFRLDDN
sp|Q56NL1|      QTIPFVEDNVWVSDLKPRISFNFFVTFSNNVSDVIPRSEVEDAIRMSRSRINDAFRLDDN
sp|Q56H28|      QTIPFVEDNVWVSNLKPRISFNFFVTASKNVSDVIPRSEVEEAIRMSRSRINDAFRLDDN
                : : *   :*.: :****:** * ** . * ...:** :** **  **.**** * *:**
tr|F6WXR7|      SLEFVGISPTLAPPYEPPVTVWMIVFGVVMGIVVIGIVYLIYTGVRDRKKRAKTSSSNDE
tr|E2DHI2|      SLEFLGIQPTLGPPYQPPVTIWLIVFGVVMAVVVVGIVVLIITGIRDRRKKDQARS--EE
sp|Q8R0I0|      SLEFLGIHPTLEPPYQPPVTIWLIIFGVVMALVVVGIIILIVTGIKGRKKKNETKR--EE
sp|Q5EGZ1|      SLEFLGIYPTLKPPYEPPVTIWLIIFGVVMGTVVVGIVILIVTGIKGRKKKNETKR--EE
tr|A0A220Q      TLEFLGIQPTLGPPDEPPVTVWLIIFGVVMGLVVVGIVVLIFTGIRDRRKKKQASS--EE
QHX39726.1      SLEFVGIQPTLEPPYESPVPIWLVVFGVVMGMIVIGIVVLIFTGIKDRRKQKQAKR--EE
tr|A0A2J8K      SLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARS--EE
sp|Q9BYF1|      SLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARS--GE
BAE53380.1      SLEFLGIQPTLEPPYQPPVTIWLIVFGVVMGVVVVGIFLLIFSGIRNRRKNNQARS--EE
sp|Q56NL1|      SLEFLGIEPTLSPPYRPPVTIWLIVFGVVMGAIVVGIVLLIVSGIRNRRKNDQAGS--EE
sp|Q56H28|      SLEFLGIQPTLSPPYQPPVTIWLIVFGVVMGVVVVGIVLLIVSGIRNRRKNNQARS--EE
                :***:** *** **  .**.:*:::*****. :*:**. ** :*:..*.*. ::     *
tr|F6WXR7|      NPYVDVDVAGGQHNPAFQSSEDAQTSF
tr|E2DHI2|      NPYSSVDLSKGENNPGFQNGNDVQTSF
sp|Q8R0I0|      NPYDSMDIGKGESNAGFQNSDDAQTSF
sp|Q5EGZ1|      NPYDSMDIGKGESNAGFQNSDDAQTSF
tr|A0A220Q      NPYGSMDLSKGESNSGFQNGDDIQTSF
QHX39726.1      NPYGFVDMSKGENNSGFQNSDDIQTSF
tr|A0A2J8K      NPYASVDTSKGENNPGFQNTDDVQTSF
sp|Q9BYF1|      NPYASIDISKGENNPGFQNTDDVQTSF
BAE53380.1      NPYASVDLSKGENNPGFQNVDDVQTSF
sp|Q56NL1|      NPYASVDLNKGENNPGFQHADDVQTSF
sp|Q56H28|      NPYASVDLSKGENNPGFQHADDVQTSF
                ***  :*   *: *..**  :* ****
  • Based on the alignment above, the ACE2 sequence is highly conserved among mammals. This is indicated by the great amount of "*" and ":" symbols below the alignment. There are not many spaces or "." symbols in the alignment.
  • I decided to analyze the conservation of the amino acids in the key positions 378, 19, 211, 206, 219, 341, 468, and 547. These amino acids were identified as key residues for structure and function of the human ACE2 receptor in a study about genetic variation in human ACE2 that was published in June.
    • Six of the amino acids are invariantly conserved in the 11 species.
    • One of the amino acids showed weak conservation in the alignment. However, the only species that showed a variance was opossum, which is serving as the outgroup.
    • One amino acid showed no conservation between the 11 mammals.
  • I also made a table of the 8 key residue positions for the 11 mammals that my partner and I studied.

DuranWk6residues.png

  • Because the majority of the residues were highly conserved, my findings further indicate the importance of these residues to structure and function of ACE2.
  • Then, I navigated back to the results page and selected the tab that said 6. Tree Rendering to generate a phylogenetic tree of the sequences.
  • I saved the phylogenetic tree and have included it below:

DuranWk6-phylotree.png

  • The key structural and functional residues that we analyzed were distinct from the key residues for viral binding from the Wan et al. article. I used the NCBI Structure Database to create two ACE2 models, one highlighting the viral-binding hotspots, and the other highlighting the eight structural and functional residues. I used the 1R42 model for the figures below.

DuranWk6binding domain.png DuranWk6ACE2 structural residues.png

  • Because the structural residues that we analyzed were all different from the viral-binding residues for coronaviruses, for future research, I think it would be interesting to learn more about how ACE2 could potentially be targeted by SARS-CoV-2 treatments.

Presentation Slides

Final Presentation Slides

Scientific Conclusion

The eight identified ACE2 structural and functional residues in humans are highly conserved in a variety of mammals, further supporting their importance. The structural and functional residues that were analyzed are distinct from the key viral-binding residues identified in the Wan et al. paper. Knowledge on the ACE2 receptor sequences are helpful for further understanding the receptor's interaction with SARS-CoV-2, and could potentially lead to the development of treatments for COVID19.

Acknowledgments

  1. I contacted my partner, Nathan R. Beshai, over Zoom and text to discuss our research project.
  2. I copied and modified the protocol outlined on the Week 6 Assignment page.
  3. I used the Wan et al. article for background information for my research.
  4. I used the Guo et al. article for background information for my research.
  5. I used UniProt Knowledgebase to find entries of ACE2 protein sequences.
  6. I used NCBI GenBank to find entries of ACE2 protein sequences.
  7. I used Phylogeny.fr to generate a multiple sequence alignment and phylogenetic tree.
  8. I used the NCBI iCn3D viewer to visualize and analyze human ACE2 protein structure.
  9. Except for what is noted above, this individual journal entry was completed by me and not copied from another source.

(Macie Duran (talk) 19:44, 14 October 2020 (PDT))

References