A0A0U2GRF0 · A0A0U2GRF0_CVH22
- ProteinORF1ab polyprotein
- Geneorf1ab
- StatusUniProtKB unreviewed (TrEMBL)
- Organism
- Amino acids6763 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
Function
function
Forms a primer, NSP9-pU, which is utilized by the polymerase for the initiation of RNA chains. Interacts with ribosome signal recognition particle RNA (SRP). Together with NSP8, suppress protein integration into the cell membrane, thereby disrupting host immune defenses.
Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.
RNA-directed RNA polymerase that catalyzes the transcription of viral genomic and subgenomic RNAs. Acts in complex with nsp7 and nsp8 to transcribe both the minus and positive strands of genomic RNA. The kinase-like NiRAN domain of NSP12 attaches one or more nucleotides to the amino terminus of NSP9, forming a covalent RNA-protein intermediate that serves as transcription/replication primer. Subgenomic RNAs (sgRNAs) are formed by discontinuous transcription: The polymerase has the ability to pause at transcription-regulating sequences (TRS) and jump to the leader TRS, resulting in a major deletion. This creates a series of subgenomic RNAs that are replicated, transcribed and translated. In addition, Nsp12 is a subunit of the viral RNA capping enzyme that catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. Subsequently, the NiRAN domain transfers RNA to GDP, and forms the core cap structure GpppA-RNA.
The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3.
Catalytic activity
- ATP + H2O = ADP + H+ + phosphate
- ATP + H2O = ADP + H+ + phosphate
- uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl-2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside-RNA
Cofactor
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 5687 | |||||
Sequence: D | ||||||
Active site | 5689 | |||||
Sequence: E | ||||||
Active site | 5788 | |||||
Sequence: E | ||||||
Active site | 5864 | |||||
Sequence: H | ||||||
Active site | 5869 | |||||
Sequence: D | ||||||
Binding site | 5927-5933 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: DIGNPKG | ||||||
Active site | 6350 | |||||
Sequence: H | ||||||
Active site | 6365 | |||||
Sequence: H | ||||||
Active site | 6406 | |||||
Sequence: K |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameORF1ab polyprotein
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Pisuviricota > Pisoniviricetes > Nidovirales > Cornidovirineae > Coronaviridae > Orthocoronavirinae > Alphacoronavirus > Duvinacovirus > Human coronavirus 229E
Accessions
- Primary accessionA0A0U2GRF0
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Host membrane ; Multi-pass membrane protein
Membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 1935-1958 | Helical | ||||
Sequence: FLVHNFVTFFTWLLSMFTLCKTAV | ||||||
Transmembrane | 2005-2025 | Helical | ||||
Sequence: LLLLIYTLYSVVLLGVLFGPF | ||||||
Transmembrane | 2079-2096 | Helical | ||||
Sequence: LFSNMQPFIVMVLLLIFG | ||||||
Transmembrane | 2103-2121 | Helical | ||||
Sequence: FLLYFVAQMISTVGVFLGY | ||||||
Transmembrane | 2500-2522 | Helical | ||||
Sequence: WLWLLCGLVCLIQFYLCFFMPYF | ||||||
Transmembrane | 2735-2754 | Helical | ||||
Sequence: GLWNLVFNILSMFSSSFSVA | ||||||
Transmembrane | 2760-2777 | Helical | ||||
Sequence: ILLNCALGAFAIFCCFLV | ||||||
Transmembrane | 2784-2800 | Helical | ||||
Sequence: FGDLSVGVCTVVMAVLL | ||||||
Transmembrane | 2806-2824 | Helical | ||||
Sequence: IVTQNLVTMIAYAVLYFFA | ||||||
Transmembrane | 2831-2856 | Helical | ||||
Sequence: AWIWCAAYLIAYISFAPWWLCAWYFL | ||||||
Transmembrane | 3168-3189 | Helical | ||||
Sequence: MLTVNVVAFLYAAILNGCIWWL | ||||||
Transmembrane | 3283-3304 | Helical | ||||
Sequence: LSLFAGFFIMFWAELFVYTTTV | ||||||
Transmembrane | 3310-3329 | Helical | ||||
Sequence: FLTPFMILLVALSLCLTSFV | ||||||
Transmembrane | 3334-3357 | Helical | ||||
Sequence: LFLQVFLLPSIIVAAIQNCAWDYH | ||||||
Transmembrane | 3377-3395 | Helical | ||||
Sequence: IQGFVNIFICLFVALLHTW | ||||||
Transmembrane | 3402-3420 | Helical | ||||
Sequence: CTHWCTYLFSLLAVLYTAL | ||||||
Transmembrane | 3440-3464 | Helical | ||||
Sequence: WYIGAIIFRICRFGVACLPVAYVAY | ||||||
Transmembrane | 3471-3492 | Helical | ||||
Sequence: VLLFYMLLGFVSCMYYGLLYWI |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Disulfide bond | 2028↔2055 | |||||
Sequence: CSETVNGYAKSNFVKDDYCDGSLGCKMC | ||||||
Disulfide bond | 2046↔2052 | |||||
Sequence: CDGSLGC |
Keywords
- PTM
Interaction
Subunit
3CL-PRO exists as monomer and homodimer. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer. Nsp9 is a dimer. Nsp10 forms a dodecamer.
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 2-109 | CoV Nsp1 globular | ||||
Sequence: ACNRVTLAVASDTEISATGCSTIALAVRRYSEAASNGFRACRFVSFGLHDCVVGIANDDYVMGLHGNQTLSCNIMKFSDRPFMLRGWLVFSNSNYLLEEFDVVFGKRG | ||||||
Domain | 113-359 | CoV Nsp2 N-terminal | ||||
Sequence: VTYTDQYLCGADGKPVISDDLWQFVDHFGENEEIIINGHTYVCAWLTKRKPLDYKRQNNLAIEEIEYVRGDALHTLRNGSVLEMAKEVKTSSKVVLSDALDKLYKVFGSPVMTNGSNILEAFIKPVFISAFVQCTCGNKSWSVGDWTGFKSTCCNVLSNKLCVVPGNVKPGDAVVTTQQAGVGVKYFCGMTLKFVANIEGVSVWRVIAVQSVDGFVASATFVEEEHANRMDTFCFNVRNSTTDECRL | ||||||
Domain | 389-775 | CoV Nsp2 middle | ||||
Sequence: YDDIFAENKPWFVRKAEDIFGPCWSALVSVLKQLKVTTGELMRFVKSICSSAVAVVSGTIQIVASVPDMFLPAFDVFVKAVQTVFDCAVETSTIAGKSFDKVFDYVLLDNALVKLVTIKLKGVRASGLKTVKYATAVVGSTEEVKSSRVERSTAVLTIANNYPKLSDEGYTAVIGDVAYFVSDGYFRLMASPNSVLTTAVYKPLFAFNVNVMGTRPEKFPTIVTCENLESAVLFVNDKITEFQLDCSVDVIDNEIIVKPNISLCVPLYVRDYVDKWDDFCRQYSNESWFEDDYRAFISVLDVADADVKAAESKAFIDTIIPSCPSILKIIDGGKIWSGIIKAVSSVADWLKSLKLTLTPEGLFGTCAKRFKRFLTVLLDAYNAFLDT | ||||||
Domain | 773-897 | CoV Nsp2 C-terminal | ||||
Sequence: LDTVASIVKIGGKAFKKYAFDKPYIVVCDIVCKVEHKTDADWVELMPRNDRIKSFSTFENAYLPIADPTHFDIEEVELLDTEFVEPGCGGILALIDDHVFYKKDDIYYPSNGTKILPVAFTKAAG | ||||||
Domain | 898-993 | Ubiquitin-like | ||||
Sequence: GKVSFSDAVEVKDIPPVYRVKLCFEFEDEKLVDVCEKAIGEKIKHEGDWDSFCKTIQSALSVVSSYVNLPTYYIYDEQGGTDLSLPVMISEWPLSE | ||||||
Domain | 1023-1276 | Peptidase C16 | ||||
Sequence: VNSSFAIEAVDVKYEVSPFEMPFEELNGLKILKQMDNNCWVNSVMLQLQLTGILDDDYAMQFFKIGRVSKMVERCYNAEQCIRGAMGDVGLCLYRLLKDLHTGFMVMDYKCSCTSGRLEESGSVLFCTPTKKAFPYGTCLNCNAPRMCTIRQLQGTIIFVQQNPEPVNPCAFVVKPVCASVFRGAVSSGHYQINIYPQKLCVDGFGVNKIQPWPNDALNTICIRDANYSAKVEKPVTPGKPPAELAPIDETVVK | ||||||
Domain | 1275-1443 | Macro | ||||
Sequence: VKVKLNSFLTCNNVSFYQGDIDAVVNGVDFDFIVNAANENLAHCGGLAKALDVYTKGKLQRLSKEHIGLAGKVKVGAGVMVECDGLRIFNVVGPRKGKHERDLLIKAYNTINNEQGIPLTPILSCGIFGVKLETSLEVLFAVCNTKEVKVFVYTDTEVCKVKDFVSGLV | ||||||
Domain | 1607-1662 | Ubiquitin-like | ||||
Sequence: SKVITIKVTEDGVNVHDVTVTTDKSFEQQVGVIAVKDKDLSGAVPSDLNTSELLTK | ||||||
Domain | 1670-1921 | Peptidase C16 | ||||
Sequence: EFYGFGDAVTFATVDHSDFAYDSAVVNGFRVLKTSDNNCWVNAVCISLQYLKPHFISQGLDAAWNKFVLGDVETFVAFIYYVAGLVKGAKGDAEDILNKLSKYLANEAQVQLEHYSSCVECEATFKNPVASVNSAIVCASVKRDGVQVGYCAHGIKYYSRVRSVSGRAIIFSVEQLEPCSQSRLLSGVAYTAFSGPADNGHYTVYDTAKKSMYDGDRFVKHDLSLLSVTSVVMVGGYVAPVKTVKPKPVINQ | ||||||
Domain | 2012-2077 | 3Ecto | ||||
Sequence: LYSVVLLGVLFGPFNLCSETVNGYAKSNFVKDDYCDGSLGCKMCLFGYQELSQFSHLDVVWKHITD | ||||||
Region | 2151-2241 | Y1 | ||||
Sequence: SFVRHVLFGCENPDCIACSKSARLKRFPVNTIVNGVQRSFYVNANGGSKFCKKHRFFCVDCDSYGYGNTFITPEVSRELGNITKTNVQPTG | ||||||
Domain | 2151-2490 | CoV Nsp3 Y | ||||
Sequence: SFVRHVLFGCENPDCIACSKSARLKRFPVNTIVNGVQRSFYVNANGGSKFCKKHRFFCVDCDSYGYGNTFITPEVSRELGNITKTNVQPTGPAYVMVDKVEFENGFYRLYSGEAFWRYNFDITESKYSCKEVLKNCNVLDDFIVFNNNGTNVTQVKNASVYFSQLLCRPIKLVDSELLSTLSVDFNGVLHKAYIDVLRNSFGKDLNANMSLAECKSALGLSISDHEFTSAISNAHRCDVLLSDLSFNNFVSSYAKPDEKLSAYDLACCMRAGAKVVNANVLTKDQTPIVWHAKDFNSLSAEGRKYIVKTSKAKGLTFLLTINENQAVTQIPATSIVAKQG | ||||||
Region | 2155-2168 | ZF1 | ||||
Sequence: HVLFGCENPDCIAC | ||||||
Region | 2201-2211 | ZF2 | ||||
Sequence: CKKHRFFCVDC | ||||||
Region | 2242-2490 | CoV-Y | ||||
Sequence: PAYVMVDKVEFENGFYRLYSGEAFWRYNFDITESKYSCKEVLKNCNVLDDFIVFNNNGTNVTQVKNASVYFSQLLCRPIKLVDSELLSTLSVDFNGVLHKAYIDVLRNSFGKDLNANMSLAECKSALGLSISDHEFTSAISNAHRCDVLLSDLSFNNFVSSYAKPDEKLSAYDLACCMRAGAKVVNANVLTKDQTPIVWHAKDFNSLSAEGRKYIVKTSKAKGLTFLLTINENQAVTQIPATSIVAKQG | ||||||
Region | 2389-2490 | Y4 | ||||
Sequence: VLLSDLSFNNFVSSYAKPDEKLSAYDLACCMRAGAKVVNANVLTKDQTPIVWHAKDFNSLSAEGRKYIVKTSKAKGLTFLLTINENQAVTQIPATSIVAKQG | ||||||
Domain | 2875-2970 | Nsp4C | ||||
Sequence: LFEGDKFVGTFESAAAGTFVIDMRSYEKLANSISPEKLKSYAASYNRYKYYSGNANEADYRCACYAYLAKAMLDFSRDHNDILYTPPTVSYGSTLQ | ||||||
Domain | 2971-3272 | Peptidase C30 | ||||
Sequence: AGLRKMAQPSGIVEKCVVRVCYGNTVLNGLWLGDIVYCPRHVIASNTTAAIDYDHEYSIMRLHNFSINSGTAFLGVVGATMHGATLKIKVSQTNMHTPRHSFKTLKSGEGFNILACYDGCAQGVFGVNMRTNWTIRGSFINGACGSPGYNLKNGEVEFVYMHQIELGSGSHVGSSFDGVMYGGFEDQPNLQVESANQMLTVNVVAFLYAAILNGCIWWLKGDKLSVEHYNEWAQANGFTAMNGEDAFSILAAKTGVCVERLLHAIQVLNNGFGGKNILGYSSLNDEFNINEVVKQMFGVNLQ | ||||||
Domain | 3552-3634 | RdRp Nsp7 cofactor | ||||
Sequence: SKLTDLKCTNVVLMGILSNMNIASNSKEWAYCVETHNKINLCDNPETAQELLLALLAFFLSKHSDFGLGDLVDSYFENDSILQ | ||||||
Domain | 3635-3829 | RdRp Nsp8 cofactor | ||||
Sequence: SVASSFVGMPSFVAYETARQEYENAVANGSSPQIIKQLKKAMNVAKAEFDRESSVQRKINRMAEQAAAAMYKEARAVNRKSKVVSAMHSLLFGMLRRLDMSSVDTILNMARNGVVPLSVIPATSASKLVVVVPDHDSFARMMVDGFVHYAGVVWTLQEVKDNDGKNVHLKDVTKENQETLVWPLILTCERVVKLQ | ||||||
Domain | 3830-3938 | Nsp9 ssRNA-binding | ||||
Sequence: NNEIMPGKMKVKATKAEGDGGITSEGNALYNNEGGRAFMYAYVTTKPDMKYVKWEHDSGVVTVELEPPCRFVVDTPTGPQIKYLYFVKNLNTLRRGAVLGYIGATVRLQ | ||||||
Domain | 3939-4077 | ExoN/MTase coactivator | ||||
Sequence: AGKQTEFVSNSHLLTHCSFAVDPAAAYLDAVKQGAKPVGNCVKMLTNGSGSGQAITSTIDSNTTQDTYGGASVCIYCRAHVAHPTMDGFCQYKGKWVQVPIGTNDPIRFCLENTVCKVCGCWLNHGCTCDRTAIQSFDN | ||||||
Domain | 4079-4328 | NiRAN | ||||
Sequence: YLKRVRGSSAARLEPCNGTDIDYCVRAFDVYNKDASFIGKNLKSNCVRFKNADKDDAFYIVKRCIKSVMDHEQSMYNLLKGCNAVAKHDFFTWHEGRTIYGNVSRQDLTKYTMMDLCFALRNFDEKDCEVLKEILVLTGCCGTDYFEMKNWFDPVENEDIHRVYAALGTVVANAMLKCVALCDEMVLRGVVGVLTLDNQDLNGNFYDFGDFVLCPPGMGIPYCTSYYSYMMPVMGMTNCLASECFMKSDI | ||||||
Domain | 4334-4432 | Nsp12 Interface | ||||
Sequence: KTYDLLKYDFTEHKLVLFNKYFKYWGQGYHPDCVDCYDEMCILHCSNFNTLFATTIPNTAFGPLCRKVFIDGVPVVATAGYHFKQLGLVWNKDVNTHST | ||||||
Domain | 4433-5000 | Nsp12 RNA-dependent RNA polymerase | ||||
Sequence: RLTITELLQFVTDPALIVASSPALVDKRTVCFSVAALSTGLTSQTVKPGHFNKEFYDFLRSQGFFDEGSELTLKHFFFTQKGDAAIKDFDYYRYNRPTMLDIGQARVAYQVASRYFDCYEGGCITSREVVVTNLNKSAGWPLNKFGKAGLYYESISYEEQDAMFALTKRNILPTMTQLNLKYAISGKERARTVGGVSLLATMTTRQFHQKCLKSIVATRNATVVIGTTKFYGGWDNMLKNLIADVDDPKLMGWDYPKCDRAMPSMIRMLSAMILGSKHVTCCTASDKFYRLSNELAQVLTEVVYSNGGFYFKPGGTTSGDATTAYANSVFNIFQAVSSNINRILSVNSSNCNNLNVKKLQKQLYDNCYRNSNVDESFVDDFYGYLQKHFSMMILSDDGVVCYNKIYAELGYIADISAFKATLYYQNGVFMSTAKCWTEEDLSVGPHEFCSQHTMQIVDENGKYYLPYPDPSRIISAGVFVDDITKTDAVILLERYVSLAIDAYPLSKHPKPEYRKVFYALLDWVKYLNKTLNEGVLESFSVTLLDEQESKFWDESFYASMYEKSTVLQ | ||||||
Domain | 4680-4842 | RdRp catalytic | ||||
Sequence: PKLMGWDYPKCDRAMPSMIRMLSAMILGSKHVTCCTASDKFYRLSNELAQVLTEVVYSNGGFYFKPGGTTSGDATTAYANSVFNIFQAVSSNINRILSVNSSNCNNLNVKKLQKQLYDNCYRNSNVDESFVDDFYGYLQKHFSMMILSDDGVVCYNKIYAELG | ||||||
Domain | 5001-5084 | CV ZBD | ||||
Sequence: AAGLCVVCGSQTVLRCGDCLRKPMLCTKCAYDHVFGTDHKFILAITPYVCNTSGCNVNDVTKLYLGGLNYYCVDHKPHLSFPLC | ||||||
Domain | 5258-5612 | +RNA virus helicase C-terminal | ||||
Sequence: NVSDAYANLVPYYQLIGKQRITTIQGPPGSGKSHCSIGIGVYYPGARIVFTACSHAAVDSLCAKAATAYSVDKCTRIIPARARVECYSGFKPNNNSAQYVFSTVNALPEVNADIVVVDEVSMCTNYDLSVINQRISYKHIVYVGDPQQLPAPRVLISKGVMEPIDYNVVTQRMCAIGPDVFLHKCYRCPAEIVNTVSELVYENKFVPVKEASKQCFKIFERGSVQVDNGSSINRRQLDVVKRFIHKNPTWSKAVFISPYNSQNYVAARLLGLQTQTVDSAQGSEYDYVIFAQTSDTAHACNANRFNVAITRAKKGIFCIMSDRTLFDALKFFEITMTDLQSENSCGLFKDCARNP | ||||||
Domain | 5669-5883 | ExoN | ||||
Sequence: LFCTRDFAMRHVRGWLGMDVEGAHVTGDNVGTNVPLQVGFSNGVDFVAQPEGCVVTNIGSVVKPVRARAPPGEQFTHLVPLLRKGQPWSVLRKRIVQMIADYLAGSSDVLVFVLWAGGLELTTMRYFVKIGAVKHCQCGTVATCYNSVSNDYCCFKHALGCDYVYNPYVIDIQQWGYVGSLSINHHAICNVHRNEHVASGDAIMTRCLAVYDCFV | ||||||
Domain | 5892-6113 | N7-MTase | ||||
Sequence: YPMIANEKAINRGGRTVQSHIMRAAIKLYNPKAIHDIGNPKGIRCAVTDAKWYCYDKDPINSNVKTLEYDYMTHGQMDGLCLFWNCNVDMYPEFSIVCRFDTRTRSTLNLEGVNGGSLYVNNHAFHTPAYDKRAMAKLKPAPFFYYDDGPCEVVHDQVNYVPLRATNCITKCNIGGAVCSKHANLYRAYVESYNTFTQAGFNIWVPTTFDCYNLWQTFTEVN | ||||||
Region | 6004-6018 | GpppA-binding | ||||
Sequence: VNGGSLYVNNHAFHT | ||||||
Domain | 6116-6176 | Nsp15 N-terminal oligomerization | ||||
Sequence: GLENIAFNVLKKGSFVCADGELPVAISGDKVFVRDGNIDNLVFVNKTSLPTNIAFELFAKR | ||||||
Domain | 6177-6303 | AV-Nsp11N/CoV-Nsp15M | ||||
Sequence: KVGLTPPLSILKNLGVVATYKFVLWDYEAERPFTSFTKSVCGYTDFTEDVCTCYDNSIQGSYERFTLSNNAVLFSATAVKAGGKSLPAIKLNFGMLNGNAIATVKSEDGNIKNVNWFVYVRKDGKPV | ||||||
Domain | 6320-6460 | NendoU | ||||
Sequence: LPRSTMEEDFLNMDIGVFIQKYGLEDFNFEHVVYGDVSKTTLGGLHLLISQVRLSKMGILKAEEFVSASDITLKCCTVTYLNDPSYKTVCTYMDLLLDDFVAILKSLDLTVVSKVHEVIIDNKPWRWMLWCKDNAVATFYP | ||||||
Domain | 6464-6760 | Nidovirus-type SAM-dependent 2'-O-MTase | ||||
Sequence: SAEWKCGYSMPGIYKTQRMCLEPCNLYNYGAGLKLPSGIMFNVVKYTQLCQYLNSTTLCVPHNMRVLHLGAGSDYGVAPGTAVLKRWLPHDAIVVDNDVVDYVSDADFSVTGDCATVYLEDKFDLLISDMYDGRTKAIDGENVSKEGFFTYINGVICEKLAIGGSVAIKVTEYSWNKKLYELVQKFSFWTMFCTSVNTSSSEAFVVGINYLGDFAKGPFIDGNIIHANYVFWRNSTVMTLSYNSVLDLSKFNCKHKATVVVQLKDGDINEMVLSLVRNGKLLVRGNGKCLSFSNHLV |
Sequence similarities
Belongs to the coronaviruses polyprotein 1ab family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length6,763
- Mass (Da)753,321
- Last updated2016-03-16 v1
- ChecksumC08A7E39B04FB786
Keywords
- Coding sequence diversity