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P0C6X6

- R1AB_CVHOC

UniProt

P0C6X6 - R1AB_CVHOC

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Protein
Replicase polyprotein 1ab
Gene
rep, 1a-1b
Organism
Human coronavirus OC43 (HCoV-OC43)
Status
Reviewed - Annotation score: 5 out of 5 - Protein inferred from homologyi

Functioni

The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.
The papain-like proteinase 1 (PL1-PRO) and papain-like proteinase 2 (PL2-PRO) 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. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3 By similarity.
The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function By similarity.
The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G) By similarity.
The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction By similarity.
Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter By similarity.
Nsp9 is a ssRNA-binding protein By similarity.
NendoU is a Mn2+-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond By similarity.
Non-structural protein 1: binds to the 40S ribosomal subunit and inhibits host translation. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response By similarity.

Catalytic activityi

Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
ATP + H2O = ADP + phosphate.
TSAVLQ-|-SGFRK-NH2 and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei246 – 2472Cleavage; by PL1-PRO By similarity
Sitei851 – 8522Cleavage; by PL1-PRO By similarity
Active sitei1074 – 10741For PL1-PRO activity By similarity
Active sitei1225 – 12251For PL1-PRO activity By similarity
Active sitei1671 – 16711For PL2-PRO activity By similarity
Active sitei1828 – 18281For PL2-PRO activity By similarity
Sitei2750 – 27512Cleavage; by PL2-PRO By similarity
Sitei3246 – 32472Cleavage; by 3CL-PRO By similarity
Active sitei3287 – 32871For 3CL-PRO activity By similarity
Active sitei3391 – 33911For 3CL-PRO activity By similarity
Sitei3549 – 35502Cleavage; by 3CL-PRO By similarity
Sitei3836 – 38372Cleavage; by 3CL-PRO By similarity
Sitei3925 – 39262Cleavage; by 3CL-PRO By similarity
Sitei4122 – 41232Cleavage; by 3CL-PRO By similarity
Sitei4232 – 42332Cleavage; by 3CL-PRO By similarity
Sitei4369 – 43702Cleavage; by 3CL-PRO By similarity
Sitei5297 – 52982Cleavage; by 3CL-PRO By similarity
Sitei5900 – 59012Cleavage; by 3CL-PRO By similarity
Sitei6421 – 64222Cleavage; by 3CL-PRO By similarity
Sitei6796 – 67972Cleavage; by 3CL-PRO By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri1151 – 117929C4-type 1 By similarity
Add
BLAST
Zinc fingeri1749 – 178537C4-type 2 By similarity
Add
BLAST
Zinc fingeri4306 – 432217 By similarity
Add
BLAST
Zinc fingeri4348 – 436114 By similarity
Add
BLAST
Nucleotide bindingi5578 – 55858ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. RNA binding Source: UniProtKB-KW
  3. RNA-directed RNA polymerase activity Source: UniProtKB-KW
  4. cysteine-type endopeptidase activity Source: InterPro
  5. endonuclease activity Source: UniProtKB-KW
  6. exoribonuclease activity, producing 5'-phosphomonoesters Source: InterPro
  7. helicase activity Source: UniProtKB-KW
  8. methyltransferase activity Source: InterPro
  9. omega peptidase activity Source: InterPro
  10. zinc ion binding Source: InterPro
Complete GO annotation...

GO - Biological processi

  1. induction by virus of catabolism of host mRNA Source: UniProtKB-KW
  2. induction by virus of host autophagy Source: UniProtKB-KW
  3. modulation by virus of host protein ubiquitination Source: UniProtKB-KW
  4. suppression by virus of host ISG15 activity Source: UniProtKB-KW
  5. suppression by virus of host translation Source: UniProtKB-KW
  6. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
  7. transcription, DNA-templated Source: InterPro
  8. viral RNA genome replication Source: InterPro
  9. viral protein processing Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Exonuclease, Helicase, Hydrolase, Nuclease, Nucleotidyltransferase, Protease, RNA-directed RNA polymerase, Thiol protease, Transferase

Keywords - Biological processi

Activation of host autophagy by virus, Decay of host mRNAs by virus, Eukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virus, Host gene expression shutoff by virus, Host mRNA suppression by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host ISG15 by virus, Modulation of host ubiquitin pathway by viral deubiquitinase, Modulation of host ubiquitin pathway by virus, Ubl conjugation pathway, Viral immunoevasion, Viral RNA replication

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Zinc

Protein family/group databases

MEROPSiC16.006.

Names & Taxonomyi

Protein namesi
Recommended name:
Replicase polyprotein 1ab
Short name:
pp1ab
Alternative name(s):
ORF1ab polyprotein
Cleaved into the following 15 chains:
Non-structural protein 1
Short name:
nsp1
Alternative name(s):
p28
Non-structural protein 2
Short name:
nsp2
Alternative name(s):
p65
Alternative name(s):
PL1-PRO/PL2-PRO
PL1/PL2
Papain-like proteinases 1/2
p210
Non-structural protein 4
Short name:
nsp4
Alternative name(s):
Peptide HD2
p44
3C-like proteinase (EC:3.4.22.-)
Short name:
3CL-PRO
Short name:
3CLp
Alternative name(s):
M-PRO
nsp5
p27
Non-structural protein 6
Short name:
nsp6
Non-structural protein 7
Short name:
nsp7
Alternative name(s):
p10
Non-structural protein 8
Short name:
nsp8
Alternative name(s):
p22
Non-structural protein 9
Short name:
nsp9
Alternative name(s):
p12
Non-structural protein 10
Short name:
nsp10
Alternative name(s):
Growth factor-like peptide
Short name:
GFL
p15
RNA-directed RNA polymerase (EC:2.7.7.48)
Short name:
Pol
Short name:
RdRp
Alternative name(s):
nsp12
p100
Helicase (EC:3.6.4.12, EC:3.6.4.13)
Short name:
Hel
Alternative name(s):
nsp13
p67
Exoribonuclease (EC:3.1.13.-)
Short name:
ExoN
Alternative name(s):
nsp14
Alternative name(s):
NendoU
nsp15
p35
Alternative name(s):
nsp16
Gene namesi
Name:rep
ORF Names:1a-1b
OrganismiHuman coronavirus OC43 (HCoV-OC43)
Taxonomic identifieri31631 [NCBI]
Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageNidoviralesCoronaviridaeCoronavirinaeBetacoronavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000007552: Genome

Subcellular locationi

Chain Non-structural protein 7 : Host cytoplasmhost perinuclear region By similarity
Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity.
Chain Non-structural protein 8 : Host cytoplasmhost perinuclear region By similarity
Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity.
Chain Non-structural protein 9 : Host cytoplasmhost perinuclear region By similarity
Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity.
Chain Non-structural protein 10 : Host cytoplasmhost perinuclear region By similarity
Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity.
Chain Helicase : Host endoplasmic reticulum-Golgi intermediate compartment Reviewed prediction
Note: The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA By similarity.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei2138 – 215821Helical; Reviewed prediction
Add
BLAST
Transmembranei2199 – 221921Helical; Reviewed prediction
Add
BLAST
Transmembranei2221 – 224121Helical; Reviewed prediction
Add
BLAST
Transmembranei2313 – 233321Helical; Reviewed prediction
Add
BLAST
Transmembranei2343 – 236321Helical; Reviewed prediction
Add
BLAST
Transmembranei2365 – 238521Helical; Reviewed prediction
Add
BLAST
Transmembranei2752 – 277221Helical; Reviewed prediction
Add
BLAST
Transmembranei2824 – 284421Helical; Reviewed prediction
Add
BLAST
Transmembranei3009 – 302921Helical; Reviewed prediction
Add
BLAST
Transmembranei3031 – 305121Helical; Reviewed prediction
Add
BLAST
Transmembranei3063 – 308321Helical; Reviewed prediction
Add
BLAST
Transmembranei3090 – 311021Helical; Reviewed prediction
Add
BLAST
Transmembranei3115 – 313521Helical; Reviewed prediction
Add
BLAST
Transmembranei3558 – 357821Helical; Reviewed prediction
Add
BLAST
Transmembranei3588 – 360821Helical; Reviewed prediction
Add
BLAST
Transmembranei3615 – 363521Helical; Reviewed prediction
Add
BLAST
Transmembranei3657 – 367721Helical; Reviewed prediction
Add
BLAST
Transmembranei3684 – 370421Helical; Reviewed prediction
Add
BLAST
Transmembranei3711 – 373121Helical; Reviewed prediction
Add
BLAST
Transmembranei3755 – 377521Helical; Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. host cell endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB-SubCell
  2. host cell membrane Source: UniProtKB-SubCell
  3. host cell perinuclear region of cytoplasm Source: UniProtKB-SubCell
  4. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 246246Non-structural protein 1 By similarity
PRO_0000283826Add
BLAST
Chaini247 – 851605Non-structural protein 2 By similarity
PRO_0000283827Add
BLAST
Chaini852 – 27501899Non-structural protein 3 By similarity
PRO_0000283828Add
BLAST
Chaini2751 – 3246496Non-structural protein 4 By similarity
PRO_0000283829Add
BLAST
Chaini3247 – 35493033C-like proteinase By similarity
PRO_0000283830Add
BLAST
Chaini3550 – 3836287Non-structural protein 6 By similarity
PRO_0000283831Add
BLAST
Chaini3837 – 392589Non-structural protein 7 By similarity
PRO_0000283832Add
BLAST
Chaini3926 – 4122197Non-structural protein 8 By similarity
PRO_0000283833Add
BLAST
Chaini4123 – 4232110Non-structural protein 9 By similarity
PRO_0000283834Add
BLAST
Chaini4233 – 4369137Non-structural protein 10 By similarity
PRO_0000283835Add
BLAST
Chaini4370 – 5297928RNA-directed RNA polymerase By similarity
PRO_0000037308Add
BLAST
Chaini5298 – 5900603Helicase By similarity
PRO_0000283836Add
BLAST
Chaini5901 – 6421521Exoribonuclease By similarity
PRO_0000283837Add
BLAST
Chaini6422 – 6796375Uridylate-specific endoribonuclease By similarity
PRO_0000283838Add
BLAST
Chaini6797 – 7095299Putative 2'-O-methyl transferase By similarity
PRO_0000283839Add
BLAST

Post-translational modificationi

Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed By similarity.

Interactioni

Subunit structurei

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 By similarity.

Structurei

3D structure databases

ProteinModelPortaliP0C6X6.
SMRiP0C6X6. Positions 3964-4114, 4238-4362, 6422-6791.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1036 – 1274239Peptidase C16 1
Add
BLAST
Domaini1275 – 1435161Macro
Add
BLAST
Domaini1631 – 1892262Peptidase C16 2
Add
BLAST
Domaini3247 – 3549303Peptidase C30
Add
BLAST
Domaini4977 – 5139163RdRp catalytic
Add
BLAST
Domaini5298 – 538184CV MBD
Add
BLAST
Domaini5553 – 5734182(+)RNA virus helicase ATP-binding
Add
BLAST
Domaini5735 – 5904170(+)RNA virus helicase C-terminal
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2138 – 2385248HD1 By similarity
Add
BLAST
Regioni2752 – 3135384HD2 By similarity
Add
BLAST
Regioni3319 – 3775457HD3 By similarity
Add
BLAST

Domaini

The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane.

Sequence similaritiesi

Contains 1 Macro domain.

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix, Zinc-finger

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR027351. (+)RNA_virus_helicase_core_dom.
IPR022570. Coronavirus_NSP1.
IPR009461. Coronavirus_NSP16.
IPR027352. CV_MBD_dom.
IPR002589. Macro_dom.
IPR009466. NSP11.
IPR014828. NSP7.
IPR014829. NSP8.
IPR014822. NSP9.
IPR027417. P-loop_NTPase.
IPR002705. Pept_C30/C16_B_coronavir.
IPR008740. Peptidase_C30.
IPR013016. Peptidase_C30/C16.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009469. RNA_pol_N_coronovir.
IPR018995. RNA_synth_NSP10_coronavirus.
IPR029063. SAM-dependent_MTases-like.
IPR009003. Trypsin-like_Pept_dom.
IPR014827. Viral_protease.
[Graphical view]
PfamiPF06478. Corona_RPol_N. 1 hit.
PF11963. DUF3477. 1 hit.
PF01661. Macro. 1 hit.
PF09401. NSP10. 1 hit.
PF06471. NSP11. 1 hit.
PF06460. NSP13. 1 hit.
PF08716. nsp7. 1 hit.
PF08717. nsp8. 1 hit.
PF08710. nsp9. 1 hit.
PF01831. Peptidase_C16. 1 hit.
PF05409. Peptidase_C30. 1 hit.
PF00680. RdRP_1. 1 hit.
PF08715. Viral_protease. 1 hit.
[Graphical view]
SMARTiSM00506. A1pp. 1 hit.
[Graphical view]
SUPFAMiSSF101816. SSF101816. 1 hit.
SSF144246. SSF144246. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53335. SSF53335. 1 hit.
PROSITEiPS51653. CV_MBD. 1 hit.
PS51442. M_PRO. 1 hit.
PS51154. MACRO. 1 hit.
PS51124. PEPTIDASE_C16. 2 hits.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by ribosomal frameshifting. Align

Isoform Replicase polyprotein 1ab (identifier: P0C6X6-1) [UniParc]FASTAAdd to Basket

Also known as: pp1ab

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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MSKINKYGLE LHWAPEFPWM FEDAEEKLDN PSSSEVDMIC STTAQKLETD     50
GICPENHVMV DCRRLLKQEC CVQSSLIREI VMNASPYHLE VLLQDALQSR 100
EAVLVTTPLG MSLEACYVRG CNPKGWTMGL FRRRSVCNTG RCTVNKHVAY 150
QLYMIDPAGV CLGAGQFVGW VIPLAFMPVQ SRKFIVPWVM YLRKRGEKGA 200
YNKDHGCGGF GHVYDFKVED AYDQVHDEPK GKFSKKAYAL IRGYRGVKPL 250
LYVDQYGCDY TGSLADGLEA YADKTLQEMK ALFPTWSQEL PFDVIVAWHV 300
VRDPRYVMRL QSAATICSVA YVANPTEDLC DGSVVIKEPV HVYADDSIIL 350
RQYNLFDIMS HFYMEADTVV NAFYGVALKD CGFVMQFGYI DCEQDSCDFK 400
GWIPGNMIDG FACTTCGHVY EVGDLIAQSS GVLPVNPVLH TKSAAGYGGF 450
GCKDSFTLYG QTVVYFGGCV YWSPARNIWI PILKSSVKSY DSLVYTGVLG 500
CKAIVKETNL ICKALYLDYV QHKCGNLHQR ELLGVSDVWH KQLLINRGVY 550
KPLLENIDYF NMRRAKFSLE TFTVCADGFM PFLLDDLVPR AYYLAVSGQA 600
FCDYADKLCH AVVSKSKELL DVSLDSLGAA IHYLNSKIVD LAQHFSDFGT 650
SFVSKIVHFF KTFTTSTALA FAWVLFHVLH GAYIVVESDI YFVKNIPRYA 700
SAVAQAFQSV AKVVLDSLRV TFIDGLSCFK IGRRRICLSG RKIYEVERGL 750
LHSSQLPLDV YDLTMPSQVQ KAKQKPIYLK GSGSDFSLAD SVVEVVTTSL 800
TPCGYSEPPK VADKICIVDN VYMAKAGDKY YPVVVDDHVG LLDQAWRVPC 850
AGRRVTFKEQ PTVKEIISMP KIIKVFYELD NDFNTILNTA CGVFEVDDTV 900
DMEEFYAVVI DAIEEKLSPC KELEGVGAKV SAFLQKLEDN PLFLFDEAGE 950
EVFAPKLYCA FTAPEDDDFL EESDVEEDDV EGEETDLTIT SAGQPCVASE 1000
QEESSEVLED TLDDGPSVET SDSQVEEDVE MSDFVDLESV IQDYENVCFE 1050
FYTTEPEFVK VLGLYVPKAT RNNCWLRSVL AVMQKLPCQF KDKNLQDLWV 1100
LYKQQYSQLF VDTLVNKIPA NIVLPQGGYV ADFAYWFLTL CDWQCVAYWK 1150
CIKCDLALKL KGLDAMFFYG DVVSHICKCG ESMVLIDVDV PFTAHFALKD 1200
KLFCAFITKR IVYKAACVVD VNDSHSMAVV DGKQIDDHRI TSITSDKFDF 1250
IIGHGMSFSM TTFEIAQLYG SCITPNVCFV KGDIIKVSKL VKAEVVVNPA 1300
NGHMVHGGGV AKAIAVAAGQ QFVKETTNMV KSKGVCATGD CYVSTGGKLC 1350
KTVLNVVGPD ARTQGKQSYV LLERVYKHFN NYDCVVTTLI SAGIFSVPSD 1400
VSLTYLLGTA KKQVVLVSNN QEDFDLISKC QITAVEGTKK LAARLSFNVG 1450
RSIVYETDAN KLILINDVAF VSTFNVLQDV LSLRHDIALD DDARTFVQSN 1500
VDVLPEGWRV VNKFYQINGV RTVKYFECTG GIDICSQDKV FGYVQQGIFN 1550
KATVAQIKAL FLDKVDILLT VDGVNFTNRF VPVGESFGKS LGNVFCDGVN 1600
VTKHKCDINY KGKVFFQFDN LSSEDLKAVR SSFNFDQKEL LAYYNMLVNC 1650
FKWQVVVNGK YFTFKQANNN CFVNVSCLML QSLHLTFKIV QWQEAWLEFR 1700
SGRPARFVAL VLAKGGFKFG DPADSRDFLR VVFSQVDLTG AICDFEIACK 1750
CGVKQEQRTG LDAVMHFGTL SREDLEIGYT VDCSCGKKLI HCVRFDVPFL 1800
ICSNTPASVK LPKGVGSANI FIGDNVGHYV HVKCEQSYQL YDASNVKKVT 1850
DVTGKLSDCL YLKNLKQTFK SVLTTYYLDD VKKIEYKPDL SQYYCDGGKY 1900
YTQRIIKAQF KTFEKVDGVY TNFKLIGHTV CDSLNSKLGF DSSKEFVEYK 1950
ITEWPTATGD VVLANDDLYV KRYERGCITF GKPVIWLSHE KASLNSLTYF 2000
NRPLLVDDNK FDVLKVDDVD DSGDSSESGA KETKEINIIK LSGVKKPFKV 2050
EDSVIVNDDT SETKYVKSLS IVDVYDMWLT GCKYVVRTAN ALSRAVNVPT 2100
IRKFIKFGMT LVSIPIDLLN LREIKPAVNV VKAVRNKTSA CFNFIKWLFV 2150
LLFGWIKISA DNKVIYTTEI ASKLTCKLVA LAFKNAFLTF KWSMVARGAC 2200
IIATIFLLWF NFIYANVIFS DFYLPKIGFL PTFVGKIAQW IKNTFSLVTI 2250
CDLYSIQDVG FKNQYCNGSI ACQFCLAGFD MLDNYKAIDV VQYEADRRAF 2300
VDYTGVLKIV IELIVSYALY TAWFYPLFAL ISIQILTTWL PELFMLSTLH 2350
WSFRLLVALA NMLPAHVFMR FYIIIASFIK LFSLFKHVAY GCSKSGCLFC 2400
YKRNRSLRVK CSTIVGGMIR YYDVMANGGT GFCSKHQWNC IDCDSYKPGN 2450
TFITVEAALD LSKELKRPIQ PTDVAYHTVT DVKQVGCSMR LFYDRDGQRI 2500
YDDVNASLFV DYSNLLHSKV KSVPNMHVVV VENDADKANF LNAAVFYAQS 2550
LFRPILMVDK NLITTANTGT SVTETMFDVY VDTFLSMFDV DKKSLNALIA 2600
TAHSSIKQGT QIYKVLDTFL SCARKSCSID SDVDTKCLAD SVMSAVSAGL 2650
ELTDESCNNL VPTYLKSDNI VAADLGVLIQ NSAKHVQGNV AKIAGVSCIW 2700
SVDAFNQFSS DFQHKLKKAC CKTGLKLKLT YNKQMANVSV LTTPFSLKGG 2750
AVFSYFVYVC FVLSLVCFIG LWCLMPTYTV HKSDFQLPVY ASYKVLDNGV 2800
IRDVSVEDVC FANKFEQFDQ WYESTFGLSY YSNSMACPIV VAVIDQDFGS 2850
TVFNVPTKVL RYGYHVLHFI THALSADGVQ CYTPHSQISY SNFYASGCVL 2900
SSACTMFTMA DGSPQPYCYT DGLMQNASLY SSLVPHVRYN LANAKGFIRF 2950
PEVLREGLVR VVRTRSMSYC RVGLCEEADE GICFNFNGSW VLNNDYYRSL 3000
PGTFCGRDVF DLIYQLFKGL AQPVDFLALT ASSIAGAILA VIVVLVFYYL 3050
IKLKRAFGDY TSVVFVNVIV WCVNFMMLFV FQVYPTLSCV YAICYFYATL 3100
YFPSEISVIM HLQWLVMYGT IMPLWFCLLY IAVVVSNHAF WVFSYCRKLG 3150
TSVRSDGTFE EMALTTFMIT KDSYCKLKNS LSDVAFNRYL SLYNKYRYYS 3200
GKMDTAAYRE AACSQLAKAM DTFTNNNGSD VLYQPPTASV STSFLQSGIV 3250
KMVNPTSKVE PCVVSVTYGN MTLNGLWLDD KVYCPRHVIC SASDMTNPDY 3300
TNLLCRVTSS DFTVLFDRLS LTVMSYQMRG CMLVLTVTLQ NSRTPKYTFG 3350
VVKPGETFTV LAAYNGKPQG AFHVTMRSSY TIKGSFLCGS CGSVGYVIMG 3400
DCVKFVYMHQ LELSTGCHTG TDFNGDFYGP YKDAQVVQLP IQDYIQSVNF 3450
LAWLYAAILN NCNWFIQSDK CSVEDFNVWA LSNGFSQVKS DLVIDALASM 3500
TGVSLETLLA AIKRLKNGFQ GRQIMGSCSF EDELTPSDVY QQLAGIKLQS 3550
KRTRLFKGTV CWIMASTFLF SCIITAFVKW TMFMYVTTNM FSITFCALCV 3600
ISLAMLLVKH KHLYLTMYIT PVLFTLLYNN YLVVYKHTFR GYVYAWLSYY 3650
VPSVEYTYTD EVIYGMLLLV GMVFVTLRSI NHDLFSFIMF VGRLISVFSL 3700
WYKGSNLEEE ILLMLASLFG TYTWTTVLSM AVAKVIAKWV AVNVLYFTDI 3750
PQIKIVLLCY LFIGYIISCY WGLFSLMNSL FRMPLGVYNY KISVQELRYM 3800
NANGLRPPKN SFEALMLNFK LLGIGGVPII EVSQFQSKLT DVKCANVVLL 3850
NCLQHLHVAS NSKLWHYCST LHNEILATSD LSVAFEKLAQ LLIVLFANPA 3900
AVDSKCLTSI EEVCDDYAKD NTVLQALQSE FVNMASFVEY EVAKKNLDEA 3950
RFSGSANQQQ LKQLEKACNI AKSAYERDRA VAKKLERMAD LALTNMYKEA 4000
RINDKKSKVV SALQTMLFSM VRKLDNQALN SILDNAVKGC VPLNAIPSLA 4050
ANTLNIIVPD KSVYDQIVDN IYVTYAGNVW QIQTIQDSDG TNKQLNEISD 4100
DCNWPLVIIA NRYNEVSATV LQNNELMPAK LKIQVVNSGP DQTCNTPTQC 4150
YYNNSNNGKI VYAILSDVDG LKYTKILKDD GNFVVLELDP PCKFTVQDAK 4200
GLKIKYLYFV KGCNTLARGW VVGTISSTVR LQAGTATEYA SNSSILSLCA 4250
FSVDPKKTYL DFIQQGGTPI ANCVKMLCDH AGTGMAITVK PDATTSQDSY 4300
GGASVCIYCR ARVEHPDVDG LCKLRGKFVQ VPVGIKDPVS YVLTHDVCRV 4350
CGFWRDGSCS CVSTDTTVQS KDTNFLNRVR GASVDARLVP CASGLSTDVQ 4400
LRAFDIYNAS VAGIGLHLKV NCCRFQRVDE NGDKLDQFFV VKRTDLTIYN 4450
REMKCYERVK DCKFVAEHDF FTFDVEGSRV PHIVRKDLTK YTMLDLCYAL 4500
RHFDRNDCML LCDILSIYAG CEQSYFTKKD WYDFVENPDI INVYKKLGPI 4550
FNRALVSATE FADKLVEVGL VGVLTLDNQD LNGKWYDFGD YVIAAPGCGV 4600
AIADSYYSYI MPMLTMCHAL DCELYVNNAY RLFDLVQYDF TDYKLELFNK 4650
YFKHWSMPYH PNTVDCQDDR CIIHCANFNI LFSMVLPNTC FGPLVRQIFV 4700
DGVPFVVSIG YHYKELGIVM NMDVDTHRYR LSLKDLLLYA ADPALHVASA 4750
SALYDLRTCC FSVAAITSGV KFQTVKPGNF NQDFYDFVLS KGLLKEGSSV 4800
DLKHFFFTQD GNAAITDYNY YKYNLPTMVD IKQLLFVLEV VYKYFEIYDG 4850
GCIPASQVIV NNYDKSAGYP FNKFGKARLY YEALSFEEQD EIYAYTKRNV 4900
LPTLTQMNLK YAISAKNRAR TVAGVSILST MTGRMFHQKC LKSIAATRGV 4950
PVVIGTTKFY GGWDDMLRRL IKDVDNPVLM GWDYPKCDRA MPNILRIVSS 5000
LVLARKHETC CSQSDRFYRL ANECAQVLSE IVMCGGCYYV KPGGTSSGDA 5050
TTAFANSVFN ICQAVSANVC ALMSCNGNKI EDLSIRALQK RLYSHVYRSD 5100
KVDSTFVTEY YEFLNKHFSM MILSDDGVVC YNSDYASKGY IANISAFQQV 5150
LYYQNNVFMS ESKCWVEHDI NNGPHEFCSQ HTMLVKMDGD DVYLPYPNPS 5200
RILGAGCFVD DLLKTDSVLL IERFVSLAID AYPLVYHENE EYQKVFRVYL 5250
AYIKKLYNDL GNQILDSYSV ILSTCDGQKF TDESFYKNMY LRSAVMQSVG 5300
ACVVCSSQTS LRCGSCIRKP LLCCKCCYDH VMATDHKYVL SVSPYVCNAP 5350
GCDVNDVTKL YLGGMSYYCE DHKPQYSFKL VMNGLVFGLY KQSCTGSPYI 5400
DDFNRIASCK WTDVDDYILA NECTERLKLF AAETQKATEE AFKQSYASAT 5450
IQEIVSEREL ILSWEIGKVK PPLNKNYVFT GYHFTKNGKT VLGEYVFDKS 5500
ELTNGVYYRA TTTYKLSVGD VFVLTSHSVA NLSAPTLVPQ ENYSSIRFAS 5550
VYSVLETFQN NVVNYQHIGM KRYCTVQGPP GTGKSHLAIG LAVFYCTARV 5600
VYTAASHAAV DALCEKAYKF LNINDCTRIV PAKVRVECYD KFKINDTTRK 5650
YVFTTINALP EMVTDIVVVD EVSMLTNYEL SVINARIRAK HYVYIGDPAQ 5700
LPAPRVLLSK GTLEPKYFNT VTKLMCCLGP DIFLGTCYRC PKEIVDTVSA 5750
LVYENKLKAK NESSLLCFKV YYKGVTTHES SSAVNMQQIY LINKFLKANP 5800
LWHKAVFISP YNSQNFAAKR VLGLQTQTVD SAQGSEYDYV IYSQTAETAH 5850
SVNVNRFNVA ITRAKKGILC VMSNMQLFEA LQFTTLTLDK VPQAVETKVQ 5900
CSTNLFKDCS KSYSGYHPAH APSFLAVDDK YKATGDLAVC LGIGDSAVTY 5950
SRLISLMGFK LDVTLDGYCK LFITKEEAVK RVRAWVGFDA EGAHATLDSI 6000
GTNFPLQLGF STGIDFVVEA TGLFADRDGY SFKKAVAKAP PGEQFKHLIP 6050
LMTRGHRWDV VRPRIVQMFA DHLIDLSDCV VLVTWAANFE LTCLRYFAKV 6100
GREISCNVCT KRATVYNSRT GYYGCWRHSV TCDYLYNPLI VDIQQWGYIG 6150
SLSSNHDLYC SVHKGAHVAS SDAIMTRCLA VYDCFCNNIN WNVEYPIISN 6200
ELSINTSCRV LQRVILKAAM LCNRYTLCYD IGNPKGIACV KDFDFKFYDA 6250
QPIVKSVKTL LYSFEAHKDS FKDGLCMFWN CNVDKYPPNA VVCRFDTRVL 6300
NNLNLPGCNG GSLYVNKHAF HTKPFARAAF EHLKPMPFFY YSDTPCVYMD 6350
GMDAKQVDYV PLKSATCITR CNLGGAVCLK HAEEYREYLE SYNTATTAGF 6400
TFWVYKTFDF YNLWNTFTKL QSLENVVYNL VKTGHYTGQA GEMPCAIIND 6450
KVVTKIDKED VVIFINNTTY PTNVAVELFA KRSVRHHPEL KLFRNLNIDV 6500
CWKHVIWDYA RESIFCSNTY GVCMYTDLKF IDKLNVLFDG RDNGAFEAFK 6550
RSNNGVYIST TKVKSLSMIR GPPRAELNGV VVDKVGDTDC VFYFAVRKEG 6600
QDVIFSQFDS LGVSSNQSPQ GNLGSNGKPG NVGGNDALSI STIFTQSRVI 6650
SSFTCRTDME KDFIALDQDV FIQKYGLEDY AFEHIVYGNF NQKIIGGLHL 6700
LIGLYRRQQT SNLVVQEFVS YDSSIHSYFI TDEKSGGSKS VCTVIDILLD 6750
DFVTLVKSLN LNCVSKVVNV NVDFKDFQFM LWCNDEKVMT FYPRLQAASD 6800
WKPGYSMPVL YKYLNSPMER VSLWNYGKPV TLPTGCMMNV AKYTQLCQYL 6850
NTTTLAVPVN MRVLHLGAGS EKGVAPGSAV LRQWLPAGTI LVDNDLYPFV 6900
SDSVATYFGD CITLPFDCQW DLIISDMYDP ITKNIGEYNV SKDGFFTYIC 6950
HMIRDKLALG GSVAIKITEF SWNAELYKLM GYFAFWTVFC TNANASSSEG 7000
FLIGINYLCK PKVEIDGNVM HANYLFWRNS TVWNGGAYSL FDMAKFPLKL 7050
AGTAVINLRA DQINDMVYSL LEKGKLLIRD TNKEVFVGDS LVNVI 7095

Note: Produced by -1 ribosomal frameshifting at the 1a-1b genes boundary.

Length:7,095
Mass (Da):797,914
Last modified:June 10, 2008 - v1
Checksum:i157CDEBD4CE45D4A
GO
Isoform Replicase polyprotein 1a (identifier: P0C6U7-1) [UniParc]FASTAAdd to Basket

Also known as: pp1a, ORF1a polyprotein

The sequence of this isoform can be found in the external entry P0C6U7.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by conventional translation.

Length:4,383
Mass (Da):491,305
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti88 – 881H → D in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti207 – 2071C → R in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti291 – 2911P → L in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti317 – 3171C → R in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti356 – 3561F → V in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti545 – 5451I → L in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti762 – 7621D → N in strain: Isolate 87309 Belgium 2003.
Natural varianti953 – 9531F → L in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate 87309 Belgium 2003.
Natural varianti989 – 9891I → V in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate 87309 Belgium 2003.
Natural varianti1305 – 13051V → A in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate 87309 Belgium 2003.
Natural varianti1328 – 13281N → D in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti1379 – 13791F → L in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti1504 – 15041L → V in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti1740 – 17401G → E in strain: Isolate 87309 Belgium 2003.
Natural varianti1825 – 18251N → K in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti1936 – 19361S → A in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate 87309 Belgium 2003.
Natural varianti1965 – 19651N → T in strain: ATCC VR-759, Isolate clinical OC43-Paris.
Natural varianti2004 – 20041L → S in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate 87309 Belgium 2003.
Natural varianti2022 – 20221S → G in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti2138 – 21403TSA → ISV in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti2256 – 22561I → M in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti2257 – 22571Q → H in strain: Isolate 87309 Belgium 2003.
Natural varianti2386 – 23861K → R in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti2500 – 25001I → T in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate 87309 Belgium 2003.
Natural varianti2921 – 29211D → E in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti2961 – 29611V → I in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti3086 – 30861T → I in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti3440 – 34401P → L in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti3451 – 34511L → V in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti3466 – 34661I → V in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti4067 – 40671I → V in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti4071 – 40711I → V in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate 87309 Belgium 2003.
Natural varianti4382 – 43821A → T in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti4994 – 49941I → L in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate Tulsa 1999 and Isolate 87309 Belgium 2003.
Natural varianti5014 – 50152SD → RT in strain: Isolate Tulsa 1999.
Natural varianti5765 – 57651L → S in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate 87309 Belgium 2003.
Natural varianti5997 – 59971L → R in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti6236 – 62361G → A in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti6454 – 64541T → A in strain: ATCC VR-759 and Isolate clinical OC43-Paris.
Natural varianti6546 – 65461F → L in strain: ATCC VR-759, Isolate clinical OC43-Paris and Isolate 87309 Belgium 2003.
Natural varianti6636 – 66361D → E in strain: Isolate 87309 Belgium 2003.
Natural varianti6665 – 66651A → T in strain: Isolate 87309 Belgium 2003.
Natural varianti6754 – 67541T → A in strain: ATCC VR-759 and Isolate clinical OC43-Paris.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti426 – 4261I → M in AAT84359. 1 Publication
Sequence conflicti426 – 4261I → M in AAT84351. 1 Publication
Sequence conflicti813 – 8131D → A in AAT84359. 1 Publication
Sequence conflicti813 – 8131D → A in AAT84351. 1 Publication
Sequence conflicti4376 – 43772LN → FK in AAR01012. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY903459 Genomic RNA. Translation: AAX85666.1.
AY903460 Genomic RNA. Translation: AAX85675.1.
AY585228 Genomic RNA. Translation: AAT84351.1.
AY585229 Genomic RNA. Translation: AAT84359.1.
AY391777 Genomic RNA. Translation: AAR01012.1.
AF124989 Genomic RNA. Translation: AAD32993.1.

Keywords - Coding sequence diversityi

Ribosomal frameshifting

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY903459 Genomic RNA. Translation: AAX85666.1 .
AY903460 Genomic RNA. Translation: AAX85675.1 .
AY585228 Genomic RNA. Translation: AAT84351.1 .
AY585229 Genomic RNA. Translation: AAT84359.1 .
AY391777 Genomic RNA. Translation: AAR01012.1 .
AF124989 Genomic RNA. Translation: AAD32993.1 .

3D structure databases

ProteinModelPortali P0C6X6.
SMRi P0C6X6. Positions 3964-4114, 4238-4362, 6422-6791.
ModBasei Search...

Protein family/group databases

MEROPSi C16.006.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

Gene3Di 3.40.50.300. 2 hits.
InterProi IPR027351. (+)RNA_virus_helicase_core_dom.
IPR022570. Coronavirus_NSP1.
IPR009461. Coronavirus_NSP16.
IPR027352. CV_MBD_dom.
IPR002589. Macro_dom.
IPR009466. NSP11.
IPR014828. NSP7.
IPR014829. NSP8.
IPR014822. NSP9.
IPR027417. P-loop_NTPase.
IPR002705. Pept_C30/C16_B_coronavir.
IPR008740. Peptidase_C30.
IPR013016. Peptidase_C30/C16.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009469. RNA_pol_N_coronovir.
IPR018995. RNA_synth_NSP10_coronavirus.
IPR029063. SAM-dependent_MTases-like.
IPR009003. Trypsin-like_Pept_dom.
IPR014827. Viral_protease.
[Graphical view ]
Pfami PF06478. Corona_RPol_N. 1 hit.
PF11963. DUF3477. 1 hit.
PF01661. Macro. 1 hit.
PF09401. NSP10. 1 hit.
PF06471. NSP11. 1 hit.
PF06460. NSP13. 1 hit.
PF08716. nsp7. 1 hit.
PF08717. nsp8. 1 hit.
PF08710. nsp9. 1 hit.
PF01831. Peptidase_C16. 1 hit.
PF05409. Peptidase_C30. 1 hit.
PF00680. RdRP_1. 1 hit.
PF08715. Viral_protease. 1 hit.
[Graphical view ]
SMARTi SM00506. A1pp. 1 hit.
[Graphical view ]
SUPFAMi SSF101816. SSF101816. 1 hit.
SSF144246. SSF144246. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53335. SSF53335. 1 hit.
PROSITEi PS51653. CV_MBD. 1 hit.
PS51442. M_PRO. 1 hit.
PS51154. MACRO. 1 hit.
PS51124. PEPTIDASE_C16. 2 hits.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Circulation of genetically distinct contemporary human coronavirus OC43 strains."
    Vijgen L., Keyaerts E., Lemey P., Moes E., Li S., Vandamme A.M., Van Ranst M.
    Virology 337:85-92(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: Isolate 19572 Belgium 2004 and Isolate 87309 Belgium 2003.
  2. "Human respiratory coronavirus OC43: genetic stability and neuroinvasion."
    St Jean J.R., Jacomy H., Desforges M., Vabret A., Freymuth F., Talbot P.J.
    J. Virol. 78:8824-8834(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: Isolate ATCC VR-759 and Isolate clinical OC43-Paris.
  3. "Complete genomic sequence of human coronavirus OC43: molecular clock analysis suggests a relatively recent zoonotic coronavirus transmission event."
    Vijgen L., Keyaerts E., Moes E., Thoelen I., Wollants E., Lemey P., Vandamme A.M., Van Ranst M.
    J. Virol. 79:1595-1604(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: Isolate ATCC VR-759.
  4. "Phylogenetic analysis of a highly conserved region of the polymerase gene from 11 coronaviruses and development of a consensus polymerase chain reaction assay."
    Stephensen C.B., Casebolt D.B., Gangopadhyay N.N.
    Virus Res. 60:181-189(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 4871-5177.
    Strain: Isolate Tulsa 1999.

Entry informationi

Entry nameiR1AB_CVHOC
AccessioniPrimary (citable) accession number: P0C6X6
Secondary accession number(s): Q4VID8
, Q4VIE7, Q696Q1, Q6TNG2, Q9WAC3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: June 10, 2008
Last modified: September 3, 2014
This is version 57 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

The sequence shown is that of isolate 19572 Belgium 2004.

Keywords - Technical termi

Complete proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi