Results | viHumans

UniProt ID

P0C6U6

Status

Reviewed

Host

Homo Sapiens (Human) [TaxID: 9606]

Gene Name

1a

Protein Name

♦Replicase polyprotein 1a (pp1a) (ORF1a polyprotein) [Cleaved into: Non-structural protein 1 (nsp1) (p9)
♦ Non-structural protein 2 (nsp2) (p87)
♦ Non-structural protein 3 (nsp3) (EC 3.4.19.12) (EC 3.4.22.-) (PL1-PRO/PL2-PRO) (PLP1/PLP2) (Papain-like proteinases 1/2) (p195)
♦ Non-structural protein 4 (nsp4) (Peptide HD2)
♦ 3C-like proteinase (3CL-PRO) (3CLp) (EC 3.4.22.-) (M-PRO) (nsp5) (p34)
♦ Non-structural protein 6 (nsp6)
♦ Non-structural protein 7 (nsp7) (p5)
♦ Non-structural protein 8 (nsp8) (p23)
♦ Non-structural protein 9 (nsp9) (p12)
♦ Non-structural protein 10 (nsp10) (Growth factor-like peptide) (GFL) (p14)
♦ Non-structural protein 11 (nsp11)]

Organism Name

Human Coronavirus NL63 (HCoV-NL63)

Taxonomic Lineage

Viruses> SsRNA Viruses> SsRNA Positive-strand Viruses> No DNA Stage> Nidovirales> Coronaviridae> Coronavirinae> Alphacoronavirus> Human Coronavirus NL63 (HCoV-NL63)

RefSeq

NC_005831.2 ; AY567487.2

PubMed ID

15034574 ; 20181693

Pathways Involved

Various pathway(s) in which protein is involved

KEGG

Not Available

Reactome

Not Available

Sequence

							MFYNQVTLAVASDSEISGFGFAIPSVAVRTYSEAAAQGFQACRFVAFGLQDCVTGINDDDYVIALTGTNQLCAKILPFSDRPLNLRGWLIFSNSNYVLQD
FDVVFGHGAGSVVFVDKYMCGFDGKPVLPKNMWEFRDYFNNNTDSIVIGGVTYQLAWDVIRKDLSYEQQNVLAIESIHYLGTTGHTLKSGCKLTNAKPPK
YSSKVVLSGEWNAVYRAFGSPFITNGMSLLDIIVKPVFFNAFVKCNCGSESWSVGAWDGYLSSCCGTPAKKLCVVPGNVVPGDVIITSTSAGCGVKYYAG
LVVKHITNITGVSLWRVTAVHSDGMFVASSSYDALLHRNSLDPFCFDVNTLLSNQLRLAFLGASVTEDVKFAASTGVIDISAGMFGLYDDILTNNKPWFV
RKASGLFDAIWDAFVAAIKLVPTTTGVLVRFVKSIASTVLTVSNGVIIMCADVPDAFQSVYRTFTQAICAAFDFSLDVFKIGDVKFKRLGDYVLTENALV
RLTTEVVRGVRDARIKKAMFTKVVVGPTTEVKFSVIELATVNLRLVDCAPVVCPKGKIVVIAGQAFFYSGGFYRFMVDPTTVLNDPVFTGDLFYTIKFSG
FKLDGFNHQFVTASSATDAIIAVELLLLDFKTAVFVYTCVVDGCSVIVRRDATFATHVCFKDCYNVWEQFCIDNCGEPWFLTDYNAILQSNNPQCAIVQA
SESKVLLERFLPKCPEILLSIDDGHLWNLFVEKFNFVTDWLKTLKLTLTSNGLLGNCAKRFRRVLVKLLDVYNGFLETVCSVAYTAGVCIKYYAVNVPYV
VISGFVSRVIRRERCDMTFPCVSCVTFFYEFLDTCFGVSKPNAIDVEHLELKETVFVEPKDGGQFFVSGDYLWYVVDDIYYPASCNGVLPVAFTKLAGGK
ISFSDDVIVHDVEPTHKVKLIFEFEDDVVTSLCKKSFGKSIIYTGDWEGLHEVLTSAMNVIGQHIKLPQFYIYDEEGGYDVSKPVMISQWPISNDSNGCV
VEASTDFHQLECIVDDSVREEVDIIEQPFEEVEHVLSIKQPFSFSFRDELGVRVLDQSDNNCWISTTLVQLQLTKLLDDSIEMQLFKVGKVDSIVQKCYE
LSHLISGSLGDSGKLLSELLKEKYTCSITFEMSCDCGKKFDDQVGCLFWIMPYTKLFQKGECCICHKMQTYKLVSMKGTGVFVQDPAPIDIDAFPVKPIC
SSVYLGVKGSGHYQTNLYSFNKAIDGFGVFDIKNSSVNTVCFVDVDFHSVEIEAGEVKPFAVYKNVKFYLGDISHLVNCVSFDFVVNAANENLLHGGGVA
RAIDILTEGQLQSLSKDYISSNGPLKVGAGVMLECEKFNVFNVVGPRTGKHEHSLLVEAYNSILFENGIPLMPLLSCGIFGVRIENSLKALFSCDINKPL
QVFVYSSNEEQAVLKFLDGLDLTPVIDDVDVVKPFRVEGNFSFFDCGVNALDGDIYLLFTNSILMLDKQGQLLDTKLNGILQQAALDYLATVKTVPAGNL
VKLFVESCTIYMCVVPSINDLSFDKNLGRCVRKLNRLKTCVIANVPAIDVLKKLLSSLTLTVKFVVESNVMDVNDCFKNDNVVLKITEDGINVKDVVVES
SKSLGKQLGVVSDGVDSFEGVLPINTDTVLSVAPEVDWVAFYGFEKAALFASLDVKPYGYPNDFVGGFRVLGTTDNNCWVNATCIILQYLKPTFKSKGLN
VLWNKFVTGDVGPFVSFIYFITMSSKGQKGDAEEALSKLSEYLISDSIVTLEQYSTCDICKSTVVEVKSAIVCASVLKDGCDVGFCPHRHKLRSRVKFVN
GRVVITNVGEPIISQPSKLLNGIAYTTFSGSFDNGHYVVYDAANNAVYDGARLFSSDLSTLAVTAIVVVGGCVTSNVPTIVSEKISVMDKLDTGAQKFFQ
FGDFVMNNIVLFLTWLLSMFSLLRTSIMKHDIKVIAKAPKRTGVILTRSFKYNIRSALFVIKQKWCVIVTLFKFLLLLYAIYALVFMIVQFSPFNSLLCG
DIVSGYEKSTFNKDIYCGNSMVCKMCLFSYQEFNDLDHTSLVWKHIRDPILISLQPFVILVILLIFGNMYLRFGLLYFVAQFISTFGSFLGFHQKQWFLH
FVPFDVLCNEFLATFIVCKIVLFVRHIIVGCNNADCVACSKSARLKRVPLQTIINGMHKSFYVNANGGTCFCNKHNFFCVNCDSFGPGNTFINGDIAREL
GNVVKTAVQPTAPAYVIIDKVDFVNGFYRLYSGDTFWRYDFDITESKYSCKEVLKNCNVLENFIVYNNSGSNITQIKNACVYFSQLLCEPIKLVNSELLS
TLSVDFNGVLHKAYVDVLCNSFFKELTANMSMAECKATLGLTVSDDDFVSAVANAHRYDVLLSDLSFNNFFISYAKPEDKLSVYDIACCMRAGSKVVNHN
VLIKESIPIVWGVKDFNTLSQEGKKYLVKTTKAKGLTFLLTFNDNQAITQVPATSIVAKQGAGFKRTYNFLWYVCLFVVALFIGVSFIDYTTTVTSFHGY
DFKYIENGQLKVFEAPLHCVRNVFDNFNQWHEAKFGVVTTNSDKCPIVVGVSERINVVPGVPTNVYLVGKTLVFTLQAAFGNTGVCYDFDGVTTSDKCIF
NSACTRLEGLGGDNVYCYNTDLIEGSKPYSTLQPNAYYKYDAKNYVRFPEILARGFGLRTIRTLATRYCRVGECRDSHKGVCFGFDKWYVNDGRVDDGYI
CGDGLIDLLVNVLSIFSSSFSVVAMSGHMLFNFLFAAFITFLCFLVTKFKRVFGDLSYGVFTVVCATLINNISYVVTQNLFFMLLYAILYFVFTRTVRYA
WIWHIAYIVAYFLLIPWWLLTWFSFAAFLELLPNVFKLKISTQLFEGDKFIGTFESAAAGTFVLDMRSYERLINTISPEKLKNYAASYNKYKYYSGSASE
ADYRCACYAHLAKAMLDYAKDHNDMLYSPPTISYNSTLQSGLKKMAQPSGCVERCVVRVCYGSTVLNGVWLGDTVTCPRHVIAPSTTVLIDYDHAYSTMR
LHNFSVSHNGVFLGVVGVTMHGSVLRIKVSQSNVHTPKHVFKTLKPGDSFNILACYEGIASGVFGVNLRTNFTIKGSFINGACGSPGYNVRNDGTVEFCY
LHQIELGSGAHVGSDFTGSVYGNFDDQPSLQVESANLMLSDNVVAFLYAALLNGCRWWLCSTRVNVDGFNEWAMANGYTSVSSVECYSILAAKTGVSVEQ
LLASIQHLHEGFGGKNILGYSSLCDEFTLAEVVKQMYGVNLQSGKVIFGLKTMFLFSVFFTMFWAELFIYTNTIWINPVILTPIFCLLLFLSLVLTMFLK
HKFLFLQVFLLPTVIATALYNCVLDYYIVKFLADHFNYNVSVLQMDVQGLVNVLVCLFVVFLHTWRFSKERFTHWFTYVCSLIAVAYTYFYSGDFLSLLV
MFLCAISSDWYIGAIVFRLSRLIVFFSPESVFSVFGDVKLTLVVYLICGYLVCTYWGILYWFNRFFKCTMGVYDFKVSAAEFKYMVANGLHAPHGPFDAL
WLSFKLLGIGGDRCIKISTVQSKLTDLKCTNVVLLGCLSSMNIAANSSEWAYCVDLHNKINLCDDPEKAQSMLLALLAFFLSKHSDFGLDGLIDSYFDNS
STLQSVASSFVSMPSYIAYENARQAYEDAIANGSSSQLIKQLKRAMNIAKSEFDHEISVQKKINRMAEQAATQMYKEARSVNRKSKVISAMHSLLFGMLR
RLDMSSVETVLNLARDGVVPLSVIPATSASKLTIVSPDLESYSKIVCDGSVHYAGVVWTLNDVKDNDGRPVHVKEITKENVETLTWPLILNCERVVKLQN
NEIMPGKLKQKPMKAEGDGGVLGDGNALYNTEGGKTFMYAYISNKADLKFVKWEYEGGCNTIELDSPCRFMVETPNGPQVKYLYFVKNLNTLRRGAVLGF
IGATIRLQAGKQTELAVNSGLLTACAFSVDPATTYLEAVKHGAKPVSNCIKMLSNGAGNGQAITTSVDANTNQDSYGGASICLYCRAHVPHPSMDGYCKF
KGKCVQVPIGCLDPIRFCLENNVCNVCGCWLGHGCACDRTTIQSVDISYLNEQGVLVQLD
						

Length

4060

Alternate Sequence

Not Available

Non-standard residue

Not Available

Date of last Sequence modification

10-06-2008

Protein Existence

Evidence at protein level

Amino Acid composition

Amino Acid	Count	% Frequency	Amino Acid	Count	% Frequency
Alanine (A)			Leucine (L)
Arginine (R)			Lysine (K)
Asparagine (N)			Methionine (M)
Aspartic Acid (D)			Phenylalanine (F)
Cysteine (C)			Proline (P)
Glutamine (Q)			Serine (S)
Glutamic Acid (E)			Threonine (T)
Glycine (G)			Tryptophan (W)
Histidine (H)			Tyrosine (Y)
Isoleucine (I)			Valine (V)

Sum of Absolute Deviation from Amino Acid Occurrence Frequencies

Aliphatic Index

Instability Index

Secondary Structure features

% Number of Residues in Helices	% Number of Residues in Strands	% Number of Residues in Coils

Structural Difficulty(SD) index

Role(s)

♦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.
♦ 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).
♦ Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.
♦ Nsp9 is a ssRNA-binding protein.

EC

3.4.19.12 , 3.4.22.- , 3.4.22.-

Experimentally known GO terms

GO:0003723 ;   GO:0003968 ;   GO:0004197 ;   GO:0008242 ;   GO:0008270 ;
GO:0016021 ;   GO:0019079 ;   GO:0019082 ;   GO:0033644 ;   GO:0036459 ;
GO:0039520 ;   GO:0039548 ;   GO:0039648 ;   GO:0044220

Subcellular Location

♦ Non-structural protein 3: Host membrane
♦ Multi-pass membrane protein .
♦ Non-structural protein 4: Host membrane
♦ Multi-pass membrane protein .
♦ Non-structural protein 6: Host membrane
♦ Multi-pass membrane protein .
♦ Non-structural protein 7: Host cytoplasm, host perinuclear region . Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). .
♦ Non-structural protein 8: Host cytoplasm, host perinuclear region . Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). .
♦ Non-structural protein 9: Host cytoplasm, host perinuclear region . Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). .
♦ Non-structural protein 10: Host cytoplasm, host perinuclear region . Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). .

Domain(s)

♦DOMAIN 1021 1262 Peptidase C16 1.
♦ DOMAIN 1263 1421 Macro.
♦ DOMAIN 1640 1886 Peptidase C16 2.
♦ DOMAIN 2940 3242 Peptidase C30.

Motif(s)

Not Available

Methods of 3D structure generation

X-ray crystallography (3)

Experimetally known structure

2VRI 3TLO 5GWY

Active Site(s)

♦ACT_SITE 1062 1062 For PL1-PRO activity.
♦ ACT_SITE 1212 1212 For PL1-PRO activity.
♦ ACT_SITE 1678 1678 For PL2-PRO activity.
♦ ACT_SITE 1836 1836 For PL2-PRO activity.
♦ ACT_SITE 2980 2980 For 3CL-PRO activity.
♦ ACT_SITE 3083 3083 For 3CL-PRO activity.

Predicted 3D Structures

Protein couldn't be modeled using I-Tasser and Raptor X because of length constraints of the software.

Experimentally known Ligand(s)

CHEMBL3232683

Virtually Screened Ligands

Not Applicable