Results | viHumans

UniProt ID

P0C6U3

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) (p28)
♦ Non-structural protein 2 (nsp2) (p65)
♦ Non-structural protein 3 (nsp3) (EC 3.4.19.12) (EC 3.4.22.69) (PL1-PRO/PL2-PRO) (PL1/PL2) (Papain-like proteinases 1/2) (p210)
♦ Non-structural protein 4 (nsp4) (Peptide HD2) (p44)
♦ 3C-like proteinase (3CL-PRO) (3CLp) (EC 3.4.22.-) (M-PRO) (nsp5) (p27)
♦ Non-structural protein 6 (nsp6)
♦ Non-structural protein 7 (nsp7) (p10)
♦ Non-structural protein 8 (nsp8) (p22)
♦ Non-structural protein 9 (nsp9) (p12)
♦ Non-structural protein 10 (nsp10) (Growth factor-like peptide) (GFL) (p15)
♦ Non-structural protein 11 (nsp11)]

Organism Name

Human Coronavirus HKU1 (isolate N1) (HCoV-HKU1)

Taxonomic Lineage

Viruses> SsRNA Viruses> SsRNA Positive-strand Viruses> No DNA Stage> Nidovirales> Coronaviridae> Coronavirinae> Betacoronavirus> Human Coronavirus HKU1 (HCoV-HKU1)> Human Coronavirus HKU1 (isolate N1) (HCoV-HKU1)

RefSeq

NC_006577.2 ; AY597011.2

PubMed ID

15613317

Pathways Involved

Various pathway(s) in which protein is involved

KEGG

Not Available

Reactome

Not Available

Sequence

							MIKTSKYGLGFKWAPEFRWLLPDAAEELASPMKSDEGGLCPSTGQAMESVGFVYDNHVKIDCRCILGQEWHVQSNLIRDIFVHEDLHVVEVLTKTAVKSG
TAILIKSPLHSLGGFPKGYVMGLFRSYKTKRYVVHHLSMTTSTTNFGEDFLGWIVPFGFMPSYVHKWFQFCRLYIEESDLIISNFKFDDYDFSVEDAYAE
VHAEPKGKYSQKAYALLRQYRGIKPVLFVDQYGCDYSGKLADCLQAYGHYSLQDMRQKQSVWLANCDFDIVVAWHVVRDSRFVMRLQTIATICGIKYVAQ
PTEDVVDGDVVIREPVHLLSADAIVLKLPSLMKVMTHMDDFSIKSIYNVDLCDCGFVMQYGYVDCFNDNCDFYGWVSGNMMDGFSCPLCCTVYDSSEVKA
QSSGVIPENPVLFTNSTDTVNHDSFNLYGYSVTPFGSCIYWSPRPGLWIPIIKSSVKSYDDLVYSGVVGCKSIVKETALITHALYLDYVQCKCGNLEQNH
ILGVNNSWCRQLLLNRGDYNMLLKNIDLFVKRRADFACKFAVCGDGFVPFLLDGLIPRSYYLIQSGIFFTSLMSQFSQEVSDMCLKMCILFMDRVSVATF
YIEHYVNRLVTQFKLLGTTLVNKMVNWFNTMLDASAPATGWLLYQLLNGLFVVSQANFNFVALIPDYAKILVNKFYTFFKLLLECVTVDVLKDMPVLKTI
NGLVCIVGNKFYNVSTGLIPGFVLPCNAQEQQIYFFEGVAESVIVEDDVIENVKSSLSSYEYCQPPKSVEKICIIDNMYMGKCGDKFFPIVMNDKNICLL
DQAWRFPCAGRKVNFNEKPVVMEIPSLMTVKVMFDLDSTFDDILGKVCSEFEVEKGVTVDDFVAVVCDAIENALNSCKEHPVVGYQVRAFLNKLNENVVY
LFDEAGDEAMASRMYCTFAIEDVEDVISSEAVEDTIDGVVEDTINDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDV
VTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNNDEEIVTGDNDDQIV
VTGDDVDDIESIYDFDTYKALLVFNDVYNDALFVSYGSSVETETYFKVNGLWSPTITHTNCWLRSVLLVMQKLPFKFKDLAIENMWLSYKVGYNQSFVDY
LLTTIPKAIVLPQGGFVADFAYWFLNQFDINAYANWCCLKCGFSFDLNGLDALFFYGDIVSHVCKCGHNMTLIAADLPCTLHFSLFDDNFCAFCTPKKIF
IAACAVDVNVCHSVAVIGDEQIDGKFVTKFSGDKFDFIVGYGMSFSMSSFELPQLYGLCITPNVCFVKGDIINVARLVKADVIVNPANGHMLHGGGVAKA
IAVAAGKKFSKETAAMVKSKGVCQVGDCYVSTGGKLCKTILNIVGPDARQDGRQSYVLLARAYKHLNNYDCCLSTLISAGIFSVPADVSLTYLLGVVDKQ
VILVSNNKEDFDIIQKCQITSVVGTKALAVRLTANVGRVIKFETDAYKLFLSGDDCFVSNSSVIQEVLLLRHDIQLNNDVRDYLLSKMTSLPKDWRLINK
FDVINGVKTVKYFECPNSIYICSQGKDFGYVCDGSFYKATVNQVCVLLAKKIDVLLTVDGVNFKSISLTVGEVFGKILGNVFCDGIDVTKLKCSDFYADK
ILYQYENLSLADISAVQSSFGFDQQQLLAYYNFLTVCKWSVVVNGPFFSFEQSHNNCYVNVACLMLQHINLKFNKWQWQEAWYEFRAGRPHRLVALVLAK
GHFKFDEPSDATDFIRVVLKQADLSGAICELELICDCGIKQESRVGVDAVMHFGTLAKTDLFNGYKIGCNCAGRIVHCTKLNVPFLICSNTPLSKDLPDD
VVAANMFMGVGVGHYTHLKCGSPYQHYDACSVKKYTGVSGCLTDCLYLKNLTQTFTSMLTNYFLDDVEMVAYNPDLSQYYCDNGKYYTKPIIKAQFKPFA
KVDGVYTNFKLVGHDICAQLNDKLGFNVDLPFVEYKVTVWPVATGDVVLASDDLYVKRYFKGCETFGKPVIWFCHDEASLNSLTYFNKPSFKSENRYSVL
SVDSVSEESQGNVVTSVMESQISTKEVKLKGVRKTVKIEDAIIVNDENSSIKVVKSLSLVDVWDMYLTGCDYVVWVANELSRLVKSPTVREYIRYGIKPI
TIPIDLLCLRDDNQTLLVPKIFKARAIEFYGFLKWLFIYVFSLLHFTNDKTIFYTTEIASKFTFNLFCLALKNAFQTFRWSIFIKGFLVVATVFLFWFNF
LYINVIFSDFYLPNISVFPIFVGRIVMWIKATFGLVTICDFYSKLGVGFTSHFCNGSFICELCHSGFDMLDTYAAIDFVQYEVDRRVLFDYVSLVKLIVE
LVIGYSLYTVWFYPLFCLIGLQLFTTWLPDLFMLETMHWLIRFIVFVANMLPAFVLLRFYIVVTAMYKVVGFIRHIVYGCNKAGCLFCYKRNCSVRVKCS
TIVGGVIRYYDITANGGTGFCVKHQWNCFNCHSFKPGNTFITVEAAIELSKELKRPVNPTDASHYVVTDIKQVGCMMRLFYDRDGQRVYDDVDASLFVDI
NNLLHSKVKVVPNLYVVVVESDADRANFLNAVVFYAQSLYRPILLVDKKLITTACNGISVTQTMFDVYVDTFMSHFDVDRKSFNNFVNIAHASLREGVQL
EKVLDTFVGCVRKCCSIDSDVETRFITKSMISAVAAGLEFTDENYNNLVPTYLKSDNIVAADLGVLIQNGAKHVQGNVAKAANISCIWFIDAFNQLTADL
QHKLKKACVKTGLKLKLTFNKQEASVPILTTPFSLKGGVVLSNLLYILFFVSLICFILLWALLPTYSVYKSDIHLPAYASFKVIDNGVVRDISVNDLCFA
NKFFQFDQWYESTFGSVYYHNSMDCPIVVAVMDEDIGSTMFNVPTKVLRHGFHVLHFLTYAFASDSVQCYTPHIQISYNDFYASGCVLSSLCTMFKRGDG
TPHPYCYSDGVMKNASLYTSLVPHTRYSLANSNGFIRFPDVISEGIVRIVRTRSMTYCRVGACEYAEEGICFNFNSSWVLNNDYYRSMPGTFCGRDLFDL
FYQFFSSLIRPIDFFSLTASSIFGAILAIVVVLVFYYLIKLKRAFGDYTSVVVINVVVWCINFLMLFVFQVYPICACVYACFYFYVTLYFPSEISVIMHL
QWIVMYGAIMPFWFCVTYVAMVIANHVLWLFSYCRKIGVNVCSDSTFEETSLTTFMITKDSYCRLKNSVSDVAYNRYLSLYNKYRYYSGKMDTAAYREAA
CSQLAKAMETFNHNNGNDVLYQPPTASVSTSFLQSGIVKMVSPTSKIEPCIVSVTYGSMTLNGLWLDDKVYCPRHVICSSSNMNEPDYSALLCRVTLGDF
TIMSGRMSLTVVSYQMQGCQLVLTVSLQNPYTPKYTFGNVKPGETFTVLAAYNGRPQGAFHVTMRSSYTIKGSFLCGSCGSVGYVLTGDSVKFVYMHQLE
LSTGCHTGTDFTGNFYGPYRDAQVVQLPVKDYVQTVNVIAWLYAAILNNCAWFVQNDVCSTEDFNVWAMANGFSQVKADLVLDALASMTGVSIETLLAAI
KRLYMGFQGRQILGSCTFEDELAPSDVYQQLAGVKLQSKTKRFIKETIYWILISTFLFSCIISAFVKWTIFMYINTHMIGVTLCVLCFVSFMMLLVKHKH
FYLTMYIIPVLCTLFYVNYLVVYKEGFRGFTYVWLSYFVPAVNFTYVYEVFYGCILCVFAIFITMHSINHDIFSLMFLVGRIVTLISMWYFGSNLEEDVL
LFITAFLGTYTWTTILSLAIAKIVANWLSVNIFYFTDVPYIKLILLSYLFIGYILSCYWGFFSLLNSVFRMPMGVYNYKISVQELRYMNANGLRPPRNSF
EAILLNLKLLGIGGVPVIEVSQIQSKLTDVKCANVVLLNCLQHLHVASNSKLWQYCSVLHNEILSTSDLSVAFDKLAQLLIVLFANPAAVDTKCLASIDE
VSDDYVQDSTVLQALQSEFVNMASFVEYEVAKKNLADAKNSGSVNQQQIKQLEKACNIAKSVYERDKAVARKLERMADLALTNMYKEARINDKKSKVVSA
LQTMLFSMVRKLDNQALNSILDNAVKGCVPLSAIPALAANTLTIVIPDKQVFDKVVDNVYVTYAGSVWHIQTVQDADGINKQLTDISVDSNWPLVIIANR
YNEVANAVMQNNELMPHKLKIQVVNSGSDMNCNIPTQCYYNNGSSGRIVYAVLSDVDGLKYTKIMKDDGNCVVLELDPPCKFSIQDVKGLKIKYLYFIKG
CNTLARGWVVGTLSSTIRLQAGVATEYAANSSILSLCAFSVDPKKTYLDYIQQGGVPIINCVKMLCDHAGTGMAITIKPEATINQDSYGGASVCIYCRAR
VEHPDVDGICKLRGKFVQVPLGIKDPILYVLTHDVCQVCGFWRDGSCSCVGSSVAVQSKDLNFLNGFGVLV
						

Length

4471

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 (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).
♦ 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.
♦ 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).

EC

3.4.19.12 , 3.4.22.69 , 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:0039502 ;   GO:0039520 ;   GO:0039548 ;   GO:0039579 ;   GO:0039595 ;
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.
♦ 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.
♦ 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.
♦ 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.

Domain(s)

♦DOMAIN 1123 1373 Peptidase C16 1.
♦ DOMAIN 1351 1522 Macro.
♦ DOMAIN 1718 1978 Peptidase C16 2.
♦ DOMAIN 3335 3637 Peptidase C30.

Motif(s)

Not Available

Methods of 3D structure generation

X-ray crystallography (1)

Experimetally known structure

3D23

Active Site(s)

♦ACT_SITE 1161 1161 For PL1-PRO activity.
♦ ACT_SITE 1312 1312 For PL1-PRO activity.
♦ ACT_SITE 1757 1757 For PL2-PRO activity.
♦ ACT_SITE 1914 1914 For PL2-PRO activity.
♦ ACT_SITE 3375 3375 For 3CL-PRO activity.
♦ ACT_SITE 3479 3479 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)

Not Available

Virtually Screened Ligands

Virtual screening has been performed using RASPD

						Million Molecules

					
Best 20 Hit molecules 
Not Available