Results | viHumans

UniProt ID

P0C6U5

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 N5) (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 N5) (HCoV-HKU1)

RefSeq

NC_006577.2 ; AY597011.2

PubMed ID

16809319

Pathways Involved

Various pathway(s) in which protein is involved

KEGG

Not Available

Reactome

Not Available

Sequence

							MIKTSKYGLGFKWAPEFRWLLPDAAEELASPMKSDEGGLCPSTGQAMESVGFVYDNHVKIDCRCILGQEWHVQSNLIRDIFVHEDLHVVEVLTKTAVKSG
TAILIKSPLHSLGGFPKGYVMGLFRSYKTKRYVVHHLSMTTSTTNFGEDFFGWIVPFGFMPSYVHKWFQFCRLYIEESDLIISNFKFDDYDFSVEAAYAE
VHAEPKGKYSQKAYALLRQYRGIKPVLFVDQYGCDYSGKLADCLQAYGHYSLQDMRQKQSVWLANCDFDIVVAWHVVRDSRFVMRLQTIATICGIKYVAQ
PTEDVVDGDVVIREPVHLLSADAIVLKLPSLMKVMTHMDDFSIKSIYNVDLCDCGFVMQYGYVDCFNDNCDFYGWVSGNMMDGFSCPLCCTVYDSSEVKA
QSSGVIPENPVLFTNSTDTVNPDSFNLYGYSVTPFGSCIYWSPRPGLWIPIIKSSVKSYDDLVYSGVVGCKSIVKETALITHALYLDYVQCKCGNLEQNH
ILGVNNSWCRQLLLNRGDYNMLLKNIDLFVKRRADFACKFAVCGDGFVPFLLDGLIPRSYYLIQSGIFFTSLMSQFSQEVSDMCLKMCILFMDRVSVATF
YIEHYVNRLVTQFKLLGTTLVNKMVNWFNTMLDASAPATGWLLYQLLNGFFVVSQANLNFVALIPDYAKILVNKFYTFFKLLLECVTVDVLKDMPVLKTI
NGLVCIVGNKFYNVSTGLIPGFVLPCNAQEQQIYFFEGVAESVIVEDDVIENVKSSLSSYEYCQPPKSVEKICIIDNMYMGKCGDKFFPIVMNDKNICLL
DHAWRFPCAGRKVNFNEKPVVMEIPSLMTVKVMFDLDSTFDDILGKVCSEFEVEKGVTVDDFVAVVCDAIENALNSCKEHPVVGYQVRAFLNKLNENVVY
LFDEAGDEAMASRMYCTFAIEDVEDVISSEAVEDTIDGVVEDTINDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDV
VTGDNDDEDVVTGDNDDEDVVTGDNNDEDVVTGDNNDEESVTGDNDDQIVVTGDDVDDIESIYDFDTYKALLVFNDVYNDALFVSYGSSVETETYFKVNG
LWSPTITHTNCWLRSVLLVMQKLPFKFKDLAIENMWLSYKVGYNQSFVDYLLTTIPKAIVLPQGGYVADFAYWFLNQFDINAYANWCCLKCGFSFDLNGL
DAVFFYGDIVSHVCKCGHNMTLIAADLPCTLHFSLFDDNFCAFCTPKKIFIAACAVDVNVCHSVAVIGDEQIDGKFVTKFSGDKFDFIVGYGMSFSMSSF
ELAQLYGLCITPNVCFVKGDIINVARLVKADVIVNPANGHMLHGGGVAKAIAVAAGKKFSKETAAMVKSKGVCQVGDCYVSTGGKLCKTILNIVGPDARQ
DGRQSYVLLARAYKHLNNYDCCLSTLISAGIFSVPADVSLTYLLGVVDKQVILVSNNKEDFDIIQKCQITSVVGTKALAVRLTANVGRVIKFETDAYKLF
LSGDDCFVSNSSVIQEVLLLRHDIQLNNDVRDYLLSKMTSLPKDWRLINKFDVINGVKTVKYFECPNSIYICSQGKDFGYVCDGSFYKATVNQVCVLLAK
KIDVLLTVDGVNFKSISLTVGEVFGKILGNVFCDGIDVTKLKCSDFYADKILYQYENLSLADISAVQSSFGFDQQQLLAYYNFLTVCKWSVVVNGPFFSF
EQSHNNCYVNVACLMLQHINLKFNKWQWQEAWYEFRAGRPHRLVALVLAKGHFKFDEPSDATDFIRVVLKQADLSGAICELELICDCGIKQESRVGVDAV
MHFGTLAKTDLFNGYKIGCNCAGRIVHCTKLNVPFLICSNTPLSKDLPDDVVAANMFMGVGVGHYTHLKCGSPYQHYDACSVKKYTGVSGCLTDCLYLKN
LTQTFTSMLTNYFLDDVEMVAYNPDLSQYYCDNGKYYTKPIIKAQFKPFAKVDGVYTNFKLVGHDICAQLNDKLGFNVDLPFVEYKVTVWPVATGDVVLA
SDDLYVKRYFKGCETFGKPVIWFCHDEASLNSLTYFNKPSFKSENRYSVLSVDSVSEESQGNVVTSVMESQISTKEVKLKGVRKTVKIEDAIIVNDENSS
IKVVKSLSLVDVWDMYLTGCDYVVWVANELSRLVKSPTVREYIRYGIKPITIPIDLLCLRDDNQTLLVPKIFKARAIEFYGFLKWLFIYVFSLLHFTNDK
TIFYTTEIASKFTFNLFCLALKNAFQTFRWSIFIKGFLVVATVFLFWFNFLYINVIFSDFYLPNISVFPIFVGRIVMWIKATFGLVTICDFYSKLGVGFT
SHFCNGSFICELCHSGFDMLDTYAAIDFVQYEVDRRVLFDYVSLVKLIVELVIGYSLYTVWFYPLFCLIGLQLFTTWLPDLFMLETMHWLIRFIVFVANM
LPAFVLLRFYIVVTAMYKVVGFIRHIVYGCNKAGCLFCYKRNCSVRVKCSTIVGGVIRYYDITANGGTGFCVKHQWNCFNCHSFKPGNTFITVEAAIELS
KELKRPVNPTDASHYVVTDIKQVGCMMRLFYDRDGQRVYDDVDASLFVDINNLLHSKVKVVPNLYVVVVESDADRANFLNAVVFYAQSLYRPILLVDKKL
ITTACNGISVTQIMFDVYVDTFMSHFDVDRKSFNNFVNIAHASLREGVQLEKVLDTFVGCVRKCCSIDSDVETRFITKSMISAVAAGLEFTDENYNNLVP
TYLKSDNIVAADLGVLIQNGAKHVQGNVAKVANISCIWFIDAFNQLTADLQHKLKKACVKTGLKLKLTFNKQEASVPILTTPFSLKGGVVLSNLLYILFF
ISLICFILLWALLPTYSVYKSDIHLPAYASFKVIDNGVVRDISVNDLCFANKFFQFDQWYESTFGSVYYHNSMDCPIVVAVMDEDIGSTMFNVPTKVLRY
GFHVLHFLTYAFASDSVQCYTPHIQISYNDFYASGCVLSSLCTMFKRGDGTPHPYCYTDGVMKNASLYTSLVPHTRYSLANSNGFIRFPDVISEGIVRIV
RTRSMTYCRVGACEYAEEGICFNFNSSWVLNNDYYRSMPGTFCGRDFFDLFYQFFSSLIRPIDFFSLTASSIFGAILAIVVVLVFYYLIKLKRAFGDYTS
VVVINVIVWCINFLMLFVFQVYPICACVYACFYFYVTLYFPSEISVIMHLQWIVMYGAIMPFWFCVTYVAMVIANHVLWLFSYCRKIGVNVCSDSTFEET
SLTTFMITKDSYCRLKNSVSDVAYNRYLSLYNKYRYYSGKMDTAAYREAACSQLAKAMETFNHNNGNDVLYQPPTASVSTSFLQSGIVKMVSPTSKIEPC
LVSVTYGSMTLNGLWLDDKVYCPRHVICLSSNMNEPDYSALLCRVTLGDFTIMSGRMSLTVVSYQMQGCQLVLTVSLQNPYTPKYTFGVVKPGETFTVLA
AYNGRPQGAFHVTMRSSYTIKGSFLCGSCGSVGYVLTGDSVKFVYMHQLELSTGCHTGTDFNGNFYGPYRDAQVVQLPVKDYVQTVNVIAWLYAAILNNC
AWFVQNDVCSIEDFNVWAMTNGFSQVKADLVLDALASMTGVSIETLLAAIKRLYMGFQGRQILGSCTFEDELAPSDVYQQLAGVKLQSKTKRFIKETIYW
ILISTFLFSCIISAFVKWTIFMYINTHMIGVTLCVLCFVSFMMLLVKHKHFYLTMYIIPVLCTLFYVNYLVVYKEGFRGFTYVWLSHFVPAVNFTYVYEV
FYGCILCVFAIFITMHSINHDIFSLMFLVGRIVTLISMWYFGSNLEEDVLLFITAFLGTYTWTTILSLAIAKIVANWLSVNIFYFTDVPYIKLILLSYLF
IGYILSCYWGFFSLLNSVFRMPMGVYNYKISVQELRYMNANGLRPPRNSFEAILLNLKLLGIGGVPVIEVSQIQSKLTDVKCANVVLLNCLQHLHVASNS
KLWQYCSVLHNEILSTSDLSVAFDKLAQLLIVLFSNPAAVDTKCLASIDEVSDDYVQDSTVLQALQSEFVNMASFVEYEVAKKNLADAKNSGSVNQQQIK
QLEKACNIAKSVYERDKAVARKLERMADLALTNMYKEARINDKKSKVVSALQTMLFSMVRKLDNQALNSILDNAVKGCVPLSAIPALAANTLTIIIPDKQ
VFDKVVDNVYVTYAGSVWHIQTVQDADGINKQLTDISVDSNWPLVIIANRYNEVANAVMQNNELMPHKLKIQVVNSGSDINCNIPTQCYYNNVSSGRIVY
AVLSDVDGLKYTKIMKDDGNCVVLELDPPCKFSIQDVKGLKIKYLYFIKGCNTLARGWVVGTLSSTIRLQAGVATEYAANSSILSLCAFSVDPKKTYLDY
IQQGGVPIINCVKMLCDHAGTGMAITIKPEATINQDSYGGASVCIYCRARVEHPDVDGICKLRGKFVQVPLGIKDPILYVLTHDVCQVCGFWRDGSCSCV
GSSVAVQSKDLNFLNGLGVLV
						

Length

4421

Alternate Sequence

Not Available

Non-standard residue

Not Available

Date of last Sequence modification

10-06-2008

Protein Existence

Inferred from homology

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 1073 1323 Peptidase C16 1.
♦ DOMAIN 1301 1472 Macro.
♦ DOMAIN 1668 1928 Peptidase C16 2.
♦ DOMAIN 3285 3587 Peptidase C30.

Motif(s)

Not Available

Methods of 3D structure generation

Predicted/Modelled

Experimetally known structure

Not Available

Active Site(s)

♦ACT_SITE 1111 1111 For PL1-PRO activity.
♦ ACT_SITE 1262 1262 For PL1-PRO activity.
♦ ACT_SITE 1707 1707 For PL2-PRO activity.
♦ ACT_SITE 1864 1864 For PL2-PRO activity.
♦ ACT_SITE 3325 3325 For 3CL-PRO activity.
♦ ACT_SITE 3429 3429 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