Reviewed, UniProtKB/Swiss-Prot P28887 (L_HRSVA)

Names and origin

Protein names

Recommended name:
    Large structural protein
      Short name=Protein L
Alternative name(s):
    Transcriptase
    Replicase
Including the following 3 domains:
    1- Recommended name:
            RNA-directed RNA polymerase
              EC=2.7.7.48
    2- Recommended name:
            mRNA (guanine-N(7)-)-methyltransferase
              EC=2.1.1.56
    3- Recommended name:
            mRNA guanylyltransferase
              EC=2.7.7.-

Gene names

Name:

L

Organism

Human respiratory syncytial virus A (strain A2)

Taxonomic identifier

11259 [NCBI]

Taxonomic lineage

Viruses › ssRNA negative-strand viruses › Mononegavirales › Paramyxoviridae › Pneumovirinae › Pneumovirus

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	2165 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Inferred from homology.

General annotation (Comments)

Function	Displays RNA-directed RNA polymerase, mRNA guanylyl transferase, mRNA (guanine-N(7)-)-methyltransferase and poly(A) synthetase activities. The viral mRNA guanylyl transferase displays a different biochemical reaction than the cellular enzyme. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). Functions either as transcriptase or as replicase. The transcriptase synthesizes subsequently the subgenomic RNAs, assuring their capping and polyadenylation by a stuttering mechanism. The replicase mode is dependent on intracellular protein N concentration. In this mode, the polymerase replicates the whole viral genome without recognizing the transcriptional signals By similarity.
Catalytic activity	Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1). S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppR-RNA.
Subunit structure	Interacts with protein P By similarity.
Subcellular location	Virion Potential. Host cytoplasm By similarity.
Sequence similarities	Belongs to the paramyxoviruses L protein family. Contains 1 RdRp catalytic domain.

Ontologies

Keywords
Biological process	RNA replication mRNA capping mRNA processing
Cellular component	Cytoplasm Virion
Ligand	ATP-binding Nucleotide-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Nucleotidyltransferase RNA-directed RNA polymerase Transferase
Technical term	Multifunctional enzyme
Gene Ontology (GO)
Biological process	mRNA capping Inferred from electronic annotation. Source: UniProtKB-KW transcription, RNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: InterPro RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW mRNA (guanine-N7-)-methyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2165	2165	Large structural protein		PRO_0000142727
Regions
	Domain	693 – 877	185	RdRp catalytic
Natural variations
	Natural variant	17	1	S → G
	Natural variant	319	1	C → Y in strain: Cold-passage attenuated.
	Natural variant	831	1	Q → L
	Natural variant	1049	1	N → D
	Natural variant	1183	1	D → E
	Natural variant	1690	1	H → Y in strain: Cold-passage attenuated.

Sequences

	Sequence		Length	Mass (Da)
	P28887-1 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 5A3DCA0805305197	FASTA	2,165	250,386
	10 20 30 40 50 60 MDPIINGNSA NVYLTDSYLK GVISFSECNA LGSYIFNGPY LKNDYTNLIS RQNPLIEHMN 70 80 90 100 110 120 LKKLNITQSL ISKYHKGEIK LEEPTYFQSL LMTYKSMTSS EQIATTNLLK KIIRRAIEIS 130 140 150 160 170 180 DVKVYAILNK LGLKEKDKIK SNNGQDEDNS VITTIIKDDI LSAVKDNQSH LKADKNHSTK 190 200 210 220 230 240 QKDTIKTTLL KKLMCSMQHP PSWLIHWFNL YTKLNNILTQ YRSNEVKNHG FTLIDNQTLS 250 260 270 280 290 300 GFQFILNQYG CIVYHKELKR ITVTTYNQFL TWKDISLSRL NVCLITWISN CLNTLNKSLG 310 320 330 340 350 360 LRCGFNNVIL TQLFLYGDCI LKLFHNEGFY IIKEVEGFIM SLILNITEED QFRKRFYNSM 370 380 390 400 410 420 LNNITDAANK AQKNLLSRVC HTLLDKTVSD NIINGRWIIL LSKFLKLIKL AGDNNLNNLS 430 440 450 460 470 480 ELYFLFRIFG HPMVDERQAM DAVKINCNET KFYLLSSLSM LRGAFIYRII KGFVNNYNRW 490 500 510 520 530 540 PTLRNAIVLP LRWLTYYKLN TYPSLLELTE RDLIVLSGLR FYREFRLPKK VDLEMIINDK 550 560 570 580 590 600 AISPPKNLIW TSFPRNYMPS HIQNYIEHEK LKFSESDKSR RVLEYYLRDN KFNECDLYNC 610 620 630 640 650 660 VVNQSYLNNP NHVVSLTGKE RELSVGRMFA MQPGMFRQVQ ILAEKMIAEN ILQFFPESLT 670 680 690 700 710 720 RYGDLELQKI LELKAGISNK SNRYNDNYNN YISKCSIITD LSKFNQAFRY ETSCICSDVL 730 740 750 760 770 780 DELHGVQSLF SWLHLTIPHV TIICTYRHAP PYIGDHIVDL NNVDEQSGLY RYHMGGIEGW 790 800 810 820 830 840 CQKLWTIEAI SLLDLISLKG KFSITALING DNQSIDISKP IRLMEGQTHA QADYLLALNS 850 860 870 880 890 900 LKLLYKEYAG IGHKLKGTET YISRDMQFMS KTIQHNGVYY PASIKKVLRV GPWINTILDD 910 920 930 940 950 960 FKVSLESIGS LTQELEYRGE SLLCSLIFRN VWLYNQIALQ LKNHALCNNK LYLDILKVLK 970 980 990 1000 1010 1020 HLKTFFNLDN IDTALTLYMN LPMLFGGGDP NLLYRSFYRR TPDFLTEAIV HSVFILSYYT 1030 1040 1050 1060 1070 1080 NHDLKDKLQD LSDDRLNKFL TCIITFDKNP NAEFVTLMRD PQALGSERQA KITSEINRLA 1090 1100 1110 1120 1130 1140 VTEVLSTAPN KIFSKSAQHY TTTEIDLNDI MQNIEPTYPH GLRVVYESLP FYKAEKIVNL 1150 1160 1170 1180 1190 1200 ISGTKSITNI LEKTSAIDLT DIDRATEMMR KNITLLIRIL PLDCNRDKRE ILSMENLSIT 1210 1220 1230 1240 1250 1260 ELSKYVRERS WSLSNIVGVT SPSIMYTMDI KYTTSTISSG IIIEKYNVNS LTRGERGPTK 1270 1280 1290 1300 1310 1320 PWVGSSTQEK KTMPVYNRQV LTKKQRDQID LLAKLDWVYA SIDNKDEFME ELSIGTLGLT 1330 1340 1350 1360 1370 1380 YEKAKKLFPQ YLSVNYLHRL TVSSRPCEFP ASIPAYRTTN YHFDTSPINR ILTEKYGDED 1390 1400 1410 1420 1430 1440 IDIVFQNCIS FGLSLMSVVE QFTNVCPNRI ILIPKLNEIH LMKPPIFTGD VDIHKLKQVI 1450 1460 1470 1480 1490 1500 QKQHMFLPDK ISLTQYVELF LSNKTLKSGS HVNSNLILAH KISDYFHNTY ILSTNLAGHW 1510 1520 1530 1540 1550 1560 ILIIQLMKDS KGIFEKDWGE GYITDHMFIN LKVFFNAYKT YLLCFHKGYG KAKLECDMNT 1570 1580 1590 1600 1610 1620 SDLLCVLELI DSSYWKSMSK VFLEQKVIKY ILSQDASLHR VKGCHSFKLW FLKRLNVAEF 1630 1640 1650 1660 1670 1680 TVCPWVVNID YHPTHMKAIL TYIDLVRMGL INIDRIHIKN KHKFNDEFYT SNLFYINYNF 1690 1700 1710 1720 1730 1740 SDNTHLLTKH IRIANSELEN NYNKLYHPTP ETLENILANP IKSNDKKTLN DYCIGKNVDS 1750 1760 1770 1780 1790 1800 IMLPLLSNKK LIKSSAMIRT NYSKQDLYNL FPMVVIDRII DHSGNTAKSN QLYTTTSHQI 1810 1820 1830 1840 1850 1860 SLVHNSTSLY CMLPWHHINR FNFVFSSTGC KISIEYILKD LKIKDPNCIA FIGEGAGNLL 1870 1880 1890 1900 1910 1920 LRTVVELHPD IRYIYRSLKD CNDHSLPIEF LRLYNGHINI DYGENLTIPA TDATNNIHWS 1930 1940 1950 1960 1970 1980 YLHIKFAEPI SLFVCDAELS VTVNWSKIII EWSKHVRKCK YCSSVNKCML IVKYHAQDDI 1990 2000 2010 2020 2030 2040 DFKLDNITIL KTYVCLGSKL KGSEVYLVLT IGPANIFPVF NVVQNAKLIL SRTKNFIMPK 2050 2060 2070 2080 2090 2100 KADKESIDAN IKSLIPFLCY PITKKGINTA LSKLKSVVSG DILSYSIAGR NEVFSNKLIN 2110 2120 2130 2140 2150 2160 HKHMNILKWF NHVLNFRSTE LNYNHLYMVE STYPYLSELL NSLTTNELKK LIKITGSLLY NFHNE

References

[1]	"Sequence analysis of the polymerase L gene of human respiratory syncytial virus and predicted phylogeny of nonsegmented negative-strand viruses." Stec D.S., Hill M.G. III, Collins P.L. Virology 183:273-287(1991) [PubMed: 2053282] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Functional cDNA clones of the human respiratory syncytial (RS) virus N, P, and L proteins support replication of RS virus genomic RNA analogs and define minimal trans-acting requirements for RNA replication." Yu Q., Hardy R.W., Wertz G.W. J. Virol. 69:2412-2419(1995) [PubMed: 7884888] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]	"A cold-passaged, attenuated strain of human respiratory syncytial virus contains mutations in the F and L genes." Connors M., Crowe J.E. Jr., Firestone C.Y., Murphy B.R., Collins P.L. Virology 208:478-484(1995) [PubMed: 7747420] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Cold-passage attenuated.
[4]	"Acquisition of the ts phenotype by a chemically mutagenized cold-passaged human respiratory syncytial virus vaccine candidate results from the acquisition of a single mutation in the polymerase (L) gene." Crowe J.E. Jr., Firestone C.Y., Whitehead S.S., Collins P.L., Murphy B.R. Virus Genes 13:269-273(1996) [PubMed: 9035372] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Cold-passage attenuated.
[5]	"Nucleotide sequence analysis of the respiratory syncytial virus subgroup A cold-passaged (cp) temperature sensitive (ts) cpts-248/404 live attenuated virus vaccine candidate." Firestone C.Y., Whitehead S.S., Collins P.L., Murphy B.R., Crowe J.E. Jr. Virology 225:419-422(1996) [PubMed: 8918930] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Cold-passage attenuated.
[6]	"Recombinant respiratory syncytial virus (RSV) bearing a set of mutations from cold-passaged RSV is attenuated in chimpanzees." Whitehead S.S., Juhasz K., Firestone C.Y., Collins P.L., Murphy B.R. J. Virol. 72:4467-4471(1998) [PubMed: 9557743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Cold-passage attenuated.
[7]	"The structure of the 5' terminal cap of the respiratory syncytial virus mRNA." Barik S. J. Gen. Virol. 74:485-490(1993) [PubMed: 8445369] [Abstract] Cited for: FUNCTION.
[8]	"Unravelling the complexities of respiratory syncytial virus RNA synthesis." Cowton V.M., McGivern D.R., Fearns R. J. Gen. Virol. 87:1805-1821(2006) [PubMed: 16760383] [Abstract] Cited for: REVIEW.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M75730 Genomic RNA. Translation: AAA47418.1. U27298 Genomic RNA. Translation: AAA84898.1. U50362 Genomic RNA. Translation: AAB86667.1. U50363 Genomic RNA. Translation: AAB86679.1. U63644 Genomic RNA. Translation: AAC55973.1. AF035006 Genomic RNA. Translation: AAC14905.1.
PIR	RRNZA2. A40317.
3D structure databases
ModBase	Search...
Family and domain databases
InterPro	IPR014023. RNA_pol_cat. IPR001016. RNA_pol_L_viral. [Graphical view]
Pfam	PF00946. Paramyx_RNA_pol. 1 hit. [Graphical view]
PROSITE	PS50526. RDRP_SSRNA_NEG_NONSEG. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

L_HRSVA

Accession

Primary (citable) accession number: P28887
Secondary accession number(s): O41355 , O41356, P90197, Q82021

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	June 16, 2009
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)