P16289 (L_RABVS) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Large structural protein
Short name=Protein L

Alternative name(s):
Replicase
Transcriptase

Including the following 3 domains:

1. RNA-directed RNA polymerase
   EC=2.7.7.48
2. mRNA (guanine-N(7)-)-methyltransferase
   EC=2.1.1.56
3. mRNA guanylyltransferase
   EC=2.7.7.-

Gene names

Name:

L

Organism

Rabies virus (strain SAD B19) (RABV) [Complete proteome]

Taxonomic identifier

11300 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Mononegavirales › Rhabdoviridae › Lyssavirus › Rabies virus

Virus host

Homo sapiens (Human) [TaxID: 9606]
Mammalia [TaxID: 40674]

Protein attributes

Sequence length	2127 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Displays RNA-directed RNA polymerase, mRNA guanylyltransferase, mRNA (guanine-N(7)-)-methyltransferase and poly(A) synthetase activities. The viral mRNA guanylyltransferase 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 five subgenomic RNAs, assuring their capping and polyadenylation by a stuttering mechanism. The replicase mode is dependent on intracellular N protein 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 the P protein to form the functional polymerase By similarity.
Subcellular location	Virion. Host cytoplasm By similarity.
Sequence similarities	Belongs to the rhabdoviruses protein L family. Contains 1 RdRp catalytic domain.

Ontologies

Keywords
Biological process	Viral RNA replication mRNA capping mRNA processing
Cellular component	Host cytoplasm Virion
Ligand	ATP-binding Nucleotide-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Nucleotidyltransferase RNA-directed RNA polymerase Transferase
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological_process	RNA (guanine-N7)-methylation Inferred from electronic annotation. Source: GOC
Cellular_component	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-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 – 2127	2127	Large structural protein		PRO_0000222841
Regions
	Domain	611 – 799	189	RdRp catalytic
	Nucleotide binding	1701 – 1710	10	ATP Potential
	Region	1562 – 2127	566	Interaction with P protein By similarity
Natural variations
	Natural variant	26	1	I → T in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	365	1	F → Y in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	391	1	L → I in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	394	1	M → V in strain: SRV9, Isolate SAD1-3670 var 1, Isolate SAD1-3670 var 2, Isolate SAD Bern, Isolate SAD Bern original var 1, Isolate SAD Bern original var 2, Isolate SAD Bern original var 3, Isolate SAD Bern original var 4, Isolate SAD Bern original var 5, Isolate SAD P5/88, Isolate SAD VA1 and Isolate SAG 2.
	Natural variant	524	1	R → K in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	901	1	I → V in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	933	1	Q → H in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	1018	1	I → T in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	1100	1	L → Q in strain: SRV9.
	Natural variant	1212	1	A → T in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	1450	1	V → I in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	1516	1	I → V in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	1541	1	S → T in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	1761	1	L → F in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	1990	1	S → L in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
	Natural variant	2097	1	R → G in strain: Isolate SAD1-3670 var 1 and Isolate SAD1-3670 var 2.
Experimental info
	Mutagenesis	725	1	L → I or M: Complete loss of polymerase activity. Ref.4
	Mutagenesis	726	1	A → G, S or V: Complete loss of polymerase activity. Ref.4
	Mutagenesis	727	1	Q → E or N: Complete loss of polymerase activity. Ref.4
	Mutagenesis	728 – 730	3	GDN → SDD: Complete loss of polymerase activity. Ref.4
	Mutagenesis	728	1	G → A: Complete loss of polymerase activity. Ref.4
	Mutagenesis	729	1	D → E or N: Complete loss of polymerase activity. Ref.4
	Mutagenesis	730	1	N → A, D, E or Q: Complete loss of polymerase activity. Ref.4
	Mutagenesis	731	1	Q → E or N: Complete loss of polymerase activity. Ref.4
	Mutagenesis	732	1	V → A: Partial loss of polymerase activity. Ref.4
	Mutagenesis	732	1	V → S or T: Complete loss of polymerase activity. Ref.4
	Mutagenesis	733	1	L → I: No effect on polymerase activity. Ref.4
	Mutagenesis	733	1	L → N: Partial loss of polymerase activity. Ref.4
	Mutagenesis	733	1	L → S: Partial loss of polymerase activity. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P16289 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 6D74F0779CCBBDF9	FASTA	2,127	242,979
	10 20 30 40 50 60 MLDPGEVYDD PIDPIELEAE PRGTPIVPNI LRNSDYNLNS PLIEDPARLM LEWLKTGNRP 70 80 90 100 110 120 YRMTLTDNCS RSFRVLKDYF KKVDLGSLKV GGMAAQSMIS LWLYGAHSES NRSRRCITDL 130 140 150 160 170 180 AHFYSKSSPI EKLLNLTLGN RGLRIPPEGV LSCLERVDYD NAFGRYLANT YSSYLFFHVI 190 200 210 220 230 240 TLYMNALDWD EEKTILALWK DLTSVDIGKD LVKFKDQIWG LLIVTKDFVY SQSSNCLFDR 250 260 270 280 290 300 NYTLMLKDLF LSRFNSLMVL LSPPEPRYSD DLISQLCQLY IAGDQVLSMC GNSGYEVIKI 310 320 330 340 350 360 LEPYVVNSLV QRAEKFRPLI HSLGDFPVFI KDKVSQLEET FGPCARRFFR ALDQFDNIHD 370 380 390 400 410 420 LVFVFGCYRH WGHPYIDYRK GLSKLYDQVH LKKMIDKSYQ ECLASDLARR ILRWGFDKYS 430 440 450 460 470 480 KWYLDSRFLA RDHPLTPYIK TQTWPPKHIV DLVGDTWHKL PITQIFEIPE SMDPSEILDD 490 500 510 520 530 540 KSHSFTRTRL ASWLSENRGG PVPSEKVIIT ALSKPPVNPR EFLRSIDLGG LPDEDLIIGL 550 560 570 580 590 600 KPKERELKIE GRFFALMSWN LRLYFVITEK LLANYILPLF DALTMTDNLN KVFKKLIDRV 610 620 630 640 650 660 TGQGLLDYSR VTYAFHLDYE KWNNHQRLES TEDVFSVLDQ VFGLKRVFSR THEFFQKAWI 670 680 690 700 710 720 YYSDRSDLIG LREDQIYCLD ASNGPTCWNG QDGGLEGLRQ KGWSLVSLLM IDRESQIRNT 730 740 750 760 770 780 RTKILAQGDN QVLCPTYMLS PGLSQEGLLY ELERISRNAL SIYRAVEEGA SKLGLIIKKE 790 800 810 820 830 840 ETMCSYDFLI YGKTPLFRGN ILVPESKRWA RVSCVSNDQI VNLANIMSTV STNALTVAQH 850 860 870 880 890 900 SQSLIKPMRD FLLMSVQAVF HYLLFSPILK GRVYKILSAE GESFLLAMSR IIYLDPSLGG 910 920 930 940 950 960 ISGMSLGRFH IRQFSDPVSE GLSFWREIWL SSQESWIHAL CQEAGNPDLG ERTLESFTRL 970 980 990 1000 1010 1020 LEDPTTLNIR GGASPTILLK DAIRKALYDE VDKVENSEFR EAILLSKTHR DNFILFLISV 1030 1040 1050 1060 1070 1080 EPLFPRFLSE LFSSSFLGIP ESIIGLIQNS RTIRRQFRKS LSKTLEESFY NSEIHGISRM 1090 1100 1110 1120 1130 1140 TQTPQRVGGV WPCSSERADL LREISWGRKV VGTTVPHPSE MLGLLPKSSI SCTCGATGGG 1150 1160 1170 1180 1190 1200 NPRVSVSVLP SFDQSFFSRG PLKGYLGSST SMSTQLFHAW EKVTNVHVVK RALSLKESIN 1210 1220 1230 1240 1250 1260 WFITRDSNLA QALIRNIMSL TGPDFPLEEA PVFKRTGSAL HRFKSARYSE GGYSSVCPNL 1270 1280 1290 1300 1310 1320 LSHISVSTDT MSDLTQDGKN YDFMFQPLML YAQTWTSELV QRDTRLRDST FHWHLRCNRC 1330 1340 1350 1360 1370 1380 VRPIDDVTLE TSQIFEFPDV SKRISRMVSG AVPHFQRLPD IRLRPGDFES LSGREKSHHI 1390 1400 1410 1420 1430 1440 GSAQGLLYSI LVAIHDSGYN DGTIFPVNIY GKVSPRDYLR GLARGVLIGS SICFLTRMTN 1450 1460 1470 1480 1490 1500 ININRPLELV SGVISYILLR LDNHPSLYIM LREPSLRGEI FSIPQKIPAA YPTTMKEGNR 1510 1520 1530 1540 1550 1560 SILCYLQHVL RYEREIITAS PENDWLWIFS DFRSAKMTYL SLITYQSHLL LQRVERNLSK 1570 1580 1590 1600 1610 1620 SMRDNLRQLS SLMRQVLGGH GEDTLESDDN IQRLLKDSLR RTRWVDQEVR HAARTMTGDY 1630 1640 1650 1660 1670 1680 SPNKKVSRKV GCSEWVCSAQ QVAVSTSANP APVSELDIRA LSKRFQNPLI SGLRVVQWAT 1690 1700 1710 1720 1730 1740 GAHYKLKPIL DDLNVFPSLC LVVGDGSGGI SRAVLNMFPD AKLVFNSLLE VNDLMASGTH 1750 1760 1770 1780 1790 1800 PLPPSAIMRG GNDIVSRVID LDSIWEKPSD LRNLATWKYF QSVQKQVNMS YDLIICDAEV 1810 1820 1830 1840 1850 1860 TDIASINRIT LLMSDFALSI DGPLYLVFKT YGTMLVNPNY KAIQHLSRAF PSVTGFITQV 1870 1880 1890 1900 1910 1920 TSSFSSELYL RFSKRGKFFR DAEYLTSSTL REMSLVLFNC SSPKSEMQRA RSLNYQDLVR 1930 1940 1950 1960 1970 1980 GFPEEIISNP YNEMIITLID SDVESFLVHK MVDDLELQRG TLSKVAIIIA IMIVFSNRVF 1990 2000 2010 2020 2030 2040 NVSKPLTDPS FYPPSDPKIL RHFNICCSTM MYLSTALGDV PSFARLHDLY NRPITYYFRK 2050 2060 2070 2080 2090 2100 QVIRGNVYLS WSWSNDTSVF KRVACNSSLS LSSHWIRLIY KIVKTTRLVG SIKDLSREVE 2110 2120 RHLHRYNRWI TLEDIRSRSS LLDYSCL

References

[1]	"Molecular cloning and complete nucleotide sequence of the attenuated rabies virus SAD B19." Conzelmann K.-K., Cox J.H., Schneider L.G., Thiel H.-J. Virology 175:485-499(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Analysis of the whole sequence of rabies virus vaccine strain SRV9." Wang T., Zhang S., Hu R. Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: SRV9.
[3]	"Complete nucleotide sequencing of SAD derivatives of attenuated rabies virus vaccine strains." Geue L., Schares S., Schnick C., Kliemt J., Beckert A., Hoffmann B., Freuling C., Marston D., McElhinney L., Fooks A., Zanoni R., Peterhans E., Cox J., Mueller T. Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate SAD Bern, Isolate SAD Bern original var 1, Isolate SAD Bern original var 2, Isolate SAD Bern original var 3, Isolate SAD Bern original var 4, Isolate SAD Bern original var 5, Isolate SAD P5/88, Isolate SAD VA1, Isolate SAD1-3670 var 1, Isolate SAD1-3670 var 2 and Isolate SAG 2.
[4]	"Polymerase activity of in vitro mutated rabies virus L protein." Schnell M.J., Conzelmann K.K. Virology 214:522-530(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LEU-725; ALA-726; GLN-727; GLY-728; ASP-729; ASN-730; GLN-731; VAL-732 AND LEU-733.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M31046 Genomic RNA. Translation: AAA47203.1. AF499686 Genomic RNA. Translation: AAT48626.1. EF206708 Genomic RNA. Translation: ABN11300.1. EF206709 Genomic RNA. Translation: ABN11305.1. EF206710 Genomic RNA. Translation: ABN11310.1. EF206711 Genomic RNA. Translation: ABN11315.1. EF206712 Genomic RNA. Translation: ABN11320.1. EF206713 Genomic RNA. Translation: ABN11325.1. EF206714 Genomic RNA. Translation: ABN11330.1. EF206715 Genomic RNA. Translation: ABN11335.1. EF206716 Genomic RNA. Translation: ABN11340.1. EF206717 Genomic RNA. Translation: ABN11345.1. EF206718 Genomic RNA. Translation: ABN11350.1. EF206719 Genomic RNA. Translation: ABN11355.1. EF206720 Genomic RNA. Translation: ABN11360.1.
PIR	ZLVNSB. E34746.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR026890. Mononeg_mRNAcap. IPR014023. Mononeg_RNA_pol_cat. IPR017234. RNA-dir_pol_rhabdovirus. IPR025786. RNA-direct_RNA_pol_L. [Graphical view]
Pfam	PF14318. Mononeg_mRNAcap. 1 hit. PF00946. Mononeg_RNA_pol. 1 hit. [Graphical view]
PIRSF	PIRSF037546. RNA_pol_RhabdoV_sub. 1 hit.
TIGRFAMs	TIGR04198. paramyx_RNAcap. 1 hit.
PROSITE	PS50526. RDRP_SSRNA_NEG_NONSEG. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

L_RABVS

Accession

Primary (citable) accession number: P16289
Secondary accession number(s): A3F5M4, A3F5R9, Q6HA95

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	May 1, 2013
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program