P14240 (L_LYCVA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RNA-directed RNA polymerase L
Short name=Protein L
EC=2.7.7.48

Alternative name(s):
Large structural protein
Replicase
Transcriptase

Gene names

Name:

L

Organism

Lymphocytic choriomeningitis virus (strain Armstrong) (LCMV)

Taxonomic identifier

11624 [NCBI]

Taxonomic lineage

Viruses › ssRNA negative-strand viruses › Arenaviridae › Arenavirus › Old world arenaviruses

Virus host

Homo sapiens (Human) [TaxID: 9606]
Mesocricetus auratus (Golden hamster) [TaxID: 10036]
Mus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length	2210 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	RNA-dependent RNA polymerase which is responsible for replication and transcription of the viral RNA genome. During transcription, synthesizes 4 subgenomic RNAs, and assures their capping by a cap-snatching mechanism, in which cellular capped pre-mRNA are used to generate primers for viral transcription. The 3'-end of subgenomic mRNAs molecules are heterogeneous and not polyadenylated. The replicase function is to direct synthesis of antigenomic and genomic RNA which are encapsidated and non capped. As a consequence of the use of the same enzyme for both transcription and replication, these mechanisms need to be well coordinated. These processes may be regulated by proteins N and Z in a dose-dependent manner. Ref.5
Catalytic activity	Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
Subunit structure	Homomultimerizes; the oligomeric structure is essential for the polymerase activity. Interacts with the nucleocapsid protein N By similarity. Interacts with protein Z; this interaction inhibits viral transcription and replication By similarity. Ref.6
Subcellular location	Virion. Host cytoplasm.
Sequence similarities	Belongs to the arenaviridae RNA polymerase family. Contains 1 RdRp catalytic domain.

Ontologies

Keywords
Biological process	Cap snatching RNA replication
Cellular component	Host cytoplasm Virion
Ligand	Nucleotide-binding
Molecular function	Nucleotidyltransferase RNA-directed RNA polymerase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	RNA biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW viral genome replication Inferred from electronic annotation. Source: InterPro
Cellular component	host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2210

2210

RNA-directed RNA polymerase L

PRO_0000079198

Regions

Domain

1166 – 1360

195

RdRp catalytic

Compositional bias

613 – 618

6

Poly-Leu

Natural variations

Natural variant

108

1

S → T in strain: Isolate Armstrong 53b and Isolate Armstrong-derived variant Cl13.

Natural variant

1079

1

K → Q in strain: Isolate Armstrong-derived variant Cl13.

Natural variant

1513

1

T → K in strain: Isolate Armstrong 53b and Isolate Armstrong-derived variant Cl13.

Natural variant

2185

1

I → T in strain: Isolate Armstrong 53b and Isolate Armstrong-derived variant Cl13.

Experimental info

Mutagenesis

1182

1

D → A: Complete loss of polymerase activity. Ref.6

Mutagenesis

1182

1

D → E: Complete loss of polymerase activity. Ref.6

Mutagenesis

1182

1

D → N: Complete loss of polymerase activity. Ref.6

Mutagenesis

1320

1

S → G: Complete loss of polymerase activity. Ref.6

Mutagenesis

1321

1

D → A: Complete loss of polymerase activity. Ref.6

Mutagenesis

1321

1

D → N: Complete loss of polymerase activity. Ref.6

Sequence conflict

164

1

L → Y in AAA46258. Ref.4

Sequence conflict

354

1

Q → R in AAA46258. Ref.4

Sequence conflict

361

1

K → E in AAA46258. Ref.4

Sequence conflict

382

1

H → D in AAA46258. Ref.4

Sequence conflict

552

1

C → S in AAA46259. Ref.4

Sequence conflict

1727

1

R → L in AAA46260. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

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.

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.

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.

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.

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2210

Helix Strand Turn

Details...

Helix

2 – 15

14

Helix

20 – 22

3

Helix

23 – 29

7

Helix

35 – 40

6

Helix

44 – 57

14

Helix

69 – 74

6

Beta strand

92 – 94

3

Beta strand

97 – 103

7

Helix

109 – 124

16

Helix

127 – 132

6

Beta strand

136 – 142

7

Helix

154 – 170

17

Sequences

	Sequence		Length	Mass (Da)
	P14240 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 470C8E623176AFD3	FASTA	2,210	254,532
	10 20 30 40 50 60 MDEIISELRE LCLNYIEQDE RLSRQKLNFL GQREPRMVLI EGLKLLSRCI EIDSADKSGC 70 80 90 100 110 120 THNHDDKSVE TILVESGIVC PGLPLIIPDG YKLIDNSLIL LECFVRSSPA SFEKKFIEDT 130 140 150 160 170 180 NKLACIREDL AVAGVTLVPI VDGRCDYDNS FMPEWANFKF RDLLFKLLEY SNQNEKVFEE 190 200 210 220 230 240 SEYFRLCESL KTTIDKRSGM DSMKILKDAR STHNDEIMRM CHEGINPNMS CDDVVFGINS 250 260 270 280 290 300 LFSRFRRDLE SGKLKRNFQK VNPEGLIKEF SELYENLADS DDILTLSREA VESCPLMRFI 310 320 330 340 350 360 TAETHGHERG SETSTEYERL LSMLNKVKSL KLLNTRRRQL LNLDVLCLSS LIKQSKFKGL 370 380 390 400 410 420 KNDKHWVGCC YSSVNDRLVS FHSTKEEFIR LLRNRKKSKV FRKVSFEELF RASISEFIAK 430 440 450 460 470 480 IQKCLLVVGL SFEHYGLSEH LEQECHIPFT EFENFMKIGA HPIMYYTKFE DYNFQPSTEQ 490 500 510 520 530 540 LKNIQSLRRL SSVCLALTNS MKTSSVARLR QNQIGSVRYQ VVECKEVFCQ VIKLDSEEYH 550 560 570 580 590 600 LLYQKTGESS RCYSIQGPDG HLISFYADPK RFFLPIFSDE VLYNMIDIMI SWIRSCPDLK 610 620 630 640 650 660 DCLTDIEVAL RTLLLLMLTN PTKRNQKQVQ SVRYLVMAIV SDFSSTSLMD KLREDLITPA 670 680 690 700 710 720 EKVVYKLLRF LIKTIFGTGE KVLLSAKFKF MLNVSYLCHL ITKETPDRLT DQIKCFEKFF 730 740 750 760 770 780 EPKSQFGFFV NPKEAITPEE ECVFYEQMKR FTSKEIDCQH TTPGVNLEAF SLMVSSFNNG 790 800 810 820 830 840 TLIFKGEKKL NSLDPMTNSG CATALDLASN KSVVVNKHLN GERLLEYDFN KLLVSAVSQI 850 860 870 880 890 900 TESFVRKQKY KLSHSDYEYK VSKLVSRLVI GSKGEETGRS EDNLAEICFD GEEETSFFKS 910 920 930 940 950 960 LEEKVNTTIA RYRRGRRAND KGDGEKLTNT KGLHHLQLIL TGKMAHLRKV ILSEISFHLV 970 980 990 1000 1010 1020 EDFDPSCLTN DDMKFICEAV EGSTELSPLY FTSVIKDQCG LDEMAKNLCR KFFSENDWFS 1030 1040 1050 1060 1070 1080 CMKMILLQMN ANAYSGKYRH MQRQGLNFKF DWDKLEEDVR ISERESNSES LSKALSLTKC 1090 1100 1110 1120 1130 1140 MSAALKNLCF YSEESPTSYT SVGPDSGRLK FALSYKEQVG GNRELYIGDL RTKMFTRLIE 1150 1160 1170 1180 1190 1200 DYFESFSSFF SGSCLNNDKE FENAILSMTI NVREGFLNYS MDHSKWGPMM CPFLFLMFLQ 1210 1220 1230 1240 1250 1260 NLKLGDDQYV RSGKDHVSTL LTWHMHKLVE VPFPVVNAMM KSYVKSKLKL LRGSETTVTE 1270 1280 1290 1300 1310 1320 RIFRQYFEMG IVPSHISSLI DMGQGILHNA SDFYGLLSER FINYCIGVIF GERPEAYTSS 1330 1340 1350 1360 1370 1380 DDQITLFDRR LSDLVVSDPE EVLVLLEFQS HLSGLLNKFI SPKSVAGRFA AEFKSRFYVW 1390 1400 1410 1420 1430 1440 GEEVPLLTKF VSAALHNVKC KEPHQLCETI DTIADQAIAN GVPVSLVNSI QRRTLDLLKY 1450 1460 1470 1480 1490 1500 ANFPLDPFLL NTNTDVKDWL DGSRGYRIQR LIEELCPNET KVVRKLVRKL HHKLKNGEFN 1510 1520 1530 1540 1550 1560 EEFFLDLFNR DKTEAILQLG DLLGLEEDLN QLADVNWLNL NEMFPLRMVL RQKVVYPSVM 1570 1580 1590 1600 1610 1620 TFQEERIPSL IKTLQNKLCS KFTRGAQKLL SEAINKSAFQ SCISSGFIGL CKTLGSRCVR 1630 1640 1650 1660 1670 1680 NKNRENLYIK KLLEDLTTDD HVTRVCNRDG ITLYICDKQS HPEAHRDHIC LLRPLLWDYI 1690 1700 1710 1720 1730 1740 CISLSNSFEL GVWVLAEPTK GKNNSENLTL KHLNPCDYVA RKPESSRLLE DKVNLNQVIQ 1750 1760 1770 1780 1790 1800 SVRRLYPKIF EDQLLPFMSD MSSKNMRWSP RIKFLDLCVL IDINSESLSL ISHVVKWKRD 1810 1820 1830 1840 1850 1860 EHYTVLFSDL ANSHQRSDSS LVDEFVVSTR DVCKNFLKQV YFESFVREFV ATTRTLGNFS 1870 1880 1890 1900 1910 1920 WFPHKEMMPS EDGAEALGPF QSFVSKVVNK NVERPMFRND LQFGFGWFSY RMGDVVCNAA 1930 1940 1950 1960 1970 1980 MLIRQGLTNP KAFKSLKDLW DYMLNYTKGV LEFSISVDFT HNQNNTDCLR KFSLIFLVRC 1990 2000 2010 2020 2030 2040 QLQNPGVAEL LSCSHLFKGE IDRRMLDECL HLLRTDSVFK VNDGVFDIRS EEFEDYMEDP 2050 2060 2070 2080 2090 2100 LILGDSLELE LLGSKRILDG IRSIDFERVG PEWEPVPLTV KMGALFEGRN LVQNIIVKLE 2110 2120 2130 2140 2150 2160 TKDMKVFLAG LEGYEKISDV LGNLFLHRFR TGEHLLGSEI SVILQELCID RSILLIPLSL 2170 2180 2190 2200 2210 LPDWFAFKDC RLCFSKSRST LMYEIVGGRF RLKGRSCDDW LGGSVAEDID

References

[1]	"The primary structure of the lymphocytic choriomeningitis virus L gene encodes a putative RNA polymerase." Salvato M.S., Shimomaye E.M., Oldstone M.B.A. Virology 169:377-384(1989) [PubMed: 2705303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence." Grande-Perez A., Gomez-Mariano G., Lowenstein P.R., Domingo E. J. Virol. 79:10451-10459(2005) [PubMed: 16051837] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Armstrong 53b.
[3]	"Recovery of an arenavirus entirely from RNA polymerase I/II-driven cDNA." Flatz L., Bergthaler A., de la Torre J.C., Pinschewer D.D. Proc. Natl. Acad. Sci. U.S.A. 103:4663-4668(2006) [PubMed: 16537369] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Armstrong-derived variant Cl13.
[4]	"Analysis of the genomic L RNA segment from lymphocytic choriomeningitis virus." Singh M.K., Fuller-Pace F.V., Buchmeier M.J., Southern P.J. Virology 161:448-456(1987) [PubMed: 3318094] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 161-387; 424-619 AND 1646-1906.
[5]	"Concurrent sequence analysis of 5' and 3' RNA termini by intramolecular circularization reveals 5' nontemplated bases and 3' terminal heterogeneity for lymphocytic choriomeningitis virus mRNAs." Meyer B.J., Southern P.J. J. Virol. 67:2621-2627(1993) [PubMed: 7682625] [Abstract] Cited for: FUNCTION.
[6]	"Genetic and biochemical evidence for an oligomeric structure of the functional L polymerase of the prototypic arenavirus lymphocytic choriomeningitis virus." Sanchez A.B., de la Torre J.C. J. Virol. 79:7262-7268(2005) [PubMed: 15890965] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF ASP-1182; SER-1320 AND ASP-1321.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J04331 Genomic RNA. Translation: AAA66591.1.
AY847351 Genomic RNA. Translation: AAX49344.1.
DQ361066 Genomic RNA. Translation: ABC96004.1.
M18381 Genomic RNA. Translation: AAA46258.1. Sequence problems.
M18382 Genomic RNA. Translation: AAA46259.1.
M18383 Genomic RNA. Translation: AAA46260.1. Sequence problems.

PIR

RRXPLC. A30181.

RefSeq

NP_694845.1. NC_004291.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3JSB	X-ray	2.13	A/B	2-197	[»]

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

956589.

Family and domain databases

InterPro

IPR014386. RNA-dir_pol_arenavirus.
IPR007099. RNA-dir_pol_NSvirus.
IPR010453. RNA_pol_arenavir.
[Graphical view]

Pfam

PF06317. Arena_RNA_pol. 1 hit.
[Graphical view]

PIRSF

PIRSF000836. L_ArenaV. 1 hit.

PROSITE

PS50525. RDRP_SSRNA_NEG_SEG. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

L_LYCVA

Accession

Primary (citable) accession number: P14240
Secondary accession number(s): Q27V69, Q49K84

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	September 21, 2011
This is version 60 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program