Q6TQR6 (L_CCHFI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Large structural protein
Replicase
Transcriptase

Including the following 2 domains:

1. Ubiquitin thioesterase
   EC=3.4.19.12
2. RNA-directed RNA polymerase
   EC=2.7.7.48

Gene names

Name:

L

Organism

Crimean-Congo hemorrhagic fever virus (strain Nigeria/IbAr10200/1970) (CCHFV) [Reference proteome]

Taxonomic identifier

652961 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Bunyaviridae › Nairovirus › Crimean-Congo hemorrhagic fever virus

Virus host

Boophilus microplus (Cattle tick) [TaxID: 6941]
Bos taurus (Bovine) [TaxID: 9913]
Capra hircus (Goat) [TaxID: 9925]
Homo sapiens (Human) [TaxID: 9606]
Hyalomma [TaxID: 34625]
Ovis aries (Sheep) [TaxID: 9940]

Protein attributes

Sequence length	3945 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Displays RNA-directed RNA polymerase, deubiquitinating and deISGylase activities. RNA-dependent RNA polymerase is responsible for replication and transcription of the viral RNA genome. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent innate immunity. Ref.2
Catalytic activity	Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
Domain	The OTU domain is responsible for the deubiquitinating and deISGylation activities of Nsp2 Probable.
Sequence similarities	Belongs to the nairovirus RNA polymerase family. Contains 1 OTU domain. Contains 1 RdRp catalytic domain.

Ontologies

Keywords
Biological process	Host-virus interaction Inhibition of host ISG15 by virus Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway by virus Modulation of host ubiquitin pathway by viral deubiquitinase Modulation of host ubiquitin pathway by virus Viral RNA replication Viral immunoevasion
Ligand	Nucleotide-binding
Molecular function	Nucleotidyltransferase RNA-directed RNA polymerase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	modulation by virus of host protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host ISG15 activity Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host type I interferon-mediated signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro viral genome replication Inferred from electronic annotation. Source: InterPro
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 – 3945

3945

RNA-directed RNA polymerase L

PRO_0000396080

Regions

Domain

29 – 158

130

OTU

Domain

2342 – 2551

210

RdRp catalytic

Compositional bias

183 – 186

4

Poly-Ser

Compositional bias

2698 – 2745

48

Ser-rich

Sites

Active site

40

1

For ubiquitin thioesterase activity Probable

Active site

151

1

For ubiquitin thioesterase activity Probable

Experimental info

Mutagenesis

40

1

C → A: Loss of deubiquitinating and deISGylase activities. Ref.2

Mutagenesis

151

1

H → A: Loss of deubiquitinating and deISGylase activities; when associated with Ala-40. Ref.2

Secondary structure

1

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3945

Helix Strand Turn

Details...

Helix

3 – 6

4

Beta strand

10 – 13

4

Beta strand

16 – 19

4

Helix

25 – 28

4

Beta strand

29 – 32

4

Helix

40 – 49

10

Turn

55 – 57

3

Helix

58 – 72

15

Helix

73 – 75

3

Helix

79 – 82

4

Helix

86 – 93

8

Helix

102 – 112

11

Beta strand

116 – 120

5

Beta strand

129 – 135

7

Turn

138 – 140

3

Beta strand

141 – 147

7

Turn

148 – 150

3

Beta strand

151 – 157

7

Helix

159 – 161

3

Helix

171 – 182

12

Sequences

	Sequence		Length	Mass (Da)
	Q6TQR6 [UniParc]. Last modified August 16, 2004. Version 2. Checksum: 0F95F82432B0DBE1	FASTA	3,945	447,851
	10 20 30 40 50 60 MDFLRSLDWT QVIAGQYVSN PRFNISDYFE IVRQPGDGNC FYHSIAELTM PNKTDHSYHY 70 80 90 100 110 120 IKRLTESAAR KYYQEEPEAR LVGLSLEDYL KRMLSDNEWG STLEASMLAK EMGITIIIWT 130 140 150 160 170 180 VAASDEVEAG IKFGDGDVFT AVNLLHSGQT HFDALRILPQ FETDTREALS LMDRVIAVDQ 190 200 210 220 230 240 LTSSSSDELQ DYEDLALALT SAEESNRRSS LDEVTLSKKQ AEILRQKASQ LSKLVNKSQN 250 260 270 280 290 300 IPTRVGRVLD CMFNCKLCVE ISADTLILRP ESKEKIGEIM SLRQLGHKLL TRDKQIKQEF 310 320 330 340 350 360 SRMKLYVTKD LLDHLDVGGL LRAAFPGTGI ERHMQLLHSE MILDICTVSL GVMLSTFLYG 370 380 390 400 410 420 SNNKNKKKFI TNCLLSTALS GKKVYKVLGN LGNELLYKAP RKALATVCSA LFGKQINKLQ 430 440 450 460 470 480 NCFRTISPVS LLALRNLDFD CLSVQDYNGM IENMSKLDNT DVEFNHREIA DLNQLTSRLI 490 500 510 520 530 540 TLRKEKDTDL LKQWFPESDL TRRSIRNAAN AEEFVISEFF KKKDIMKFIS TSGRAMSAGK 550 560 570 580 590 600 IGNVLSYAHN LYLSKSSLNM TSEDISQLLI EIKRLYALQE DSEVEPIAII CDGIESNMKQ 610 620 630 640 650 660 LFAILPPDCA RECEVLFDDI RNSPTHSTAW KHALRLKGTA YEGLFANCYG WQYIPEDIKP 670 680 690 700 710 720 SLTMLIQTLF PDKFEDFLDR TQLHPEFRDL TPDFSLTQKV HFKRNQIPSV ENVQISIDAT 730 740 750 760 770 780 LPESVEAVPV TERKMFPLPE TPLSEVHSIE RIMENFTRLM HGGRLSTKKR DGDPAEQGNQ 790 800 810 820 830 840 QSITEHESSS ISAFKDYGER GIVEENHMKF SGEDQLETRQ LLLVEVGFQT DIDGKIRTDH 850 860 870 880 890 900 KKWKDILKLL ELLGIKCSFI ACADCSSTPP DRWWITEDRV RVLKNSVSFL FNKLSRNSPT 910 920 930 940 950 960 EVTDIVVGAI STQKVRSYLK AGTATKTPVS TKDVLETWEK MKEHILNRPT GLTLPTSLEQ 970 980 990 1000 1010 1020 AMRKGLVEGV VISKEGSESC INMLKENLDR ITDEFERTKF KHELTQNITT SEKMLLSWLS 1030 1040 1050 1060 1070 1080 EDIKSSRCGE CLSNIKKAVD ETANLSGKIE LLAYNLQLTN HCSNCHPNGV NISNTSNVCK 1090 1100 1110 1120 1130 1140 RCPKIEVVSH CENKGFEDSN ECLTDLDRLV RLTLPGKTEK ERRVKRNVEY LIKLMMSMSG 1150 1160 1170 1180 1190 1200 IDCIKYPTGQ LITHGRVSAK HNDGNLKDRS DDDQRLAEKI DTVRKELSES KLKDYSTYAR 1210 1220 1230 1240 1250 1260 GVISNSLKNL SRQGKSKCSV PRSWLEKVLF DLKVPTKDEE VLINIRNSLK ARSEFVRNND 1270 1280 1290 1300 1310 1320 KLLIRSKEEL KKCFDVQSFK LKKNKQPVPF QVDCILFKEV AAECMKRYIG TPYEGIVDTL 1330 1340 1350 1360 1370 1380 VSLINVLTRF TWFQEVVLYG KICETFLRCC TEFNRSGVKL VKIRHCNINL SVKLPSNKKE 1390 1400 1410 1420 1430 1440 NMLCCLYSGN MELLQGPFYL NRRQAVLGSS YLYIVITLYI QVLQQYRCLE VINSVSEKTL 1450 1460 1470 1480 1490 1500 QDIENHSMTL LEDSFREITF ALEGRFEESY KIRTSRCRAS GNFLNRSSRD HFISVVSGLN 1510 1520 1530 1540 1550 1560 LVYGFLIKDN LLANSQQQNK QLQMLRFGML AGLSRLVCPN ELGKKFSTSC RRIEDNIARL 1570 1580 1590 1600 1610 1620 YLQTSIYCSV RDVEDNVKHW KQRDLCPEVT IPCFTVYGTF VNSDRQLIFD IYNVHIYNKE 1630 1640 1650 1660 1670 1680 MDNFDEGCIS VLEETAERHM LWELDLMNSL CSDEKKDTRP ARLLLGCPNV RKAATREGKK 1690 1700 1710 1720 1730 1740 LLKLNSDTST DTQSIASEVS DRRSYSSSKS RIRSIFGRYN SQKKPFELRS GLEVFNDPFN 1750 1760 1770 1780 1790 1800 DYQQAITDIC QFSEYTPNKE SILKDCLQII RKNPSHTMGS FELIQAISEF GMSKFPPENI 1810 1820 1830 1840 1850 1860 DKARRDPKNW VSISEVTETT SIVASPRTHM MLKDCFKIIL GTENKKIVKM LRGKLKKLGA 1870 1880 1890 1900 1910 1920 ISTNIEIGKR DCLDLLSTVD GLTDQQKENI VNGIFEPSKL SFYHWKELVK KNIDEVLLTE 1930 1940 1950 1960 1970 1980 DGNLIFCWLK TISSSVKGSL KKRLKFMNIH SPELMPENCL FSSEEFNELI KLKKLLLNEQ 1990 2000 2010 2020 2030 2040 QDEQELKQDL LISSWIKCIT ACKDFASIND KIQKFIYHLS EELYDIRLQH LELSKLKQEH 2050 2060 2070 2080 2090 2100 PSVSFTKEEV LIKRLEKNFL KQHNLEIMET VNLVFFAALS APWCLHYKAL ESYLVRHPEI 2110 2120 2130 2140 2150 2160 LDCGSKEDCK LTLLDLSVSK LLVCLYQKDD EELINSSSLK LGFLVKYVVT LFTSNGEPFS 2170 2180 2190 2200 2210 2220 LSLNDGGLDL DLHKTTDEKL LHQTKIVFAK IGLSGNSYDF IWTTQMIANS NFNVCKRLTG 2230 2240 2250 2260 2270 2280 RSTGERLPRS VRSKVIYEMV KLVGETGMAI LQQLAFAQAL NYEHRFYAVL APKAQLGGAR 2290 2300 2310 2320 2330 2340 DLLVQETGTK VMHATTEMFS RNLLKTTSDD GLTNPHLKET ILNVGLDCLA NMRNLDGKPI 2350 2360 2370 2380 2390 2400 SEGSNLVNFY KVICISGDNT KWGPIHCCSF FSGMMQQVLK NVPDWCSFYK LTFIKNLCRQ 2410 2420 2430 2440 2450 2460 VEIPAGSIKK ILNVLRYRLC SKGGVEQHSE EDLRRLLTDN LDSWDGNDTV KFLVTTYISK 2470 2480 2490 2500 2510 2520 GLMALNSYNH MGQGIHHATS SVLTSLAAVL FEELAIFYLK RSLPQTTVHV EHAGSSDDYA 2530 2540 2550 2560 2570 2580 KCIVVTGILS KELYSQYDET FWKHACRLKN FTAAVQRCCQ MKDSAKTLVS DCFLEFYSEF 2590 2600 2610 2620 2630 2640 MMGYRVTPAV IKFMFTGLIN SSVTSPQSLM QACQVSSQQA MYNSVPLVTN TAFTLLRQQI 2650 2660 2670 2680 2690 2700 FFNHVEDFIR RYGILTLGTL SPFGRLFVPT YSGLVSSAVA LEDAEVIARA AQTLQMNSVS 2710 2720 2730 2740 2750 2760 IQSSSLTTLD SLGRSRTSST AEDSSSVSDT TAASHDSGSS SSSFSFELNR PLSETELQFI 2770 2780 2790 2800 2810 2820 KALSSLKSTQ ACEVIQNRIT GLYCNSNEGP LDRHNVIYSS RMADSCDWLK DGKRRGNLEL 2830 2840 2850 2860 2870 2880 ANRIQSVLCI LIAGYYRSFG GEGTEKQVKA SLNRDDNKII EDPMIQLIPE KLRRELERLG 2890 2900 2910 2920 2930 2940 VSRMEVDELM PSISPDDTLA QLVAKKLISL NVSTEEYSAE VSRLKQTLTA RNVLHGLAGG 2950 2960 2970 2980 2990 3000 IKELSLPIYT IFMKSYFFKD NVFLSLTDRW STKHSTNYRD SCGKQLKGRI ITKYTHWLDT 3010 3020 3030 3040 3050 3060 FLGCSVSINR HTTVKEPSLF NPNIRCVNLI TFEDGLRELS VIQSHLKVFE NEFTNLNLQF 3070 3080 3090 3100 3110 3120 SDPNRQKLRI VESRPAESEL EANRAVIVKT KLFSATEQVR LSNNPAVVMG YLLDESAISE 3130 3140 3150 3160 3170 3180 VKPTKVDFSN LLKDRFKIMQ FFPSVFTLIK MLTDESSDSE KSGLSPDLQQ VARYSNHLTL 3190 3200 3210 3220 3230 3240 LSRMIQQAKP TVTVFYMLKG NLMNTEPTVA ELVSYGIKEG RFFRLSDTGV DASTYSVKYW 3250 3260 3270 3280 3290 3300 KILHCISAIG CLPLSQADKS SLLMSFLNWR VNMDIRTSDC PLSSHEASIL SEFDGQVIAN 3310 3320 3330 3340 3350 3360 ILASELSSVK RDSEREGLTD LLDYLNSPTE LLKKKPYLGT TCKFNTWGDS NRSGKFTYSS 3370 3380 3390 3400 3410 3420 RSGESIGIFI AGKLHIHLSS ESVALLCETE RQVLSWMSKR RTEVITKEQH QLFLSLLPQS 3430 3440 3450 3460 3470 3480 HECLQKHKDG SALSVIPDSS NPRLLKFVPL KKGLAVVKIK KQILTVKKQV VFDAESEPRL 3490 3500 3510 3520 3530 3540 QWGHGCLSIV YDETDTQTTY HENLLKVKHL VDCSTDRKKL LPQSVFSDSK VVLSRIKFKT 3550 3560 3570 3580 3590 3600 ELLLNSLTLL HCFLKHAPSD AIMEVESKSS LLHKYLKSGG VRQRNTEVLF REKLNKVVIK 3610 3620 3630 3640 3650 3660 DNLEQGVEEE IEFCNNLTKT VSENPLPLSC WSEVQNYIED IGFNNVLVNI DRNTVKSELL 3670 3680 3690 3700 3710 3720 WKFTLDTNVS TTSTIKDVRT LVSYVSTETI PKFLLAFLLY EEVLMNLINQ CKAVKELINS 3730 3740 3750 3760 3770 3780 TGLSDLELES LLTLCAFYFQ SECSKRDGPR CSFAALLSLI HEDWQRIGKN ILVRANNELG 3790 3800 3810 3820 3830 3840 DVSLKVNIVL VPLKDMSKPK SERVVMARRS LNHALSLMFL DEMSLPELKS LSVNCKMGNF 3850 3860 3870 3880 3890 3900 EGQECFEFTI LKDNSARLDY NKLIDHCVDM EKKREAVRAV EDLILMLTGR AVKPSAVTQF 3910 3920 3930 3940 VHGDEQCQEQ ISLDDLMAND TVTDFPDREA EALKTGNLGF NWDSD

References

[1]

"Sequence determination of the Crimean-Congo hemorrhagic fever virus L segment." Kinsella E., Martin S.G., Grolla A., Czub M., Feldmann H., Flick R. Virology 321:23-28(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

[2]

"Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses." Frias-Staheli N., Giannakopoulos N.V., Kikkert M., Taylor S.L., Bridgen A., Paragas J., Richt J.A., Rowland R.R., Schmaljohn C.S., Lenschow D.J., Snijder E.J., Garcia-Sastre A., Virgin H.W. Cell Host Microbe 2:404-416(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-40 AND HIS-151.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY389361 Genomic DNA. Translation: AAR25663.2.

RefSeq

YP_325663.1. NC_005301.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3PHU	X-ray	2.20	A/B	1-217	[»]
3PHW	X-ray	2.00	A/C/E/G	1-183	[»]
3PHX	X-ray	1.60	A	1-183	[»]
3ZNH	X-ray	2.30	A	1-183	[»]

ProteinModelPortal

Q6TQR6.

ModBase

Search...

Protein family/group databases

MEROPS

C87.001.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

2943075.

Family and domain databases

InterPro

IPR003323. OTU.
IPR015843. RNA-dir_pol_nairovirus.
IPR007099. RNA-dir_pol_NSvirus.
IPR007322. RNA_pol_bunyavir.
[Graphical view]

Pfam

PF04196. Bunya_RdRp. 1 hit.
PF02338. OTU. 1 hit.
[Graphical view]

PIRSF

PIRSF036900. RdRPol_NRV. 1 hit.

PROSITE

PS50802. OTU. 1 hit.
PS50525. RDRP_SSRNA_NEG_SEG. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit. Uncertain.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q6TQR6.

Entry information

Entry name

L_CCHFI

Accession

Primary (citable) accession number: Q6TQR6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 10, 2010
Last sequence update:	August 16, 2004
Last modified:	May 1, 2013
This is version 48 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program