Q9TTC1 (POL_KORV) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pro-Pol polyprotein

Alternative name(s):
Pr125Pol

Cleaved into the following 2 chains:

1. Protease/Reverse transcriptase/ribonuclease H
   EC=2.7.7.49
   EC=2.7.7.7
   EC=3.1.26.4
   EC=3.4.23.-
   Alternative name(s):
   p87Pro-RT-RNaseH
2. Integrase
   Short name=IN
   Alternative name(s):
   p42In

Gene names

Name:

pro-pol

Organism

Koala retrovirus (KoRV) [Complete proteome]

Taxonomic identifier

394239 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Gammaretrovirus › unclassified Gammaretrovirus

Virus host

Phascolarctos cinereus (Koala) [TaxID: 38626]

Protein attributes

Sequence length	1127 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology

General annotation (Comments)

Function	The aspartyl protease activity mediates proteolytic cleavages of Gag and Pol polyproteins. The reverse transcriptase (RT) activity converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell (early reverse transcription) or after proviral DNA transcription (late reverse transcription). RT consists of a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primer. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends By similarity. Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA. In the second step, the PIC access cell chromosomes during cell division. The third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5'-ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands (see above) are filled in and then ligated By similarity.
Catalytic activity	Endonucleolytic cleavage to 5'-phosphomonoester. Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Cofactor	Binds 2 magnesium ions for reverse transcriptase polymerase activity By similarity. Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding By similarity. Magnesium ions for integrase activity. Binds at least 1, maybe 2 magnesium ions By similarity.
Subcellular location	Integrase: Virion Potential. Host nucleus By similarity. Host cytoplasm Potential. Note: Nuclear at initial phase, cytoplasmic at assembly Potential. Protease/Reverse transcriptase/ribonuclease H: Host nucleus By similarity. Host cytoplasm Potential. Note: Nuclear at initial phase, cytoplasmic at assembly Potential.
Domain	The reverse transcriptase/ribonuclease H (RT) is structured in five subdomains: finger, palm, thumb, connection and RNase H. Within the palm subdomain, the "primer grip" region is thought to be involved in the positioning of the primer terminus for accommodating the incoming nucleotide. The RNase H domain stabilizes the association of RT with primer-template By similarity. Integrase core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D35E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein By similarity.
Post-translational modification	Specific enzymatic cleavages in vivo by viral protease yield mature proteins. The protease is not cleaved off from Pol. Since cleavage efficiency is not optimal for all sites, long and active p65Pro-RT, p87Pro-RT-RNaseH and even some Pr125Pol are detected in infected cells By similarity.
Miscellaneous	The reverse transcriptase is an error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template switching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains, reverse transcription will give rise to highly recombinated proviral DNAs. Koala retrovirus is both a circulating virus and an endogenous retrovirus of koala, except in some isolated populations in south Australia.
Sequence similarities	Contains 1 integrase catalytic domain. Contains 1 peptidase A2 domain. Contains 1 reverse transcriptase domain. Contains 1 RNase H domain.

Ontologies

Keywords
Biological process	DNA integration DNA recombination Viral genome integration Virus entry into host cell
Cellular component	Host cytoplasm Host nucleus Virion
Coding sequence diversity	RNA suppression of termination
Ligand	Magnesium Metal-binding RNA-binding
Molecular function	Aspartyl protease DNA-directed DNA polymerase Endonuclease Hydrolase Nuclease Nucleotidyltransferase Protease RNA-directed DNA polymerase Transferase
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological_process	DNA integration Inferred from electronic annotation. Source: UniProtKB-KW DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW RNA-dependent DNA replication Inferred from electronic annotation. Source: InterPro establishment of integrated proviral latency Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC proteolysis Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW aspartic-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW ribonuclease H 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 – 1127	1127	Pro-Pol polyprotein		PRO_0000249431
	Chain	1 – ?742	742	Protease/Reverse transcriptase/ribonuclease H By similarity		PRO_0000249432
	Chain	?743 – 1127	385	Integrase By similarity		PRO_0000249433
Regions
	Domain	22 – 92	71	Peptidase A2
	Domain	202 – 393	192	Reverse transcriptase
	Domain	635 – 781	147	RNase H
	Domain	905 – 1063	159	Integrase catalytic
Sites
	Metal binding	229	1	Magnesium; catalytic; for reverse transcriptase activity By similarity
	Metal binding	303	1	Magnesium; catalytic; for reverse transcriptase activity By similarity
	Metal binding	304	1	Magnesium; catalytic; for reverse transcriptase activity By similarity
	Metal binding	661	1	Magnesium; catalytic; for RNase H activity By similarity
	Metal binding	731	1	Magnesium; catalytic; for RNase H activity By similarity
	Metal binding	904	1	Magnesium; catalytic; for integrase activity By similarity
	Site	?742 – ?743	2	Cleavage; by viral protease By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9TTC1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 010ADD971CA957BF	FASTA	1,127	125,817
	10 20 30 40 50 60 MGKMGSKRTV VAGATGSKVY PWTTKRLLKI GQKQVTHSFL VIPECPAPLL GRDLLTKLKA 70 80 90 100 110 120 QIQFSTEGPQ VTWEDRPAMC LVLNLEEEYR LHEKPVPPSI DPSWLQLFPM VWAEKAGMGL 130 140 150 160 170 180 ANQVPPVVVE LKSDASPVAV RQYPMSKEAR EGIRPHIQRF LDLGILVPCQ SPWNTPLLPV 190 200 210 220 230 240 KKPGTNDYRP VQDLREVNKR VQDIHPTVPN PYNLLSSLPP SHTWYSVLDL KDAFFCLKLH 250 260 270 280 290 300 PNSQPLFAFE WRDPEKGNTG QLTWTRLPQG FKNSPTLFDE ALHRDLASFR ALNPQVVMLQ 310 320 330 340 350 360 YVDDLLVAAP TYRDCKEGTR RLLQELSKLG YRVSAKKAQL CREEVTYLGY LLKGGKRWLT 370 380 390 400 410 420 PARKATVMKI PTPTTPRQVR EFLGTAGFCR LWIPGFASLA APLYPLTREK VPFTWTEAHQ 430 440 450 460 470 480 EAFGRIKEAL LSAPALALPD LTKPFALYVD EKEGVARGVL TQTLGPWRRP VAYLSKKLDP 490 500 510 520 530 540 VASGWPTCLK AIAAVALLLK DADKLTLGQN VLVIAPHNLE SIVRQPPDRW MTNARMTHYQ 550 560 570 580 590 600 SLLLNERVSF APPAILNPAT LLPVESDDTP IHICSEILAE ETGTRPDLRD QPLPGVPAWY 610 620 630 640 650 660 TDGSSFIMDG RRQAGAAIVD NKRTVWASNL PEGTSAQKAE LIALTQALRL AEGKSINIYT 670 680 690 700 710 720 DSRYAFATAH VHGAIYKQRG LLTSAGKDIK NKEEILALLE AIHLPKRVAI IHCPGHQRGT 730 740 750 760 770 780 DPVATGNRKA DEAAKQAAQS TRILTETTKN QEHFEPTRGK IKPRELTPDQ GREFIQRLHQ 790 800 810 820 830 840 LTHLGPDKLL QLVGRTSFHI PNLQSVVREI TSKCQVCAVT NAVTTYREPG RRQRGDRPGV 850 860 870 880 890 900 YWEVDFTEVK PGRYGNRYLL VFIDTFSGWV EAFPTKTETA LTVCKKILEE ILPRFGIPKV 910 920 930 940 950 960 LGSDNGPAFV AQVSQGLATQ LGIDWKLHCA YRPQSSGQVE RMNRTIKETL TKLALETGGK 970 980 990 1000 1010 1020 DWVTLLPLAL LRARNTPGQF GLTPYEILHG GPPPVLASGE VVGSNGDFFP VLFTHLKALE 1030 1040 1050 1060 1070 1080 VVRTQIWDQI KEAYRPGTVA IPHPFQVGDR VLVRRHRSGS LEPRWKGPYL VLLTTPTAVK 1090 1100 1110 1120 VDGIAAWVHA SHLKPAPPGA PDESWELEKT DHPLKLRVRR RRNESTA

References

[1]

"The nucleotide sequence of koala (Phascolarctos cinereus) retrovirus: a novel type C endogenous virus related to Gibbon ape leukemia virus." Hanger J.J., Bromham L.D., McKee J.J., O'Brien T.M., Robinson W.F. J. Virol. 74:4264-4272(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF151794 Genomic DNA. Translation: AAF15098.1.
3D structure databases
HSSP	HSSP built from PDB template 1RW3 based on UniProtKB P03355.
ProteinModelPortal	Q9TTC1.
SMR	Q9TTC1. Positions 103-552, 583-738.
ModBase	Search...
Protein family/group databases
MEROPS	A02.020.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR001584. Integrase_cat-core. IPR018061. Pept_A2A_retrovirus_sg. IPR001995. Peptidase_A2_cat. IPR021109. Peptidase_aspartic. IPR012337. RNaseH-like_dom. IPR002156. RNaseH_domain. IPR000477. RVT. [Graphical view]
Pfam	PF00075. RNase_H. 1 hit. PF00665. rve. 1 hit. PF00077. RVP. 1 hit. PF00078. RVT_1. 1 hit. [Graphical view]
SUPFAM	SSF50630. Pept_Aspartic. 1 hit. SSF53098. RNaseH_fold. 2 hits.
PROSITE	PS50175. ASP_PROT_RETROV. 1 hit. PS50994. INTEGRASE. 1 hit. PS50879. RNASE_H. 1 hit. PS50878. RT_POL. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POL_KORV

Accession

Primary (citable) accession number: Q9TTC1

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	May 1, 2000
Last modified:	April 3, 2013
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program