P03355 (POL_MLVMS) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 139. History...
Names and origin
|Protein names||Recommended name:|
Cleaved into the following 7 chains:
|Organism||Moloney murine leukemia virus (isolate Shinnick) (MoMLV) [Reference proteome]|
|Taxonomic identifier||928306 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Gammaretrovirus › Murine leukemia virus ›|
|Virus host||Mus musculus (Mouse) [TaxID: 10090]|
|Sequence length||1738 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Gag-Pol polyprotein plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin ligases that conjugate ubiquitin molecules to Gag, or to Gag binding host factors. Interaction with HECT ubiquitin ligases probably link the viral protein to the host ESCRT pathway and facilitate release.
Matrix protein p15 targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex By similarity.
Capsid protein p30 forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex By similarity.
Nucleocapsid protein p10 is involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization.
The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell By similarity.
Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays 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 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 primers. 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, leaving recessed CA OH's at the 3' ends. In the second step that requires cell division, the PIC enters cell nucleus. In 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 last step is viral DNA integration into host chromosome By similarity.
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Endonucleolytic cleavage to 5'-phosphomonoester.
Binds 2 magnesium ions for reverse transcriptase polymerase activity By similarity.
Binds 2 magnesium ions for ribonuclease H (RNase H) activity By similarity.
Magnesium ions for integrase activity. Binds at least 1, maybe 2 magnesium ions By similarity.
The viral protease p14 is most effciently inhibited by amprenavir, which is able to block Gag processing in MoLV-infected cells.
Capsid protein p30 is a homohexamer, that further associates as homomultimer. The virus core is composed of a lattice formed from hexagonal rings, each containing six capsid monomers. The protease is a homodimer, whose active site consists of two apposed aspartic acid residues. The reverse transcriptase is a monomer By similarity. Capsid protein p30 interacts with mouse UBE2I and mouse PIAS4. Reverse transcriptase/ribonuclease H p80 interacts (via RT and RNase domains) with host release factor ETF1; this interaction is essential for translational readthrough of amber codon between viral gag and pol genes. Gag-Pol polyprotein also interacts with host release factor ETF1. Ref.7 Ref.8 Ref.9
Late-budding domains (L domains) are short sequence motifs essential for viral particle release. They can occur individually or in close proximity within structural proteins. They interacts with sorting cellular proteins of the multivesicular body (MVB) pathway. Most of these proteins are class E vacuolar protein sorting factors belonging to ESCRT-I, ESCRT-II or ESCRT-III complexes. RNA-binding phosphoprotein p12 contains one L domain: a PPXY motif which potentially interacts with the WW domain 3 of NEDD4 E3 ubiquitin ligase. PPXY motif is essential for virus egress. Matrix protein p15 contains one L domain: a PTAP/PSAP motif, which potentially interacts with the UEV domain of TSG101. The junction between the matrix protein p15 and RNA-binding phosphoprotein p12 also contains one L domain: a LYPX(n)L motif which potentially interacts with PDCD6IP. Both PSAP and LYPX(n)L domains might play little to no role in budding and possibly drive residual virus release. contains By similarity.
Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation By similarity. Ref.10
Capsid protein p30 is sumoylated; which is required for virus replication. Ref.9
RNA-binding phosphoprotein p12 is phosphorylated on serine residues. Ref.6
This protein is translated as a gag-pol fusion protein by episodic readthrough of the gag protein termination codon. Readthrough of the terminator codon TAG occurs between the codons for 538-Asp and 540-Gly.
The nucleocapsid protein p10 released from Pol polyprotein (NC-pol) is a few amino acids shorter than the nucleocapsid protein p10 released from Gag polyprotein (NC-gag).
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 swiching 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 By similarity.
Contains 1 CCHC-type zinc finger.
Contains 1 integrase catalytic domain.
Contains 1 integrase-type DNA-binding domain.
Contains 1 peptidase A2 domain.
Contains 1 reverse transcriptase domain.
Contains 1 RNase H domain.
Optimum pH is 5.0 for protease activity.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed; by host Ref.3|
|Chain||2 – 1738||1737||Gag-Pol polyprotein||PRO_0000390795|
|Chain||2 – 131||130||Matrix protein p15||PRO_5000053618|
|Chain||132 – 215||84||RNA-binding phosphoprotein p12||PRO_5000053619|
|Chain||216 – 478||263||Capsid protein p30||PRO_5000053620|
|Chain||479 – 534||56||Nucleocapsid protein p10||PRO_5000053621|
|Chain||535 – 659||125||Protease p14||PRO_5000053622|
|Chain||660 – 1330||671||Reverse transcriptase/ribonuclease H p80||PRO_5000053623|
|Chain||1331 – 1738||408||Integrase p46||PRO_5000053624|
|Domain||560 – 631||72||Peptidase A2|
|Domain||741 – 932||192||Reverse transcriptase|
|Domain||1174 – 1320||147||RNase H|
|Domain||1444 – 1602||159||Integrase catalytic|
|Zinc finger||502 – 519||18||CCHC-type|
|Coiled coil||438 – 478||41||Potential|
|Motif||111 – 114||4||PTAP/PSAP motif|
|Motif||130 – 134||5||LYPX(n)L motif|
|Motif||162 – 165||4||PPXY motif|
|Compositional bias||71 – 193||123||Pro-rich|
|Active site||566||1||Protease; shared with dimeric partner By similarity|
|Metal binding||809||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||883||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||884||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||1183||1||Magnesium; for RNase H activity By similarity|
|Metal binding||1221||1||Magnesium; for RNase H activity By similarity|
|Metal binding||1242||1||Magnesium; for RNase H activity By similarity|
|Metal binding||1312||1||Magnesium; for RNase H activity By similarity|
|Metal binding||1455||1||Magnesium; catalytic; for integrase activity By similarity|
|Metal binding||1514||1||Magnesium; catalytic; for integrase activity By similarity|
|Site||131 – 132||2||Cleavage; by viral protease p14|
|Site||215 – 216||2||Cleavage; by viral protease p14|
|Site||478 – 479||2||Cleavage; by viral protease p14|
|Site||534 – 535||2||Cleavage; by viral protease p14|
|Site||659 – 660||2||Cleavage; by viral protease p14|
|Site||1330 – 1331||2||Cleavage; by viral protease p14|
Amino acid modifications
|Modified residue||192||1||Phosphoserine; by host Probable|
|Lipidation||2||1||N-myristoyl glycine; by host Ref.3|
|Mutagenesis||114||1||P → A: Slight reduction in the number of virus-like particles produced.|
|Mutagenesis||137||1||S → A: No effect on reverse transcription activity. Ref.6|
|Mutagenesis||148||1||S → A: No effect on reverse transcription activity; when associated with A-150. Ref.6|
|Mutagenesis||150||1||S → A: No effect on reverse transcription activity; when associated with A-148. Ref.6|
|Mutagenesis||165||1||Y → A: Drastic reduction in the number of virus-like particles produced. Ref.8|
|Mutagenesis||192||1||S → A: Complete loss of reverse transcription activity. Ref.6|
|Mutagenesis||192||1||S → D: Complete loss of reverse transcription activity. Ref.6|
|Mutagenesis||196||1||S → A: No effect on reverse transcription activity. Ref.6|
|Mutagenesis||209||1||S → A: Strongly reduced reverse transcription activity. Ref.6|
|Mutagenesis||209||1||S → D: Strongly reduced reverse transcription activity. Ref.6|
|Mutagenesis||212||1||S → A: No effect on reverse transcription activity. Ref.6|
Helix Strand Turn
|Helix||684 – 687||4|
|Turn||689 – 691||3|
|Helix||693 – 696||4|
|Beta strand||702 – 704||3|
|Helix||727 – 742||16|
|Beta strand||745 – 749||5|
|Beta strand||757 – 760||4|
|Beta strand||763 – 766||4|
|Beta strand||769 – 772||4|
|Helix||775 – 778||4|
|Helix||791 – 795||5|
|Beta strand||804 – 810||7|
|Turn||811 – 813||3|
|Helix||814 – 816||3|
|Beta strand||817 – 819||3|
|Turn||821 – 823||3|
|Helix||824 – 827||4|
|Beta strand||829 – 833||5|
|Helix||834 – 836||3|
|Beta strand||838 – 846||9|
|Helix||854 – 872||19|
|Beta strand||876 – 881||6|
|Beta strand||884 – 891||8|
|Helix||892 – 909||18|
|Turn||915 – 917||3|
|Beta strand||919 – 927||9|
|Beta strand||930 – 933||4|
|Helix||941 – 948||8|
|Helix||956 – 966||11|
|Helix||967 – 969||3|
|Helix||976 – 979||4|
|Turn||980 – 985||6|
|Helix||997 – 1011||15|
|Beta strand||1025 – 1044||20|
|Beta strand||1047 – 1057||11|
|Helix||1060 – 1063||4|
|Helix||1067 – 1086||20|
|Beta strand||1091 – 1094||4|
|Turn||1100 – 1104||5|
|Helix||1116 – 1123||8|
|Turn||1126 – 1128||3|
|Beta strand||1129 – 1131||3|
|Turn||1139 – 1141||3|
|Beta strand||1169 – 1171||3|
|Beta strand||1177 – 1189||13|
|Beta strand||1192 – 1200||9|
|Beta strand||1205 – 1211||7|
|Helix||1217 – 1231||15|
|Turn||1232 – 1234||3|
|Beta strand||1235 – 1241||7|
|Helix||1244 – 1249||6|
|Helix||1273 – 1282||10|
|Beta strand||1285 – 1293||9|
|Helix||1303 – 1321||19|
|Helix||1346 – 1355||10|
|Beta strand||1358 – 1360||3|
|Turn||1361 – 1364||4|
|Beta strand||1365 – 1368||4|
|Beta strand||1371 – 1374||4|
|Helix||1376 – 1390||15|
|Helix||1394 – 1402||9|
|Turn||1403 – 1405||3|
|Beta strand||1407 – 1410||4|
|Helix||1413 – 1422||10|
|Helix||1425 – 1431||7|
|Beta strand||1661 – 1667||7|
|Beta strand||1670 – 1673||4|
|Beta strand||1676 – 1687||12|
|Beta strand||1690 – 1693||4|
|Beta strand||1696 – 1698||3|
|Helix||1702 – 1704||3|
|Beta strand||1705 – 1707||3|
|Turn||1714 – 1716||3|
|Beta strand||1717 – 1719||3|
|Turn||1726 – 1728||3|
|||"Nucleotide sequence of Moloney murine leukaemia virus."|
Shinnick T.M., Lerner R.A., Sutcliffe J.G.
Nature 293:543-548(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] (CLONE PMLV-1).
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Myristyl amino-terminal acylation of murine retrovirus proteins: an unusual post-translational proteins modification."|
Henderson L.E., Krutzsch H.C., Oroszlan S.
Proc. Natl. Acad. Sci. U.S.A. 80:339-343(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-31, MYRISTOYLATION AT GLY-2.
|||"Primary structure of the low molecular weight nucleic acid-binding proteins of murine leukemia viruses."|
Henderson L.E., Copeland T.D., Sowder R.C., Smythers G.W., Oroszlan S.
J. Biol. Chem. 256:8400-8406(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 479-529.
|||"Murine leukemia virus protease is encoded by the gag-pol gene and is synthesized through suppression of an amber termination codon."|
Yoshinaka Y., Katoh I., Copeland T.D., Oroszlan S.
Proc. Natl. Acad. Sci. U.S.A. 82:1618-1622(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: READTHROUGH OF AMBER CODON.
|||"Phosphorylated serine residues and an arginine-rich domain of the moloney murine leukemia virus p12 protein are required for early events of viral infection."|
Yueh A., Goff S.P.
J. Virol. 77:1820-1829(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-192, MUTAGENESIS OF SER-137; SER-148; SER-150; SER-192; SER-196; SER-209 AND SER-212.
|||"Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic release factor 1 to modulate suppression of translational termination."|
Orlova M., Yueh A., Leung J., Goff S.P.
Cell 115:319-331(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF REVERSE TRANSCRIPTASE/RIBONUCLEASE H P80 WITH MOUSE RELEASE FACTOR ETF1, INTERACTION OF GAG-POL POLYPROTEIN WITH MOUSE RELEASE FACTOR ETF1.
|||"Tsg101 and Alix interact with murine leukemia virus Gag and cooperate with Nedd4 ubiquitin ligases during budding."|
Segura-Morales C., Pescia C., Chatellard-Causse C., Sadoul R., Bertrand E., Basyuk E.
J. Biol. Chem. 280:27004-27012(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MOUSE NEDD4; TSG101 AND PDCD6IP/ALIX, MUTAGENESIS OF TYR-165.
|||"Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection."|
Yueh A., Leung J., Bhattacharyya S., Perrone L.A., de los Santos K., Pu S.-Y., Goff S.P.
J. Virol. 80:342-352(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE2I AND PIAS4, SUMOYLATION.
|||"Characterization of the murine leukemia virus protease and its comparison with the human immunodeficiency virus type 1 protease."|
Feher A., Boross P., Sperka T., Miklossy G., Kadas J., Bagossi P., Oroszlan S., Weber I.T., Tozser J.
J. Gen. Virol. 87:1321-1330(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF PROTEASE P14, PROTEOLYTIC PROCESSING OF POLYPROTEIN.
|||"Mechanistic implications from the structure of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase."|
Georgiadis M.M., Jessen S.M., Ogata C.M., Telesnitsky A., Goff S.P., Hendrickson W.A.
Structure 3:879-892(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 683-937.
|+||Additional computationally mapped references.|
|AF033811 Genomic RNA. Translation: AAC82568.1. Sequence problems.|
J02255 Genomic RNA. No translation available.
|PIR||GNMV1M. A03956. |
|RefSeq||NP_057933.2. NC_001501.1. |
3D structure databases
Protein family/group databases
Protocols and materials databases
Genome annotation databases
Family and domain databases
|Gene3D||188.8.131.52. 1 hit. |
1.10.375.10. 1 hit.
184.108.40.206. 1 hit.
3.30.420.10. 2 hits.
220.127.116.11. 1 hit.
|InterPro||IPR001969. Aspartic_peptidase_AS. |
|Pfam||PF01140. Gag_MA. 1 hit. |
PF01141. Gag_p12. 1 hit.
PF02093. Gag_p30. 1 hit.
PF00075. RNase_H. 1 hit.
PF00665. rve. 1 hit.
PF00077. RVP. 1 hit.
PF00078. RVT_1. 1 hit.
|SMART||SM00343. ZnF_C2HC. 1 hit. |
|SUPFAM||SSF47836. SSF47836. 1 hit. |
SSF47943. SSF47943. 1 hit.
SSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 2 hits.
SSF57756. SSF57756. 1 hit.
|PROSITE||PS50175. ASP_PROT_RETROV. 1 hit. |
PS00141. ASP_PROTEASE. 1 hit.
PS50994. INTEGRASE. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
PS50158. ZF_CCHC. 1 hit.
|Accession||Primary (citable) accession number: P03355|
Secondary accession number(s): O92808
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|