Gag-Pol polyprotein

Details

Name
Gag-Pol polyprotein
Synonyms
  • Pr180gag-pol
Gene Name
gag-pol
Organism
MoMLV
Amino acid sequence
>lcl|BSEQ0019503|Gag-Pol polyprotein
MGQTVTTPLSLTLGHWKDVERIAHNQSVDVKKRRWVTFCSAEWPTFNVGWPRDGTFNRDL
ITQVKIKVFSPGPHGHPDQVPYIVTWEALAFDPPPWVKPFVHPKPPPPLPPSAPSLPLEP
PRSTPPRSSLYPALTPSLGAKPKPQVLSDSGGPLIDLLTEDPPPYRDPRPPPSDRDGNGG
EATPAGEAPDPSPMASRLRGRREPPVADSTTSQAFPLRAGGNGQLQYWPFSSSDLYNWKN
NNPSFSEDPGKLTALIESVLITHQPTWDDCQQLLGTLLTGEEKQRVLLEARKAVRGDDGR
PTQLPNEVDAAFPLERPDWDYTTQAGRNHLVHYRQLLLAGLQNAGRSPTNLAKVKGITQG
PNESPSAFLERLKEAYRRYTPYDPEDPGQETNVSMSFIWQSAPDIGRKLERLEDLKNKTL
GDLVREAEKIFNKRETPEEREERIRRETEEKEERRRTEDEQKEKERDRRRHREMSKLLAT
VVSGQKQDRQGGERRRSQLDRDQCAYCKEKGHWAKDCPKKPRGPRGPRPQTSLLTLDDGG
GQGQEPPPEPRITLKVGGQPVTFLVDTGAQHSVLTQNPGPLSDKSAWVQGATGGKRYRWT
TDRKVHLATGKVTHSFLHVPDCPYPLLGRDLLTKLKAQIHFEGSGAQVMGPMGQPLQVLT
LNIEDEHRLHETSKEPDVSLGSTWLSDFPQAWAETGGMGLAVRQAPLIIPLKATSTPVSI
KQYPMSQEARLGIKPHIQRLLDQGILVPCQSPWNTPLLPVKKPGTNDYRPVQDLREVNKR
VEDIHPTVPNPYNLLSGLPPSHQWYTVLDLKDAFFCLRLHPTSQPLFAFEWRDPEMGISG
QLTWTRLPQGFKNSPTLFDEALHRDLADFRIQHPDLILLQYVDDLLLAATSELDCQQGTR
ALLQTLGNLGYRASAKKAQICQKQVKYLGYLLKEGQRWLTEARKETVMGQPTPKTPRQLR
EFLGTAGFCRLWIPGFAEMAAPLYPLTKTGTLFNWGPDQQKAYQEIKQALLTAPALGLPD
LTKPFELFVDEKQGYAKGVLTQKLGPWRRPVAYLSKKLDPVAAGWPPCLRMVAAIAVLTK
DAGKLTMGQPLVILAPHAVEALVKQPPDRWLSNARMTHYQALLLDTDRVQFGPVVALNPA
TLLPLPEEGLQHNCLDILAEAHGTRPDLTDQPLPDADHTWYTDGSSLLQEGQRKAGAAVT
TETEVIWAKALPAGTSAQRAELIALTQALKMAEGKKLNVYTDSRYAFATAHIHGEIYRRR
GLLTSEGKEIKNKDEILALLKALFLPKRLSIIHCPGHQKGHSAEARGNRMADQAARKAAI
TETPDTSTLLIENSSPYTSEHFHYTVTDIKDLTKLGAIYDKTKKYWVYQGKPVMPDQFTF
ELLDFLHQLTHLSFSKMKALLERSHSPYYMLNRDRTLKNITETCKACAQVNASKSAVKQG
TRVRGHRPGTHWEIDFTEIKPGLYGYKYLLVFIDTFSGWIEAFPTKKETAKVVTKKLLEE
IFPRFGMPQVLGTDNGPAFVSKVSQTVADLLGIDWKLHCAYRPQSSGQVERMNRTIKETL
TKLTLATGSRDWVLLLPLALYRARNTPGPHGLTPYEILYGAPPPLVNFPDPDMTRVTNSP
SLQAHLQALYLVQHEVWRPLAAAYQEQLDRPVVPHPYRVGDTVWVRRHQTKNLEPRWKGP
YTVLLTTPTALKVDGIAAWIHAAHVKAADPGGGPSSRLTWRVQRSQNPLKIRLTREAP
Number of residues
1738
Molecular Weight
194839.015
Theoretical pI
9.66
GO Classification
Functions
aspartic-type endopeptidase activity / DNA binding / DNA-directed DNA polymerase activity / RNA binding / RNA-directed DNA polymerase activity / RNA-DNA hybrid ribonuclease activity / structural constituent of virion / zinc ion binding
Processes
DNA integration / DNA recombination / establishment of integrated proviral latency / viral entry into host cell / virion assembly
Components
host cell plasma membrane / membrane / viral nucleocapsid
General Function
Zinc ion binding
Specific Function
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.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.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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Host cell membrane
Gene sequence
>lcl|BSEQ0019504|Gag-Pol polyprotein (gag-pol)
ATGGGCCAGACTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAG
CGGATCGCTCACAACCAGTCGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCT
GCAGAATGGCCAACCTTTAACGTCGGATGGCCGCGAGACGGCACCTTTAACCGAGACCTC
ATCACCCAGGTTAAGATCAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGACCAGGTC
CCCTACATCGTGACCTGGGAAGCCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTT
GTACACCCTAAGCCTCCGCCTCCTCTTCCTCCATCCGCCCCGTCTCTCCCCCTTGAACCT
CCTCGTTCGACCCCGCCTCGATCCTCCCTTTATCCAGCCCTCACTCCTTCTCTAGGCGCC
AAACCTAAACCTCAAGTTCTTTCTGACAGTGGGGGGCCGCTCATCGACCTACTTACAGAA
GACCCCCCGCCTTATAGGGACCCAAGACCACCCCCTTCCGACAGGGACGGAAATGGTGGA
GAAGCGACCCCTGCGGGAGAGGCACCGGACCCCTCCCCAATGGCATCTCGCCTACGTGGG
AGACGGGAGCCCCCTGTGGCCGACTCCACTACCTCGCAGGCATTCCCCCTCCGCGCAGGA
GGAAACGGACAGCTTCAATACTGGCCGTTCTCCTCTTCTGACCTTTACAACTGGAAAAAT
AATAACCCTTCTTTTTCTGAAGATCCAGGTAAACTGACAGCTCTGATCGAGTCTGTTCTC
ATCACCCATCAGCCCACCTGGGACGACTGTCAGCAGCTGTTGGGGACTCTGCTGACCGGA
GAAGAAAAACAACGGGTGCTCTTAGAGGCTAGAAAGGCGGTGCGGGGCGATGATGGGCGC
CCCACTCAACTGCCCAATGAAGTCGATGCCGCTTTTCCCCTCGAGCGCCCAGACTGGGAT
TACACCACCCAGGCAGGTAGGAACCACCTAGTCCACTATCGCCAGTTGCTCCTAGCGGGT
CTCCAAAACGCGGGCAGAAGCCCCACCAATTTGGCCAAGGTAAAAGGAATAACACAAGGG
CCCAATGAGTCTCCCTCGGCCTTCCTAGAGAGACTTAAGGAAGCCTATCGCAGGTACACT
CCTTATGACCCTGAGGACCCAGGGCAAGAAACTAATGTGTCTATGTCTTTCATTTGGCAG
TCTGCCCCAGACATTGGGAGAAAGTTAGAGAGGTTAGAAGATTTAAAAAACAAGACGCTT
GGAGATTTGGTTAGAGAGGCAGAAAAGATCTTTAATAAACGAGAAACCCCGGAAGAAAGA
GAGGAACGTATCAGGAGAGAAACAGAGGAAAAAGAAGAACGCCGTAGGACAGAGGATGAG
CAGAAAGAGAAAGAAAGAGATCGTAGGAGACATAGAGAGATGAGCAAGCTATTGGCCACT
GTCGTTAGTGGACAGAAACAGGATAGACAGGGAGGAGAACGAAGGAGGTCCCAACTCGAT
CGCGACCAGTGTGCCTACTGCAAAGAAAAGGGGCACTGGGCTAAAGATTGTCCCAAGAAA
CCACGAGGACCTCGGGGACCAAGACCCCAGACCTCCCTCCTGACCCTAGATGACGGAGGT
CAGGGTCAGGAGCCCCCCCCTGAACCCAGGATAACCCTCAAAGTCGGGGGGCAACCCGTC
ACCTTCCTGGTAGATACTGGGGCCCAACACTCCGTGCTGACCCAAAATCCTGGACCCCTA
AGTGATAAGTCTGCCTGGGTCCAAGGGGCTACTGGAGGAAAGCGGTATCGCTGGACCACG
GATCGCAAAGTACATCTAGCTACCGGTAAGGTCACCCACTCTTTCCTCCATGTACCAGAC
TGTCCCTATCCTCTGTTAGGAAGAGATTTGCTGACTAAACTAAAAGCCCAAATCCACTTT
GAGGGATCAGGAGCTCAGGTTATGGGACCAATGGGGCAGCCCCTGCAAGTGTTGACCCTA
AATATAGAAGATGAGCATCGGCTACATGAGACCTCAAAAGAGCCAGATGTTTCTCTAGGG
TCCACATGGCTGTCTGATTTTCCTCAGGCCTGGGCGGAAACCGGGGGCATGGGACTGGCA
GTTCGCCAAGCTCCTCTGATCATACCTCTGAAAGCAACCTCTACCCCCGTGTCCATAAAA
CAATACCCCATGTCACAAGAAGCCAGACTGGGGATCAAGCCCCACATACAGAGACTGTTG
GACCAGGGAATACTGGTACCCTGCCAGTCCCCCTGGAACACGCCCCTGCTACCCGTTAAG
AAACCAGGGACTAATGATTATAGGCCTGTCCAGGATCTGAGAGAAGTCAACAAGCGGGTG
GAAGACATCCACCCCACCGTGCCCAACCCTTACAACCTCTTGAGCGGGCTCCCACCGTCC
CACCAGTGGTACACTGTGCTTGATTTAAAGGATGCCTTTTTCTGCCTGAGACTCCACCCC
ACCAGTCAGCCTCTCTTCGCCTTTGAGTGGAGAGATCCAGAGATGGGAATCTCAGGACAA
TTGACCTGGACCAGACTCCCACAGGGTTTCAAAAACAGTCCCACCCTGTTTGATGAGGCA
CTGCACAGAGACCTAGCAGACTTCCGGATCCAGCACCCAGACTTGATCCTGCTACAGTAC
GTGGATGACTTACTGCTGGCCGCCACTTCTGAGCTAGACTGCCAACAAGGTACTCGGGCC
CTGTTACAAACCCTAGGGAACCTCGGGTATCGGGCCTCGGCCAAGAAAGCCCAAATTTGC
CAGAAACAGGTCAAGTATCTGGGGTATCTTCTAAAAGAGGGTCAGAGATGGCTGACTGAG
GCCAGAAAAGAGACTGTGATGGGGCAGCCTACTCCGAAGACCCCTCGACAACTAAGGGAG
TTCCTAGGGACGGCAGGCTTCTGTCGCCTCTGGATCCCTGGGTTTGCAGAAATGGCAGCC
CCCTTGTACCCTCTCACCAAAACGGGGACTCTGTTTAATTGGGGCCCAGACCAACAAAAG
GCCTATCAAGAAATCAAGCAAGCTCTTCTAACTGCCCCAGCCCTGGGGTTGCCAGATTTG
ACTAAGCCCTTTGAACTCTTTGTCGACGAGAAGCAGGGCTACGCCAAAGGTGTCCTAACG
CAAAAACTGGGACCTTGGCGTCGGCCGGTGGCCTACCTGTCCAAAAAGCTAGACCCAGTA
GCAGCTGGGTGGCCCCCTTGCCTACGGATGGTAGCAGCCATTGCCGTACTGACAAAGGAT
GCAGGCAAGCTAACCATGGGACAGCCACTAGTCATTCTGGCCCCCCATGCAGTAGAGGCA
CTAGTCAAACAACCCCCCGACCGCTGGCTTTCCAACGCCCGGATGACTCACTATCAGGCC
TTGCTTTTGGACACGGACCGGGTCCAGTTCGGACCGGTGGTAGCCCTGAACCCGGCTACG
CTGCTCCCACTGCCTGAGGAAGGGCTGCAACACAACTGCCTTGATATCCTGGCCGAAGCC
CACGGAACCCGACCCGACCTAACGGACCAGCCGCTCCCAGACGCCGACCACACCTGGTAC
ACGGATGGAAGCAGTCTCTTACAAGAGGGACAGCGTAAGGCGGGAGCTGCGGTGACCACC
GAGACCGAGGTAATCTGGGCTAAAGCCCTGCCAGCCGGGACATCCGCTCAGCGGGCTGAA
CTGATAGCACTCACCCAGGCCCTAAAGATGGCAGAAGGTAAGAAGCTAAATGTTTATACT
GATAGCCGTTATGCTTTTGCTACTGCCCATATCCATGGAGAAATATACAGAAGGCGTGGG
TTGCTCACATCAGAAGGCAAAGAGATCAAAAATAAAGACGAGATCTTGGCCCTACTAAAA
GCCCTCTTTCTGCCCAAAAGACTTAGCATAATCCATTGTCCAGGACATCAAAAGGGACAC
AGCGCCGAGGCTAGAGGCAACCGGATGGCTGACCAAGCGGCCCGAAAGGCAGCCATCACA
GAGACTCCAGACACCTCTACCCTCCTCATAGAAAATTCATCACCCTACACCTCAGAACAT
TTTCATTACACAGTGACTGATATAAAGGACCTAACCAAGTTGGGGGCCATTTATGATAAA
ACAAAGAAGTATTGGGTCTACCAAGGAAAACCTGTGATGCCTGACCAGTTTACTTTTGAA
TTATTAGACTTTCTTCATCAGCTGACTCACCTCAGCTTCTCAAAAATGAAGGCTCTCCTA
GAGAGAAGCCACAGTCCCTACTACATGCTGAACCGGGATCGAACACTCAAAAATATCACT
GAGACCTGCAAAGCTTGTGCACAAGTCAACGCCAGCAAGTCTGCCGTTAAACAGGGAACT
AGGGTCCGCGGGCATCGGCCCGGCACTCATTGGGAGATCGATTTCACCGAGATAAAGCCC
GGATTGTATGGCTATAAATATCTTCTAGTTTTTATAGATACCTTTTCTGGCTGGATAGAA
GCCTTCCCAACCAAGAAAGAAACCGCCAAGGTCGTAACCAAGAAGCTACTAGAGGAGATC
TTCCCCAGGTTCGGCATGCCTCAGGTATTGGGAACTGACAATGGGCCTGCCTTCGTCTCC
AAGGTGAGTCAGACAGTGGCCGATCTGTTGGGGATTGATTGGAAATTACATTGTGCATAC
AGACCCCAAAGCTCAGGCCAGGTAGAAAGAATGAATAGAACCATCAAGGAGACTTTAACT
AAATTAACGCTTGCAACTGGCTCTAGAGACTGGGTGCTCCTACTCCCCTTAGCCCTGTAC
CGAGCCCGCAACACGCCGGGCCCCCATGGCCTCACCCCATATGAGATCTTATATGGGGCA
CCCCCGCCCCTTGTAAACTTCCCTGACCCTGACATGACAAGAGTTACTAACAGCCCCTCT
CTCCAAGCTCACTTACAGGCTCTCTACTTAGTCCAGCACGAAGTCTGGAGACCTCTGGCG
GCAGCCTACCAAGAACAACTGGACCGACCGGTGGTACCTCACCCTTACCGAGTCGGCGAC
ACAGTGTGGGTCCGCCGACACCAGACTAAGAACCTAGAACCTCGCTGGAAAGGACCTTAC
ACAGTCCTGCTGACCACCCCCACCGCCCTCAAAGTAGACGGCATCGCAGCTTGGATACAC
GCCGCCCACGTGAAGGCTGCCGACCCCGGGGGTGGACCATCCTCTAGACTGACATGGCGC
GTTCAACGCTCTCAAAACCCCTTAAAAATAAGGTTAACCCGCGAGGCCCCCTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP03355
UniProtKB Entry NamePOL_MLVMS
GenBank Protein ID331935
GenBank Gene IDJ02255
General References
  1. Shinnick TM, Lerner RA, Sutcliffe JG: Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15-21;293(5833):543-8. [Article]
  2. Henderson LE, Krutzsch HC, Oroszlan S: Myristyl amino-terminal acylation of murine retrovirus proteins: an unusual post-translational proteins modification. Proc Natl Acad Sci U S A. 1983 Jan;80(2):339-43. [Article]
  3. Henderson LE, Copeland TD, Sowder RC, Smythers GW, Oroszlan S: Primary structure of the low molecular weight nucleic acid-binding proteins of murine leukemia viruses. J Biol Chem. 1981 Aug 25;256(16):8400-6. [Article]
  4. Yoshinaka Y, Katoh I, Copeland TD, Oroszlan S: Murine leukemia virus protease is encoded by the gag-pol gene and is synthesized through suppression of an amber termination codon. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1618-22. [Article]
  5. Yang F, Roth MJ: Assembly and catalysis of concerted two-end integration events by Moloney murine leukemia virus integrase. J Virol. 2001 Oct;75(20):9561-70. [Article]
  6. Yueh A, Goff SP: Phosphorylated serine residues and an arginine-rich domain of the moloney murine leukemia virus p12 protein are required for early events of viral infection. J Virol. 2003 Feb;77(3):1820-9. [Article]
  7. Orlova M, Yueh A, Leung J, Goff SP: Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic release factor 1 to modulate suppression of translational termination. Cell. 2003 Oct 31;115(3):319-31. [Article]
  8. Segura-Morales C, Pescia C, Chatellard-Causse C, Sadoul R, Bertrand E, Basyuk E: Tsg101 and Alix interact with murine leukemia virus Gag and cooperate with Nedd4 ubiquitin ligases during budding. J Biol Chem. 2005 Jul 22;280(29):27004-12. Epub 2005 May 21. [Article]
  9. Yueh A, Leung J, Bhattacharyya S, Perrone LA, de los Santos K, Pu SY, Goff SP: Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection. J Virol. 2006 Jan;80(1):342-52. [Article]
  10. Feher A, Boross P, Sperka T, Miklossy G, Kadas J, Bagossi P, Oroszlan S, Weber IT, Tozser J: Characterization of the murine leukemia virus protease and its comparison with the human immunodeficiency virus type 1 protease. J Gen Virol. 2006 May;87(Pt 5):1321-30. [Article]
  11. Georgiadis MM, Jessen SM, Ogata CM, Telesnitsky A, Goff SP, Hendrickson WA: Mechanistic implications from the structure of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase. Structure. 1995 Sep 15;3(9):879-92. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB07499N-(4-{[amino(imino)methyl]amino}butyl)-2,4'-bi-1,3-thiazole-4-carboxamideexperimentalunknownDetails
DB08331N-1H-imidazol-2-yl-N'-[4-(1H-imidazol-2-ylamino)phenyl]benzene-1,4-diamineexperimentalunknownDetails