P11283 (POL_MMTVC) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 71. History...
Names and origin
|Protein names||Recommended name:|
Cleaved into the following 10 chains:
|Organism||Mouse mammary tumor virus (strain C3H) (MMTV) [Reference proteome]|
|Taxonomic identifier||11759 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Betaretrovirus ›|
|Virus host||Mus musculus (Mouse) [TaxID: 10090]|
|Sequence length||1755 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Matrix protein p10: Matrix protein By similarity.
Nucleocapsid protein p14: Nucleocapsid protein. Binds to single-stranded DNA By similarity.
Capsid protein p27: capsid protein By similarity.
NC-dUTPase has dUTPase activity, thereby preventing incorporation of uracil into DNA.
The aspartyl protease mediates proteolytic cleavages of Gag, Gag-Pro and Gag-Pro-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.
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.
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Endonucleolytic cleavage to 5'-phosphomonoester.
RT polymerase domain: Binds 2 magnesium ions By similarity.
Magnesium ions for NC-dUTPase.
NC-dUTPase is a homotrimer. Ref.5
Specific enzymatic cleavages in vivo yield mature proteins.
p10 is myristoylated.
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 2 CCHC-type zinc fingers.
Contains 1 integrase catalytic domain.
Contains 1 integrase-type DNA-binding domain.
Contains 1 integrase-type zinc finger.
Contains 1 peptidase A2 domain.
Contains 1 reverse transcriptase domain.
Contains 1 RNase H domain.
|This entry describes 3 isoforms produced by ribosomal frameshifting. [Align] [Select]|
Note: Translation results in the formation of the Gag-Pro. Ribosomal frameshifting at the gag-pro/pol genes boundary produces the Gag-Pro-Pol polyprotein.
|Isoform Gag-Pro-Pol polyprotein (identifier: P11283-1) |
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Note: Produced by -1 ribosomal frameshifting between gag-pro and pro-pol.|
|Isoform Gag-Pro polyprotein (identifier: Q9IZT2-1) |
The sequence of this isoform can be found in the external entry Q9IZT2.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
|Note: Produced by -1 ribosomal frameshifting between gag-pro.|
|Isoform Gag polyprotein (identifier: P11284-1) |
The sequence of this isoform can be found in the external entry P11284.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
|Note: Produced by conventional translation.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed; by host By similarity|
|Chain||2 – 1755||1754||Gag-Pro-Pol polyprotein||PRO_0000125493|
|Chain||2 – 99||98||Matrix protein p10||PRO_0000403612|
|Chain||100 – 195||96||Phosphorylated protein pp21||PRO_0000403613|
|Chain||196 – 228||33||Protein p3||PRO_0000403614|
|Chain||229 – 252||24||Protein p8 Potential||PRO_0000403615|
|Chain||253 – 269||17||Protein n||PRO_0000403616|
|Chain||270 – 496||227||Capsid protein p27||PRO_0000403617|
|Chain||497 – 745||249||Nucleocapsid protein-dUTPase Potential||PRO_0000403618|
|Chain||746 – 833||88||Protease Potential||PRO_0000403619|
|Chain||834 – 1437||604||Reverse transcriptase/ribonuclease H Potential||PRO_0000403620|
|Chain||1438 – 1755||318||Integrase Potential||PRO_0000403621|
|Domain||766 – 841||76||Peptidase A2|
|Domain||905 – 1093||189||Reverse transcriptase|
|Domain||1307 – 1435||129||RNase H|
|Domain||1490 – 1647||158||Integrase catalytic|
|Zinc finger||525 – 542||18||CCHC-type 1|
|Zinc finger||552 – 569||18||CCHC-type 2|
|Zinc finger||1436 – 1477||42||Integrase-type|
|DNA binding||1653 – 1702||50||Integrase-type By similarity|
|Compositional bias||278 – 281||4||Poly-Asp|
|Compositional bias||716 – 719||4||Poly-Leu|
|Active site||771||1||Protease; shared with dimeric partner By similarity|
|Metal binding||970||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||1045||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||1046||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||1316||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||1346||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||1366||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||1429||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||1501||1||Magnesium; catalytic; for integrase activity By similarity|
|Metal binding||1558||1||Magnesium; catalytic; for integrase activity By similarity|
|Site||99 – 100||2||Cleavage; by viral protease By similarity|
|Site||195 – 196||2||Cleavage; by viral protease By similarity|
|Site||228 – 229||2||Cleavage; by viral protease By similarity|
|Site||252 – 253||2||Cleavage; by viral protease By similarity|
|Site||269 – 270||2||Cleavage; by viral protease By similarity|
|Site||496 – 497||2||Cleavage; by viral protease By similarity|
|Site||745 – 746||2||Cleavage; by viral protease By similarity|
|Site||833 – 834||2||Cleavage; by viral protease By similarity|
|Site||1437 – 1438||2||Cleavage; by viral protease By similarity|
Amino acid modifications
|Lipidation||2||1||N-myristoyl glycine; by host By similarity|
|Natural variant||523||1||E → K.|
|Sequence conflict||857 – 860||4||SQDL → FTGF in AAA66625. Ref.2|
|Sequence conflict||867||1||S → T in AAA66625. Ref.2|
|Sequence conflict||952||1||P → L in AAA66625. Ref.2|
|||"Genetics of mouse mammary tumor virus-induced mammary tumors: linkage of tumor induction to the gag gene."|
Hook L.M., Agafonova Y., Ross S.R., Turner S.J., Golovkina T.V.
J. Virol. 74:8876-8883(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"Two efficient ribosomal frameshifting events are required for synthesis of mouse mammary tumor virus gag-related polyproteins."|
Jacks T., Townsley K., Varmus H.E., Majors J.
Proc. Natl. Acad. Sci. U.S.A. 84:4298-4302(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 359-591 AND 857-970, RIBOSOMAL FRAMESHIFT.
|||"Analysis of gag proteins from mouse mammary tumor virus."|
Hizi A., Henderson L.E., Copeland T.D., Sowder R.C., Krutzsch H.C., Oroszlan S.
J. Virol. 63:2543-2549(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-58; 65-116; 194-218; 227-241; 251-252; 270-276 AND 362-591, PROTEOLYTIC PROCESSING OF POLYPROTEIN, MYRISTOYLATION AT GLY-2.
|||"Purification and characterization of the mouse mammary tumor virus protease expressed in Escherichia coli."|
Menendez-Arias L., Young M., Oroszlan S.
J. Biol. Chem. 267:24134-24139(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
|||"The protein p30, encoded at the gag-pro junction of mouse mammary tumor virus, is a dUTPase fused with a nucleocapsid protein."|
Bergman A.C., Bjornberg O., Nord J., Nyman P.O., Rosengren A.M.
Virology 204:420-424(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: RIBOSOMAL FRAMESHIFT, SUBUNIT, CHARACTERIZATION OF NC-DUTPASE.
|AF228552 Genomic DNA. Translation: AAF31474.1.|
M16766 Genomic RNA. Translation: AAA66623.1.
M16766 Genomic RNA. Translation: AAA66625.1.
3D structure databases
|SMR||P11283. Positions 550-580, 619-724. |
Protocols and materials databases
Family and domain databases
|Gene3D||184.108.40.206. 1 hit. |
1.10.1200.30. 1 hit.
1.10.375.10. 1 hit.
220.127.116.11. 1 hit.
18.104.22.168. 1 hit.
|InterPro||IPR001969. Aspartic_peptidase_AS. |
|Pfam||PF00692. dUTPase. 1 hit. |
PF02337. Gag_p10. 1 hit.
PF00607. Gag_p24. 1 hit.
PF00552. IN_DBD_C. 1 hit.
PF02022. Integrase_Zn. 1 hit.
PF00075. RNase_H. 1 hit.
PF00665. rve. 1 hit.
PF00077. RVP. 1 hit.
PF00078. RVT_1. 1 hit.
PF06817. RVT_thumb. 1 hit.
PF00098. zf-CCHC. 1 hit.
|ProDom||PD004265. B_retro_matrix_N. 1 hit. |
[Graphical view] [Entries sharing at least one domain]
|SMART||SM00343. ZnF_C2HC. 2 hits. |
|SUPFAM||SSF46919. SSF46919. 1 hit. |
SSF47353. SSF47353. 1 hit.
SSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF50122. SSF50122. 1 hit.
SSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 2 hits.
SSF57756. SSF57756. 2 hits.
|PROSITE||PS50175. ASP_PROT_RETROV. 1 hit. |
PS00141. ASP_PROTEASE. 1 hit.
PS50994. INTEGRASE. 1 hit.
PS51027. INTEGRASE_DBD. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
PS50158. ZF_CCHC. 1 hit.
PS50876. ZF_INTEGRASE. 1 hit.
|Accession||Primary (citable) accession number: P11283|
Secondary accession number(s): Q9IZT3
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|