P11283 (POL_MMTVC) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gag-Pro-Pol polyprotein

Cleaved into the following 10 chains:

1. Matrix protein p10
2. Phosphorylated protein pp21
3. Protein p3
4. Protein p8
5. Protein n
6. Capsid protein p27
7. Nucleocapsid protein-dUTPase
   Short name=NC-dUTPase
8. Protease
   EC=3.4.23.-
9. Reverse transcriptase/ribonuclease H
   Short name=RT
   EC=2.7.7.49
   EC=2.7.7.7
   EC=3.1.26.4
10. Integrase
    Short name=IN

Gene names

Name:

gag-pro-pol

Organism

Mouse mammary tumor virus (strain C3H) (MMTV) [Reference proteome]

Taxonomic identifier

11759 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Betaretrovirus › Mouse mammary tumor virus

Virus host

Mus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length	1755 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	p10 is the matrix protein By similarity. P14 is the nucleocapsid protein. Binds to single stranded DNA By similarity. p27 is the 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.
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). Endonucleolytic cleavage to 5'-phosphomonoester.
Cofactor	RT polymerase domain: Binds 2 magnesium ions By similarity. Magnesium ions for NC-dUTPase.
Subunit structure	NC-dUTPase is a homotrimer. Ref.5
Subcellular location	Matrix protein p10: Virion Potential. Capsid protein p27: Virion Potential. Nucleocapsid protein-dUTPase: Virion Potential.
Post-translational modification	Specific enzymatic cleavages in vivo yield mature proteins. p10 is myristoylated.
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 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.
Sequence similarities	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.

Ontologies

Keywords
Biological process	DNA integration DNA recombination Viral genome integration Virus entry into host cell
Cellular component	Viral matrix protein Virion
Coding sequence diversity	Ribosomal frameshifting
Domain	Repeat Zinc-finger
Ligand	DNA-binding Magnesium Metal-binding Nucleotide-binding Viral nucleoprotein Zinc
Molecular function	Aspartyl protease Capsid protein DNA-directed DNA polymerase Endonuclease Hydrolase Nuclease Nucleotidyltransferase Protease RNA-directed DNA polymerase Transferase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
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 dUTP metabolic process 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	viral capsid Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: InterPro RNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW aspartic-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW ribonuclease H activity Inferred from electronic annotation. Source: EC structural molecule activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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
Molecule processing
	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
Regions
	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
Sites
	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 variations
	Natural variant	523	1	E → K.
Experimental info
	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

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gag-Pro-Pol polyprotein [UniParc]. Last modified January 11, 2011. Version 2. Checksum: 0E99A2ADD96823A4	FASTA	1,755	197,329
	10 20 30 40 50 60 MGVSGSKGQK LFVSVLQRLL SERGLHVKES SAIEFYQFLI KVSPWFPEEG GLNLQDWKRV 70 80 90 100 110 120 GREMKKYAAE HGTDSIPKQA YPIWLQLREI LTEQSDLVLL SAEAKSVTEE ELEEGLTGLL 130 140 150 160 170 180 SASSQEKTYG TRGTAYAEID TEVDKLSEHI YDEPYEEKEK ADKNEEKDHV RKVKKIVQRK 190 200 210 220 230 240 ENSEHKRKEK DQKAFLATDW NNDDLSPEDW DDLEEQAAHY HDDDELILPV KRKVDKKKPL 250 260 270 280 290 300 ALRRKPLPPV GFAGAMAEAR EKGDLTFTFP VVFMGESDDD DTPVWEPLPL KTLKELQSAV 310 320 330 340 350 360 RTMGPSAPYT LQVVDMVASQ WLTPSDWHQT ARATLSPGDY VLWRTEYEEK SKETVQKTAG 370 380 390 400 410 420 KRKGKVSLDM LLGTGQFLSP SSQIKLSKDV LKDVTTNAVL AWRAIPPPGV KKTVLAGLKQ 430 440 450 460 470 480 GNEESYETFI SRLEEAVYRM MPRGEGSDIL IKQLAWENAN SLCQDLIRPM RKTGTMQDYI 490 500 510 520 530 540 RACLDASPAV VQGMAYAAAM RGQKYSTFVK QTYGGGKGGQ GSEGPVCFSC GKTGHIKRDC 550 560 570 580 590 600 KEEKGSKRAP PGLCPRCKKG YHWKSECKSK FDKDGNPLPP LETNAENSKN LVKGQSPSPT 610 620 630 640 650 660 QKGDKGKDSG LNPEAPPFTI HDLPRGTPGS AGLDLSSQKD LILSLEDGVS LVPTLVKGTL 670 680 690 700 710 720 PEGTTGLIIG RSSNYKKGLE VLPGVIDSDF QGEIKVMVKA AKNAVIIHKG ERIAQLLLLP 730 740 750 760 770 780 YLKLPNPIIK EERGSEGFGS TSHVHWVQEI SDSRPMLHIS LNGRRFLGLL DTGADKTCIA 790 800 810 820 830 840 GRDWPANWPI HQTESSLQGL GMACGVARSS QPLRWQHEDK SGIIHPFVIP TLPFTLWGRD 850 860 870 880 890 900 IMKEIKVRLM TDSPDDSQDL MIGAIESNLF ADQISWKSDQ PVWLNQWPLK QEKLQALQQL 910 920 930 940 950 960 VTEQLQLGHL EESNSPWNTP VFVIKKKSGK WRLLQDLRAV NATMHDMGAL QPGLPSPVAV 970 980 990 1000 1010 1020 PKGWEIIIID LQDCFFNIKL HPEDCKRFAF SVPSPNFKRP YQRFQWKVLP QGMKNSPTLC 1030 1040 1050 1060 1070 1080 QKFVDKAILT VRDKYQDSYI VHYMDDILLA HPSRSIVDEI LTSMIQALNK HGLVVSTEKI 1090 1100 1110 1120 1130 1140 QKYDNLKYLG THIQGDAVSY QKLQIRTDKL RTLNDFQKLL GNINWIRPFL KLTTGELKPL 1150 1160 1170 1180 1190 1200 FEILNGDSNP ISIRKLTPEA CKALQLVNER LSIARVKRLD LSRPWSLCIL KTEYTPTACL 1210 1220 1230 1240 1250 1260 WQNGVLEWIH LPHISPKVIT PYDIFCTQLI IKGRHRSKEL FSKDPDYIVV PYTKVQFDLL 1270 1280 1290 1300 1310 1320 LQEKEDWPIS LLGFLGEVHF HLPKDPLLTF TLQTAIIFPH MTSTTPLEKG IVIFTDGSAN 1330 1340 1350 1360 1370 1380 GRSVTYIQGR EPIIKENTQN TAQQAEIVAV ITAFEEVSQS FNLYTDSKYV TGLFPEIETA 1390 1400 1410 1420 1430 1440 TLSPRTKIYT ELRHLQRLIH KRQEKFYIGH IRGHTGLPGP LAQGNAYADS LTRILTALES 1450 1460 1470 1480 1490 1500 AQESHALHHQ NAAALRFQFH ITREQAREIV KLCPNCPDWG HAPQLGVNPR GLKPRVLWQM 1510 1520 1530 1540 1550 1560 DVTHVSEFGK LKYVHVTVDT YSHFTFATAR TGEATKDVLQ HLAQSFAYMG FPQKIKTDNA 1570 1580 1590 1600 1610 1620 PAYVSRSIQE FLARWKISHV TGIPYNPQGQ AIVERTHQNI KAQLNKLQKA GKYYTPHHLL 1630 1640 1650 1660 1670 1680 AHALFVLNHV NMDNQGHTAA ERHWGPISAD PKPMVMWKDL LAGSWKGPDV LITAGRGYAC 1690 1700 1710 1720 1730 1740 VFPQDAETPI WVPDRFIRPF TERKEATPTP GTAEKTPPRD EKDQQKSPED ESSPHQREDG 1750 LATSAGVNLR SGGGS
	Isoform Gag-Pro polyprotein [UniParc]. See Q9IZT2.		–	–
	Isoform Gag polyprotein [UniParc]. See P11284.		–	–

References

[1]	"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].
[2]	"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.
[3]	"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.
[4]	"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.
[5]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF228552 Genomic DNA. Translation: AAF31474.1. M16766 Genomic RNA. Translation: AAA66623.1. M16766 Genomic RNA. Translation: AAA66625.1.
PIR	B29029.
3D structure databases
HSSP	HSSP built from PDB template 1DSV based on UniProtKB P11284.
ProteinModelPortal	P11283.
SMR	P11283. Positions 550-580, 619-724.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
Gene3D	1.10.10.200. 1 hit. 1.10.1200.30. 1 hit. 1.10.375.10. 1 hit. 2.40.70.10. 1 hit. 4.10.60.10. 1 hit.
InterPro	IPR003322. B_retro_matrix_N. IPR008180. dUTP_pyroPase. IPR000721. Gag_p24. IPR001037. Integrase_C_retrovir. IPR001584. Integrase_cat-core. IPR017856. Integrase_Zn-bd_dom-like_N. IPR003308. Integrase_Zn-bd_dom_N. IPR018061. Pept_A2A_retrovirus_sg. IPR001995. Peptidase_A2_cat. IPR021109. Peptidase_aspartic. IPR001969. Peptidase_aspartic_AS. IPR008916. Retrov_capsid_C. IPR008919. Retrov_capsid_N. IPR010999. Retrovr_matrix_N. IPR012337. RNaseH-like_dom. IPR002156. RNaseH_domain. IPR000477. RVT. IPR010661. RVT_thumb. IPR001878. Znf_CCHC. [Graphical view]
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. [Graphical view]
ProDom	PD004265. B_retro_matrix_N. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00343. ZnF_C2HC. 2 hits. [Graphical view]
SUPFAM	SSF50122. Integrase_C. 1 hit. SSF46919. Integrase_Zn_N. 1 hit. SSF50630. Pept_Aspartic. 1 hit. SSF47353. Retrov_capsid_C. 1 hit. SSF47943. Retrov_capsid_N. 1 hit. SSF47836. Retrovir_matrix. 1 hit. SSF53098. RNaseH_fold. 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. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POL_MMTVC

Accession

Primary (citable) accession number: P11283
Secondary accession number(s): Q9IZT3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 67 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program