P19560 (POL_BIV29) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gag-Pol polyprotein

Alternative name(s):
Pr170Gag-Pol

Cleaved into the following 8 chains:

1. Matrix protein p16
   Short name=MA
2. p2L
3. Capsid protein p26
   Short name=CA
4. p3
5. Transframe peptide
   Alternative name(s):
   p11
6. Protease
   EC=3.4.23.-
   Alternative name(s):
   P119
   Retropepsin
7. Reverse transcriptase/ribonuclease H
   Short name=RT
   EC=2.7.7.49
   EC=2.7.7.7
   EC=3.1.26.13
   Alternative name(s):
   Exoribonuclease H
   EC=3.1.13.2
   P72
8. Integrase
   Short name=IN

Gene names

Name:

gag-pol

Organism

Bovine immunodeficiency virus (strain R29) (BIV) (Bovine immunodeficiency-like virus)

Taxonomic identifier

417296 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Bovine lentivirus group

Virus host

Bos taurus (Bovine) [TaxID: 9913]

Protein attributes

Sequence length	1475 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	Matrix protein p16 forms the outer shell of the core of the virus, lining the inner surface of the viral membrane By similarity. Ref.4 Capsid protein p26 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. Interaction between incoming particle-associated Gag proteins and host dynein allows intracellular microtubule-dependent virus transport toward the perinuclear region, prior to nucleus translocation and integration into host genome. Ref.4 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. Ref.4 Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral 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 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. Ref.4 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 By similarity. Ref.4
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus. 3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.
Subunit structure	Interacts with host light chain cytoplasmic dynein DYNLL1; this interaction is critical for intracellular microtubule-dependent viral genome transport. Ref.4
Subcellular location	Matrix protein p16: Virion Potential. Capsid protein p26: Virion Potential.
Post-translational modification	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.3
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 By similarity. The sequence shown is that of isolate R29-127.
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	Capsid maturation Cytoplasmic active transport of viral material DNA integration DNA recombination Host-virus interaction Initiation of viral infection Microtubule-dependent active transport of viral material Viral genome integration
Cellular component	Viral matrix protein Virion
Coding sequence diversity	Ribosomal frameshifting
Domain	Coiled coil Repeat Zinc-finger
Ligand	DNA-binding Magnesium Metal-binding RNA-binding Viral nucleoprotein Zinc
Molecular function	Aspartyl protease Capsid protein DNA-directed DNA polymerase Endonuclease Hydrolase Nuclease Nucleotidyltransferase Protease RNA-directed DNA polymerase Transferase
Technical term	3D-structure 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 interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW viral procapsid maturation 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: 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 exoribonuclease H activity Inferred from electronic annotation. Source: EC ribonuclease H activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select]

Note: This strategy of translation probably allows the virus to modulate the quantity of each viral protein.

Isoform Gag-Pol polyprotein (identifier: P19560-1)

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 at the gag-pol genes boundary.

Isoform Gag polyprotein (identifier: P19558-1)

The sequence of this isoform can be found in the external entry P19558.
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

Chain

1 – 1475

1475

Gag-Pol polyprotein

PRO_0000272324

Chain

1 – 126

126

Matrix protein p16 Potential

PRO_0000272325

Peptide

127 – 148

22

p2L By similarity

PRO_0000272326

Chain

149 – 367

219

Capsid protein p26 Potential

PRO_0000272327

Peptide

368 – 392

25

p3 By similarity

PRO_0000272328

Chain

393 – 472

80

Transframe peptide Potential

PRO_0000272329

Chain

473 – 562

90

Protease Potential

PRO_0000038823

Chain

563 – 1193

631

Reverse transcriptase/ribonuclease H Potential

PRO_0000038824

Chain

1194 – 1475

282

Integrase Potential

PRO_0000038825

Regions

Domain

492 – 565

74

Peptidase A2

Domain

619 – 806

188

Reverse transcriptase

Domain

999 – 1119

121

RNase H

Domain

1248 – 1400

153

Integrase catalytic

Zinc finger

403 – 420

18

CCHC-type 1

Zinc finger

421 – 438

18

CCHC-type 2

Zinc finger

1199 – 1240

42

Integrase-type

DNA binding

1419 – 1465

47

Integrase-type

Sites

Active site

497

1

By similarity

Site

126 – 127

2

Cleavage; by viral protease Potential

Site

148 – 149

2

Cleavage; by viral protease Potential

Site

367 – 368

2

Cleavage; by viral protease By similarity

Site

392 – 393

2

Cleavage; by viral protease By similarity

Site

472 – 473

2

Cleavage; by viral protease Potential

Site

562 – 563

2

Cleavage; by viral protease Potential

Site

1193 – 1194

2

Cleavage; by viral protease Potential

Natural variations

Natural variant

17

1

P → L in strain: Isolate R29-106 and Isolate R29-Nadin.

Natural variant

117

1

D → E in strain: Isolate R29-106.

Natural variant

454

1

T → I in strain: Isolate R29-Nadin.

Natural variant

577

1

V → I in strain: Isolate R29-Nadin.

Natural variant

645

1

R → K in strain: Isolate R29-Nadin.

Natural variant

729

1

V → I in strain: Isolate R29-Nadin.

Natural variant

1095

1

V → I in strain: Isolate R29-Nadin.

Natural variant

1226

1

K → R in strain: Isolate R29-106 and Isolate R29-Nadin.

Natural variant

1244

1

T → A in strain: Isolate R29-106 and Isolate R29-Nadin.

Secondary structure

1

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1475

Helix Strand Turn

Details...

Beta strand

1257 – 1265

9

Beta strand

1268 – 1276

9

Beta strand

1281 – 1289

9

Helix

1291 – 1304

14

Beta strand

1308 – 1311

4

Turn

1317 – 1319

3

Helix

1321 – 1329

9

Beta strand

1333 – 1335

3

Turn

1342 – 1344

3

Helix

1348 – 1362

15

Helix

1369 – 1382

14

Helix

1392 – 1401

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gag-Pol polyprotein [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 4D249DCBB6158A78	FASTA	1,475	168,063
	10 20 30 40 50 60 MKRRELEKKL RKVRVTPQQD KYYTIGNLQW AIRMINLMGI KCVCDEECSA AEVALIITQF 70 80 90 100 110 120 SALDLENSPI RGKEEVAIKN TLKVFWSLLA GYKPESTETA LGYWEAFTYR EREARADKEG 130 140 150 160 170 180 EIKSIYPSLT QNTQNKKQTS NQTNTQSLPA ITTQDGTPRF DPDLMKQLKI WSDATERNGV 190 200 210 220 230 240 DLHAVNILGV ITANLVQEEI KLLLNSTPKW RLDVQLIESK VREKENAHRT WKQHHPEAPK 250 260 270 280 290 300 TDEIIGKGLS SAEQATLISV ECRETFRQWV LQAAMEVAQA KHATPGPINI HQGPKEPYTD 310 320 330 340 350 360 FINRLVAALE GMAAPETTKE YLLQHLSIDH ANEDCQSILR PLGPNTPMEK KLEACRVVGS 370 380 390 400 410 420 QKSKMQFLVA AMKEMGIQSP IPAVLPHTPE AYASQTSGPE DGRRCYGCGK TGHLKRNCKQ 430 440 450 460 470 480 QKCYHCGKPG HQARNCRSKN REVLLCPLWA EEPTTEQFSP EQHEFCDPIC TPSYIRLDKQ 490 500 510 520 530 540 PFIKVFIGGR WVKGLVDTGA DEVVLKNIHW DRIKGYPGTP IKQIGVNGVN VAKRKTHVEW 550 560 570 580 590 600 RFKDKTGIID VLFSDTPVNL FGRSLLRSIV TCFTLLVHTE KIEPLPVKVR GPGPKVPQWP 610 620 630 640 650 660 LTKEKYQALK EIVKDLLAEG KISEAAWDNP YNTPVFVIKK KGTGRWRMLM DFRELNKITV 670 680 690 700 710 720 KGQEFSTGLP YPPGIKECEH LTAIDIKDAY FTIPLHEDFR PFTAFSVVPV NREGPIERFQ 730 740 750 760 770 780 WNVLPQGWVC SPAIYQTTTQ KIIENIKKSH PDVMLYQYMD DLLIGSNRDD HKQIVQEIRD 790 800 810 820 830 840 KLGSYGFKTP DEKVQEERVK WIGFELTPKK WRFQPRQLKI KNPLTVNELQ QLVGNCVWVQ 850 860 870 880 890 900 PEVKIPLYPL TDLLRDKTNL QEKIQLTPEA IKCVEEFNLK LKDPEWKDRI REGAELVIKI 910 920 930 940 950 960 QMVPRGIVFD LLQDGNPIWG GVKGLNYDHS NKIKKILRTM NELNRTVVIM TGREASFLLP 970 980 990 1000 1010 1020 GSSEDWEAAL QKEESLTQIF PVKFYRHSCR WTSICGPVRE NLTTYYTDGG KKGKTAAAVY 1030 1040 1050 1060 1070 1080 WCEGRTKSKV FPGTNQQAEL KAICMALLDG PPKMNIITDS RYAYEGMREE PETWAREGIW 1090 1100 1110 1120 1130 1140 LEIAKILPFK QYVGVGWVPA HKGIGGNTEA DEGVKKALEQ MAPCSPPEAI LLKPGEKQNL 1150 1160 1170 1180 1190 1200 ETGIYMQGLR PQSFLPRADL PVAITGTMVD SELQLQLLNI GTEHIRIQKD EVFMTCFLEN 1210 1220 1230 1240 1250 1260 IPSATEDHER WHTSPDILVR QFHLPKRIAK EIVARCQECK RTTTSPVRGT NPRGRFLWQM 1270 1280 1290 1300 1310 1320 DNTHWNKTII WVAVETNSGL VEAQVIPEET ALQVALCILQ LIQRYTVLHL HSDNGPCFTA 1330 1340 1350 1360 1370 1380 HRIENLCKYL GITKTTGIPY NPQSQGVVER AHRDLKDRLA AYQGDCETVE AALSLALVSL 1390 1400 1410 1420 1430 1440 NKKRGGIGGH TPYEIYLESE HTKYQDQLEQ QFSKQKIEKW CYVRNRRKEW KGPYKVLWDG 1450 1460 1470 DGAAVIEEEG KTALYPHRHM RFIPPPDSDI QDGSS
	Isoform Gag polyprotein [UniParc]. See P19558.		–	–

References

[1]	"Nucleotide sequence and genome organization of biologically active proviruses of the bovine immunodeficiency-like virus." Garvey K.J., Oberste M.S., Elser J.E., Braun M.J., Gonda M.A. Virology 175:391-409(1990) [PubMed: 2183467] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate R29-106 and Isolate R29-127.
[2]	"Isolation and characterization of cDNAs encoding rev and tat of bovine immunodeficiency-like virus." Nadin-Davis S.A., Chang S.C., Roth J.A., Carpenter S. Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Isolate R29-Nadin.
[3]	"Immunological characterization of the gag gene products of bovine immunodeficiency virus." Battles J.K., Hu M.Y., Rasmussen L., Tobin G.J., Gonda M.A. J. Virol. 66:6868-6877(1992) [PubMed: 1331499] [Abstract] Cited for: RIBOSOMAL FRAMESHIFT, PROTEOLYTIC PROCESSING OF POLYPROTEIN. Strain: Isolate R29-127.
[4]	"Microtubule-dependent retrograde transport of bovine immunodeficiency virus." Su Y., Qiao W., Guo T., Tan J., Li Z., Chen Y., Li X., Li Y., Zhou J., Chen Q. Cell. Microbiol. 12:1098-1107(2010) [PubMed: 20148896] [Abstract] Cited for: FUNCTION, INTERACTION WITH HOST DYNLL1.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M32690 Genomic RNA. Translation: AAA91271.1. Sequence problems.
L04972 Genomic DNA. Translation: AAA42767.1. Sequence problems.

PIR

GNLJBT. B34742.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3KKR	X-ray	2.45	A	1257-1405	[»]
3KKS	X-ray	2.20	A/B	1257-1405	[»]

ProteinModelPortal

P19560.

ModBase

Search...

Protein family/group databases

MEROPS

A02.005.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

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.
IPR009007. Peptidase_aspartic_catalytic.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR012337. RNaseH-like_dom.
IPR002156. RNaseH_domain.
IPR000477. RVT.
IPR010659. RVT_connect.
IPR010661. RVT_thumb.
IPR013084. Znf_CCH_retrovir.
IPR001878. Znf_CCHC.
[Graphical view]

Gene3D

G3DSA:2.30.30.10. Integrase_C. 1 hit.
G3DSA:1.10.10.200. Intgrase_N_Zn_bd. 1 hit.
G3DSA:2.40.70.10. Pept_Aspartc_cat. 1 hit.
G3DSA:1.10.1200.30. Retrov_capsid_C. 1 hit.
G3DSA:1.10.375.10. Retrov_capsid_N. 1 hit.
G3DSA:4.10.60.10. Znf_CCH_retrovir. 1 hit.

Pfam

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.
PF06815. RVT_connect. 1 hit.
PF06817. RVT_thumb. 1 hit.
PF00098. zf-CCHC. 2 hits.
[Graphical view]

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.
SSF53098. RNaseH_fold. 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. 2 hits.
PS50876. ZF_INTEGRASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

POL_BIV29

Accession

Primary (citable) accession number: P19560
Secondary accession number(s): P19561, Q65593

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	January 23, 2007
Last modified:	December 14, 2011
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program