P04591 (GAG_HV1H2) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gag polyprotein

Alternative name(s):
Pr55Gag

Cleaved into the following 6 chains:

1. Matrix protein p17
   Short name=MA
2. Capsid protein p24
   Short name=CA
3. Spacer peptide p2
4. Nucleocapsid protein p7
   Short name=NC
5. Spacer peptide p1
6. p6-gag

Gene names

Name:

gag

Organism

Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1) [Reference proteome]

Taxonomic identifier

11706 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group › Human immunodeficiency virus 1 › HIV-1 group M › HIV-1 M:B

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	500 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 p17 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. Implicated in the release from host cell mediated by Vpu. Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. p6-gag plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1 By similarity.
Subunit structure	Matrix protein p17, and probably Pr55Gag form hexamer rings of trimers Probable. Oligomerization possibly creates a central hole into which the cytoplasmic tail of the gp41 envelope protein may be inserted. Pr55Gag interacts with host TRIM22; this interaction seems to disrupt proper trafficking of Gag polyprotein and may interfere with budding. p6-gag interacts with Vpr. p6-gag interacts with host TSG101. p6-gag interacts with host PDCD6IP/AIP1 By similarity. Pr55Gag interacts with host PDZD8 By similarity. Ref.5 Ref.6
Subcellular location	Matrix protein p17: Virion Potential Ref.2. Host nucleus By similarity. Host cytoplasm By similarity. Host cell membrane; Lipid-anchor Potential. Note: Following virus entry, the nuclear localization signal (NLS) of the matrix protein participates with Vpr to the nuclear localization of the viral genome. During virus production, the nuclear export activity of the matrix protein counteracts the NLS to maintain the Gag and Gag-Pol polyproteins in the cytoplasm, thereby directing unspliced RNA to the plasma membrane By similarity. Ref.2 Capsid protein p24: Virion Potential Ref.2. Nucleocapsid protein p7: Virion Potential Ref.2.
Domain	Late-budding domains (L domains) are short sequence motifs essential for viral particle budding. They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins. p6-gag contains two L domains: a PTAP/PSAP motif, which interacts with the UEV domain of TSG101 and a LYPX(n)L motif which interacts with PDCD6IP/AIP1 By similarity.
Post-translational modification	Capsid protein p24 is phosphorylated. Specific enzymatic cleavages by the viral protease yield mature proteins. The polyprotein is cleaved during and after budding, this process is termed maturation By similarity. Nucleocapsid protein p7 is methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription By similarity.
Miscellaneous	HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).
Sequence similarities	Belongs to the primate lentivirus group gag polyprotein family. Contains 2 CCHC-type zinc fingers.

Ontologies

Keywords
Biological process	Host-virus interaction Viral budding Viral budding via the host ESCRT complexes Virus exit from host cell
Cellular component	Host cell membrane Host cytoplasm Host membrane Host nucleus Membrane Virion
Coding sequence diversity	Ribosomal frameshifting
Disease	AIDS
Domain	Repeat Zinc-finger
Ligand	Metal-binding RNA-binding Viral nucleoprotein Zinc
Molecular function	Capsid protein
PTM	Lipoprotein Methylation Myristate Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA-dependent DNA replication Traceable author statement. Source: Reactome egress of virus within host cell Traceable author statement. Source: Reactome entry into host cell Traceable author statement. Source: Reactome uncoating of virus Traceable author statement. Source: Reactome viral release from host cell Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome endosome membrane Traceable author statement. Source: Reactome host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome viral capsid Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW structural molecule activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AIMP1	Q12904	3	EBI-6179719,EBI-1045802	From a different organism.
AIMP2	Q13155	3	EBI-6179719,EBI-745226	From a different organism.
CTNNA3	Q9UI47	2	EBI-6179727,EBI-3937546	From a different organism.
EEF1E1	O43324	4	EBI-6179719,EBI-1048486	From a different organism.
LRRC47	Q8N1G4	2	EBI-6179727,EBI-2509921	From a different organism.
MRPL11	Q9Y3B7	3	EBI-6179727,EBI-5453723	From a different organism.
NHP2L1	P55769	2	EBI-6179727,EBI-712228	From a different organism.
NOLC1	Q14978	2	EBI-6179719,EBI-396155	From a different organism.
OLA1	Q9NTK5	4	EBI-6179719,EBI-766468	From a different organism.
PRMT1	Q99873	2	EBI-6179727,EBI-78738	From a different organism.
SDCCAG8	Q86SQ7	2	EBI-6179719,EBI-1047850	From a different organism.
SEPSECS	Q9HD40	3	EBI-6163428,EBI-6163446	From a different organism.
YTHDF3	Q7Z739	2	EBI-6179727,EBI-2849837	From a different organism.

Alternative products

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

Note: Translation results in the formation of the Gag polyprotein most of the time. Ribosomal frameshifting at the gag-pol genes boundary occurs at low frequency and produces the Gag-Pol polyprotein. This strategy of translation probably allows the virus to modulate the quantity of each viral protein. Maintenance of a correct Gag to Gag-Pol ratio is essential for RNA dimerization and viral infectivity.

Isoform Gag polyprotein (identifier: P04591-1)

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 conventional translation.

Isoform Gag-Pol polyprotein (identifier: P04585-1)

The sequence of this isoform can be found in the external entry P04585.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by -1 ribosomal frameshifting.

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 – 500

499

Gag polyprotein

PRO_0000261216

Chain

2 – 132

131

Matrix protein p17 By similarity

PRO_0000038593

Chain

133 – 363

231

Capsid protein p24 By similarity

PRO_0000038594

Peptide

364 – 377

14

Spacer peptide p2 By similarity

PRO_0000038595

Chain

378 – 432

55

Nucleocapsid protein p7 By similarity

PRO_0000038596

Peptide

433 – 448

16

Spacer peptide p1 By similarity

PRO_0000038597

Chain

449 – 500

52

p6-gag By similarity

PRO_0000038598

Regions

Zinc finger

390 – 407

18

CCHC-type 1

Zinc finger

411 – 428

18

CCHC-type 2

Motif

16 – 22

7

Nuclear export signal

Motif

26 – 32

7

Nuclear localization signal

Motif

455 – 458

4

PTAP/PSAP motif

Motif

483 – 492

10

LYPX(n)L motif

Sites

Site

132 – 133

2

Cleavage; by viral protease By similarity

Site

363 – 364

2

Cleavage; by viral protease By similarity

Site

377 – 378

2

Cleavage; by viral protease By similarity

Site

432 – 433

2

Cleavage; by viral protease By similarity

Site

448 – 449

2

Cleavage; by viral protease By similarity

Amino acid modifications

Modified residue

387

1

Asymmetric dimethylarginine; in Nucleocapsid protein p7; by host PRMT6 By similarity

Modified residue

409

1

Asymmetric dimethylarginine; in Nucleocapsid protein p7; by host PRMT6 By similarity

Lipidation

2

1

N-myristoyl glycine; by host By similarity

Experimental info

Mutagenesis

18

1

K → A: Replication-defective, induces nuclear mislocalization of matrix protein; when associated with G-22. Ref.2

Mutagenesis

22

1

R → G: Replication-defective, induces nuclear mislocalization of matrix protein; when associated with A-18. Ref.2

Mutagenesis

27

1

K → A: No effect on subcellular localization of matrix protein; when associated with A-18 and G-22. Ref.2

Secondary structure

1

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500

Helix Strand Turn

Details...

Turn

5 – 6

2

Beta strand

7 – 10

4

Helix

11 – 18

8

Beta strand

19 – 21

3

Beta strand

23 – 25

3

Helix

31 – 45

15

Beta strand

46 – 48

3

Turn

50 – 52

3

Helix

54 – 67

14

Turn

68 – 70

3

Helix

72 – 90

19

Helix

97 – 112

16

Beta strand

116 – 118

3

Helix

149 – 162

14

Turn

163 – 164

2

Turn

166 – 167

2

Helix

168 – 175

8

Turn

176 – 178

3

Helix

181 – 189

9

Turn

190

1

Helix

195 – 215

21

Turn

218 – 219

2

Helix

233 – 236

4

Turn

237 – 240

4

Helix

243 – 250

8

Beta strand

251 – 254

4

Helix

258 – 277

20

Helix

282 – 284

3

Turn

289 – 290

2

Helix

293 – 305

13

Turn

306

1

Helix

311 – 324

14

Turn

325

1

Helix

328 – 337

10

Turn

339 – 340

2

Helix

343 – 349

7

Turn

350

1

Beta strand

393 – 395

3

Turn

399

1

Turn

402 – 404

3

Beta strand

414 – 416

3

Turn

423 – 425

3

Turn

427 – 428

2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gag polyprotein [UniParc]. Last modified January 23, 2007. Version 3. Checksum: B74C3858C20EF82C	FASTA	500	55,930
	10 20 30 40 50 60 MGARASVLSG GELDRWEKIR LRPGGKKKYK LKHIVWASRE LERFAVNPGL LETSEGCRQI 70 80 90 100 110 120 LGQLQPSLQT GSEELRSLYN TVATLYCVHQ RIEIKDTKEA LDKIEEEQNK SKKKAQQAAA 130 140 150 160 170 180 DTGHSNQVSQ NYPIVQNIQG QMVHQAISPR TLNAWVKVVE EKAFSPEVIP MFSALSEGAT 190 200 210 220 230 240 PQDLNTMLNT VGGHQAAMQM LKETINEEAA EWDRVHPVHA GPIAPGQMRE PRGSDIAGTT 250 260 270 280 290 300 STLQEQIGWM TNNPPIPVGE IYKRWIILGL NKIVRMYSPT SILDIRQGPK EPFRDYVDRF 310 320 330 340 350 360 YKTLRAEQAS QEVKNWMTET LLVQNANPDC KTILKALGPA ATLEEMMTAC QGVGGPGHKA 370 380 390 400 410 420 RVLAEAMSQV TNSATIMMQR GNFRNQRKIV KCFNCGKEGH TARNCRAPRK KGCWKCGKEG 430 440 450 460 470 480 HQMKDCTERQ ANFLGKIWPS YKGRPGNFLQ SRPEPTAPPE ESFRSGVETT TPPQKQEPID 490 500 KELYPLTSLR SLFGNDPSSQ
	Isoform Gag-Pol polyprotein [UniParc]. See P04585.		–	–

References

[1]	"Complete nucleotide sequences of functional clones of the AIDS virus." Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C., Wong-Staal F. AIDS Res. Hum. Retroviruses 3:57-69(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"A novel nuclear export activity in HIV-1 matrix protein required for viral replication." Dupont S., Sharova N., DeHoratius C., Virbasius C.M., Zhu X., Bukrinskaya A.G., Stevenson M., Green M.R. Nature 402:681-685(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION OF POLYPROTEIN, MUTAGENESIS OF LYS-18; ARG-22 AND LYS-27.
[3]	"Maintenance of the Gag/Gag-Pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity." Shehu-Xhilaga M., Crowe S.M., Mak J. J. Virol. 75:1834-1841(2001) [PubMed] [Europe PMC] [Abstract] Cited for: GAG/GAG-POL RATIO.
[4]	"Role of HIV-1 Gag domains in viral assembly." Scarlata S., Carter C. Biochim. Biophys. Acta 1614:62-72(2003) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[5]	"Human immunodeficiency virus type 1 matrix protein assembles on membranes as a hexamer." Alfadhli A., Huseby D., Kapit E., Colman D., Barklis E. J. Virol. 81:1472-1478(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[6]	"The interferon response inhibits HIV particle production by induction of TRIM22." Barr S.D., Smiley J.R., Bushman F.D. PLoS Pathog. 4:E1000007-E1000007(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN TRIM22.
+	Additional computationally mapped references.

Web resources

BioAfrica HIV proteomics resource

Gag entry

BioAfrica HIV proteomics resource

MA (p17) entry

BioAfrica HIV proteomics resource

CA (p24) entry

BioAfrica HIV proteomics resource

p2 entry

BioAfrica HIV proteomics resource

NC (p7) entry

BioAfrica HIV proteomics resource

p1 entry

BioAfrica HIV proteomics resource

p6 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

K03455 Genomic RNA. Translation: AAB50258.1.

RefSeq

NP_057850.1. NC_001802.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TSQ	X-ray	2.00	P	429-437	[»]
1TSU	X-ray	2.10	P	429-436	[»]

ProteinModelPortal

P04591.

SMR

P04591. Positions 1-432, 449-500.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04591. 39 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Family and domain databases

Gene3D

1.10.1200.30. 1 hit.
1.10.150.90. 1 hit.
1.10.375.10. 1 hit.
4.10.60.10. 1 hit.

InterPro

IPR000721. Gag_p24.
IPR014817. Gag_p6.
IPR000071. Lentvrl_matrix_N.
IPR012344. Matrix_N_HIV/RSV.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix_N.
IPR001878. Znf_CCHC.
[Graphical view]

Pfam

PF00540. Gag_p17. 1 hit.
PF00607. Gag_p24. 1 hit.
PF08705. Gag_p6. 1 hit.
PF00098. zf-CCHC. 2 hits.
[Graphical view]

PRINTS

PR00234. HIV1MATRIX.

SMART

SM00343. ZnF_C2HC. 2 hits.
[Graphical view]

SUPFAM

SSF47353. Retrov_capsid_C. 1 hit.
SSF47943. Retrov_capsid_N. 1 hit.
SSF47836. Retrovir_matrix. 1 hit.
SSF57756. SSF57756. 1 hit.

PROSITE

PS50158. ZF_CCHC. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P04591.

Entry information

Entry name

GAG_HV1H2

Accession

Primary (citable) accession number: P04591

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 130 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program