P12495 (GAG_HV1Z2) 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 D (isolate Z2/CDC-Z34) (HIV-1)

Taxonomic identifier

11683 [NCBI]

Taxonomic lineage

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

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	501 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. 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.
Subcellular location	Matrix protein p17: Virion Potential. 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. Capsid protein p24: Virion Potential. Nucleocapsid protein p7: Virion Potential.
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
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...

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: P12495-1)

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: P12499-1)

The sequence of this isoform can be found in the external entry P12499.
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 – 501

500

Gag polyprotein

PRO_0000261239

Chain

2 – 133

132

Matrix protein p17 By similarity

PRO_0000038499

Chain

134 – 364

231

Capsid protein p24 By similarity

PRO_0000038500

Peptide

365 – 379

15

Spacer peptide p2 By similarity

PRO_0000038501

Chain

380 – 434

55

Nucleocapsid protein p7 By similarity

PRO_0000038502

Peptide

435 – 450

16

Spacer peptide p1 By similarity

PRO_0000038503

Chain

451 – 501

51

p6-gag By similarity

PRO_0000038504

Regions

Zinc finger

392 – 409

18

CCHC-type 1

Zinc finger

413 – 430

18

CCHC-type 2

Motif

16 – 22

7

Nuclear export signal By similarity

Motif

26 – 32

7

Nuclear localization signal By similarity

Motif

457 – 460

4

PTAP/PSAP motif

Motif

484 – 493

10

LYPX(n)L motif

Sites

Site

133 – 134

2

Cleavage; by viral protease By similarity

Site

364 – 365

2

Cleavage; by viral protease By similarity

Site

379 – 380

2

Cleavage; by viral protease By similarity

Site

434 – 435

2

Cleavage; by viral protease By similarity

Site

450 – 451

2

Cleavage; by viral protease By similarity

Amino acid modifications

Modified residue

389

1

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

Modified residue

411

1

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

Lipidation

2

1

N-myristoyl glycine; by host By similarity

Secondary structure

1

.

.

.

501

Helix Strand Turn

Details...

Turn

178 – 180

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gag polyprotein [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 827C2609BC3E5963	FASTA	501	55,678
	10 20 30 40 50 60 MGARASVLSG GKLDAWEKIR LRPGGKKKYR LKHLVWASRE LERFALNPGL LETSDGCKQI 70 80 90 100 110 120 IGQLQPAIRT GSEELRSLFN TVATLYCVHE RIEVKDTKEA LEKMEEEQNK SKNKKAQQAA 130 140 150 160 170 180 ADAGNNSQVS QNYPIVQNLQ GQMVHQAISP RTLNAWVKVI EEKAFSPEVI PMFSALSEGA 190 200 210 220 230 240 TPQDLNTMLN TVGGHQAAMQ MLKETINEEA AEWDRLHPVH AGPIAPGQMR EPRGSDIAGT 250 260 270 280 290 300 TSTLQEQIAW MTSNPPIPVG EIYKRWIILG LNKIVRMYSP VSILDIRQGP KEPFRDYVDR 310 320 330 340 350 360 FYKTLRAEQA SQEVKGWMTE TLLVQNANPD CKTILKALGP QATLEEMMTA CQGVGGPSHK 370 380 390 400 410 420 ARVLAEAMSQ ATNSAAAVMM QRGNFKGPRK TIKCFNCGKE GHIAKNCRAP RRKGCWKCGK 430 440 450 460 470 480 EGHQLKDCTE RQANFLGKIW PSHKGRPGNF LQSRPEPTAP PAESFGFGEE ITPSQKQEQK 490 500 DKELYPSTAL KSLFGNDPLL Q
	Isoform Gag-Pol polyprotein [UniParc]. See P12499.		–	–

References

[1]	Theodore T., Buckler-White A.J. Submitted (JUL-1989) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M22639 Genomic RNA. Translation: AAA45365.1.

PIR

S54377.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SJE	X-ray	2.45	C	167-182	[»]
1SJH	X-ray	2.25	C	167-179	[»]
3D3T	X-ray	2.80	P	446-455	[»]

ProteinModelPortal

P12495.

SMR

P12495. Positions 2-434, 451-501.

ModBase

Search...

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

P12495.

Entry information

Entry name

GAG_HV1Z2

Accession

Primary (citable) accession number: P12495

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 126 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program