P03347 (GAG_HV1B1) 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 BH10) (HIV-1) [Complete proteome]

Taxonomic identifier

11678 [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	512 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 By similarity. p6-gag interacts with host PDCD6IP/AIP1. Pr55Gag interacts with PDZD8 By similarity. Ref.5 Ref.7
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. Ref.7
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	Complete 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
PDCD6IP	Q8WUM4	2	EBI-1220741,EBI-310624	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: P03347-1)

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: P03366-1)

The sequence of this isoform can be found in the external entry P03366.
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 – 512	511	Gag polyprotein		PRO_0000261209
	Chain	2 – 132	131	Matrix protein p17 By similarity		PRO_0000038475
	Chain	133 – 363	231	Capsid protein p24 By similarity		PRO_0000038476
	Peptide	364 – 377	14	Spacer peptide p2 By similarity		PRO_0000038477
	Chain	378 – 432	55	Nucleocapsid protein p7 By similarity		PRO_0000038478
	Peptide	433 – 448	16	Spacer peptide p1 By similarity		PRO_0000038479
	Chain	449 – 512	64	p6-gag By similarity		PRO_0000038480
Regions
	Zinc finger	390 – 407	18	CCHC-type 1
	Zinc finger	411 – 428	18	CCHC-type 2
	Motif	16 – 22	7	Nuclear export signal By similarity
	Motif	26 – 32	7	Nuclear localization signal By similarity
	Motif	455 – 458	4	PTAP/PSAP motif 1
	Motif	467 – 470	4	PTAP/PSAP motif 2
	Motif	495 – 504	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 Ref.7
	Modified residue	409	1	Asymmetric dimethylarginine; in Nucleocapsid protein p7; by host PRMT6 Ref.7
	Lipidation	2	1	N-myristoyl glycine; by host By similarity
Natural variations
	Natural variant	297	1	V → L in strain: Isolate PV22.

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gag polyprotein [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 535DA188EE80D444	FASTA	512	57,256
	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 DTGHSSQVSQ 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 TNTATIMMQR GNFRNQRKMV KCFNCGKEGH TARNCRAPRK KGCWKCGKEG 430 440 450 460 470 480 HQMKDCTERQ ANFLGKIWPS YKGRPGNFLQ SRPEPTAPPF LQSRPEPTAP PEESFRSGVE 490 500 510 TTTPPQKQEP IDKELYPLTS LRSLFGNDPS SQ
	Isoform Gag-Pol polyprotein [UniParc]. See P03366.		–	–

References

[1]	"Complete nucleotide sequence of the AIDS virus, HTLV-III." Ratner L., Haseltine W.A., Patarca R., Livak K.J., Starcich B.R., Josephs S.F., Doran E.R., Rafalski J.A., Whitehorn E.A., Baumeister K., Ivanoff L., Petteway S.R. Jr., Pearson M.L., Lautenberger J.A., Papas T.S., Ghrayeb J., Chang N.T., Gallo R.C., Wong-Staal F. Nature 313:277-284(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus." Muesing M.A., Smith D.H., Cabradilla C.D., Benton C.V., Lasky L.A., Capon D.J. Nature 313:450-458(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Isolate PV22.
[3]	Muesing M.A. Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"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.
[5]	"AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding." Strack B., Calistri A., Craig S., Popova E., Goettlinger H.G. Cell 114:689-699(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION OF P6-GAG WITH HUMAN PDCD6IP/AIP1.
[6]	"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.
[7]	"Arginine methylation of the HIV-1 nucleocapsid protein results in its diminished function." Invernizzi C.F., Xie B., Frankel F.A., Feldhammer M., Roy B.B., Richard S., Wainberg M.A. AIDS 21:795-805(2007) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT ARG-387 AND ARG-409 BY HUMAN PRMT6, INTERACTION WITH HUMAN PRMT6.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M15654 Genomic RNA. Translation: AAA44201.1. K02083 Genomic DNA. Translation: AAB59866.1. X01762 Genomic RNA. Translation: CAA25902.1. Sequence problems.
PIR	FOVWH3. A03945. FOVWVL. A03948.
3D structure databases
ProteinModelPortal	P03347.
SMR	P03347. Positions 1-432, 461-512.
ModBase	Search...
Protein-protein interaction databases
IntAct	P03347. 1 interaction.
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...

Entry information

Entry name

GAG_HV1B1

Accession

Primary (citable) accession number: P03347
Secondary accession number(s): P03350

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program