P03345 (GAG_HTL1A) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gag polyprotein

Alternative name(s):
Pr53Gag

Cleaved into the following 3 chains:

1. Matrix protein p19
   Short name=MA
2. Capsid protein p24
   Short name=CA
3. Nucleocapsid protein p15-gag
   Short name=NC-gag

Gene names

Name:

gag

Organism

Human T-cell leukemia virus 1 (strain Japan ATK-1 subtype A) (HTLV-1) [Complete proteome]

Taxonomic identifier

11926 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Deltaretrovirus › Primate T-lymphotropic virus 1 › Human T-lymphotropic virus 1 › HTLV-1 subtype A

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	429 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 p19 targets Gag, Gag-Pro and Gag-Pro-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 By similarity. Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex By similarity. Nucleocapsid protein p15 is involved in the packaging and encapsidation of two copies of the genome By similarity.
Subunit structure	Interacts with human TSG101 and NEDD4. These interactions are essential for budding and release of viral particles. Ref.8
Subcellular location	Matrix protein p19: Virion Potential. Capsid protein p24: Virion Potential. Nucleocapsid protein p15-gag: Virion Potential.
Domain	Late-budding domains (L domains) are short sequence motifs essential for viral particle release. They can occur individually or in close proximity within structural proteins. They interacts with sorting cellular proteins of the multivesicular body (MVB) pathway. Most of these proteins are class E vacuolar protein sorting factors belonging to ESCRT-I, ESCRT-II or ESCRT-III complexes. Matrix protein p19 contains two L domains: a PTAP/PSAP motif which interacts with the UEV domain of TSG101, and a PPXY motif which binds to the WW domains of HECT (homologous to E6-AP C-terminus) E3 ubiquitin ligases, like NEDD4. Ref.8 The capsid protein N-terminus seems to be involved in Gag-Gag interactions. Ref.8
Post-translational modification	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. Ref.5 Phosphorylation of the matrix protein p19 by MAPK1 seems to play a role in budding.
Miscellaneous	HTLV-1 lineages are divided in four clades, A (Cosmopolitan), B (Central African group), C (Melanesian group) and D (New Central African group).
Sequence similarities	Contains 2 CCHC-type zinc fingers.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Virion
Coding sequence diversity	Ribosomal frameshifting
Domain	Repeat Zinc-finger
Ligand	Metal-binding Viral nucleoprotein Zinc
Molecular function	Capsid protein
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological_process	virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	viral nucleocapsid Inferred from electronic annotation. Source: InterPro
Molecular_function	nucleic acid 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 3 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 polyprotein (identifier: P03345-1)

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-Pro polyprotein (identifier: P10274-1)

The sequence of this isoform can be found in the external entry P10274.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by -1 ribosomal frameshifting at the gag-pro genes boundary.

Isoform Gag-Pro-Pol polyprotein (identifier: P03362-1)

The sequence of this isoform can be found in the external entry P03362.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by -1 ribosomal frameshifting at the gag-pro and gag-pol genes boundaries.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed; by host

Chain

2 – 429

428

Gag polyprotein

PRO_0000259771

Chain

2 – 130

129

Matrix protein p19

PRO_0000038811

Chain

131 – 344

214

Capsid protein p24

PRO_0000038812

Chain

345 – 429

85

Nucleocapsid protein p15-gag

PRO_0000038813

Regions

Zinc finger

355 – 372

18

CCHC-type 1

Zinc finger

378 – 395

18

CCHC-type 2

Motif

118 – 121

4

PPXY motif

Motif

124 – 127

4

PTAP/PSAP motif

Compositional bias

95 – 144

50

Pro-rich

Sites

Site

130 – 131

2

Cleavage; by viral protease

Site

344 – 345

2

Cleavage; by viral protease

Amino acid modifications

Modified residue

105

1

Phosphoserine; by host MAPK1 Ref.9

Lipidation

2

1

N-myristoyl glycine; by host Ref.6

Experimental info

Mutagenesis

105

1

S → A: 70% loss of viral particle release. Ref.9

Mutagenesis

118 – 120

3

PPP → AAA: Complete loss of interaction with human NEDD4. Ref.8

Mutagenesis

124 – 127

4

PTAP → ATAA: Complete loss of interaction with human TSG101. Ref.8

Sequence conflict

416

1

A → T AA sequence Ref.4

Sequence conflict

424

1

S → F in AAA96672. Ref.1

Secondary structure

1

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429

Helix Strand Turn

Details...

Helix

147 – 159

13

Beta strand

162 – 164

3

Helix

167 – 175

9

Turn

176 – 178

3

Helix

182 – 192

11

Helix

195 – 215

21

Turn

222 – 224

3

Helix

228 – 231

4

Helix

238 – 252

15

Beta strand

254 – 257

4

Helix

263 – 265

3

Helix

274 – 286

13

Helix

296 – 303

8

Turn

304 – 306

3

Helix

309 – 317

9

Beta strand

321 – 323

3

Helix

325 – 332

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gag polyprotein [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 03FFD4E5A4500284	FASTA	429	47,496
	10 20 30 40 50 60 MGQIFSRSAS PIPRPPRGLA AHHWLNFLQA AYRLEPGPSS YDFHQLKKFL KIALETPARI 70 80 90 100 110 120 CPINYSLLAS LLPKGYPGRV NEILHILIQT QAQIPSRPAP PPPSSPTHDP PDSDPQIPPP 130 140 150 160 170 180 YVEPTAPQVL PVMHPHGAPP NHRPWQMKDL QAIKQEVSQA APGSPQFMQT IRLAVQQFDP 190 200 210 220 230 240 TAKDLQDLLQ YLCSSLVASL HHQQLDSLIS EAETRGITGY NPLAGPLRVQ ANNPQQQGLR 250 260 270 280 290 300 REYQQLWLAA FAALPGSAKD PSWASILQGL EEPYHAFVER LNIALDNGLP EGTPKDPILR 310 320 330 340 350 360 SLAYSNANKE CQKLLQARGH TNSPLGDMLR ACQTWTPKDK TKVLVVQPKK PPPNQPCFRC 370 380 390 400 410 420 GKAGHWSRDC TQPRPPPGPC PLCQDPTHWK RDCPRLKPTI PEPEPEEDAL LLDLPADIPH PKNSIGGEV
	Isoform Gag-Pro polyprotein [UniParc]. See P10274.		–	–
	Isoform Gag-Pro-Pol polyprotein [UniParc]. See P03362.		–	–

References

[1]	"Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA." Seiki M., Hattori S., Hirayama Y., Yoshida M.C. Proc. Natl. Acad. Sci. U.S.A. 80:3618-3622(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Identification of a protease gene of human T-cell leukemia virus type I (HTLV-I) and its structural comparison." Nam S.H., Hatanaka M. Biochem. Biophys. Res. Commun. 139:129-135(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 395-429.
[3]	"Primary structure analysis of the major internal protein p24 of human type C T-cell leukemia virus." Oroszlan S., Sarngadharan M.G., Copeland T.D., Kalyanaraman V.S., Gilden R.V., Gallo R.C. Proc. Natl. Acad. Sci. U.S.A. 79:1291-1294(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 131-155.
[4]	"Complete amino acid sequence of human T-cell leukemia virus structural protein p15." Copeland T.D., Oroszlan S., Kalyanaraman V.S., Sarngadharan M.G., Gallo R.C. FEBS Lett. 162:390-395(1983) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 345-429.
[5]	"Processing of gag precursor polyprotein of human T-cell leukemia virus type I by virus-encoded protease." Nam S.H., Kidokoro M., Shida H., Hatanaka M. J. Virol. 62:3718-3728(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[6]	"Myristoylation-dependent membrane targeting and release of the HTLV-I Gag precursor, Pr53gag, in yeast." Hayakawa T., Miyazaki T., Misumi Y., Kobayashi M., Fujisawa Y. Gene 119:273-277(1992) [PubMed] [Europe PMC] [Abstract] Cited for: MYRISTOYLATION AT GLY-2.
[7]	"The NH2-terminal domain of the human T-cell leukemia virus type 1 capsid protein is involved in particle formation." Rayne F., Bouamr F., Lalanne J., Mamoun R.Z. J. Virol. 75:5277-5287(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF CAPSID PROTEIN P24.
[8]	"PPPYVEPTAP motif is the late domain of human T-cell leukemia virus type 1 Gag and mediates its functional interaction with cellular proteins Nedd4 and Tsg101." Bouamr F., Melillo J.A., Wang M.Q., Nagashima K., de Los Santos M., Rein A., Goff S.P. J. Virol. 77:11882-11895(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN LATE-BUDDING, INTERACTION WITH HUMAN NEDD4 AND TSG101, MUTAGENESIS OF 118-PRO--PRO-120 AND 124-PRO--PRO-127.
[9]	"Phosphorylation of the HTLV-1 matrix L-domain-containing protein by virus-associated ERK-2 kinase." Hemonnot B., Molle D., Bardy M., Gay B., Laune D., Devaux C., Briant L. Virology 349:430-439(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-105 BY MAPK1, MUTAGENESIS OF SER-105.
[10]	"Sequence-specific 1H, 13C and 15N chemical shift assignment and secondary structure of the HTLV-I capsid protein." Khorasanizadeh S., Campos-Olivas R., Clark C.A., Summers M.F. J. Biomol. NMR 14:199-200(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 146-344.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02029 Genomic DNA. Translation: AAA96672.1.
M13810 Genomic RNA. Translation: AAA46205.1.

PIR

FOLJGH. B93954.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QRJ	NMR	-	A	146-344	[»]

ProteinModelPortal

P03345.

SMR

P03345. Positions 1-130, 146-344.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

1.10.1200.30. 1 hit.
1.10.185.10. 1 hit.
1.10.375.10. 1 hit.
4.10.60.10. 1 hit.

InterPro

IPR003139. D_retro_matrix_N.
IPR000721. Gag_p24.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix_N.
IPR001878. Znf_CCHC.
[Graphical view]

Pfam

PF02228. Gag_p19. 1 hit.
PF00607. Gag_p24. 1 hit.
PF00098. zf-CCHC. 1 hit.
[Graphical view]

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. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P03345.

EvolutionaryTrace

P03345.

Entry information

Entry name

GAG_HTL1A

Accession

Primary (citable) accession number: P03345
Secondary accession number(s): Q85589

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 105 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program