GAG_HTL1A
ID GAG_HTL1A Reviewed; 429 AA.
AC P03345; Q85589;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 23-FEB-2022, entry version 138.
DE RecName: Full=Gag polyprotein;
DE AltName: Full=Pr53Gag;
DE Contains:
DE RecName: Full=Matrix protein p19;
DE Short=MA;
DE Contains:
DE RecName: Full=Capsid protein p24;
DE Short=CA;
DE Contains:
DE RecName: Full=Nucleocapsid protein p15-gag;
DE Short=NC-gag;
GN Name=gag;
OS Human T-cell leukemia virus 1 (strain Japan ATK-1 subtype A) (HTLV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus.
OX NCBI_TaxID=11926;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6304725; DOI=10.1073/pnas.80.12.3618;
RA Seiki M., Hattori S., Hirayama Y., Yoshida M.C.;
RT "Human adult T-cell leukemia virus: complete nucleotide sequence of the
RT provirus genome integrated in leukemia cell DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:3618-3622(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 395-429.
RX PubMed=3021121; DOI=10.1016/s0006-291x(86)80089-4;
RA Nam S.H., Hatanaka M.;
RT "Identification of a protease gene of human T-cell leukemia virus type I
RT (HTLV-I) and its structural comparison.";
RL Biochem. Biophys. Res. Commun. 139:129-135(1986).
RN [3]
RP PROTEIN SEQUENCE OF 131-155, AND PROTEOLYTIC CLEAVAGE (GAG POLYPROTEIN).
RX PubMed=6280175; DOI=10.1073/pnas.79.4.1291;
RA Oroszlan S., Sarngadharan M.G., Copeland T.D., Kalyanaraman V.S.,
RA Gilden R.V., Gallo R.C.;
RT "Primary structure analysis of the major internal protein p24 of human type
RT C T-cell leukemia virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:1291-1294(1982).
RN [4]
RP PROTEIN SEQUENCE OF 345-429.
RX PubMed=6313426; DOI=10.1016/0014-5793(83)80793-5;
RA Copeland T.D., Oroszlan S., Kalyanaraman V.S., Sarngadharan M.G.,
RA Gallo R.C.;
RT "Complete amino acid sequence of human T-cell leukemia virus structural
RT protein p15.";
RL FEBS Lett. 162:390-395(1983).
RN [5]
RP PROTEOLYTIC CLEAVAGE (GAG POLYPROTEIN).
RX PubMed=2843670; DOI=10.1128/jvi.62.10.3718-3728.1988;
RA Nam S.H., Kidokoro M., Shida H., Hatanaka M.;
RT "Processing of gag precursor polyprotein of human T-cell leukemia virus
RT type I by virus-encoded protease.";
RL J. Virol. 62:3718-3728(1988).
RN [6]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=1398108; DOI=10.1016/0378-1119(92)90282-t;
RA Hayakawa T., Miyazaki T., Misumi Y., Kobayashi M., Fujisawa Y.;
RT "Myristoylation-dependent membrane targeting and release of the HTLV-I Gag
RT precursor, Pr53gag, in yeast.";
RL Gene 119:273-277(1992).
RN [7]
RP RIBOSOMAL FRAMESHIFT.
RX PubMed=8416368; DOI=10.1128/jvi.67.1.196-203.1993;
RA Nam S.H., Copeland T.D., Hatanaka M., Oroszlan S.;
RT "Characterization of ribosomal frameshifting for expression of pol gene
RT products of human T-cell leukemia virus type I.";
RL J. Virol. 67:196-203(1993).
RN [8]
RP DOMAIN (CAPSID PROTEIN P24), MUTAGENESIS OF GLY-2, AND MYRISTOYLATION AT
RP GLY-2.
RX PubMed=11333909; DOI=10.1128/jvi.75.11.5277-5287.2001;
RA Rayne F., Bouamr F., Lalanne J., Mamoun R.Z.;
RT "The NH2-terminal domain of the human T-cell leukemia virus type 1 capsid
RT protein is involved in particle formation.";
RL J. Virol. 75:5277-5287(2001).
RN [9]
RP DOMAIN LATE-BUDDING (GAG POLYPROTEIN), INTERACTION WITH HOST TSG101 (GAG
RP POLYPROTEIN), INTERACTION WITH HOST NEDD4 (GAG POLYPROTEIN), AND
RP MUTAGENESIS OF 118-PRO--PRO-120 AND 124-PRO--PRO-127.
RX PubMed=14581525; DOI=10.1128/jvi.77.22.11882-11895.2003;
RA Bouamr F., Melillo J.A., Wang M.Q., Nagashima K., de Los Santos M.,
RA Rein A., Goff S.P.;
RT "PPPYVEPTAP motif is the late domain of human T-cell leukemia virus type 1
RT Gag and mediates its functional interaction with cellular proteins Nedd4
RT and Tsg101.";
RL J. Virol. 77:11882-11895(2003).
RN [10]
RP DOMAIN LATE-BUDDING (GAG POLYPROTEIN), INTERACTION WITH HOST NEDD4 (GAG
RP POLYPROTEIN), AND INTERACTION WITH HOST TSG101 (GAG POLYPROTEIN).
RX PubMed=15126635; DOI=10.1242/jcs.01095;
RA Blot V., Perugi F., Gay B., Prevost M.C., Briant L., Tangy F., Abriel H.,
RA Staub O., Dokhelar M.C., Pique C.;
RT "Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101
RT ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior
RT to virus budding.";
RL J. Cell Sci. 117:2357-2367(2004).
RN [11]
RP DISULFIDE BOND, SUBUNIT (GAG POLYPROTEIN), SUBUNIT (MATRIX PROTEIN P19),
RP MUTAGENESIS OF CYS-61, SUBCELLULAR LOCATION (MATRIX PROTEIN P19), FUNCTION
RP (GAG POLYPROTEIN), AND FUNCTION (MATRIX PROTEIN P19).
RX PubMed=15476809; DOI=10.1016/j.jmb.2004.09.013;
RA Rayne F., Kajava A.V., Lalanne J., Mamoun R.Z.;
RT "In vivo homodimerisation of HTLV-1 Gag and MA gives clues to the
RT retroviral capsid and TM envelope protein arrangement.";
RL J. Mol. Biol. 343:903-916(2004).
RN [12]
RP PHOSPHORYLATION AT SER-105 BY MAPK1, AND MUTAGENESIS OF SER-105.
RX PubMed=16635502; DOI=10.1016/j.virol.2006.02.043;
RA Hemonnot B., Molle D., Bardy M., Gay B., Laune D., Devaux C., Briant L.;
RT "Phosphorylation of the HTLV-1 matrix L-domain-containing protein by virus-
RT associated ERK-2 kinase.";
RL Virology 349:430-439(2006).
RN [13]
RP FUNCTION (NUCLEOCAPSID PROTEIN P15-GAG), AND DOMAIN (NUCLEOCAPSID PROTEIN
RP P15-GAG).
RX PubMed=25686502; DOI=10.1016/j.bbrc.2015.02.025;
RA Qualley D.F., Sokolove V.L., Ross J.L.;
RT "Bovine leukemia virus nucleocapsid protein is an efficient nucleic acid
RT chaperone.";
RL Biochem. Biophys. Res. Commun. 458:687-692(2015).
RN [14]
RP STRUCTURE BY NMR OF 146-344.
RX PubMed=10427751; DOI=10.1023/a:1008307507462;
RA Khorasanizadeh S., Campos-Olivas R., Clark C.A., Summers M.F.;
RT "Sequence-specific 1H, 13C and 15N chemical shift assignment and secondary
RT structure of the HTLV-I capsid protein.";
RL J. Biomol. NMR 14:199-200(1999).
CC -!- FUNCTION: [Gag polyprotein]: The matrix domain targets Gag, Gag-Pro and
CC Gag-Pro-Pol polyproteins to the plasma membrane via a multipartite
CC membrane binding signal, that includes its myristoylated N-terminus.
CC {ECO:0000269|PubMed:15476809}.
CC -!- FUNCTION: [Matrix protein p19]: Matrix protein.
CC {ECO:0000269|PubMed:15476809}.
CC -!- FUNCTION: [Capsid protein p24]: Forms the spherical core of the virus
CC that encapsulates the genomic RNA-nucleocapsid complex. {ECO:0000305}.
CC -!- FUNCTION: [Nucleocapsid protein p15-gag]: Binds strongly to viral
CC nucleic acids and promote their aggregation. Also destabilizes the
CC nucleic acids duplexes via highly structured zinc-binding motifs.
CC {ECO:0000269|PubMed:25686502}.
CC -!- SUBUNIT: [Gag polyprotein]: Homodimer; the homodimers are part of the
CC immature particles (PubMed:15476809). Interacts with human TSG101 and
CC NEDD4; these interactions are essential for budding and release of
CC viral particles (PubMed:14581525, PubMed:15126635).
CC {ECO:0000269|PubMed:14581525, ECO:0000269|PubMed:15476809}.
CC -!- SUBUNIT: [Matrix protein p19]: Homodimer; further assembles as
CC homohexamers (PubMed:15476809). {ECO:0000269|PubMed:15476809}.
CC -!- SUBCELLULAR LOCATION: [Matrix protein p19]: Virion
CC {ECO:0000269|PubMed:15476809}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Nucleocapsid protein p15-gag]: Virion
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=3;
CC Comment=This strategy of translation probably allows the virus to
CC modulate the quantity of each viral protein. {ECO:0000305};
CC Name=Gag polyprotein;
CC IsoId=P03345-1; Sequence=Displayed;
CC Name=Gag-Pro polyprotein;
CC IsoId=P10274-1; Sequence=External;
CC Name=Gag-Pro-Pol polyprotein;
CC IsoId=P03362-1; Sequence=External;
CC -!- DOMAIN: [Gag polyprotein]: Late-budding domains (L domains) are short
CC sequence motifs essential for viral particle release. They can occur
CC individually or in close proximity within structural proteins. They
CC interacts with sorting cellular proteins of the multivesicular body
CC (MVB) pathway. Most of these proteins are class E vacuolar protein
CC sorting factors belonging to ESCRT-I, ESCRT-II or ESCRT-III complexes.
CC Matrix protein p19 contains two L domains: a PTAP/PSAP motif which
CC interacts with the UEV domain of TSG101, and a PPXY motif which binds
CC to the WW domains of the ubiquitin ligase NEDD4.
CC {ECO:0000269|PubMed:14581525, ECO:0000269|PubMed:15126635}.
CC -!- DOMAIN: [Capsid protein p24]: The capsid protein N-terminus seems to be
CC involved in Gag-Gag interactions. {ECO:0000269|PubMed:11333909}.
CC -!- DOMAIN: [Nucleocapsid protein p15-gag]: The C-terminus is acidic.
CC {ECO:0000269|PubMed:25686502}.
CC -!- PTM: [Gag polyprotein]: Specific enzymatic cleavages by the viral
CC protease yield mature proteins. The polyprotein is cleaved during and
CC after budding, this process is termed maturation.
CC {ECO:0000269|PubMed:2843670, ECO:0000269|PubMed:6280175}.
CC -!- PTM: [Matrix protein p19]: Phosphorylation of the matrix protein p19 by
CC MAPK1 seems to play a role in budding. {ECO:0000269|PubMed:16635502}.
CC -!- PTM: [Gag polyprotein]: Ubiquitinated by host NEDD4.
CC {ECO:0000269|PubMed:15126635}.
CC -!- PTM: [Gag polyprotein]: Myristoylated. Myristoylation of the matrix
CC (MA) domain mediates the transport and binding of Gag polyproteins to
CC the host plasma membrane and is required for the assembly of viral
CC particles. {ECO:0000269|PubMed:11333909, ECO:0000269|PubMed:1398108}.
CC -!- MISCELLANEOUS: HTLV-1 lineages are divided in four clades, A
CC (Cosmopolitan), B (Central African group), C (Melanesian group) and D
CC (New Central African group). {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform Gag polyprotein]: Produced by conventional
CC translation. {ECO:0000269|PubMed:8416368}.
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DR EMBL; J02029; AAA96672.1; -; Genomic_DNA.
DR EMBL; M13810; AAA46205.1; -; Genomic_RNA.
DR PIR; B93954; FOLJGH.
DR PDB; 1QRJ; NMR; -; A=146-344.
DR PDBsum; 1QRJ; -.
DR BMRB; P03345; -.
DR SMR; P03345; -.
DR ELM; P03345; -.
DR iPTMnet; P03345; -.
DR EvolutionaryTrace; P03345; -.
DR Proteomes; UP000007683; Genome.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0016032; P:viral process; IEA:InterPro.
DR Gene3D; 1.10.1200.30; -; 1.
DR Gene3D; 1.10.375.10; -; 1.
DR InterPro; IPR003139; D_retro_matrix.
DR InterPro; IPR045345; Gag_p24_C.
DR InterPro; IPR000721; Gag_p24_N.
DR InterPro; IPR008916; Retrov_capsid_C.
DR InterPro; IPR008919; Retrov_capsid_N.
DR InterPro; IPR010999; Retrovr_matrix.
DR InterPro; IPR001878; Znf_CCHC.
DR InterPro; IPR036875; Znf_CCHC_sf.
DR Pfam; PF02228; Gag_p19; 1.
DR Pfam; PF00607; Gag_p24; 1.
DR Pfam; PF19317; Gag_p24_C; 1.
DR Pfam; PF00098; zf-CCHC; 1.
DR SMART; SM00343; ZnF_C2HC; 2.
DR SUPFAM; SSF47836; SSF47836; 1.
DR SUPFAM; SSF47943; SSF47943; 1.
DR SUPFAM; SSF57756; SSF57756; 1.
DR PROSITE; PS50158; ZF_CCHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Capsid protein; Direct protein sequencing; Disulfide bond;
KW Host-virus interaction; Lipoprotein; Metal-binding; Myristate;
KW Phosphoprotein; Reference proteome; Repeat; Ribosomal frameshifting;
KW Ubl conjugation; Viral nucleoprotein; Virion; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000255"
FT CHAIN 2..429
FT /note="Gag polyprotein"
FT /id="PRO_0000259771"
FT CHAIN 2..130
FT /note="Matrix protein p19"
FT /id="PRO_0000038811"
FT CHAIN 131..344
FT /note="Capsid protein p24"
FT /id="PRO_0000038812"
FT CHAIN 345..429
FT /note="Nucleocapsid protein p15-gag"
FT /id="PRO_0000038813"
FT ZN_FING 355..372
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 378..395
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 93..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 118..121
FT /note="PPXY motif"
FT /evidence="ECO:0000269|PubMed:15126635"
FT MOTIF 124..127
FT /note="PTAP/PSAP motif"
FT /evidence="ECO:0000269|PubMed:15126635"
FT COMPBIAS 95..126
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 130..131
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000305|PubMed:6280175"
FT SITE 344..345
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000305|PubMed:6280175"
FT MOD_RES 105
FT /note="Phosphoserine; by host MAPK1"
FT /evidence="ECO:0000269|PubMed:16635502"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:11333909,
FT ECO:0000269|PubMed:1398108"
FT DISULFID 61
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:15476809"
FT MUTAGEN 2
FT /note="G->A: Complete loss of myristoylation the
FT polyprotein. The concomitent loss of binding to the host
FT cell membrane impairs the formation of viral particles."
FT /evidence="ECO:0000269|PubMed:11333909"
FT MUTAGEN 61
FT /note="C->S: Complete loss of homodimerization of matrix
FT protein p19."
FT /evidence="ECO:0000269|PubMed:15476809"
FT MUTAGEN 105
FT /note="S->A: 70% loss of viral particle release."
FT /evidence="ECO:0000269|PubMed:16635502"
FT MUTAGEN 118..120
FT /note="PPP->AAA: Complete loss of interaction with human
FT NEDD4."
FT /evidence="ECO:0000269|PubMed:14581525"
FT MUTAGEN 124..127
FT /note="PTAP->ATAA: Complete loss of interaction with human
FT TSG101."
FT /evidence="ECO:0000269|PubMed:14581525"
FT CONFLICT 416
FT /note="A -> T (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 424
FT /note="S -> F (in Ref. 1; AAA96672)"
FT /evidence="ECO:0000305"
FT HELIX 147..159
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 167..177
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 182..189
FT /evidence="ECO:0007829|PDB:1QRJ"
FT TURN 190..192
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 195..214
FT /evidence="ECO:0007829|PDB:1QRJ"
FT TURN 215..219
FT /evidence="ECO:0007829|PDB:1QRJ"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 228..231
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 238..251
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 274..286
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 296..303
FT /evidence="ECO:0007829|PDB:1QRJ"
FT TURN 304..306
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 309..318
FT /evidence="ECO:0007829|PDB:1QRJ"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:1QRJ"
FT HELIX 325..332
FT /evidence="ECO:0007829|PDB:1QRJ"
SQ SEQUENCE 429 AA; 47496 MW; 03FFD4E5A4500284 CRC64;
MGQIFSRSAS PIPRPPRGLA AHHWLNFLQA AYRLEPGPSS YDFHQLKKFL KIALETPARI
CPINYSLLAS LLPKGYPGRV NEILHILIQT QAQIPSRPAP PPPSSPTHDP PDSDPQIPPP
YVEPTAPQVL PVMHPHGAPP NHRPWQMKDL QAIKQEVSQA APGSPQFMQT IRLAVQQFDP
TAKDLQDLLQ YLCSSLVASL HHQQLDSLIS EAETRGITGY NPLAGPLRVQ ANNPQQQGLR
REYQQLWLAA FAALPGSAKD PSWASILQGL EEPYHAFVER LNIALDNGLP EGTPKDPILR
SLAYSNANKE CQKLLQARGH TNSPLGDMLR ACQTWTPKDK TKVLVVQPKK PPPNQPCFRC
GKAGHWSRDC TQPRPPPGPC PLCQDPTHWK RDCPRLKPTI PEPEPEEDAL LLDLPADIPH
PKNSIGGEV
