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   10-JUN-2026, entry version 151.
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;
OC   Deltaretrovirus priTlym1; Primate T-lymphotropic virus 1.
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   PDB; 8PUG; EM; 5.90 A; A/B/C=1-429.
DR   PDB; 8PUH; EM; 6.20 A; A/B=1-429.
DR   BMRB; P03345; -.
DR   EMDB; EMD-17942; -.
DR   EMDB; EMD-17943; -.
DR   SMR; P03345; -.
DR   ELM; P03345; -.
DR   iPTMnet; P03345; -.
DR   EvolutionaryTrace; P03345; -.
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:UniProtKB-KW.
DR   GO; GO:0075523; P:viral translational frameshifting; IEA:UniProtKB-KW.
DR   FunFam; 1.10.185.10:FF:000001; Gag polyprotein; 1.
DR   Gene3D; 1.10.1200.30; -; 1.
DR   Gene3D; 1.10.185.10; Delta-retroviral matrix; 1.
DR   Gene3D; 1.10.375.10; Human Immunodeficiency Virus Type 1 Capsid Protein; 1.
DR   Gene3D; 4.10.60.10; Zinc finger, CCHC-type; 1.
DR   InterPro; IPR003139; D_retro_matrix.
DR   InterPro; IPR045345; Gag_p24_C.
DR   InterPro; IPR050195; Primate_lentivir_Gag_pol-like.
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   PANTHER; PTHR40389; ENDOGENOUS RETROVIRUS GROUP K MEMBER 24 GAG POLYPROTEIN-RELATED; 1.
DR   PANTHER; PTHR40389:SF3; IGE-BINDING PROTEIN; 1.
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; Retroviral matrix proteins; 1.
DR   SUPFAM; SSF47353; Retrovirus capsid dimerization domain-like; 1.
DR   SUPFAM; SSF47943; Retrovirus capsid protein, N-terminal core domain; 1.
DR   SUPFAM; SSF57756; Retrovirus zinc finger-like domains; 1.
DR   PROSITE; PS50158; ZF_CCHC; 1.
DR   PDBsum; 1QRJ; -.
DR   PDBsum; 8PUG; -.
DR   PDBsum; 8PUH; -.
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; Repeat; Ribosomal frameshifting; Ubl conjugation;
KW   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   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..215
FT                   /evidence="ECO:0007829|PDB:1QRJ"
FT   TURN            216..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..300
FT                   /evidence="ECO:0007829|PDB:1QRJ"
FT   HELIX           301..305
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
//