PRO_HTLV2
ID PRO_HTLV2 Reviewed; 602 AA.
AC P03353;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Gag-Pro polyprotein;
DE AltName: Full=Pr76Gag-Pro;
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-pro;
DE Short=NC';
DE Short=NC-pro;
DE Contains:
DE RecName: Full=Protease;
DE Short=PR;
DE EC=3.4.23.- {ECO:0000255|PROSITE-ProRule:PRU00275};
DE Contains:
DE RecName: Full=p1;
DE Contains:
DE RecName: Full=Transframe peptide;
DE Short=TFP;
DE AltName: Full=p8;
GN Name=gag-pro;
OS Human T-cell leukemia virus 2 (HTLV-2).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus.
OX NCBI_TaxID=11909;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2582407; DOI=10.1073/pnas.82.10.3101;
RA Shimotohno K., Takahashi Y., Shimizu N., Gojobori T., Golde D.W.,
RA Chen I.S.Y., Miwa M., Sugimura T.;
RT "Complete nucleotide sequence of an infectious clone of human T-cell
RT leukemia virus type II: an open reading frame for the protease gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:3101-3105(1985).
RN [2]
RP RIBOSOMAL FRAMESHIFT.
RX PubMed=2467996; DOI=10.1128/jvi.63.5.2400-2404.1989;
RA Mador N., Panet A., Honigman A.;
RT "Translation of gag, pro, and pol gene products of human T-cell leukemia
RT virus type 2.";
RL J. Virol. 63:2400-2404(1989).
RN [3]
RP RIBOSOMAL FRAMESHIFT.
RX PubMed=8371359; DOI=10.1128/jvi.67.10.6273-6277.1993;
RA Falk H., Mador N., Udi R., Panet A., Honigman A.;
RT "Two cis-acting signals control ribosomal frameshift between human T-cell
RT leukemia virus type II gag and pro genes.";
RL J. Virol. 67:6273-6277(1993).
RN [4]
RP RIBOSOMAL FRAMESHIFT.
RX PubMed=11222762; DOI=10.1093/nar/29.5.1125;
RA Kim Y.-G., Maas S., Rich A.;
RT "Comparative mutational analysis of cis-acting RNA signals for
RT translational frameshifting in HIV-1 and HTLV-2.";
RL Nucleic Acids Res. 29:1125-1131(2001).
RN [5]
RP STRUCTURE BY NMR OF 1-136.
RX PubMed=9000634; DOI=10.1006/jmbi.1996.0700;
RA Christensen A.M., Massiah M.A., Turner B.G., Sundquist W.I., Summers M.F.;
RT "Three-dimensional structure of the HTLV-II matrix protein and comparative
RT analysis of matrix proteins from the different classes of pathogenic human
RT retroviruses.";
RL J. Mol. Biol. 264:1117-1131(1996).
CC -!- FUNCTION: [Gag-Pro polyprotein]: The matrix domain targets Gag, Gag-Pro
CC and Gag-Pro-Pol polyproteins to the plasma membrane via a multipartite
CC membrane binding signal, that includes its myristoylated N-terminus.
CC {ECO:0000250|UniProtKB:P03345}.
CC -!- FUNCTION: [Matrix protein p19]: Matrix protein.
CC {ECO:0000250|UniProtKB:P03345}.
CC -!- FUNCTION: [Capsid protein p24]: Forms the spherical core of the virus
CC that encapsulates the genomic RNA-nucleocapsid complex.
CC {ECO:0000250|UniProtKB:P10274}.
CC -!- FUNCTION: [Nucleocapsid protein p15-pro]: 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:0000250|UniProtKB:P10274}.
CC -!- FUNCTION: [Protease]: The aspartyl protease mediates proteolytic
CC cleavages of Gag and Gag-Pol polyproteins during or shortly after the
CC release of the virion from the plasma membrane. Cleavages take place as
CC an ordered, step-wise cascade to yield mature proteins. This process is
CC called maturation. Displays maximal activity during the budding process
CC just prior to particle release from the cell (Potential). Cleaves the
CC translation initiation factor eIF4G leading to the inhibition of host
CC cap-dependent translation (By similarity).
CC {ECO:0000250|UniProtKB:P10274, ECO:0000255|PROSITE-ProRule:PRU00275}.
CC -!- SUBUNIT: [Gag-Pro polyprotein]: Homodimer; the homodimers are part of
CC the immature particles. Interacts with human TSG101 and NEDD4; these
CC interactions are essential for budding and release of viral particles.
CC {ECO:0000250|UniProtKB:P03345}.
CC -!- SUBUNIT: [Matrix protein p19]: Homodimer; further assembles as
CC homohexamers. {ECO:0000250|UniProtKB:P03345}.
CC -!- SUBCELLULAR LOCATION: [Matrix protein p19]: Virion
CC {ECO:0000250|UniProtKB:P03345}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein p24]: Virion
CC {ECO:0000250|UniProtKB:P03345}.
CC -!- SUBCELLULAR LOCATION: [Nucleocapsid protein p15-pro]: Virion
CC {ECO:0000250|UniProtKB:P03345}.
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-Pro polyprotein;
CC IsoId=P03353-1; Sequence=Displayed;
CC Name=Gag polyprotein;
CC IsoId=P03346-1; Sequence=External;
CC Name=Gag-Pro-Pol polyprotein;
CC IsoId=P03363-1; Sequence=External;
CC -!- DOMAIN: [Capsid protein p24]: The capsid protein N-terminus seems to be
CC involved in Gag-Gag interactions. {ECO:0000250|UniProtKB:P10274}.
CC -!- DOMAIN: [Gag-Pro polyprotein]: Late-budding domains (L domains) are
CC short sequence motifs essential for viral particle release. They can
CC occur individually or in close proximity within structural proteins.
CC They interacts with sorting cellular proteins of the multivesicular
CC body (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:0000250|UniProtKB:P03345}.
CC -!- PTM: [Gag-Pro 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. The protease is
CC autoproteolytically processed at its N- and C-termini.
CC {ECO:0000250|UniProtKB:P10274}.
CC -!- PTM: [Matrix protein p19]: Phosphorylation of the matrix protein p19 by
CC MAPK1 seems to play a role in budding. {ECO:0000250|UniProtKB:P03345}.
CC -!- PTM: [Gag-Pro 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:0000250|UniProtKB:P03345}.
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-Pro polyprotein]: Produced by -1 ribosomal
CC frameshifting at the gag-pro genes boundary.
CC {ECO:0000269|PubMed:11222762, ECO:0000269|PubMed:2467996,
CC ECO:0000269|PubMed:8371359}.
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DR EMBL; M10060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A03954; PNLJH2.
DR PDB; 1JVR; NMR; -; A=1-136.
DR PDBsum; 1JVR; -.
DR SMR; P03353; -.
DR MEROPS; A02.018; -.
DR EvolutionaryTrace; P03353; -.
DR Proteomes; UP000009254; Genome.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; 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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.30; -; 1.
DR Gene3D; 1.10.375.10; -; 1.
DR Gene3D; 2.40.70.10; -; 1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR003139; D_retro_matrix.
DR InterPro; IPR045345; Gag_p24_C.
DR InterPro; IPR000721; Gag_p24_N.
DR InterPro; IPR001995; Peptidase_A2_cat.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR018061; Retropepsins.
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; PF00077; RVP; 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; SSF50630; SSF50630; 1.
DR SUPFAM; SSF57756; SSF57756; 1.
DR PROSITE; PS50175; ASP_PROT_RETROV; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS50158; ZF_CCHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aspartyl protease; Capsid protein;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus;
KW Host gene expression shutoff by virus; Host-virus interaction; Hydrolase;
KW Lipoprotein; Metal-binding; Myristate; Protease; Reference proteome;
KW Repeat; Ribosomal frameshifting; Viral nucleoprotein; Virion; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000255"
FT CHAIN 2..602
FT /note="Gag-Pro polyprotein"
FT /id="PRO_0000259809"
FT CHAIN 2..136
FT /note="Matrix protein p19"
FT /id="PRO_0000259810"
FT CHAIN 137..350
FT /note="Capsid protein p24"
FT /id="PRO_0000259811"
FT CHAIN 351..446
FT /note="Nucleocapsid protein p15-pro"
FT /id="PRO_0000259812"
FT CHAIN 447..571
FT /note="Protease"
FT /id="PRO_0000199535"
FT PEPTIDE 572..579
FT /note="p1"
FT /id="PRO_0000259813"
FT CHAIN 580..602
FT /note="Transframe peptide"
FT /id="PRO_0000259814"
FT DOMAIN 473..551
FT /note="Peptidase A2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT ZN_FING 361..378
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 384..401
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 94..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 399..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 582..602
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 94..97
FT /note="PTAP/PSAP motif"
FT /evidence="ECO:0000250|UniProtKB:P03345"
FT MOTIF 124..127
FT /note="PPXY motif"
FT /evidence="ECO:0000250|UniProtKB:P03345"
FT COMPBIAS 97..121
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 478
FT /note="Protease; shared with dimeric partner"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT SITE 136..137
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT SITE 350..351
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT SITE 446..447
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT SITE 571..572
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT SITE 579..580
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000255"
SQ SEQUENCE 602 AA; 66435 MW; 15627B078EFAC16E CRC64;
MGQIHGLSPT PIPKAPRGLS THHWLNFLQA AYRLQPRPSD FDFQQLRRFL KLALKTPIWL
NPIDYSLLAS LIPKGYPGRV VEIINILVKN QVSPSAPAAP VPTPICPTTT PPPPPPPSPE
AHVPPPYVEP TTTQCFPILH PPGAPSAHRP WQMKDLQAIK QEVSSSALGS PQFMQTLRLA
VQQFDPTAKD LQDLLQYLCS SLVVSLHHQQ LNTLITEAET RGMTGYNPMA GPLRMQANNP
AQQGLRREYQ NLWLAAFSTL PGNTRDPSWA AILQGLEEPY CAFVERLNVA LDNGLPEGTP
KEPILRSLAY SNANKECQKI LQARGHTNSP LGEMLRTCQA WTPKDKTKVL VVQPRRPPPT
QPCFRCGKVG HWSRDCTQPR PPPGPCPLCQ DPSHWKRDCP QLKPPQEEGE PLLLDLPSTS
GTTEEKNLLK GGDLISPHPD QDISILPLIP LRQQQQPILG VRISVMGQTP QPTQALLDTG
ADLTVIPQTL VPGPVKLHDT LILGASGQTN TQFKLLQTPL HIFLPFRRSP VILSSCLLDT
HNKWTIIGRD ALQQCQGLLY LPDDPSPHQL LPIATPNTIG LEHLPPPPQV DQFPLNLSAS
RP
