PRO_HTL1L
ID PRO_HTL1L Reviewed; 651 AA.
AC P0C210;
DT 14-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 67.
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; Synonyms=prt;
OS Human T-cell leukemia virus 1 (isolate Melanesia mel5 subtype C) (HTLV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus.
OX NCBI_TaxID=402046;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8419636; DOI=10.1128/jvi.67.2.1015-1023.1993;
RA Gessain A., Boeri E., Yanagihara R., Gallo R.C., Franchini G.;
RT "Complete nucleotide sequence of a highly divergent human T-cell leukemia
RT (lymphotropic) virus type I (HTLV-I) variant from melanesia: genetic and
RT phylogenetic relationship to HTLV-I strains from other geographical
RT regions.";
RL J. Virol. 67:1015-1023(1993).
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=P0C210-1; Sequence=Displayed;
CC Name=Gag polyprotein;
CC IsoId=P0C209-1; Sequence=External;
CC Name=Gag-Pol polyprotein;
CC IsoId=P0C211-1; 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. {ECO:0000305}.
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DR EMBL; L02534; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 2KPZ; NMR; -; B=113-124.
DR PDBsum; 2KPZ; -.
DR BMRB; P0C210; -.
DR SMR; P0C210; -.
DR EvolutionaryTrace; P0C210; -.
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; Phosphoprotein; Protease; Repeat;
KW Ribosomal frameshifting; Viral nucleoprotein; Virion; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000255"
FT CHAIN 2..651
FT /note="Gag-Pro polyprotein"
FT /id="PRO_0000259802"
FT CHAIN 2..130
FT /note="Matrix protein p19"
FT /id="PRO_0000259803"
FT CHAIN 131..344
FT /note="Capsid protein p24"
FT /id="PRO_0000259804"
FT CHAIN 345..449
FT /note="Nucleocapsid protein p15-pro"
FT /id="PRO_0000259805"
FT CHAIN 450..574
FT /note="Protease"
FT /id="PRO_0000259806"
FT PEPTIDE 575..582
FT /note="p1"
FT /id="PRO_0000259807"
FT CHAIN 583..651
FT /note="Transframe peptide"
FT /id="PRO_0000259808"
FT DOMAIN 476..554
FT /note="Peptidase A2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
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..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 632..651
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 118..121
FT /note="PPXY motif"
FT /evidence="ECO:0000250|UniProtKB:P03345"
FT MOTIF 124..127
FT /note="PTAP/PSAP motif"
FT /evidence="ECO:0000250|UniProtKB:P03345"
FT COMPBIAS 95..126
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 481
FT /note="For protease activity; shared with dimeric partner"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT SITE 130..131
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT SITE 344..345
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT SITE 449..450
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT SITE 574..575
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT SITE 582..583
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250|UniProtKB:P10274"
FT MOD_RES 105
FT /note="Phosphoserine; by host MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P03345"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000255"
SQ SEQUENCE 651 AA; 71843 MW; DCE9DBFD49E888BD CRC64;
MGQIFPRSAN PIPRPPRGLA THHWLNFLQA AYRLEPGPSS YDFHQLKTVL KMALETPVWM
CPINYSLLAS LLPKGYPGQV NEILQVLIQT QTQIPSHPAP PPPSSPTHDP PDSDPQIPPP
YVEPTAPQVL PVMHPHGVPP THRPWQMKDL QAIKQEVSQA APGSPQFMQT IRLAVQQFDP
TAKDLQDLLQ YLCSSLVASL HHQQLDSLIS EAETRGITGY NPLAGPLRVQ ANNPQQQGLR
REYQQLWLTA FAALPGSAKD PSWASILQGL EEPYHTFVER LNVALDNGLP EGTPKDPILR
SLAYSNANKE CQKLLQARGH TNSPLGDMLR ACQAWTPRDK TKVLVVQPKK PPPNQPCFRC
GKAGHWSRDC AQPRPPPGPC PLCQDPTHWK RDCPRLKPAI PEPEPEEDAL LLDLPADIPH
PKNLHRGGGL TSPPTLRQVH PNKDPASILP VIPLDPARRP LIKAQVDTQT SHPRTIEALL
DTGADMTVLP IALFSSDTPL KDTSVLGAGG QTQDHFKLTS LPVLIRLPFR TTPIVLTSCL
VDTKNNWAII GRDALQQCQG VLYLPEAKRP PVILPIQAPA VLGLEHLPRP PEISQFPLNQ
NASRPCNTWS GRPWRQAISN RTPGQEITQY SQLKRPMEPG DSSTTCGPLI L
