P12I_HTL1A
ID P12I_HTL1A Reviewed; 99 AA.
AC P0C215;
DT 14-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 1.
DT 23-FEB-2022, entry version 40.
DE RecName: Full=Accessory protein p12I;
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 [MRNA] (ISOFORMS P27I AND P12I), AND SUBCELLULAR
RP LOCATION OF P12I.
RX PubMed=8445734; DOI=10.1128/jvi.67.4.2360-2366.1993;
RA Koralnik I.J., Fullen J., Franchini G.;
RT "The p12I, p13II, and p30II proteins encoded by human T-cell
RT leukemia/lymphotropic virus type I open reading frames I and II are
RT localized in three different cellular compartments.";
RL J. Virol. 67:2360-2366(1993).
RN [3]
RP ALTERNATIVE SPLICING (ISOFORMS P27I AND P12I).
RC STRAIN=Isolate LAF;
RX PubMed=1528897; DOI=10.1073/pnas.89.18.8813;
RA Koralnik I.J., Gessain A., Klotman M.E., Lo Monico A., Berneman Z.N.,
RA Franchini G.;
RT "Protein isoforms encoded by the pX region of human T-cell
RT leukemia/lymphotropic virus type I.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8813-8817(1992).
RN [4]
RP SUBUNIT, UBIQUITINATION, AND MUTAGENESIS OF LYS-88.
RC STRAIN=Isolate LAF;
RX PubMed=10400740; DOI=10.1128/jvi.73.8.6460-6467.1999;
RA Trovato R., Mulloy J.C., Johnson J.M., Takemoto S., de Oliveira M.P.,
RA Franchini G.;
RT "A lysine-to-arginine change found in natural alleles of the human T-cell
RT lymphotropic/leukemia virus type 1 p12(I) protein greatly influences its
RT stability.";
RL J. Virol. 73:6460-6467(1999).
RN [5]
RP INTERACTION OF P12I WITH HUMAN ATP6V0C.
RC STRAIN=Isolate LAF;
RX PubMed=7636472; DOI=10.1099/0022-1317-76-8-1909;
RA Koralnik I.J., Mulloy J.C., Andresson T., Fullen J., Franchini G.;
RT "Mapping of the intermolecular association of human T cell
RT leukaemia/lymphotropic virus type I p12I and the vacuolar H+-ATPase 16 kDa
RT subunit protein.";
RL J. Gen. Virol. 76:1909-1916(1995).
RN [6]
RP INTERACTION WITH HUMAN IL2RB AND IL2RG.
RC STRAIN=Isolate LAF;
RX PubMed=8648694; DOI=10.1128/jvi.70.6.3599-3605.1996;
RA Mulloy J.C., Crownley R.W., Fullen J., Leonard W.J., Franchini G.;
RT "The human T-cell leukemia/lymphotropic virus type 1 p12I proteins bind the
RT interleukin-2 receptor beta and gammac chains and affects their expression
RT on the cell surface.";
RL J. Virol. 70:3599-3605(1996).
RN [7]
RP SUBCELLULAR LOCATION OF P12I, AND INTERACTION OF P12I WITH HUMAN CANX AND
RP CALR.
RX PubMed=11462039; DOI=10.1128/jvi.75.16.7672-7682.2001;
RA Ding W., Albrecht B., Luo R., Zhang W., Stanley J.R., Newbound G.C.,
RA Lairmore M.D.;
RT "Endoplasmic reticulum and cis-Golgi localization of human T-lymphotropic
RT virus type 1 p12(I): association with calreticulin and calnexin.";
RL J. Virol. 75:7672-7682(2001).
RN [8]
RP FUNCTION.
RX PubMed=11468184; DOI=10.1182/blood.v98.3.823;
RA Nicot C., Mulloy J.C., Ferrari M.G., Johnson J.M., Fu K., Fukumoto R.,
RA Trovato R., Fullen J., Leonard W.J., Franchini G.;
RT "HTLV-1 p12(I) protein enhances STAT5 activation and decreases the
RT interleukin-2 requirement for proliferation of primary human peripheral
RT blood mononuclear cells.";
RL Blood 98:823-829(2001).
RN [9]
RP FUNCTION, AND INTERACTION WITH MHC-I HLA-A2; HLA-B7 AND HLA-CW4.
RC STRAIN=Isolate LAF;
RX PubMed=11390610; DOI=10.1128/jvi.75.13.6086-6094.2001;
RA Johnson J.M., Nicot C., Fullen J., Ciminale V., Casareto L., Mulloy J.C.,
RA Jacobson S., Franchini G.;
RT "Free major histocompatibility complex class I heavy chain is
RT preferentially targeted for degradation by human T-cell
RT leukemia/lymphotropic virus type 1 p12(I) protein.";
RL J. Virol. 75:6086-6094(2001).
RN [10]
RP REVIEW.
RX PubMed=16155609; DOI=10.1038/sj.onc.1208977;
RA Nicot C., Harrod R.L., Ciminale V., Franchini G.;
RT "Human T-cell leukemia/lymphoma virus type 1 nonstructural genes and their
RT functions.";
RL Oncogene 24:6026-6034(2005).
CC -!- FUNCTION: p12I is a modulator of T-lymphocyte proliferation and immune
CC function and may contribute to establish a persistent infection. Binds
CC and down-modulates cell surface expression of interleukin-2 receptors
CC IL2RB and IL2RG. Also down-modulates cell surface MHC-I molecules by
CC binding to free immature MHC-I heavy chains in the ER and targeting
CC them to the proteasome for degradation. Binding to IL2RB mediates
CC recruitment of JAK1 and JAK3. As a result of this interaction, p12I
CC increases DNA-binding and transcriptional activity of STAT5 (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:11390610,
CC ECO:0000269|PubMed:11468184}.
CC -!- SUBUNIT: p12I is a homodimer. Interacts with human CANX, CALR, ATP6V0C,
CC IL2RB, IL2RG. Binds to MHC-I heavy chains HLA-A2, HLA-B7 and HLA-Cw4.
CC {ECO:0000269|PubMed:10400740, ECO:0000269|PubMed:11390610,
CC ECO:0000269|PubMed:11462039, ECO:0000269|PubMed:7636472,
CC ECO:0000269|PubMed:8648694}.
CC -!- SUBCELLULAR LOCATION: [Isoform p12I]: Host endoplasmic reticulum
CC membrane; Multi-pass membrane protein. Host Golgi apparatus, host cis-
CC Golgi network membrane {ECO:0000305}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=p12I;
CC IsoId=P0C215-1; Sequence=Displayed;
CC Name=p27I;
CC IsoId=P0C215-2; Sequence=VSP_021562;
CC -!- PTM: Ubiquitinated; a fraction of P12I is degraded via the ubiquitin
CC system. {ECO:0000269|PubMed:10400740}.
CC -!- MISCELLANEOUS: Lys-88 seems to be associated with tropical spastic
CC paraparesis/HTLV-1-associated myelopathy (TSP/HAM).
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).
CC -!- SIMILARITY: Belongs to the HTLV-1 accessory protein p12I family.
CC {ECO:0000305}.
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DR EMBL; J02029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L08432; -; NOT_ANNOTATED_CDS; mRNA.
DR iPTMnet; P0C215; -.
DR Proteomes; UP000007683; Genome.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0046776; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR InterPro; IPR021086; p12I.
DR Pfam; PF12233; p12I; 1.
PE 1: Evidence at protein level;
KW Alternative splicing;
KW Evasion of host immunity by viral interleukin-like protein;
KW Host endoplasmic reticulum; Host Golgi apparatus; Host membrane;
KW Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
KW Inhibition of host MHC class I molecule presentation by virus;
KW Isopeptide bond; Membrane; Reference proteome; SH3-binding; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Viral immunoevasion.
FT CHAIN 1..99
FT /note="Accessory protein p12I"
FT /id="PRO_0000259953"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 48..68
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 4..11
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 33..38
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 70..77
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 88..93
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT CROSSLNK 88
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); in isolate LAF"
FT /evidence="ECO:0000269|PubMed:10400740"
FT VAR_SEQ 1
FT /note="M -> MPKTRRRPRRSQRKRPPTPWQLPPFSLQGLHLAFQLSSIAINPQLLH
FT FFFPST (in isoform p27I)"
FT /evidence="ECO:0000303|PubMed:8445734"
FT /id="VSP_021562"
FT VARIANT 23..25
FT /note="PPS -> SPG (in strain: Isolate LAF)"
FT VARIANT 51
FT /note="G -> N (in strain: Isolate LAF)"
FT VARIANT 74
FT /note="I -> L (in strain: Isolate LAF)"
FT VARIANT 88
FT /note="K -> R (in strain: Isolate ATK-1)"
FT MUTAGEN 88
FT /note="K->R: Increases the steady state of p12I."
FT /evidence="ECO:0000269|PubMed:10400740"
SQ SEQUENCE 99 AA; 11069 MW; 5D9690511F913E53 CRC64;
MLFRLLSPLS PLALTALLLF LLPPSDVSGL LLRPPPAPCL LLFLPFQILS GLLFLLFLPL
FFSLPLLLSP SLPITMRFPA RWRFLPWKAP SQPAAAFLF
