P0C215 (P12I_HTL1A) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Accessory protein p12I
Organism	Human T-cell leukemia virus 1 (strain Japan ATK-1 subtype A) (HTLV-1) [Complete proteome]
Taxonomic identifier	11926 [NCBI]
Taxonomic lineage	Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Deltaretrovirus › Primate T-lymphotropic virus 1 › Human T-lymphotropic virus 1 › HTLV-1 subtype A
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	99 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	p12I is a modulator of T-lymphocyte proliferation and immune function and may contribute to establish a persistent infection. Binds and down-modulates cell surface expression of interleukin-2 receptors IL2RB and IL2RG. Also down-modulates cell surface MHC-I molecules by binding to free immature MHC-I heavy chains in the ER and targeting them to the proteasome for degradation. Binding to IL2RB mediates recruitment of JAK1 and JAK3. As a result of this interaction, p12I increases DNA-binding and transcriptional activity of STAT5 By similarity. Ref.8 Ref.9
Subunit structure	p12I is a homodimer. Interacts with human CANX, CALR, ATP6V0C, IL2RB, IL2RG. Binds to MHC-I heavy chains HLA-A2, HLA-B7 and HLA-Cw4. Ref.4 Ref.5 Ref.6 Ref.7 Ref.9
Subcellular location	Isoform p12I: Host endoplasmic reticulum membrane; Multi-pass membrane protein. Host Golgi apparatus › host cis-Golgi network membrane; Multi-pass membrane protein Potential Ref.2 Ref.7.
Post-translational modification	Ubiquitinated; a fraction of P12I is degraded via the ubiquitin system. Ref.4
Miscellaneous	Lys-88 seems to be associated with tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). HTLV-1 lineages are divided in four clades, A (Cosmopolitan), B (Central African group), C (Melanesian group) and D (New Central African group).
Sequence similarities	Belongs to the HTLV-1 accessory protein p12I family.

Ontologies

Keywords
Biological process	Evasion of host immunity by viral interleukin-like protein Host-virus interaction Inhibition of host MHC class I molecule presentation by virus Inhibition of host adaptive immune response by virus Viral immunoevasion
Cellular component	Host Golgi apparatus Host endoplasmic reticulum Host membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	SH3-binding Transmembrane Transmembrane helix
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological_process	suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell host cell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform p12I (identifier: P0C215-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform p27I (identifier: P0C215-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MPKTRRRPRRSQRKRPPTPWQLPPFSLQGLHLAFQLSSIAINPQLLHFFFPST

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 99	99	Accessory protein p12I		PRO_0000259953
Regions
	Transmembrane	3 – 23	21	Helical; Potential
	Transmembrane	48 – 68	21	Helical; Potential
	Motif	4 – 11	8	SH3-binding Potential
	Motif	33 – 38	6	SH3-binding Potential
	Motif	70 – 77	8	SH3-binding Potential
	Motif	88 – 93	6	SH3-binding Potential
	Compositional bias	1 – 72	72	Leu-rich
Amino acid modifications
	Cross-link	88		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in isolate LAF
Natural variations
	Alternative sequence	1	1	M → MPKTRRRPRRSQRKRPPTPW QLPPFSLQGLHLAFQLSSIA INPQLLHFFFPST in isoform p27I.		VSP_021562
	Natural variant	23 – 25	3	PPS → SPG in strain: Isolate LAF.
	Natural variant	51	1	G → N in strain: Isolate LAF.
	Natural variant	74	1	I → L in strain: Isolate LAF.
	Natural variant	88	1	K → R in strain: Isolate ATK-1.
Experimental info
	Mutagenesis	88	1	K → R: Increases the steady state of p12I. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform p12I [UniParc]. Last modified November 14, 2006. Version 1. Checksum: 5D9690511F913E53	FASTA	99	11,069
	10 20 30 40 50 60 MLFRLLSPLS PLALTALLLF LLPPSDVSGL LLRPPPAPCL LLFLPFQILS GLLFLLFLPL 70 80 90 FFSLPLLLSP SLPITMRFPA RWRFLPWKAP SQPAAAFLF
	Isoform p27I [UniParc]. Checksum: A0613533BE951B9E	FASTA	151	17,200
	10 20 30 40 50 60 MPKTRRRPRR SQRKRPPTPW QLPPFSLQGL HLAFQLSSIA INPQLLHFFF PSTLFRLLSP 70 80 90 100 110 120 LSPLALTALL LFLLPPSDVS GLLLRPPPAP CLLLFLPFQI LSGLLFLLFL PLFFSLPLLL 130 140 150 SPSLPITMRF PARWRFLPWK APSQPAAAFL F

References

[1]	"Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA." Seiki M., Hattori S., Hirayama Y., Yoshida M.C. Proc. Natl. Acad. Sci. U.S.A. 80:3618-3622(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The p12I, p13II, and p30II proteins encoded by human T-cell leukemia/lymphotropic virus type I open reading frames I and II are localized in three different cellular compartments." Koralnik I.J., Fullen J., Franchini G. J. Virol. 67:2360-2366(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS P27I AND P12I), SUBCELLULAR LOCATION OF P12I.
[3]	"Protein isoforms encoded by the pX region of human T-cell leukemia/lymphotropic virus type I." Koralnik I.J., Gessain A., Klotman M.E., Lo Monico A., Berneman Z.N., Franchini G. Proc. Natl. Acad. Sci. U.S.A. 89:8813-8817(1992) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS P27I AND P12I). Strain: Isolate LAF.
[4]	"A lysine-to-arginine change found in natural alleles of the human T-cell lymphotropic/leukemia virus type 1 p12(I) protein greatly influences its stability." Trovato R., Mulloy J.C., Johnson J.M., Takemoto S., de Oliveira M.P., Franchini G. J. Virol. 73:6460-6467(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, UBIQUITINATION, MUTAGENESIS OF LYS-88. Strain: Isolate LAF.
[5]	"Mapping of the intermolecular association of human T cell leukaemia/lymphotropic virus type I p12I and the vacuolar H+-ATPase 16 kDa subunit protein." Koralnik I.J., Mulloy J.C., Andresson T., Fullen J., Franchini G. J. Gen. Virol. 76:1909-1916(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION OF P12I WITH HUMAN ATP6V0C. Strain: Isolate LAF.
[6]	"The human T-cell leukemia/lymphotropic virus type 1 p12I proteins bind the interleukin-2 receptor beta and gammac chains and affects their expression on the cell surface." Mulloy J.C., Crownley R.W., Fullen J., Leonard W.J., Franchini G. J. Virol. 70:3599-3605(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN IL2RB AND IL2RG. Strain: Isolate LAF.
[7]	"Endoplasmic reticulum and cis-Golgi localization of human T-lymphotropic virus type 1 p12(I): association with calreticulin and calnexin." Ding W., Albrecht B., Luo R., Zhang W., Stanley J.R., Newbound G.C., Lairmore M.D. J. Virol. 75:7672-7682(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION OF P12I, INTERACTION OF P12I WITH HUMAN CANX AND CALR.
[8]	"HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells." Nicot C., Mulloy J.C., Ferrari M.G., Johnson J.M., Fu K., Fukumoto R., Trovato R., Fullen J., Leonard W.J., Franchini G. Blood 98:823-829(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Free major histocompatibility complex class I heavy chain is preferentially targeted for degradation by human T-cell leukemia/lymphotropic virus type 1 p12(I) protein." Johnson J.M., Nicot C., Fullen J., Ciminale V., Casareto L., Mulloy J.C., Jacobson S., Franchini G. J. Virol. 75:6086-6094(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MHC-I HLA-A2; HLA-B7 AND HLA-CW4. Strain: Isolate LAF.
[10]	"Human T-cell leukemia/lymphoma virus type 1 nonstructural genes and their functions." Nicot C., Harrod R.L., Ciminale V., Franchini G. Oncogene 24:6026-6034(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J02029 Genomic DNA. No translation available. L08432 mRNA. No translation available.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR021086. p12I. [Graphical view]
Pfam	PF12233. p12I. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

P12I_HTL1A

Accession

Primary (citable) accession number: P0C215

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 14, 2006
Last sequence update:	November 14, 2006
Last modified:	April 3, 2013
This is version 22 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program