P14999 (LT_POVBA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Large T antigen Short name=LT Short name=LT-AG EC=3.6.4.-
Organism	BK polyomavirus (strain AS) (BKPyV) [Complete proteome]
Taxonomic identifier	10631 [NCBI]
Taxonomic lineage	Viruses › dsDNA viruses, no RNA stage › Polyomaviridae › Polyomavirus
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	691 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Isoform large T antigen is a key early protein essential for both driving viral replication and inducing cellular transformation. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle and by autoregulating the synthesis of viral early mRNA. Displays highly oncogenic activities by corrupting the host cellular checkpoint mechanisms that guard cell division and the transcription, replication, and repair of DNA. Participates in the modulation of cellular gene expression preceeding viral DNA replication. This step involves binding to host key cell cycle regulators retinoblastoma protein RB1/pRb and TP53. Induces the disassembly of host E2F1 transcription factors from RB1, thus promoting transcriptional activation of E2F1-regulated S-phase genes. Inhibits host TP53 binding to DNA, abrogating the ability of TP53 to stimulate gene expression. Plays the role of a TFIID-associated factor (TAF) in transcription initiation for all three RNA polymerases, by stabilizing the TBP-TFIIA complex on promoters. Initiates viral DNA replication and unwinding via interactions with the viral origin of replication. Binds two adjacent sites in the SV40 origin. The replication fork movement is facilitated by Large T antigen helicase activity. Activates the transcription of viral late mRNA, through host TBP and TFIIA stabilization. Interferes with histone deacetylation mediated by HDAC1, leading to activation of transcription By similarity.
Subunit structure	Forms homohexamers in the presence of ATP. Interacts with host HDAC1. Interacts (via LXCXE domain) with host RB1; the interaction induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting RB1's activity. Interacts (via LXCXE domain) with host pRB-related proteins RBL1 and RBL2. Interacts (via C-terminus) with host TOP1 and POLA1 allowing DNA replication. Interacts with host TP53, inhibiting TP53 binding to DNA. Interacts with host preinitiation complex components TBP, TFIIA and TFIID to regulate transcription initiation By similarity.
Subcellular location	Host nucleus By similarity.
Domain	The J domain is essential for multiple viral activities, including virion assembly, viral DNA replication, transformation and transcriptional activation By similarity. The LXCXE motif specifically binds to host pRB, RBL1, and RBL2 By similarity. The zinc finger region contributes to protein-protein interactions essential for the assembly of stable T-antigen hexamers at the origin of replication. The hexamers are required for subsequent alterations in the structure of origin DNA By similarity. The ATP binding/ATPase domain is required for proper hexamer assembly and helicase activity By similarity.
Post-translational modification	Phosphorylated on both serine and threonine residues. Small t antigen inhibits the dephosphorylation by the AC form of PP2A By similarity. O-Glycosylated near the C-terminal region By similarity. Acetylated by CBP in a TP53-dependent manner By similarity.
Sequence similarities	Contains 1 J domain. Contains 1 SF3 helicase domain. Contains 1 T-ag D1-type zinc finger. Contains 1 T-ag OBD DNA-binding domain.

Ontologies

Keywords
Biological process	DNA replication G1/S host cell cycle checkpoint dysregulation by virus Host-virus interaction Inhibition of host JAK1 by virus Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway by virus Modulation of host cell cycle by virus Viral immunoevasion
Cellular component	Host nucleus
Coding sequence diversity	Alternative splicing
Developmental stage	Early protein
Disease	Oncogene
Domain	Zinc-finger
Ligand	ATP-binding DNA-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	DNA replication Inferred from electronic annotation. Source: UniProtKB-KW evasion by virus of host immune response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA replication origin binding Inferred from electronic annotation. Source: InterPro heat shock protein binding Inferred from electronic annotation. Source: InterPro hydrolase activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform Large T antigen (identifier: P14999-1)

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 Small t antigen (identifier: P15000-1)

The sequence of this isoform can be found in the external entry P15000.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 691	691	Large T antigen		PRO_0000115036
Regions
	Domain	12 – 75	64	J
	Domain	402 – 562	161	SF3 helicase
	DNA binding	141 – 256	116	T-ag OBD
	Zinc finger	267 – 359	93	T-ag D1-type
	Nucleotide binding	428 – 435	8	ATP Potential
	Region	105 – 109	5	Binding to host RB1 protein and transforming activity By similarity
	Motif	127 – 134	8	Nuclear localization signal By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine; by host By similarity
	Modified residue	114	1	Phosphoserine; by host By similarity
	Modified residue	122	1	Phosphoserine; by host By similarity
	Modified residue	125	1	Phosphoserine; by host By similarity
	Modified residue	126	1	Phosphothreonine; by host By similarity
	Modified residue	661	1	Phosphoserine; by host By similarity
	Modified residue	683	1	N6-acetyllysine; by host By similarity
	Modified residue	687	1	Phosphothreonine; by host By similarity

Sequences

	Sequence		Length	Mass (Da)
	Isoform Large T antigen [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 2F26992D3C441A84	FASTA	691	80,129
	10 20 30 40 50 60 MDKVLNREES MELMDLLGLE RAAWGNLPLM RKAYLKKCKE FHPDKGGDED KMKRMNTLYK 70 80 90 100 110 120 KMEQDVKVAH QPDFGTWNSS EVPTYGTEEW ESWWSSFNEK WDEDLFCHED MFASDEEATA 130 140 150 160 170 180 DSQHSTPPKK KRKVEDPKDF PSDLHQFLSQ AVFSNRTLAC FAVYTTKEKA QILYKKLMEK 190 200 210 220 230 240 YSVTFISRHM CAGHNIIFFL TPHRHRVSAI NNFCQKLCTF SFLICKGVNK EYLLYSALTR 250 260 270 280 290 300 DPYHIIEESI QGGLKEHDFN PEEPEETKQV SWKLITEYAV ETKCEDVFLL LGMYLEFQYN 310 320 330 340 350 360 VEECKKCQKK DQPYHFKYHE KHFANAIIFA ESKNQKSICQ QAVDTVLAKK RVDTLHMTRE 370 380 390 400 410 420 EMLTERFNHI LDKMDLIFGA HGNAVLEQYM AGVAWLHCLL PKMDSVIFDF LHCVVFNVPK 430 440 450 460 470 480 RRYWLFKGPI DSGKTTLAAG LLDLCGGKAL NVNLPMERLT FELGVAIDQY MVVFEDVKGT 490 500 510 520 530 540 GAESKDLPSG HGINNLDSLR DYLDGSVKVN LEKKHLNKRT QIFPPGLVTM NEYPVPKTLQ 550 560 570 580 590 600 ARFVRQIDFR PKIYLRKSLQ NSEFLLEKRI LQSGMTLLLL LIWFRPVADF SKDIQSRIVE 610 620 630 640 650 660 WKERLDSEIS MYTFSRMKYN ICMGKCILDI TREEDSETED SGHGSSTESQ SQCSSQVSDT 670 680 690 SAPDSENPHS QELHLCKGFQ CFKRPKTPPP K
	Isoform Small t antigen [UniParc]. See P15000.		–	–

References

[1]	"Nucleotide sequence of the human polyomavirus AS virus, an antigenic variant of BK virus." Tavis J.E., Walker D.L., Gardner S.D., Frisque R.J. J. Virol. 63:901-911(1989) [PubMed: 2536111] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	M23122 Genomic DNA. Translation: AAA46878.1.
PIR	TVVPAS. A33278.
3D structure databases
ProteinModelPortal	P14999.
SMR	P14999. Positions 7-119, 133-262, 267-629.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
Gene3D	G3DSA:1.10.287.110. DnaJ_N. 1 hit. G3DSA:1.10.10.510. Znf_lg_T-Ag_D1-typ. 1 hit.
InterPro	IPR001623. DnaJ_N. IPR014015. Helicase_SF3_DNA-vir. IPR016392. Lg_T_Ag_polyomavir. IPR010932. Lg_T_Ag_Polyomavir_C. IPR003133. T_Ag_DNA-bd. IPR017910. Znf_lg_T-Ag_D1-typ. [Graphical view]
Pfam	PF00226. DnaJ. 1 hit. PF06431. Polyoma_lg_T_C. 1 hit. PF02217. T_Ag_DNA_bind. 1 hit. [Graphical view]
PIRSF	PIRSF003368. Large_T_antigen_polyomaV. 1 hit.
SMART	SM00271. DnaJ. 1 hit. [Graphical view]
SUPFAM	SSF46565. DnaJ_N. 1 hit.
PROSITE	PS00636. DNAJ_1. False negative. PS50076. DNAJ_2. 1 hit. PS51206. SF3_HELICASE_1. 1 hit. PS51287. T_AG_OBD. 1 hit. PS51341. ZF_LTAG_D1. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

LT_POVBA

Accession

Primary (citable) accession number: P14999

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	April 18, 2012
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program