P24109 (TAT_HV2CA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein Tat

Alternative name(s):
Transactivating regulatory protein

Gene names

Name:

tat

Organism

Human immunodeficiency virus type 2 subtype A (isolate CAM2) (HIV-2) [Complete proteome]

Taxonomic identifier

11715 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group › Human immunodeficiency virus 2

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	133 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive By similarity. Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors. Endosomal low pH allows Tat to cross the endosome membrane to enter the cytosol and eventually further translocate into the nucleus, thereby inducing severe cell dysfunctions ranging from cell activation to cell death. Through By similarity.
Subunit structure	Interacts with host CCNT1. Associates with the P-TEFb complex composed at least of Tat, P-TEFb (CDK9 and CCNT1), TAR RNA, RNA Pol II. Interacts with CCNT2; the resulting complex is unable to bind to TAR RNA By similarity.
Subcellular location	Host nucleus › host nucleolus By similarity.
Domain	The Arg-rich RNA-binding region binds the TAR RNA. This region also mediates the nuclear localization By similarity.
Post-translational modification	The phosphorylation by CDK9 does not seem to be important for transactivation function By similarity.
Sequence similarities	Belongs to the lentiviruses Tat family.

Ontologies

Keywords
Biological process	Host-virus interaction Transcription Transcription regulation
Cellular component	Host nucleus
Coding sequence diversity	Alternative splicing
Disease	AIDS
Ligand	RNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological_process	transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform Long (identifier: P24109-1)

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 Short (identifier: P24109-2)

The sequence of this isoform differs from the canonical sequence as follows:
     103-133: Missing.

Note: No experimental confirmation available. Expressed in the late stage of the infection cycle, when unspliced viral RNAs are exported to the cytoplasm by the viral Rev protein.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 133	133	Protein Tat		PRO_0000085368
Regions
	Region	53 – 69	17	Cysteine-rich By similarity
	Region	70 – 80	11	Core By similarity
	Motif	81 – 93	13	Nuclear localization signal, and RNA-binding (TAR) By similarity
Amino acid modifications
	Modified residue	88	1	Phosphothreonine; by host CDK9 By similarity
	Modified residue	97	1	Phosphoserine; by host CDK9 By similarity
Natural variations
	Alternative sequence	103 – 133	31	Missing in isoform Short.		VSP_022438

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified March 1, 1992. Version 1. Checksum: CFAB978387B3C1FD	FASTA	133	14,850
	10 20 30 40 50 60 MLDMETPLKE PESSLGSCNE PSSRTSGQDA TTQELAKLGE EILSQLYQPL EECDNSCYCK 70 80 90 100 110 120 RCCYHCQLCF LKKGLGICYD RKGRRRRTPK KAKAHSSSAS DKSISTRTRN SQPAKKQKKT 130 LEATVETDPG LGR
	Isoform Short [UniParc]. Checksum: 6E58535C331C391A	FASTA	102	11,469
	10 20 30 40 50 60 MLDMETPLKE PESSLGSCNE PSSRTSGQDA TTQELAKLGE EILSQLYQPL EECDNSCYCK 70 80 90 100 RCCYHCQLCF LKKGLGICYD RKGRRRRTPK KAKAHSSSAS DK

References

[1]	"Nucleotide sequence of a Guinea-Bissau-derived human immunodeficiency virus type 2 proviral clone (HIV-2CAM2)." Tristem M., Hill F., Karpas A. J. Gen. Virol. 72:721-724(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Decoding Tat: the biology of HIV Tat posttranslational modifications." Hetzer C., Dormeyer W., Schnolzer M., Ott M. Microbes Infect. 7:1364-1369(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW, ALTERNATIVE SPLICING.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D00835 Genomic DNA. Translation: BAA00714.1.
PIR	TNLJCA. I38475.
3D structure databases
ProteinModelPortal	P24109.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
Gene3D	4.10.20.10. 1 hit.
InterPro	IPR001831. IV_Tat. [Graphical view]
Pfam	PF00539. Tat. 1 hit. [Graphical view]
PRINTS	PR00055. HIVTATDOMAIN.
ProtoNet	Search...

Entry information

Entry name

TAT_HV2CA

Accession

Primary (citable) accession number: P24109

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	March 1, 1992
Last modified:	April 3, 2013
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program