Early E1A 32 kDa protein - Human adenovirus C serotype 5 (HAdV-5)

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Reviewed, UniProtKB/Swiss-Prot P03255 (E1A_ADE05)

Last modified January 19, 2010. Version 71. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names	Recommended name: Early E1A 32 kDa protein
Organism	Human adenovirus C serotype 5 (HAdV-5) (Human adenovirus 5)
Taxonomic identifier	28285 [NCBI]
Taxonomic lineage	Viruses › dsDNA viruses, no RNA stage › Adenoviridae › Mastadenovirus
Virus host	Homo sapiens (Human) [TaxID: 9606]

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Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	E1A protein has both transforming and trans-activating activities. Disrupts the function of host retinoblastoma protein RB1/pRb, which is a key regulator of the cell cycle. Induces the disassembly of the E2F1 transcription factors from RB1 by direct competition for the same binding site on RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Inactivation of the ability of RB1 to arrest the cell cycle is critical for cellular transformation, uncontrolled cellular growth and proliferation induced by viral infection. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. The tumorigenesis-restraining activity of E1A may be related to the disruption of the host CtBP-CtIP complex through the CtBP binding motif.
Subunit structure	Interacts with host UBE2I. Interaction with host RB1 induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting RB1's activity. Ref.5
Sequence similarities	Belongs to the adenoviridae E1A protein family.

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Ontologies

Keywords
Biological process	Host-virus interaction Transcription Transcription regulation
Coding sequence diversity	Alternative splicing
Developmental stage	Early protein
Disease	Oncogene
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	positive regulation of cell proliferation Inferred from direct assay. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro transcription Inferred from electronic annotation. Source: UniProtKB-KW virus-host interaction Inferred from electronic annotation. Source: InterPro
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] Note: Isoforms are derived from the E1 region of the genome.

Isoform early E1A 32 kDa protein (identifier: P03255-1) 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 early E1A 26 kDa protein (identifier: P03255-2) The sequence of this isoform differs from the canonical sequence as follows: 140-185: Missing.
Note: No experimental confirmation available.

Isoform early E1A 6 kDa protein (identifier: P03255-3) The sequence of this isoform differs from the canonical sequence as follows: 29-55: ADNLPPPSHFEPPTLHELYDLDVTAPE → CLNLSLSPSQNRSLQDLPAVLKWRLLS 56-289: Missing.
Note: No experimental confirmation available.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 289

289

Early E1A 32 kDa protein

PRO_0000221694

Regions

Zinc finger

154 – 174

Potential

Region

41 – 49

Interaction with RB1 in competition with E2F1 Probable

Region

76 – 140

Interaction with UBE2I

Region

122 – 126

Interaction with RB1 Potential

Region

279 – 283

CTBP-binding

Amino acid modifications

Modified residue

Phosphoserine; by host Ref.3

Modified residue

219

Phosphoserine; by host Ref.3

Modified residue

231

Phosphoserine; by host Ref.3

Natural variations

Alternative sequence

29 – 55

ADNLP…VTAPE → CLNLSLSPSQNRSLQDLPAV LKWRLLS in isoform early E1A 6 kDa protein.

VSP_028918

Alternative sequence

56 – 289

234

Missing in isoform early E1A 6 kDa protein.

VSP_028919

Alternative sequence

140 – 185

Missing in isoform early E1A 26 kDa protein.

VSP_000198

Experimental info

Mutagenesis

122

L → I: Abolishes binding to UBE2I. Ref.5

Mutagenesis

154

C → S: Loss of transactivation. Ref.4

Mutagenesis

157

C → S: Loss of transactivation. Ref.4

Mutagenesis

171

C → S: Loss of transactivation. Ref.4

Mutagenesis

174

C → S: Loss of transactivation. Ref.4

Secondary structure

289

Helix Strand Turn

Details...

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Sequences

Sequence		Length	Mass (Da)
Isoform early E1A 32 kDa protein [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 8C5997A3908C40D7 Show »	FASTA	289	31,851
10 20 30 40 50 60 MRHIICHGGV ITEEMAASLL DQLIEEVLAD NLPPPSHFEP PTLHELYDLD VTAPEDPNEE 70 80 90 100 110 120 AVSQIFPDSV MLAVQEGIDL LTFPPAPGSP EPPHLSRQPE QPEQRALGPV SMPNLVPEVI 130 140 150 160 170 180 DLTCHEAGFP PSDDEDEEGE EFVLDYVEHP GHGCRSCHYH RRNTGDPDIM CSLCYMRTCG 190 200 210 220 230 240 MFVYSPVSEP EPEPEPEPEP ARPTRRPKMA PAILRRPTSP VSRECNSSTD SCDSGPSNTP 250 260 270 280 PEIHPVVPLC PIKPVAVRVG GRRQAVECIE DLLNEPGQPL DLSCKRPRP « Hide
Isoform early E1A 26 kDa protein. Checksum: CA355781A92A4D42 Show »	FASTA	243	26,452
10 20 30 40 50 60 MRHIICHGGV ITEEMAASLL DQLIEEVLAD NLPPPSHFEP PTLHELYDLD VTAPEDPNEE 70 80 90 100 110 120 AVSQIFPDSV MLAVQEGIDL LTFPPAPGSP EPPHLSRQPE QPEQRALGPV SMPNLVPEVI 130 140 150 160 170 180 DLTCHEAGFP PSDDEDEEGP VSEPEPEPEP EPEPARPTRR PKMAPAILRR PTSPVSRECN 190 200 210 220 230 240 SSTDSCDSGP SNTPPEIHPV VPLCPIKPVA VRVGGRRQAV ECIEDLLNEP GQPLDLSCKR PRP « Hide
Isoform early E1A 6 kDa protein. Checksum: 001555BAD0415F3A Show »	FASTA	55	6,156
10 20 30 40 50 MRHIICHGGV ITEEMAASLL DQLIEEVLCL NLSLSPSQNR SLQDLPAVLK WRLLS « Hide

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References

[1]	"The nucleotide sequence of the transforming early region E1 of adenovirus type 5 DNA." van Ormondt H., Maat J., van Beveren C.P. Gene 11:299-309(1980) [PubMed: 6260576] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS EARLY E1A 32 KDA PROTEIN; EARLY E1A 26 KDA PROTEIN AND EARLY E1A 6 KDA PROTEIN).
[2]	"The sequence of the genome of adenovirus type 5 and its comparison with the genome of adenovirus type 2." Chroboczek J., Bieber F., Jacrot B. Virology 186:280-285(1992) [PubMed: 1727603] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Identification of the phosphorylation sites in early region 1A proteins of adenovirus type 5 by amino acid sequencing of peptide fragments." Tremblay M.L., McGlade C.J., Gerber G.E., Branton P.E. J. Biol. Chem. 263:6375-6383(1988) [PubMed: 2966155] [Abstract] Cited for: PHOSPHORYLATION AT SER-89; SER-219 AND SER-231.
[4]	"Conversion of the E1A Cys4 zinc finger to a nonfunctional His2,Cys2 zinc finger by a single point mutation." Webster L.C., Zhang K., Chance B., Ayene I., Culp J.S., Huang W.-J., Wu F.Y.-H., Ricciardi R.P. Proc. Natl. Acad. Sci. U.S.A. 88:9989-9993(1991) [PubMed: 1835093] [Abstract] Cited for: MUTAGENESIS OF CYS-154; CYS-157; CYS-171 AND CYS-174.
[5]	"mUBC9, a novel adenovirus E1A-interacting protein that complements a yeast cell cycle defect." Hateboer G., Hijmans E.M., Nooij J.B.D., Schlenker S., Jentsch S., Bernards R. J. Biol. Chem. 271:25906-25911(1996) [PubMed: 8824223] [Abstract] Cited for: INTERACTION WITH HUMAN UBE2I, MUTAGENESIS OF LEU-122.
[6]	"Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor." Liu X., Marmorstein R. Genes Dev. 21:2711-2716(2007) [PubMed: 17974914] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 40-49 IN COMPLEX WITH HUMAN RB1.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M73260 Genomic DNA. No translation available.
X02996 Genomic DNA. Translation: CAB40663.1.
X02996 Genomic DNA. Translation: CAB40664.1.
X02996 Genomic DNA. Translation: CAB40665.1.

PIR

ERAD65. A03825.
Q2AD5. C03824.

RefSeq

AP_000197.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KJE	NMR	-	B	53-91	[»]
2R7G	X-ray	1.67	B/D/E	40-49	[»]

ModBase

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Family and domain databases

InterPro

IPR014410. Aden_E1A.
IPR003853. Adeno_E1A.
[Graphical view]

Pfam

PF02703. Adeno_E1A. 1 hit.
[Graphical view]

PIRSF

PIRSF003669. Aden_E1A. 1 hit.

ProtoNet

Search...

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Entry information

Entry name

E1A_ADE05

Accession

Primary (citable) accession number: P03255
Secondary accession number(s): P06438, Q64825, Q64826

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	January 19, 2010
This is version 71 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)

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Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families