Early E1A protein

Functionⁱ

Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. E1A protein has both transforming and trans-activating activities. Induces the disassembly of the E2F1 transcription factor from RB1 by direct competition for the same binding site on RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes and of the E2 region of the adenoviral genome. Release of E2F1 leads to the ARF-mediated inhibition of MDM2 and causes TP53/p53 to accumulate because it is not targeted for degradation by MDM2-mediated ubiquitination anymore. This increase in TP53, in turn, would arrest the cell proliferation and direct its death but this effect is counteracted by the viral protein E1B-55K. 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. Interaction with RBX1 and CUL1 inhibits ubiquitination of the proteins targeted by SCF(FBXW7) ubiquitin ligase complex, and may be linked to unregulated host cell proliferation. The tumorigenesis-restraining activity of E1A may be related to the disruption of the host CtBP-CtIP complex through the CtBP binding motif. Interacts with host TBP protein; this interaction probably disrupts the TBP-TATA complex. Interaction with host TMEM173/STING impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta).By similarity

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Zinc fingerⁱ	154 – 174	By similarityAdd BLAST		21

GO - Molecular functionⁱ

metal ion binding Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

DNA-templated viral transcription
Source: UniProtKB
Inferred from direct assayⁱ
- 6723627
modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
modulation by virus of host ubiquitin-protein ligase activity Source: UniProtKB-KW
regulation of transcription, DNA-templated Source: UniProtKB-KW
suppression by virus of host gene expression Source: UniProtKB-KW
suppression by virus of host STAT1 activity Source: UniProtKB-KW
suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
transcription, DNA-templated Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Activator
Biological process	Eukaryotic host gene expression shutoff by virus, Eukaryotic host transcription shutoff by virus, G1/S host cell cycle checkpoint dysregulation by virus, Host gene expression shutoff by virus, Host-virus interaction, Inhibition of eukaryotic host transcription initiation by virus, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host STAT1 by virus, Modulation of host cell cycle by virus, Modulation of host E3 ubiquitin ligases by virus, Modulation of host ubiquitin pathway by virus, Transcription, Transcription regulation, Viral immunoevasion
Ligand	Metal-binding, Zinc

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Early E1A proteinCurated Alternative name(s): Early E1A 32 kDa protein
Organismⁱ	Human adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2)
Taxonomic identifierⁱ	10515 [NCBI]
Taxonomic lineageⁱ	Viruses › dsDNA viruses, no RNA stage › Adenoviridae › Mastadenovirus › Human mastadenovirus C
Virus hostⁱ	Homo sapiens (Human) [TaxID: 9606]
Proteomesⁱ	UP000008167 Componentⁱ: Genome

Subcellular locationⁱ

Host nucleus
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P03255 (E1A_ADE05)

GO - Cellular componentⁱ

host cell nucleus Source: UniProtKB-SubCell

View the complete GO annotation on QuickGO ...

Keywords - Cellular componentⁱ

Host nucleus

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	157	C → S: Abolishes ATF7-mediated transcriptional activation. 1 Publication	1
Mutagenesisⁱ	178	T → P: No effect on ATF7-mediated transcriptional activation. 1 Publication	1
Mutagenesisⁱ	185	S → R: Abolishes ATF7-mediated transcriptional activation. 1 Publication	1

Keywords - Diseaseⁱ

Oncogene

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000221692	1 – 289	Early E1A proteinAdd BLAST		289

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	89	Phosphoserine; by hostBy similarity	1
Modified residueⁱ	219	Phosphoserine; by hostBy similarity	1
Modified residueⁱ	231	Phosphoserine; by hostBy similarity	1

Keywords - PTMⁱ

Phosphoprotein

Expressionⁱ

Keywords - Developmental stageⁱ

Early protein

Interactionⁱ

Subunit structureⁱ

Interacts with host UBE2I; this interaction interferes with polySUMOylation. Interacts with host RB1; this interaction induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting the activity of RB1 and activating E2F1-regulated genes. Interacts with host ATF7; the interaction enhances ATF7-mediated viral transactivation activity which requires the zinc binding domains of both proteins. Isoform early E1A 32 kDa protein and isoform early E1A 26 kDa protein interact (via N-terminus) with CUL1 and E3 ubiquitin ligase RBX1; these interactions inhibit RBX1-CUL1-dependent elongation reaction of ubiquitin chains and attenuate ubiquitination of SCF(FBXW7) target proteins. Interacts (via PXLXP motif) with host ZMYND11/BS69 (via MYND-type zinc finger); this interaction inhibits E1A mediated transactivation. Interacts with host EP300; this interaction stimulates the acetylation of RB1 by recruiting EP300 and RB1 into a multimeric-protein complex. Interacts with host CTBP1 and CTBP2; this interaction seems to potentiate viral replication. Interacts with host DCAF7. Interacts with host DYRK1A. Interacts with host KPNA4; this interaction allows E1A import into the host nucleus. Interacts with host EP400; this interaction stabilizes MYC. Interacts (via LXCXE motif) with host TMEM173/STING; this interaction impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta).By similarity

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
Crebbp	P45481	3	EBI-8599077,EBI-296306	From Mus musculus.
RB1	P06400	3	EBI-8599077,EBI-491274	From Homo sapiens.

Protein-protein interaction databases

Database of interacting proteins More...DIPⁱ	DIP-570N
ELMⁱ	P03254
IntActⁱ	P03254, 3 interactors
Molecular INTeraction database More...MINTⁱ	P03254

Structureⁱ

3D structure databases

SMRⁱ	P03254
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	41 – 49	Interaction with RB1 in competition with E2F1By similarity		9
Regionⁱ	76 – 140	Interaction with UBE2IBy similarityAdd BLAST		65

Motif

Feature key	Position(s)	DescriptionActions	Length
Motifⁱ	113 – 117	PXLXP motif, interaction with host ZMYND11By similarity	5
Motifⁱ	122 – 126	LXCXE motif, interaction with host RB1 and TMEM173/STINGSequence analysis	5
Motifⁱ	258 – 289	Bipartite nuclear localization signalSequence analysisBy similarityAdd BLAST	32
Motifⁱ	279 – 283	PXDLS motif, CTBP-bindingBy similarity	5

Sequence similaritiesⁱ

Belongs to the adenoviridae E1A protein family.Curated

Zinc finger

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Zinc fingerⁱ	154 – 174	By similarityAdd BLAST		21

Keywords - Domainⁱ

Zinc-finger

Phylogenomic databases

Database of Orthologous Groups More...OrthoDBⁱ	VOG090000J6

OrthoDBⁱ

VOG090000J6

Family and domain databases

InterProⁱ	View protein in InterPro IPR014410 Aden_E1A
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF02703 Adeno_E1A, 1 hit
PIRSFⁱ	PIRSF003669 Aden_E1A, 1 hit

Sequences (3)ⁱ

Sequence statusⁱ: Complete.

This entry describes 3 isoformsⁱ produced by alternative splicing. Align Add to basket

Note: Isoforms are derived from the E1 region of the genome.

Isoform early E1A 32 kDa protein (identifier: P03254-1) [UniParc]FASTA Add to basket

Also known as: 289R, L-E1A

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.

« Hide

        10         20         30         40         50
MRHIICHGGV ITEEMAASLL DQLIEEVLAD NLPPPSHFEP PTLHELYDLD 
        60         70         80         90        100
VTAPEDPNEE AVSQIFPDSV MLAVQEGIDL LTFPPAPGSP EPPHLSRQPE 
       110        120        130        140        150
QPEQRALGPV SMPNLVPEVI DLTCHEAGFP PSDDEDEEGE EFVLDYVEHP 
       160        170        180        190        200
GHGCRSCHYH RRNTGDPDIM CSLCYMRTCG MFVYSPVSEP EPEPEPEPEP 
       210        220        230        240        250
ARPTRRPKLV PAILRRPTSP VSRECNSSTD SCDSGPSNTP PEIHPVVPLC 
       260        270        280 
PIKPVAVRVG GRRQAVECIE DLLNESGQPL DLSCKRPRP

Length:289

Mass (Da):31,851

Last modified:July 21, 1986 - v1

Checksum:ⁱ4264747DAD74FFC5

GO

Isoform early E1A 26 kDa protein (identifier: P03254-2) [UniParc]FASTA Add to basket

Also known as: 243R, S-E1A

The sequence of this isoform differs from the canonical sequence as follows:
140-185: Missing.

« Hide

        10         20         30         40         50
MRHIICHGGV ITEEMAASLL DQLIEEVLAD NLPPPSHFEP PTLHELYDLD 
        60         70         80         90        100
VTAPEDPNEE AVSQIFPDSV MLAVQEGIDL LTFPPAPGSP EPPHLSRQPE 
       110        120        130        140        150
QPEQRALGPV SMPNLVPEVI DLTCHEAGFP PSDDEDEEGP VSEPEPEPEP 
       160        170        180        190        200
EPEPARPTRR PKLVPAILRR PTSPVSRECN SSTDSCDSGP SNTPPEIHPV 
       210        220        230        240 
VPLCPIKPVA VRVGGRRQAV ECIEDLLNES GQPLDLSCKR PRP

Show »

Length:243

Mass (Da):26,452

Checksum:ⁱ0408B45F94D2F250

GO

Isoform early E1A 6 kDa protein (identifier: P03254-3) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
29-55: ADNLPPPSHFEPPTLHELYDLDVTAPE → CLNLSLSPSQNRSLQDLPGVLNWCLLS
56-289: Missing.

« Hide

        10         20         30         40         50
MRHIICHGGV ITEEMAASLL DQLIEEVLCL NLSLSPSQNR SLQDLPGVLN 

WCLLS

Show »

Length:55

Mass (Da):6,075

Checksum:ⁱ078B55A060462F3A

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	68	D → E in AAA92197 (PubMed:7142161).Curated	1
Sequence conflictⁱ	68	D → E in AAA92199 (PubMed:7142161).Curated	1
Sequence conflictⁱ	81	L → F in AAA92197 (PubMed:7142161).Curated	1
Sequence conflictⁱ	81	L → F in AAA92199 (PubMed:7142161).Curated	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_028916	29 – 55	ADNLP…VTAPE → CLNLSLSPSQNRSLQDLPGV LNWCLLS in isoform early E1A 6 kDa protein. CuratedAdd BLAST	27
Alternative sequenceⁱVSP_028917	56 – 289	Missing in isoform early E1A 6 kDa protein. CuratedAdd BLAST	234
Alternative sequenceⁱVSP_000197	140 – 185	Missing in isoform early E1A 26 kDa protein. CuratedAdd BLAST	46

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	J01917 Genomic DNA Translation: AAA92197.1 J01917 Genomic DNA Translation: AAA92198.1 J01917 Genomic DNA Translation: AAA92199.1
PIRⁱ	A03824 Q2AD2
NCBI Reference Sequences More...RefSeqⁱ	AP_000161.1, AC_000007.1

Keywords - Coding sequence diversityⁱ

Alternative splicing

Protein	Similar proteins		Species	Score	Length	Source
P03254	E1A nucleoprotein (Fragment)		HUMAN		12	UniRef100_P03254
P03254-3	6.1 kDa protein		Human mastadenovirus C		55	UniRef100_E1ARN7
E1A 6 kDa protein		ADE06		55

Protein	Similar proteins		Species	Score	Length	Source
P03254	Early E1A protein	)	ADE05		289	UniRef90_P03255
Early E1A protein		Human mastadenovirus C		289
E1A nucleoprotein (Fragment)		HUMAN		12
E1A (Fragment)		ADE01		124
Early E1A protein		ADE06		289
+35
P03254-2	Early E1A protein		Human mastadenovirus C		243	UniRef90_P03254-2
Early E1A protein		ADE05		243
Early E1A protein		ADE06		243
Early E1A protein		AD01A		243
Isoform early E1A 26 kDa protein of Early E1A protein		ADE05		243
+11
P03254-3	E1A 6 kDa protein		Human mastadenovirus C		55	UniRef90_T1UNC5
6 kDa protein		ADE05		55
E1A 6 kDa protein		ADE06		55
Isoform early E1A 6 kDa protein of Early E1A protein		ADE05		55
E1A 6 kDa protein		Human mastadenovirus C		55
+7

Protein	Similar proteins		Species	Score	Length	Source
P03254	Early E1A protein	)	ADE05		289	UniRef50_P03255
Early E1A protein		Human mastadenovirus C		289
E1A (Fragment)		ADE01		124
Early E1A protein		ADE06		289
E1A nucleoprotein (Fragment)		HUMAN		12
+52
P03254-3	E1A 6 kDa protein		Human mastadenovirus C		55	UniRef50_T1UNC5
6 kDa protein		ADE05		55
E1A 6 kDa protein		ADE06		55
Isoform early E1A 6 kDa protein of Early E1A protein		ADE05		55
E1A 6 kDa protein		Human mastadenovirus C		55
+7

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	J01917 Genomic DNA Translation: AAA92197.1 J01917 Genomic DNA Translation: AAA92198.1 J01917 Genomic DNA Translation: AAA92199.1
PIRⁱ	A03824 Q2AD2
RefSeqⁱ	AP_000161.1, AC_000007.1

3D structure databases

SMRⁱ	P03254
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

DIPⁱ	DIP-570N
ELMⁱ	P03254
IntActⁱ	P03254, 3 interactors
MINTⁱ	P03254

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Phylogenomic databases

OrthoDBⁱ	VOG090000J6

OrthoDBⁱ

VOG090000J6

Family and domain databases

InterProⁱ	View protein in InterPro IPR014410 Aden_E1A
Pfamⁱ	View protein in Pfam PF02703 Adeno_E1A, 1 hit
PIRSFⁱ	PIRSF003669 Aden_E1A, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	E1A_ADE02
Accessionⁱ	P03254Primary (citable) accession number: P03254 Secondary accession number(s): P24934, Q67788
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
	Last sequence update:	July 21, 1986
	Last modified:	September 12, 2018
	This is version 110 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Viral Protein Annotation Program

UniProtKB

UniParc

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UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - P03254 (E1A_ADE02)

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Regions

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GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

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GO - Cellular componenti

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Keywords - Diseasei

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Keywords - Developmental stagei

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Motif

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Zinc finger

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Alternative sequence

Sequence databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Phylogenomic databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

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Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Keywords - Developmental stageⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ