P03259 (E1A_ADE12) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Early E1A 29.5 kDa protein
Organism	Human adenovirus A serotype 12 (HAdV-12) (Human adenovirus 12)
Taxonomic identifier	28282 [NCBI]
Taxonomic lineage	Viruses › dsDNA viruses, no RNA stage › Adenoviridae › Mastadenovirus › Human adenovirus A
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	266 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E1A protein has both transforming and trans-activating activities. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Disrupts the function of host retinoblastoma protein RB1/pRb and isoform early E1A 26 kDa protein stabilizes TP53, which are key regulators 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. Interaction with RBX1 and CUL1 inhibits ubiquitination of the proteins targeted by SCF(FBW7) 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 By similarity.
Subunit structure	Interacts with host UBE2I; this interaction interferes with polySUMOylation. Interaction with host RB1 induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting RB1's activity. Interacts with host ATF7; the interaction enhances ATF7-mediated viral transactivation activity which requires the zinc binding domains of both proteins. Interacts (via N-terminus) with CUL1 and E3 ubiquitin ligase RBX1; these interactions inhibit RBX1-CUL1-dependent elongation reaction of ubiquitin chains. Interacts (via N-terminus) with the SCF(FBW7) complex; this interaction results in inhibition of the ubiquitin ligase activity of the SCF(FBW7) complex, ubiquitination of SCF(FBW7) target proteins being diminished. Interacts (via PXLXP motif) with host ZMYND11/BS69 (via MYND-type zinc finger); this interaction inhibits E1A mediated transactivation By similarity. Ref.4
Subcellular location	Host nucleus Potential.
Sequence similarities	Belongs to the adenoviridae E1A protein family.

Ontologies

Keywords
Biological process	G1/S host cell cycle checkpoint dysregulation by virus Host-virus interaction Inhibition of host NF-kappa-B by virus Inhibition of host STAT1 by virus Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway by virus Modulation of host E3 ubiquitin ligases by virus Modulation of host cell cycle by virus Modulation of host ubiquitin pathway by virus Transcription Transcription regulation Viral immunoevasion
Cellular component	Host nucleus
Coding sequence diversity	Alternative splicing
Developmental stage	Early protein
Disease	Oncogene
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Activator
Gene Ontology (GO)
Biological process	evasion by virus of host immune response Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform Early E1A 29.5 kDa protein (identifier: P03259-1)

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: P03259-2)

The sequence of this isoform differs from the canonical sequence as follows:
     160-190: Missing.

Isoform Early E1A 22 kDa protein (identifier: P03259-3)

The sequence of this isoform differs from the canonical sequence as follows:
     191-234: Missing.
     259-266: SVKRPRCN → KCAMGGGR

Isoform Early E1A 6 kDa protein (identifier: P03259-4)

The sequence of this isoform differs from the canonical sequence as follows:
     31-244: Missing.
     245-266: IQEEEREQTVPVDLSVKRPRCN → FPIMSLNLIALWMAMSDPHPRN

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 266	266	Early E1A 29.5 kDa protein		PRO_0000221696
Regions
	Zinc finger	159 – 179	21	Potential
	Region	39 – 47	9	Interaction with RB1 in competition with E2F1 By similarity
	Region	75 – 145	71	Interaction with UBE2I
	Motif	98 – 102	5	PXLXP motif, interaction with host ZMYND11 By similarity
	Motif	107 – 111	5	LXCXE motif, interaction with host RB1 Potential
	Motif	255 – 259	5	PXDLS motif, CTBP-binding By similarity
	Motif	261 – 265	5	Nuclear localization signal Potential
Natural variations
	Alternative sequence	31 – 244	214	Missing in isoform Early E1A 6 kDa protein.		VSP_000200
	Alternative sequence	160 – 190	31	Missing in isoform Early E1A 26 kDa protein.		VSP_000201
	Alternative sequence	191 – 234	44	Missing in isoform Early E1A 22 kDa protein.		VSP_000202
	Alternative sequence	245 – 266	22	IQEEE…RPRCN → FPIMSLNLIALWMAMSDPHP RN in isoform Early E1A 6 kDa protein.		VSP_000203
	Alternative sequence	259 – 266	8	SVKRPRCN → KCAMGGGR in isoform Early E1A 22 kDa protein.		VSP_000204

Sequences

	Sequence		Length	Mass (Da)
	Isoform Early E1A 29.5 kDa protein [UniParc]. Last modified July 21, 1986. Version 1. Checksum: A93A93A62D4541BE	FASTA	266	29,691
	10 20 30 40 50 60 MRTEMTPLVL SYQEADDILE HLVDNFFNEV PSDDDLYVPS LYELYDLDVE SAGEDNNEQA 70 80 90 100 110 120 VNEFFPESLI LAASEGLFLP EPPVLSPVCE PIGGECMPQL HPEDMDLLCY EMGFPCSDSE 130 140 150 160 170 180 DEQDENGMAH VSASAAAAAA DREREEFQLD HPELPGHNCK SCEHHRNSTG NTDLMCSLCY 190 200 210 220 230 240 LRAYNMFIYS PVSDNEPEPN STLDGDERPS PPKLGSAVPE GVIKPVPQRV TGRRRCAVES 250 260 ILDLIQEEER EQTVPVDLSV KRPRCN
	Isoform Early E1A 26 kDa protein [UniParc]. Checksum: 676F452FA17EB3CA	FASTA	235	26,050
	10 20 30 40 50 60 MRTEMTPLVL SYQEADDILE HLVDNFFNEV PSDDDLYVPS LYELYDLDVE SAGEDNNEQA 70 80 90 100 110 120 VNEFFPESLI LAASEGLFLP EPPVLSPVCE PIGGECMPQL HPEDMDLLCY EMGFPCSDSE 130 140 150 160 170 180 DEQDENGMAH VSASAAAAAA DREREEFQLD HPELPGHNCP VSDNEPEPNS TLDGDERPSP 190 200 210 220 230 PKLGSAVPEG VIKPVPQRVT GRRRCAVESI LDLIQEEERE QTVPVDLSVK RPRCN
	Isoform Early E1A 22 kDa protein [UniParc]. Checksum: 01DD89B8B01D8246	FASTA	222	24,853
	10 20 30 40 50 60 MRTEMTPLVL SYQEADDILE HLVDNFFNEV PSDDDLYVPS LYELYDLDVE SAGEDNNEQA 70 80 90 100 110 120 VNEFFPESLI LAASEGLFLP EPPVLSPVCE PIGGECMPQL HPEDMDLLCY EMGFPCSDSE 130 140 150 160 170 180 DEQDENGMAH VSASAAAAAA DREREEFQLD HPELPGHNCK SCEHHRNSTG NTDLMCSLCY 190 200 210 220 LRAYNMFIYS RCAVESILDL IQEEEREQTV PVDLKCAMGG GR
	Isoform Early E1A 6 kDa protein [UniParc]. Checksum: 68D6E5EE080ED5CC	FASTA	52	6,107
	10 20 30 40 50 MRTEMTPLVL SYQEADDILE HLVDNFFNEV FPIMSLNLIA LWMAMSDPHP RN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and gene organization in the transformed Hind III-G fragment of Ad12." Sugisaki H., Sugimoto K., Takanami M., Shiroki K., Saito I., Shimojo H., Sawada Y., Uemizu Y., Uesugi S., Fujinaga K. Cell 20:777-786(1980) [PubMed: 6251973] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Structure of two adenovirus type 12 transforming polypeptides and their evolutionary implications." Perricaudet M., le Moullec J.-M., Tiollais P., Pettersson U. Nature 288:174-176(1980) [PubMed: 7432516] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Nucleotide sequence of human adenovirus type 12 DNA: comparative functional analysis." Sprengel J., Schmitz B., Heuss-Neitzel D., Zock C., Doerfler W. J. Virol. 68:379-389(1994) [PubMed: 8254750] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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 UBE2I.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	V00004 Genomic DNA. Translation: CAA23400.1. V00004 Genomic DNA. Translation: CAA23401.1. V00004 Genomic DNA. Translation: CAA23402.1. X73487 Genomic DNA. Translation: CAA51877.1.
PIR	AQADG2. A03828.
RefSeq	NP_040910.2. NC_001460.1.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1785129.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	1460853.
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...

Entry information

Entry name

E1A_ADE12

Accession

Primary (citable) accession number: P03259

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 31, 2011
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program