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. 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) (PubMed:26405230).1 Publication5 Publications

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Zinc fingerⁱ	154 – 174	2 PublicationsAdd BLAST		21

GO - Molecular functionⁱ

activating transcription factor binding
Source: CAFA
Inferred from physical interactionⁱ
- 16605275
metal ion binding Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
modulation by virus of host ubiquitin-protein ligase activity Source: UniProtKB-KW
positive regulation of cell proliferation
Source: BHF-UCL
Inferred from direct assayⁱ
- 9054499
regulation of transcription, DNA-templated Source: InterPro
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

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 protein Alternative name(s): Early E1A 32 kDa protein
Organismⁱ	Human adenovirus C serotype 5 (HAdV-5) (Human adenovirus 5)
Taxonomic identifierⁱ	28285 [NCBI]
Taxonomic lineageⁱ	Viruses › dsDNA viruses, no RNA stage › Adenoviridae › Mastadenovirus › Human mastadenovirus C
Virus hostⁱ	Homo sapiens (Human) [TaxID: 9606]
Proteomesⁱ	UP000004992 Componentⁱ: Genome

Subcellular locationⁱ

Host nucleus
1 Publication
Manual assertion based on experiment inⁱ
- Ref.19
  "Functional analysis of the C-terminal region of human adenovirus E1A reveals a misidentified nuclear localization signal."
  Cohen M.J., King C.R., Dikeakos J.D., Mymryk J.S.
  Virology 468:238-243(2014) [PubMed] [Europe PMC] [Abstract]
  Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL.

GO - Cellular componentⁱ

host cell nucleus
Source: UniProtKB
Inferred from direct assayⁱ
- 25194920

View the complete GO annotation on QuickGO ...

Keywords - Cellular componentⁱ

Host nucleus

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	115	L → A: Complete loss of interaction with host ZMYND11. 1 Publication	1
Mutagenesisⁱ	122 – 126	LTCHE → VTSHD: Abolishes interaction with host TMEM173/STING. 1 Publication	5
Mutagenesisⁱ	122	L → I: Abolishes binding to UBE2I. 1 Publication	1
Mutagenesisⁱ	154	C → S: Loss of transactivation. 1 Publication	1
Mutagenesisⁱ	157	C → S: Loss of transactivation. 1 Publication	1
Mutagenesisⁱ	171	C → S: Loss of transactivation. 1 Publication	1
Mutagenesisⁱ	174	C → S: Loss of transactivation. 1 Publication	1
Mutagenesisⁱ	281 – 282	DL → AS: 30% decrease in virus replication efficiency. Enhanced immortalization and Ras cooperative transformation. 1 Publication	2

Keywords - Diseaseⁱ

Oncogene

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000221694	1 – 289	Early E1A proteinAdd BLAST		289

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	89	Phosphoserine; by host1 Publication	1
Modified residueⁱ	219	Phosphoserine; by host1 Publication	1
Modified residueⁱ	231	Phosphoserine; by host1 Publication	1

Keywords - PTMⁱ

Phosphoprotein

PTM databases

iPTMnetⁱ	P03255

iPTMnetⁱ

P03255

Expressionⁱ

Keywords - Developmental stageⁱ

Early protein

Interactionⁱ

Subunit structureⁱ

Interacts with host UBE2I; this interaction interferes with polySUMOylation (Probable) (PubMed:8824223, PubMed:20543865). 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 (PubMed:17974914). Interacts with host ATF7; the interaction enhances ATF7-mediated viral transactivation activity which requires the zinc binding domains of both proteins (By similarity). 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 (PubMed:19679664). Interacts (via PXLXP motif) with host ZMYND11/BS69 (via MYND-type zinc finger); this interaction inhibits E1A mediated transactivation (PubMed:11733528). Interacts with host EP300; this interaction stimulates the acetylation of RB1 by recruiting EP300 and RB1 into a multimeric-protein complex (PubMed:11433299). Interacts with host CTBP1 and CTBP2; this interaction seems to potentiate viral replication (PubMed:23747199, PubMed:7479821). Interacts with host DCAF7 (ref.16). Interacts with host DYRK1A (PubMed:23864635). Interacts with host KPNA4; this interaction allows E1A import into the host nucleus (PubMed:23864635). Interacts with host EP400; this interaction stabilizes MYC (PubMed:18413597). Interacts with host TBP protein; this interaction probably disrupts the TBP-TATA complex (PubMed:8146144). 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) (PubMed:26405230).By similarityCurated12 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
Cdkn1b	O08769	2	EBI-2603114,EBI-7796656	From Rattus norvegicus.
CREBBP	Q92793	3	EBI-2603114,EBI-81215	From Homo sapiens.
Crebbp	P45481	2	EBI-2603114,EBI-296306	From Mus musculus.
EP300	Q09472	3	EBI-6859460,EBI-447295	From Homo sapiens.
KAT2B	Q92831	3	EBI-6859460,EBI-477430	From Homo sapiens.
MDM4	O15151	3	EBI-6859460,EBI-398437	From Homo sapiens.
MED28	Q9H204	2	EBI-2603114,EBI-514199	From Homo sapiens.
PSMC3	P17980	2	EBI-6692439,EBI-359720	From Homo sapiens.
PSMC5	P62195	2	EBI-6692439,EBI-357745	From Homo sapiens.
RARB	P10826-2	2	EBI-2603114,EBI-8583223	From a different organism.
RB1	P06400	10	EBI-2603114,EBI-491274	From Homo sapiens.
RBL1	P28749	3	EBI-2603114,EBI-971402	From Homo sapiens.
RBL2	Q08999	2	EBI-2603114,EBI-971439	From Homo sapiens.
STAT1	P42224	2	EBI-6859460,EBI-1057697	From Homo sapiens.
TAF1	P21675	3	EBI-2603114,EBI-491289	From Homo sapiens.
Taf4	P47825	3	EBI-2603114,EBI-277958	From Drosophila melanogaster.
TMEM173	Q86WV6	2	EBI-2603114,EBI-2800345	From Homo sapiens.
ZMYND11	Q15326	3	EBI-2603114,EBI-2623509	From Homo sapiens.

GO - Molecular functionⁱ

activating transcription factor binding
Source: CAFA
Inferred from physical interactionⁱ
- 16605275

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

Database of interacting proteins More...DIPⁱ	DIP-40736N
ELMⁱ	P03255
IntActⁱ	P03255, 38 interactors
Molecular INTeraction database More...MINTⁱ	P03255

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	43 – 46	Combined sources	4
Helixⁱ	59 – 63	Combined sources	5
Beta strandⁱ	68 – 70	Combined sources	3
Helixⁱ	72 – 74	Combined sources	3
Helixⁱ	80 – 82	Combined sources	3

Show more details

3D structure databases

ProteinModelPortalⁱ	P03255
SMRⁱ	P03255
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P03255

EvolutionaryTraceⁱ

P03255

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	41 – 49	Interaction with RB1 in competition with E2F1Curated		9
Regionⁱ	76 – 140	Interaction with UBE2IAdd BLAST		65

Motif

Feature key	Position(s)	DescriptionActions	Length
Motifⁱ	113 – 117	PXLXP motif, interaction with host ZMYND11	5
Motifⁱ	122 – 126	LXCXE motif, interaction with host RB1 and TMEM173/STINGSequence analysis1 Publication	5
Motifⁱ	258 – 289	Bipartite nuclear localization signalSequence analysis1 PublicationAdd BLAST	32
Motifⁱ	279 – 283	PXDLS motif, CTBP-binding1 Publication	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	2 PublicationsAdd 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: P03255-1) [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
ARPTRRPKMA PAILRRPTSP VSRECNSSTD SCDSGPSNTP PEIHPVVPLC 
       260        270        280 
PIKPVAVRVG GRRQAVECIE DLLNEPGQPL DLSCKRPRP

Length:289

Mass (Da):31,851

Last modified:July 21, 1986 - v1

Checksum:ⁱ8C5997A3908C40D7

GO

Isoform early E1A 26 kDa protein (identifier: P03255-2) [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 PKMAPAILRR PTSPVSRECN SSTDSCDSGP SNTPPEIHPV 
       210        220        230        240 
VPLCPIKPVA VRVGGRRQAV ECIEDLLNEP GQPLDLSCKR PRP

Note: No experimental confirmation available.

Show »

Length:243

Mass (Da):26,452

Checksum:ⁱCA355781A92A4D42

GO

Isoform early E1A 6 kDa protein (identifier: P03255-3) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MRHIICHGGV ITEEMAASLL DQLIEEVLCL NLSLSPSQNR SLQDLPAVLK 

WRLLS

Note: No experimental confirmation available.

Show »

Length:55

Mass (Da):6,156

Checksum:ⁱ001555BAD0415F3A

GO

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_028918	29 – 55	ADNLP…VTAPE → CLNLSLSPSQNRSLQDLPAV LKWRLLS in isoform early E1A 6 kDa protein. CuratedAdd BLAST	27
Alternative sequenceⁱVSP_028919	56 – 289	Missing in isoform early E1A 6 kDa protein. CuratedAdd BLAST	234
Alternative sequenceⁱVSP_000198	140 – 185	Missing in isoform early E1A 26 kDa protein. CuratedAdd BLAST	46

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M73260 Genomic DNA No translation available. X02996 Genomic DNA Translation: CAB40663.1 X02996 Genomic DNA Translation: CAB40664.1 X02996 Genomic DNA Translation: CAB40665.1
PIRⁱ	A03825 ERAD65 C03824 Q2AD5
NCBI Reference Sequences More...RefSeqⁱ	AP_000197.1, AC_000008.1 [P03255-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Protein	Similar proteins		Species	Score	Length	Source
P03255	Early E1A protein		Human mastadenovirus C		289	UniRef100_P03255
Early E1A protein		ADE05		289
P03255-2	Early E1A protein		Human mastadenovirus C		243	UniRef100_T1UKX5
Early E1A protein		ADE05		243
P03255-3	E1A 6 kDa protein		Human mastadenovirus C		55	UniRef100_T1UNC5
6 kDa protein		ADE05		55

Protein	Similar proteins		Species	Score	Length	Source
P03255	Early E1A protein		ADE02		289	UniRef90_P03255
Early E1A protein		Human mastadenovirus C		289
Early E1A protein		ADE05		289
E1A nucleoprotein (Fragment)		HUMAN		12
E1A (Fragment)		ADE01		124
+35
P03255-2	Isoform early E1A 26 kDa protein of Early E1A protein		ADE02		243	UniRef90_P03254-2
Early E1A protein		Human mastadenovirus C		243
Early E1A protein		ADE05		243
Early E1A protein		ADE06		243
Early E1A protein		AD01A		243
+11
P03255-3	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		ADE02		55
E1A 6 kDa protein		Human mastadenovirus C		55
+7

Protein	Similar proteins		Species	Score	Length	Source
P03255	Early E1A protein		ADE02		289	UniRef50_P03255
Early E1A protein		Human mastadenovirus C		289
Early E1A protein		ADE05		289
E1A (Fragment)		ADE01		124
Early E1A protein		ADE06		289
+52
P03255-3	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		ADE02		55
E1A 6 kDa protein		Human mastadenovirus C		55
+7

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M73260 Genomic DNA No translation available. X02996 Genomic DNA Translation: CAB40663.1 X02996 Genomic DNA Translation: CAB40664.1 X02996 Genomic DNA Translation: CAB40665.1
PIRⁱ	A03825 ERAD65 C03824 Q2AD5
RefSeqⁱ	AP_000197.1, AC_000008.1 [P03255-1]

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2KJE	NMR	-	B	53-91	[»]
	2R7G	X-ray	1.67	B/D/E	40-49	[»]
ProteinModelPortalⁱ	P03255
SMRⁱ	P03255
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

DIPⁱ	DIP-40736N
ELMⁱ	P03255
IntActⁱ	P03255, 38 interactors
MINTⁱ	P03255

PTM databases

iPTMnetⁱ	P03255

iPTMnetⁱ

P03255

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Phylogenomic databases

OrthoDBⁱ	VOG090000J6

OrthoDBⁱ

VOG090000J6

Miscellaneous databases

EvolutionaryTraceⁱ	P03255

EvolutionaryTraceⁱ

P03255

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_ADE05
Accessionⁱ	P03255Primary (citable) accession number: P03255 Secondary accession number(s): P06438, Q64825, Q64826
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
	Last sequence update:	July 21, 1986
	Last modified:	November 7, 2018
	This is version 137 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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Supporting data

UniProtKB - P03255 (E1A_ADE05)

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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

PTM databases

<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

GO - Molecular functioni

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

Secondary structure

3D structure databases

Miscellaneous 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

Alternative sequence

Sequence databases

Keywords - Coding sequence diversityi

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Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Protocols and materials databases

Phylogenomic databases

Miscellaneous databases

Family and domain databases

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<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ