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UniProtKB/Swiss-Prot entry P19419


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ELK1_HUMAN
Primary accession number P19419
Secondary accession numbers O75606 O95058 Q969X8 Q9UJM4
Integrated into Swiss-Prot on November 1, 1990
Sequence was last modified on January 24, 2001 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 112)
Name and origin of the protein
Protein name ETS domain-containing protein Elk-1
Synonyms None
Gene name
Name: ELK1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASN-183.
DOI=10.1126/science.2539641; PubMed=2539641 [NCBI, ExPASy, EBI, Israel, Japan]
Rao V.N., Huebner K., Isobe M., Ar-Rushdi A., Croce C.M., Reddy E.S.P.;
"elk, tissue-specific ets-related genes on chromosomes X and 14 near translocation breakpoints.";
Science 244:66-70(1989).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
DOI=10.1016/S0378-1119(98)00448-X; PubMed=9795224 [NCBI, ExPASy, EBI, Israel, Japan]
Harindranath N., Mills F.C., Mitchell M.P., Meindl A., Max E.E.;
"The human elk-1 gene family: the functional gene and two processed pseudogenes embedded in the IgH locus.";
Gene 221:215-224(1998).
[3]
NUCLEOTIDE SEQUENCE (ISOFORM 2).
Aryee D.N.T., Kovar H.;
"Novel family members HuER71, ELFR, and ELKv among ETS-related genes coexpressed with EWS-FLI1 in Ewing tumor cell lines.";
Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
TISSUE=Hippocampus;
DOI=10.1093/dnares/6.1.21; PubMed=10231026 [NCBI, ExPASy, EBI, Israel, Japan]
Yamauchi T., Toko M., Suga M., Hatakeyama T., Isobe M.;
"Structural organization of the human ELK1 gene and its processed pseudogene ELK2 genes.";
DNA Res. 6:21-27(1999).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature03440; PubMed=15772651 [NCBI, ExPASy, EBI, Israel, Japan]
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence of the human X chromosome.";
Nature 434:325-337(2005).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Uterus;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
PROTEIN SEQUENCE OF 318-331; 336-364 AND 380-408, PHOSPHORYLATION AT SER-324; THR-336; SER-383; SER-389 AND SER-422, AND MUTAGENESIS OF SER-324; THR-336; THR-353; THR-363; THR-368; SER-383; SER-389; THR-417 AND SER-422.
PubMed=7889942 [NCBI, ExPASy, EBI, Israel, Japan]
Gille H., Kortenjann M., Thomae O., Moomaw C., Slaughter C., Cobb M.H., Shaw P.E.;
"ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation.";
EMBO J. 14:951-962(1995).
[8]
DOMAINS.
DOI=10.1093/nar/20.13.3317; PubMed=1630903 [NCBI, ExPASy, EBI, Israel, Japan]
Janknecht R., Nordheim A.;
"Elk-1 protein domains required for direct and SRF-assisted DNA-binding.";
Nucleic Acids Res. 20:3317-3324(1992).
[9]
SUMOYLATION AT LYS-249, AND MUTAGENESIS OF LYS-230 AND LYS-249.
DOI=10.1016/S1097-2765(03)00265-X; PubMed=12887893 [NCBI, ExPASy, EBI, Israel, Japan]
Yang S.-H., Jaffray E., Hay R.T., Sharrocks A.D.;
"Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity.";
Mol. Cell 12:63-74(2003).
[10]
SUMOYLATION AT LYS-230; LYS-249 AND LYS-254, AND MUTAGENESIS OF LYS-230; LYS-249 AND LYS-254.
DOI=10.1083/jcb.200310136; PubMed=15210726 [NCBI, ExPASy, EBI, Israel, Japan]
Salinas S., Briancon-Marjollet A., Bossis G., Lopez M.-A., Piechaczyk M., Jariel-Encontre I., Debant A., Hipskind R.A.;
"SUMOylation regulates nucleo-cytoplasmic shuttling of Elk-1.";
J. Cell Biol. 165:767-773(2004).
[11]
SUMOYLATION.
DOI=10.1016/S1097-2765(04)00060-7; PubMed=14992729 [NCBI, ExPASy, EBI, Israel, Japan]
Yang S.-H., Sharrocks A.D.;
"SUMO promotes HDAC-mediated transcriptional repression.";
Mol. Cell 13:611-617(2004).
[12]
INTERACTION WITH PIAS2.
DOI=10.1038/sj.emboj.7600690; PubMed=15920481 [NCBI, ExPASy, EBI, Israel, Japan]
Yang S.-H., Sharrocks A.D.;
"PIASx acts as an Elk-1 coactivator by facilitating derepression.";
EMBO J. 24:2161-2171(2005).
[13]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-94.
DOI=10.1038/74055; PubMed=10742173 [NCBI, ExPASy, EBI, Israel, Japan]
Mo Y., Vaessen B., Johnston K., Marmorstein R.;
"Structure of the elk-1-DNA complex reveals how DNA-distal residues affect ETS domain recognition of DNA.";
Nat. Struct. Biol. 7:292-297(2000).
Comments
  • FUNCTION: Stimulates transcription. Binds to purine-rich DNA sequences. Can form a ternary complex with the serum response factor and the ETS and SRF motifs of the fos serum response element.
  • SUBUNIT: Interacts in its sumoylated form with PIAS2/PIASX which enhances its transcriptional activator activity.
  • INTERACTION:
    P28482:MAPK1; NbExp=1; IntAct=EBI-726632, EBI-959949;
    P63085:Mapk1 (xeno); NbExp=1; IntAct=EBI-726632, EBI-397697;
    P27361:MAPK3; NbExp=1; IntAct=EBI-726632, EBI-73995;
  • SUBCELLULAR LOCATION: Nucleus.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDP19419-1
    This is the isoform sequence displayed in this entry.
    Name2
    SynonymsELKV
    Isoform IDP19419-2
    Features which should be applied to build the isoform sequence: VSP_001466, VSP_001467.
  • TISSUE SPECIFICITY: Lung and testis.
  • PTM: Sumoylation represses transcriptional activator activity as it results in recruitment of HDAC2 to target gene promoters which leads to decreased histone acetylation and reduced transactivator activity. It also regulates nuclear retention.
  • PTM: On mitogenic stimulation, phosphorylated on C-terminal serine and threonine residues by MAPK1. Ser-383 and Ser-389 are the preferred sites for MAPK1. In vitro, phosphorylation by MAPK1 potentiates ternary complex formation with the serum responses factors, SRE and SRF. Phosphorylation leads to loss of sumoylation and restores transcriptional activator activity.
  • SIMILARITY: Belongs to the ETS family.
  • SIMILARITY: Contains 1 ETS DNA-binding domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M25269; AAA52384.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF080616; AAC82466.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000672; AAD00862.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB016193; BAA36616.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB016194; BAA36617.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL009172; CAA15659.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC056150; AAH56150.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00220075; -.
IPI00301527; -.
PIR A41354; TVHUEK.
RefSeq NP_001107595.1; -.
NP_005220.2; -.
UniGene Hs.181128
3D structure databases
PDB
1DUX; X-ray; 2.10 A; C/F=1-94.[ExPASy / RCSB / EBI]
PDBsum 1DUX; -.
ModBase P19419.
Protein-protein interaction databases
IntAct P19419; 4.
PTM databases
PhosphoSite P19419; -.
Enzyme and pathway databases
Pathway_Interaction_DB angiopoietinreceptor_pathway; Angiopoietin receptor Tie2-mediated signaling.
bcr_5pathway; BCR signaling pathway.
cd8tcrdownstreampathway; Downstream signaling in naive CD8+ T cells.
pdgfrapathway; PDGFR-alpha signaling pathway.
tcrraspathway; Ras signaling in the CD4+ TCR pathway.
s1p_s1p2_pathway; S1P2 pathway.
met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
mapktrkpathway; Trk receptor signaling mediated by the MAPK pathway.
Reactome REACT_11061; Signalling by NGF.
Organism-specific databases
GeneCards GC0XM047379; -.
HGNC HGNC:3321; ELK1.
GenAtlas ELK1.
HPA CAB003808; -.
MIM 311040; gene. [NCBI / EBI]
PharmGKB PA27749; -.
Gene expression databases
ArrayExpress P19419; -.
Bgee P19419; -.
CleanEx HS_ELK1; -.
GermOnline ENSG00000126767; Homo sapiens.
Ontologies
GO
GO:0005634; Cellular component: nucleus (inferred by curator from UniProtKB).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0043565; Molecular function: sequence-specific DNA binding (inferred from electronic annotation from InterPro).
GO:0003700; Molecular function: transcription factor activity (inferred from direct assay from UniProtKB).
GO:0045944; Biological process: positive regulation of transcription from RNA polymerase II promoter (inferred from direct assay from UniProtKB).
GO:0006350; Biological process: transcription (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR000418; Ets.
IPR011991; Wing_hlx_DNA_bd.
Graphical view of domain structure.
Gene3D G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 1.
Pfam PF00178; Ets; 1.
Pfam graphical view of domain structure.
PRINTS PR00454; ETSDOMAIN.
SMART SM00413; ETS; 1.
SMART graphical view of domain structure.
PROSITE PS00345; ETS_DOMAIN_1; 1.
PS00346; ETS_DOMAIN_2; 1.
PS50061; ETS_DOMAIN_3; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE P19419; -.
Genome annotation databases
Ensembl ENSG00000126767; Homo sapiens. [Contig view]
GeneID 2002; -.
KEGG hsa:2002; -.
Phylogenomic databases
HOVERGEN P19419; -.
Other
NextBio 8101; -.
SOURCE ELK1; Homo sapiens.
ProtoNet P19419.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Activator; Alternative splicing; Direct protein sequencing; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; Transcription; Transcription regulation; Ubl conjugation.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   428  428     ETS domain-containing protein Elk-1. PRO_0000204095
DNA_BIND   5    86  82     ETS. 
MOD_RES   324   324        Phosphoserine; by MAPK1. 
MOD_RES   336   336        Phosphothreonine; by MAPK1. 
MOD_RES   383   383        Phosphoserine; by MAPK1. 
MOD_RES   389   389        Phosphoserine; by MAPK1. 
MOD_RES   422   422        Phosphoserine; by MAPK1. 
CROSSLNK   230   230        Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO). 
CROSSLNK   249   249        Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO). 
CROSSLNK   254   254        Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO). 
VAR_SEQ   91    95        VAGCS -> SHCAP (in isoform 2). VSP_001466
VAR_SEQ   96   428        Missing (in isoform 2). VSP_001467
VARIANT   144   144  1     G -> S (in dbSNP:rs1997639 [NCBI]). VAR_017108 
VARIANT   183   183  1     S -> N (in dbSNP:rs1059579 [NCBI]). VAR_017109 
MUTAGEN   230   230        K->R: 9-fold increase in transcriptional activator activity; when associated with R-249. Reduction in sumoylation. 
MUTAGEN   249   249        K->R: 9-fold increase in transcriptional activator activity; when associated with R-230. Reduction in sumoylation. 
MUTAGEN   254   254        K->R: Reduction in sumoylation. 
MUTAGEN   324   324        S->A: No effect on ternary complex formation. 
MUTAGEN   336   336        T->A: No effect on ternary complex formation. 
MUTAGEN   353   353        T->A: No effect on ternary complex formation. 
MUTAGEN   363   363        T->A: No effect on ternary complex formation. 
MUTAGEN   368   368        T->A: No effect on ternary complex formation. 
MUTAGEN   383   383        S->A: 17% reduction in ternary complex formation. 
MUTAGEN   389   389        S->A: 34% reduction in ternary complex formation. 
MUTAGEN   417   417        T->A: No effect on ternary complex formation. 
MUTAGEN   422   422        S->A: Slight reduction in ternary complex formation. 
HELIX   7    17  11      
STRAND   19    23  5      
STRAND   25    28  4      
TURN   29    32  4      
STRAND   33    35  3      
HELIX   39    48  10      
TURN   49    51  3      
HELIX   57    67  11      
TURN   68    71  4      
STRAND   72    75  4      
STRAND   82    87  6      
Sequence information
Length: 428 AA [This is the length of the unprocessed precursor] Molecular weight: 44888 Da [This is the MW of the unprocessed precursor] CRC64: 68F71F8ADB9D38CA [This is a checksum on the sequence]
        10         20         30         40         50         60 
MDPSVTLWQF LLQLLREQGN GHIISWTSRD GGEFKLVDAE EVARLWGLRK NKTNMNYDKL 

        70         80         90        100        110        120 
SRALRYYYDK NIIRKVSGQK FVYKFVSYPE VAGCSTEDCP PQPEVSVTST MPNVAPAAIH 

       130        140        150        160        170        180 
AAPGDTVSGK PGTPKGAGMA GPGGLARSSR NEYMRSGLYS TFTIQSLQPQ PPPHPRPAVV 

       190        200        210        220        230        240 
LPSAAPAGAA APPSGSRSTS PSPLEACLEA EEAGLPLQVI LTPPEAPNLK SEELNVEPGL 

       250        260        270        280        290        300 
GRALPPEVKV EGPKEELEVA GERGFVPETT KAEPEVPPQE GVPARLPAVV MDTAGQAGGH 

       310        320        330        340        350        360 
AASSPEISQP QKGRKPRDLE LPLSPSLLGG PGPERTPGSG SGSGLQAPGP ALTPSLLPTH 

       370        380        390        400        410        420 
TLTPVLLTPS SLPPSIHFWS TLSPIAPRSP AKLSFQFPSS GSAQVHIPSI SVDGLSTPVV 


LSPGPQKP 

P19419 in FASTA format

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