ELK4_HUMAN
ID ELK4_HUMAN Reviewed; 431 AA.
AC P28324; P28323; Q6GSJ2;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2001, sequence version 3.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=ETS domain-containing protein Elk-4;
DE AltName: Full=Serum response factor accessory protein 1;
DE Short=SAP-1;
DE Short=SRF accessory protein 1;
GN Name=ELK4; Synonyms=SAP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RX PubMed=1339307; DOI=10.1016/0092-8674(92)90194-h;
RA Dalton S., Treisman R.;
RT "Characterization of SAP-1, a protein recruited by serum response factor to
RT the c-fos serum response element.";
RL Cell 68:597-612(1992).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=8293474;
RA Dalton S., Treisman R.;
RT "Characterization of SAP-1, a protein recruited by serum response factor to
RT the c-fos serum response element.";
RL Cell 76:411-411(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-167, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 1-93.
RX PubMed=9734357; DOI=10.1016/s1097-2765(00)80130-6;
RA Mo Y., Vaessen B., Johnston K., Marmorstein R.;
RT "Structures of SAP-1 bound to DNA targets from the E74 and c-fos promoters:
RT insights into DNA sequence discrimination by Ets proteins.";
RL Mol. Cell 2:201-212(1998).
RN [9]
RP FUNCTION, AND INTERACTION WITH SIRT7.
RX PubMed=22722849; DOI=10.1038/nature11043;
RA Barber M.F., Michishita-Kioi E., Xi Y., Tasselli L., Kioi M., Moqtaderi Z.,
RA Tennen R.I., Paredes S., Young N.L., Chen K., Struhl K., Garcia B.A.,
RA Gozani O., Li W., Chua K.F.;
RT "SIRT7 links H3K18 deacetylation to maintenance of oncogenic
RT transformation.";
RL Nature 487:114-118(2012).
CC -!- FUNCTION: Involved in both transcriptional activation and repression.
CC Interaction with SIRT7 leads to recruitment and stabilization of SIRT7
CC at promoters, followed by deacetylation of histone H3 at 'Lys-18'
CC (H3K18Ac) and subsequent transcription repression. Forms a ternary
CC complex with the serum response factor (SRF). Requires DNA-bound SRF
CC for ternary complex formation and makes extensive DNA contacts to the
CC 5'side of SRF, but does not bind DNA autonomously.
CC {ECO:0000269|PubMed:22722849}.
CC -!- SUBUNIT: Interacts with SIRT7. {ECO:0000269|PubMed:22722849}.
CC -!- INTERACTION:
CC P28324; Q9NRC8: SIRT7; NbExp=3; IntAct=EBI-11277718, EBI-716046;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=SAP-1A;
CC IsoId=P28324-1; Sequence=Displayed;
CC Name=2; Synonyms=SAP-1B;
CC IsoId=P28324-2; Sequence=VSP_001468;
CC -!- SIMILARITY: Belongs to the ETS family. {ECO:0000305}.
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DR EMBL; M85165; AAA03631.1; -; mRNA.
DR EMBL; M85164; AAA03632.1; -; mRNA.
DR EMBL; CH471067; EAW91570.1; -; Genomic_DNA.
DR EMBL; BC063676; AAH63676.1; -; mRNA.
DR CCDS; CCDS1456.1; -. [P28324-1]
DR CCDS; CCDS1457.1; -. [P28324-2]
DR PIR; A42093; A42093.
DR PIR; A53012; A53012.
DR PIR; B42093; B42093.
DR RefSeq; NP_001964.2; NM_001973.3. [P28324-1]
DR RefSeq; NP_068567.1; NM_021795.2. [P28324-2]
DR RefSeq; XP_005245007.1; XM_005244950.4.
DR RefSeq; XP_005245008.1; XM_005244951.4.
DR PDB; 1BC7; X-ray; 2.01 A; C=1-93.
DR PDB; 1BC8; X-ray; 1.93 A; C=1-93.
DR PDB; 1HBX; X-ray; 3.15 A; G/H=2-156.
DR PDB; 1K6O; X-ray; 3.19 A; A=1-93.
DR PDBsum; 1BC7; -.
DR PDBsum; 1BC8; -.
DR PDBsum; 1HBX; -.
DR PDBsum; 1K6O; -.
DR AlphaFoldDB; P28324; -.
DR SMR; P28324; -.
DR BioGRID; 108320; 132.
DR CORUM; P28324; -.
DR DIP; DIP-59907N; -.
DR IntAct; P28324; 76.
DR STRING; 9606.ENSP00000350681; -.
DR GlyGen; P28324; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P28324; -.
DR PhosphoSitePlus; P28324; -.
DR BioMuta; ELK4; -.
DR DMDM; 12585557; -.
DR EPD; P28324; -.
DR jPOST; P28324; -.
DR MassIVE; P28324; -.
DR MaxQB; P28324; -.
DR PaxDb; P28324; -.
DR PeptideAtlas; P28324; -.
DR PRIDE; P28324; -.
DR ProteomicsDB; 54462; -. [P28324-1]
DR ProteomicsDB; 54463; -. [P28324-2]
DR Antibodypedia; 20682; 144 antibodies from 25 providers.
DR DNASU; 2005; -.
DR Ensembl; ENST00000289703.8; ENSP00000289703.4; ENSG00000158711.14. [P28324-2]
DR Ensembl; ENST00000357992.9; ENSP00000350681.4; ENSG00000158711.14. [P28324-1]
DR Ensembl; ENST00000616704.4; ENSP00000483628.1; ENSG00000158711.14. [P28324-1]
DR GeneID; 2005; -.
DR KEGG; hsa:2005; -.
DR MANE-Select; ENST00000357992.9; ENSP00000350681.4; NM_001973.4; NP_001964.2.
DR UCSC; uc001hcy.3; human. [P28324-1]
DR CTD; 2005; -.
DR DisGeNET; 2005; -.
DR GeneCards; ELK4; -.
DR HGNC; HGNC:3326; ELK4.
DR HPA; ENSG00000158711; Low tissue specificity.
DR MIM; 600246; gene.
DR neXtProt; NX_P28324; -.
DR OpenTargets; ENSG00000158711; -.
DR PharmGKB; PA27753; -.
DR VEuPathDB; HostDB:ENSG00000158711; -.
DR eggNOG; KOG3806; Eukaryota.
DR GeneTree; ENSGT00940000158900; -.
DR HOGENOM; CLU_036905_1_0_1; -.
DR InParanoid; P28324; -.
DR OMA; NCGKEKS; -.
DR PhylomeDB; P28324; -.
DR TreeFam; TF317732; -.
DR PathwayCommons; P28324; -.
DR SignaLink; P28324; -.
DR SIGNOR; P28324; -.
DR BioGRID-ORCS; 2005; 8 hits in 1098 CRISPR screens.
DR ChiTaRS; ELK4; human.
DR EvolutionaryTrace; P28324; -.
DR GeneWiki; ELK4; -.
DR GenomeRNAi; 2005; -.
DR Pharos; P28324; Tbio.
DR PRO; PR:P28324; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P28324; protein.
DR Bgee; ENSG00000158711; Expressed in tendon of biceps brachii and 190 other tissues.
DR ExpressionAtlas; P28324; baseline and differential.
DR Genevisible; P28324; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0070932; P:histone H3 deacetylation; IDA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR DisProt; DP01329; -.
DR Gene3D; 1.10.10.10; -; 1.
DR IDEAL; IID00148; -.
DR InterPro; IPR000418; Ets_dom.
DR InterPro; IPR046328; ETS_fam.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11849; PTHR11849; 1.
DR Pfam; PF00178; Ets; 1.
DR PRINTS; PR00454; ETSDOMAIN.
DR SMART; SM00413; ETS; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00345; ETS_DOMAIN_1; 1.
DR PROSITE; PS00346; ETS_DOMAIN_2; 1.
DR PROSITE; PS50061; ETS_DOMAIN_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..431
FT /note="ETS domain-containing protein Elk-4"
FT /id="PRO_0000204099"
FT DNA_BIND 5..85
FT /note="ETS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00237"
FT REGION 114..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 251..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 294..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 411..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..272
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..319
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 167
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 361..431
FT /note="TPIILTPSPLLSSIHFWSTLSPVAPLSPARLQGANTLFQFPSVLNSHGPFTL
FT SGLDGPSTPGPFSPDLQKT -> VACSLFMVSPLLSFICPFKQIQNLYTQVCFLLLRFV
FT LERLCVTVM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_001468"
FT CONFLICT 326
FT /note="E -> G (in Ref. 1; AAA03631)"
FT /evidence="ECO:0000305"
FT HELIX 7..14
FT /evidence="ECO:0007829|PDB:1BC8"
FT HELIX 18..20
FT /evidence="ECO:0007829|PDB:1BC8"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:1BC8"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:1BC8"
FT STRAND 28..34
FT /evidence="ECO:0007829|PDB:1BC8"
FT HELIX 38..49
FT /evidence="ECO:0007829|PDB:1BC8"
FT HELIX 56..69
FT /evidence="ECO:0007829|PDB:1BC8"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:1BC8"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:1K6O"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:1BC8"
FT TURN 85..88
FT /evidence="ECO:0007829|PDB:1BC8"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:1BC8"
FT HELIX 138..143
FT /evidence="ECO:0007829|PDB:1HBX"
FT STRAND 144..152
FT /evidence="ECO:0007829|PDB:1HBX"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:1HBX"
SQ SEQUENCE 431 AA; 46900 MW; 80EE3E69995C7A7D CRC64;
MDSAITLWQF LLQLLQKPQN KHMICWTSND GQFKLLQAEE VARLWGIRKN KPNMNYDKLS
RALRYYYVKN IIKKVNGQKF VYKFVSYPEI LNMDPMTVGR IEGDCESLNF SEVSSSSKDV
ENGGKDKPPQ PGAKTSSRND YIHSGLYSSF TLNSLNSSNV KLFKLIKTEN PAEKLAEKKS
PQEPTPSVIK FVTTPSKKPP VEPVAATISI GPSISPSSEE TIQALETLVS PKLPSLEAPT
SASNVMTAFA TTPPISSIPP LQEPPRTPSP PLSSHPDIDT DIDSVASQPM ELPENLSLEP
KDQDSVLLEK DKVNNSSRSK KPKGLELAPT LVITSSDPSP LGILSPSLPT ASLTPAFFSQ
TPIILTPSPL LSSIHFWSTL SPVAPLSPAR LQGANTLFQF PSVLNSHGPF TLSGLDGPST
PGPFSPDLQK T
