Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O60869 (EDF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endothelial differentiation-related factor 1

Short name=EDF-1
Alternative name(s):
Multiprotein-bridging factor 1
Short name=MBF1
Gene names
Name:EDF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length148 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional coactivator stimulating NR5A1 and ligand-dependent NR1H3/LXRA and PPARG transcriptional activities. Enhances the DNA-binding activity of ATF1, ATF2, CREB1 and NR5A1. Regulates nitric oxid synthase activity probably by sequestering calmodulin in the cytoplasm. May function in endothelial cells differentiation, hormone-induced cardiomyocytes hypertrophy and lipid metabolism. Ref.1 Ref.2 Ref.9 Ref.10

Subunit structure

Interacts with TBP and the transcription factor IID (TFIID) complex, NR5A2, NR1H3 and PPARG. Interaction with TBP is regulated by phosphorylation. Binds NR5A1, ATF1, FOS and JUN via their conserved basic region. Binding to calmodulin is regulated by calcium and phosphorylation of the IQ motif. Ref.2 Ref.8 Ref.9 Ref.10

Subcellular location

Cytoplasm. Nucleus. Note: Also nuclear upon binding to NR5A1 and treatment of cells with TPA or forskolin. Ref.2 Ref.8 Ref.10

Tissue specificity

Expressed in brain, liver, lung, kidney and heart (at protein level). Ubiquitously expressed. More abundant in heart, pancreas, liver, intestine and adipose tissues. Ref.1 Ref.2 Ref.9

Developmental stage

Expressed in fetal tissues. More abundant in kidney. Ref.1

Induction

Down-regulated by HIV-1 Tat or phorbol ester (TPA) treatment in endothelial cells (at mRNA and protein levels). Ref.1

Domain

The IQ motif, which is involved in calmodulin binding, overlaps with the binding domain for nuclear receptors and transcription factors. Its phosphorylation probably allows a switch between the two activities of the protein By similarity.

Post-translational modification

Phosphorylated (by PKA and PKC). Ref.8 Ref.10

Sequence similarities

Contains 1 HTH cro/C1-type DNA-binding domain.

Sequence caution

The sequence CAI12698.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processDifferentiation
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandCalmodulin-binding
DNA-binding
   Molecular functionActivator
Developmental protein
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processendothelial cell differentiation

Traceable author statement Ref.9. Source: UniProtKB

multicellular organismal development

Traceable author statement Ref.1. Source: ProtInc

positive regulation of DNA binding

Inferred from direct assay Ref.2. Source: UniProtKB

positive regulation of transcription, DNA-templated

Traceable author statement PubMed 8164657. Source: UniProtKB

regulation of lipid metabolic process

Traceable author statement Ref.9. Source: UniProtKB

regulation of transcription, DNA-templated

Traceable author statement Ref.9PubMed 8164657. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.2. Source: UniProtKB

intracellular

Traceable author statement Ref.1. Source: ProtInc

nucleolus

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay Ref.2. Source: UniProtKB

   Molecular_functionpoly(A) RNA binding

Inferred from direct assay PubMed 22658674PubMed 22681889. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.2Ref.9. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

transcription coactivator activity

Inferred from mutant phenotype Ref.2Ref.9. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60869-1)

Also known as: Alpha;

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 2 (identifier: O60869-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     130-148: LKLRGKDIGKPIEKGPRAK → ECPSTLRRVR
Isoform 3 (identifier: O60869-3)

The sequence of this isoform differs from the canonical sequence as follows:
     129-148: GLKLRGKDIGKPIEKGPRAK → DVGTRSARVLRAQ
Note: No experimental confirmation available. Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 148147Endothelial differentiation-related factor 1
PRO_0000149795

Regions

Domain81 – 13555HTH cro/C1-type
DNA binding92 – 11120H-T-H motif Potential
Region37 – 11377Interaction with NR5A2, PPARG and NR1H3
Region69 – 10840Interaction with TBP and NR5A1
Motif81 – 888IQ motif

Amino acid modifications

Modified residue21N-acetylalanine Ref.7 Ref.11 Ref.13

Natural variations

Alternative sequence129 – 14820GLKLR…GPRAK → DVGTRSARVLRAQ in isoform 3.
VSP_054701
Alternative sequence130 – 14819LKLRG…GPRAK → ECPSTLRRVR in isoform 2.
VSP_013336

Experimental info

Mutagenesis401T → D: Loss of interaction with CALM; when associated with D-58; D-91 and D-111. Ref.8
Mutagenesis581T → D: Loss of interaction with CALM; when associated with D-40; D-91 and D-111. Ref.8
Mutagenesis651T → D: No effect on CALM-binding. No effect; when associated with D-74. Ref.10
Mutagenesis741T → D: No effect on CALM-binding. No effect; when associated with D-65. Ref.10
Mutagenesis871S → A: No effect on CALM-binding. Ref.10
Mutagenesis871S → D: Loss of interaction with CALM and higher affinity for TBP. Same effect; when associated with D-65 and D-74. Ref.10
Mutagenesis911T → A: No effect on CALM-binding. Ref.8
Mutagenesis911T → D: Partial loss of interaction with CALM. Complete loss of interaction; when associated with D-40; D-58 and D-111. Ref.8
Mutagenesis1111S → D: Loss of interaction with CALM; when associated with D-40; D-58 and D-91. Ref.8

Secondary structure

.............. 148
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: ADC2C5384BF85C11

FASTA14816,369
        10         20         30         40         50         60 
MAESDWDTVT VLRKKGPTAA QAKSKQAILA AQRRGEDVET SKKWAAGQNK QHSITKNTAK 

        70         80         90        100        110        120 
LDRETEELHH DRVTLEVGKV IQQGRQSKGL TQKDLATKIN EKPQVIADYE SGRAIPNNQV 

       130        140 
LGKIERAIGL KLRGKDIGKP IEKGPRAK 

« Hide

Isoform 2 (Beta) [UniParc].

Checksum: 9F30DE6890D7E801
Show »

FASTA13915,481
Isoform 3 [UniParc].

Checksum: E31C8E26A4679A23
Show »

FASTA14115,636

References

« Hide 'large scale' references
[1]"EDF-1, a novel gene product down-regulated in human endothelial cell differentiation."
Dragoni I., Mariotti M., Consalez G.G., Soria M.R., Maier J.A.M.
J. Biol. Chem. 273:31119-31124(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, FUNCTION.
[2]"The role of human MBF1 as a transcriptional coactivator."
Kabe Y., Goto M., Shima D., Imai T., Wada T., Morohashi K., Shirakawa M., Hirose S., Handa H.
J. Biol. Chem. 274:34196-34202(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, INTERACTION WITH TBP; NR5A1; FOS; JUN AND ATF1, SUBCELLULAR LOCATION, FUNCTION.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Pancreas.
[7]Bienvenut W.V., Waridel P., Quadroni M.
Submitted (MAR-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-13 AND 99-113, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[8]"Interaction between endothelial differentiation-related factor-1 and calmodulin in vitro and in vivo."
Mariotti M., De Benedictis L., Avon E., Maier J.A.M.
J. Biol. Chem. 275:24047-24051(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CALM AND TBP, MUTAGENESIS OF THR-40; THR-58; THR-91 AND SER-111, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[9]"Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism."
Brendel C., Gelman L., Auwerx J.
Mol. Endocrinol. 16:1367-1377(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NR5A2; NR1H3; PPARG AND TFIID COMPLEX, TISSUE SPECIFICITY, FUNCTION.
[10]"The dual role of endothelial differentiation-related factor-1 in the cytosol and nucleus: modulation by protein kinase A."
Ballabio E., Mariotti M., De Benedictis L., Maier J.A.M.
Cell. Mol. Life Sci. 61:1069-1074(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-65; THR-74 AND SER-87, INTERACTION WITH TBP AND CALM, PHOSPHORYLATION, SUBCELLULAR LOCATION, FUNCTION.
[11]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Solution structures of the HTH domain of human EDF-1 protein."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 71-148.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ005259 mRNA. Translation: CAA06446.1.
AB002282 mRNA. Translation: BAA88073.1.
AB002283 mRNA. Translation: BAA88074.1.
CR541914 mRNA. Translation: CAG46712.1.
BT009863 mRNA. Translation: AAP88865.1.
AL355987 Genomic DNA. Translation: CAI12697.1.
AL355987 Genomic DNA. Translation: CAI12698.1. Sequence problems.
AL355987 Genomic DNA. Translation: CAI12699.1.
BC015500 mRNA. Translation: AAH15500.1.
CCDSCCDS7011.1. [O60869-1]
CCDS7012.1. [O60869-2]
RefSeqNP_001268226.1. NM_001281297.1. [O60869-3]
NP_001268227.1. NM_001281298.1.
NP_001268228.1. NM_001281299.1.
NP_003783.1. NM_003792.3. [O60869-1]
NP_694880.1. NM_153200.2. [O60869-2]
UniGeneHs.174050.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1X57NMR-A71-148[»]
ProteinModelPortalO60869.
SMRO60869. Positions 71-148.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114260. 13 interactions.
IntActO60869. 14 interactions.
MINTMINT-3000548.
STRING9606.ENSP00000224073.

PTM databases

PhosphoSiteO60869.

Proteomic databases

MaxQBO60869.
PaxDbO60869.
PeptideAtlasO60869.
PRIDEO60869.

Protocols and materials databases

DNASU8721.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000224073; ENSP00000224073; ENSG00000107223. [O60869-1]
ENST00000371648; ENSP00000360711; ENSG00000107223. [O60869-2]
GeneID8721.
KEGGhsa:8721.
UCSCuc004cjt.1. human. [O60869-1]
uc004cju.1. human. [O60869-2]

Organism-specific databases

CTD8721.
GeneCardsGC09M139756.
HGNCHGNC:3164. EDF1.
HPAHPA035642.
MIM605107. gene.
neXtProtNX_O60869.
PharmGKBPA27604.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1813.
HOGENOMHOG000195726.
HOVERGENHBG051440.
InParanoidO60869.
KOK03627.
OMATKVNEKP.
OrthoDBEOG7RFTJZ.
PhylomeDBO60869.
TreeFamTF300064.

Gene expression databases

BgeeO60869.
CleanExHS_EDF1.
GenevestigatorO60869.

Family and domain databases

Gene3D1.10.260.40. 1 hit.
InterProIPR001387. Cro/C1-type_HTH.
IPR010982. Lambda_DNA-bd_dom.
IPR013729. MBF1_N.
[Graphical view]
PfamPF01381. HTH_3. 1 hit.
PF08523. MBF1. 1 hit.
[Graphical view]
SMARTSM00530. HTH_XRE. 1 hit.
[Graphical view]
SUPFAMSSF47413. SSF47413. 1 hit.
PROSITEPS50943. HTH_CROC1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO60869.
GeneWikiEDF1.
GenomeRNAi8721.
NextBio32709.
PROO60869.
SOURCESearch...

Entry information

Entry nameEDF1_HUMAN
AccessionPrimary (citable) accession number: O60869
Secondary accession number(s): Q5T5T2, Q9UIM1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM