O60869 (EDF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endothelial differentiation-related factor 1
Short name=EDF-1

Alternative name(s):
Multiprotein-bridging factor 1
Short name=MBF1

Gene names

Name:

EDF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	148 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 Ref.11
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 process	Differentiation Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Calmodulin-binding DNA-binding
Molecular function	Activator Developmental protein
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	endothelial cell differentiation Traceable author statement Ref.9. Source: UniProtKB multicellular organismal development Traceable author statement. Source: ProtInc positive regulation of DNA binding Inferred from direct assay Ref.2. Source: UniProtKB positive regulation of transcription, DNA-dependent Traceable author statement. Source: UniProtKB regulation of lipid metabolic process Traceable author statement Ref.9. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay Ref.2. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA nucleus Inferred from mutant phenotype Ref.2. Source: UniProtKB
Molecular function	calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW 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

With	Entry	#Exp.	IntAct	Notes
NR1H3	Q13133	4	EBI-781301,EBI-781356
NR5A1	Q04752	4	EBI-781310,EBI-850837	From a different organism.
NR5A2	O00482	2	EBI-781301,EBI-781320
PPARG	P37231	4	EBI-781301,EBI-781384
TBP	P20226	2	EBI-781310,EBI-355371

Alternative products

This entry describes 2 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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7

Chain

2 – 148

147

Endothelial differentiation-related factor 1

PRO_0000149795

Regions

Domain

81 – 135

55

HTH cro/C1-type

DNA binding

92 – 111

20

H-T-H motif Potential

Region

37 – 113

77

Interaction with NR5A2, PPARG and NR1H3

Region

69 – 108

40

Interaction with TBP and NR5A1

Motif

81 – 88

8

IQ motif

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.7 Ref.11

Modified residue

4

1

Phosphoserine Ref.11

Modified residue

123

1

N6-acetyllysine Ref.12

Natural variations

Alternative sequence

130 – 148

19

LKLRG…GPRAK → ECPSTLRRVR in isoform 2.

VSP_013336

Experimental info

Mutagenesis

40

1

T → D: Loss of interaction with CALM; when associated with D-58; D-91 and D-111. Ref.8

Mutagenesis

58

1

T → D: Loss of interaction with CALM; when associated with D-40; D-91 and D-111. Ref.8

Mutagenesis

65

1

T → D: No effect on CALM-binding. No effect; when associated with D-74. Ref.10

Mutagenesis

74

1

T → D: No effect on CALM-binding. No effect; when associated with D-65. Ref.10

Mutagenesis

87

1

S → A: No effect on CALM-binding. Ref.10

Mutagenesis

87

1

S → D: Loss of interaction with CALM and higher affinity for TBP. Same effect; when associated with D-65 and D-74. Ref.10

Mutagenesis

91

1

T → A: No effect on CALM-binding. Ref.8

Mutagenesis

91

1

T → D: Partial loss of interaction with CALM. Complete loss of interaction; when associated with D-40; D-58 and D-111. Ref.8

Mutagenesis

111

1

S → D: Loss of interaction with CALM; when associated with D-40; D-58 and D-91. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

148

Helix Strand Turn

Details...

Helix

76 – 86

11

Turn

87 – 89

3

Helix

92 – 99

8

Helix

103 – 111

9

Helix

118 – 128

11

Turn

135 – 138

4

Beta strand

140 – 143

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified August 1, 1998. Version 1. Checksum: ADC2C5384BF85C11	FASTA	148	16,369
	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
	Isoform 2 (Beta) [UniParc]. Checksum: 9F30DE6890D7E801	FASTA	139	15,481
	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 LGKIERAIGE CPSTLRRVR

References

	« Hide 'large scale' referencesShow '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: 9813014] [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: 10567391] [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. , 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: 15164053] [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: 15489334] [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, 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: 10816571] [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: 12040021] [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: 15112053] [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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-123, MASS SPECTROMETRY.
[13]	"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: 21269460] [Abstract] Cited for: 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.

IPI

IPI00006362.
IPI00021570.

RefSeq

NP_003783.1. NM_003792.2.
NP_694880.1. NM_153200.1.

UniGene

Hs.174050.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X57	NMR	-	A	71-148	[»]

ProteinModelPortal

O60869.

SMR

O60869. Positions 71-148.

ModBase

Search...

Protein-protein interaction databases

IntAct

O60869. 15 interactions.

STRING

O60869.

PTM databases

PhosphoSite

O60869.

Proteomic databases

PeptideAtlas

O60869.

PRIDE

O60869.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000224073; ENSP00000224073; ENSG00000107223.

GeneID

8721.

KEGG

hsa:8721.

UCSC

uc004cjt.1. human.
uc004cju.1. human.

Organism-specific databases

CTD

8721.

GeneCards

GC09M139756.

H-InvDB

HIX0008561.

HGNC

HGNC:3164. EDF1.

HPA

HPA035642.

MIM

605107. gene.

neXtProt

NX_O60869.

PharmGKB

PA27604.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10685.

GeneTree

ENSGT00390000008519.

HOGENOM

HBG521662.

HOVERGEN

HBG051440.

InParanoid

O60869.

OMA

VIADYEC.

OrthoDB

EOG4XD3SD.

PhylomeDB

O60869.

Gene expression databases

ArrayExpress

O60869.

Bgee

O60869.

CleanEx

HS_EDF1.

Genevestigator

O60869.

GermOnline

ENSG00000107223. Homo sapiens.

Family and domain databases

InterPro

IPR001387. HTH_3.
IPR010982. Lambda_DNA-bd.
IPR013729. MBF1_N.
[Graphical view]

Gene3D

G3DSA:1.10.260.40. G3DSA:1.10.260.40. 1 hit.

KO

K03627.

Pfam

PF01381. HTH_3. 1 hit.
PF08523. MBF1. 1 hit.
[Graphical view]

SMART

SM00530. HTH_XRE. 1 hit.
[Graphical view]

SUPFAM

SSF47413. Lambda_like_DNA. 1 hit.

PROSITE

PS50943. HTH_CROC1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

32709.

SOURCE

Search...

Entry information

Entry name

EDF1_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.