P08047 (SP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor Sp1

Gene names

Name:	SP1
Synonyms:	TSFP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	785 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	Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Ref.13 Ref.15 Ref.16 Ref.20 Ref.23 Ref.25 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.33 Ref.35 Ref.40 Ref.43
Subunit structure	Interacts with ATF7IP, ATF7IP2, BAHD1, POGZ, HCFC1, AATF and PHC2. Interacts with varicella-zoster virus IE62 protein. Interacts with HIV-1 Vpr; the interaction is inhibited by SP1 O-glycosylation. Interacts with SV40 VP2/3 proteins. Interacts with SV40 major capsid protein VP1; this interaction leads to a cooperativity between the 2 proteins in DNA binding. Interacts with HLTF; the interaction may be required for basal transcriptional activity of HLTF. Interacts (deacetylated form) with EP300; the interaction enhances gene expression. Interacts with HDAC1 and JUN. Interacts with ELF1; the interaction is inhibited by glycosylation of SP1. Interaction with NFYA; the interaction is inhibited by glycosylation of SP1. Interacts with SMARCA4/BRG1 By similarity. Interacts with ATF7IP and TBP. Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a. Interacts with EGR1. Ref.9 Ref.12 Ref.13 Ref.14 Ref.17 Ref.18 Ref.19 Ref.21 Ref.26 Ref.37 Ref.38 Ref.39 Ref.41 Ref.42 Ref.46
Subcellular location	Nucleus. Cytoplasm. Note: Nuclear location is governed by glycosylated/phosphorylated states. Insulin promotes nuclear location, while glucagon favors cytoplasmic location. Ref.22 Ref.35
Tissue specificity	Up-regulated in adenocarcinomas of the stomach (at protein level).
Induction	By insulin. Ref.22
Post-translational modification	Phosphorylated on multiple serine and threonine residues. Phosphorylation is coupled to ubiquitination, sumoylation and proteolytic processing. Phosphorylation on Ser-59 enhances proteolytic cleavage. Phosphorylation on Ser-7 enhances ubiquitination and protein degradation. Hyperphosphorylation on Ser-101 in response to DNA damage has no effect on transcriptional activity. MAPK1/MAPK3-mediated phosphorylation on Thr-453 and Thr-739 enhances VEGF transcription but, represses FGF2-triggered PDGFR-alpha transcription. Also implicated in the repression of RECK by ERBB2. Hyperphosphorylated on Thr-278 and Thr-739 during mitosis by MAPK8 shielding SP1 from degradation by the ubiquitin-dependent pathway. Phosphorylated in the zinc-finger domain by calmodulin-activated PKCzeta. Phosphorylation on Ser-641 by PKCzeta is critical for TSA-activated LHR gene expression through release of its repressor, p107. Phosphorylation on Thr-668, Ser-670 and Thr-681 is stimulated by angiotensin II via the AT1 receptor inducing increased binding to the PDGF-D promoter. This phosphorylation is increased in injured artey wall. Ser-59 and Thr-681 can both be dephosphorylated by PP2A during cell-cycle interphase. Dephosphorylation on Ser-59 leads to increased chromatin association during interphase and increases the transcriptional activity. On insulin stimulation, sequentially glycosylated and phosphorylated on several C-terminal serine and threonine residues. Ref.16 Ref.20 Ref.22 Ref.23 Ref.25 Ref.27 Ref.30 Ref.32 Ref.33 Ref.34 Ref.35 Acetylated. Acetylation/deacetylation events affect transcriptional activity. Deacetylation leads to an increase in the expression the 12(s)-lipooxygenase gene though recruitment of p300 to the promoter. Ubiquitinated. Ubiquitination occurs on the C-terminal proteolytically-cleaved peptide and is triggered by phosphorylation. Ref.32 Sumoylated with SUMO1. Sumoylation modulates proteolytic cleavage of the N-terminal repressor domain. Sumoylation levels are attenuated during tumorigenesis. Phosphorylation mediates SP1 desumoylation. Ref.24 Ref.32 Proteolytic cleavage in the N-terminal repressor domain is prevented by sumoylation. The C-terminal cleaved product is susceptible to degradation. Ref.24 Ref.32 O-glycosylated; Contains 8 N-acetylglucosamine side chains. Levels are controlled by insulin and the SP1 phosphorylation states. Insulin-mediated O-glycosylation locates SP1 to the nucleus, where it is sequentially deglycosylated and phosphorylated. O-glycosylation affects transcriptional activity through disrupting the interaction with a number of transcription factors including ELF1 and NFYA. Also inhibits interaction with the HIV1 promoter. Inhibited by peroxisomome proliferator receptor gamma (PPARgamma). Ref.16 Ref.20 Ref.22 Ref.23 Ref.25 Ref.27 Ref.30 Ref.32 Ref.33 Ref.34 Ref.35
Miscellaneous	In the hepatoma cell line Hep-G2, SP1 precursor mRNA may undergo homotype trans-splicing leading to the duplication of exons 2 and 3.
Sequence similarities	Belongs to the Sp1 C2H2-type zinc-finger protein family. Contains 3 C2H2-type zinc fingers.
Sequence caution	The sequence AAH43224.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Host-virus interaction Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Repressor
PTM	Acetylation Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	definitive hemopoiesis Inferred from electronic annotation. Source: Compara embryonic camera-type eye morphogenesis Inferred from electronic annotation. Source: Compara embryonic placenta development Inferred from electronic annotation. Source: Compara embryonic process involved in female pregnancy Inferred from electronic annotation. Source: Compara embryonic skeletal system development Inferred from electronic annotation. Source: Compara enucleate erythrocyte differentiation Inferred from electronic annotation. Source: Compara liver development Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara megakaryocyte differentiation Inferred from electronic annotation. Source: Compara ossification Inferred from electronic annotation. Source: Compara positive regulation by host of viral transcription Inferred from direct assay PubMed 2833704. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19263243PubMed 2833704. Source: UniProtKB transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome trophectodermal cell differentiation Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome protein-DNA complex Inferred from electronic annotation. Source: Compara
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding Inferred from sequence or structural similarity. Source: BHF-UCL RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from electronic annotation. Source: Compara RNA polymerase II core promoter sequence-specific DNA binding Inferred from electronic annotation. Source: Compara RNA polymerase II repressing transcription factor binding Inferred from sequence or structural similarity. Source: BHF-UCL bHLH transcription factor binding Inferred from sequence or structural similarity. Source: BHF-UCL double-stranded DNA binding Inferred from direct assay PubMed 20371611. Source: BHF-UCL enhancer binding Inferred from electronic annotation. Source: Compara protein homodimerization activity Inferred from direct assay PubMed 10393239. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 12560508. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DLX4	Q92988	4	EBI-298336,EBI-1752755
E2F1	Q01094	2	EBI-298336,EBI-448924
ELF1	P32519	2	EBI-298336,EBI-765526
ESR1	P03372	2	EBI-298336,EBI-78473
HCFC1	P51610	4	EBI-298336,EBI-396176
KLF10	Q13118	2	EBI-298336,EBI-1389509
MYC	P01106	4	EBI-298336,EBI-447544
NCK1	P16333	2	EBI-298336,EBI-389883
Nfya	P23708	18	EBI-298336,EBI-862337	From a different organism.
PHC2	Q8IXK0	2	EBI-298336,EBI-713786
POGZ	Q7Z3K3	2	EBI-298336,EBI-1389308
POU2F1	P14859	2	EBI-298336,EBI-624770
SF3A1	Q15459	2	EBI-298336,EBI-1054743
SMAD4	Q13485	2	EBI-298336,EBI-347263
SREBF2	Q12772	3	EBI-298336,EBI-465059

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.44

Chain

2 – 785

784

Transcription factor Sp1

PRO_0000047137

Regions

Zinc finger

626 – 650

25

C2H2-type 1

Zinc finger

656 – 680

25

C2H2-type 2

Zinc finger

686 – 708

23

C2H2-type 3

Region

2 – 82

81

Repressor domain

Region

146 – 251

106

Transactivation domain A (Gln-rich)

Region

261 – 495

235

Transactivation domain B (Gln-rich)

Region

496 – 610

115

Transactivation domain C (highly charged)

Region

619 – 785

167

VZV IE62-binding

Region

708 – 785

78

Domain D

Compositional bias

36 – 143

108

Ser/Thr-rich

Compositional bias

271 – 379

109

Ser/Thr-rich

Sites

Site

63 – 64

2

Cleavage Probable

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.44 Ref.47

Modified residue

2

1

Phosphoserine Ref.44

Modified residue

7

1

Phosphoserine Ref.32 Ref.44 Ref.47

Modified residue

59

1

Phosphoserine Ref.25 Ref.29 Ref.32 Ref.35

Modified residue

101

1

Phosphoserine; by ATM Ref.30 Ref.33

Modified residue

278

1

Phosphothreonine; by MAPK8

Modified residue

453

1

Phosphothreonine; by MAPK1 AND MAPK3 Ref.16 Ref.20 Ref.23

Modified residue

612

1

Phosphoserine; alternate

Modified residue

640

1

Phosphothreonine; alternate

Modified residue

641

1

Phosphoserine; by PKC/PRKCZ; alternate Ref.27

Modified residue

651

1

Phosphothreonine; by PKC/PRKCZ Ref.36

Modified residue

668

1

Phosphothreonine Ref.34

Modified residue

670

1

Phosphoserine; by PKC/PRKCZ Ref.34

Modified residue

681

1

Phosphothreonine; by PKC/PRKCZ Ref.25 Ref.34

Modified residue

702

1

Phosphoserine; alternate

Modified residue

703

1

N6-acetyllysine Ref.26

Modified residue

739

1

Phosphothreonine; by MAPK1, MAPK3 AND MAPK8 Ref.16 Ref.20 Ref.23

Glycosylation

491

1

O-linked (GlcNAc) Ref.11 Ref.15

Glycosylation

612

1

O-linked (GlcNAc); alternate Ref.22

Glycosylation

640

1

O-linked (GlcNAc); alternate Ref.22

Glycosylation

641

1

O-linked (GlcNAc); alternate Ref.22

Glycosylation

698

1

O-linked (GlcNAc) Ref.22

Glycosylation

702

1

O-linked (GlcNAc); alternate Ref.22

Cross-link

16

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.24 Ref.32

Natural variations

Natural variant

737

1

T → A.
Corresponds to variant rs3741665 [ dbSNP | Ensembl ].

VAR_019971

Experimental info

Mutagenesis

7

1

S → A: Increase in protein stability. No change in sumoylation. Ref.32

Mutagenesis

15

1

V → R: Enhanced transcriptional activity.

Mutagenesis

16

1

K → R: Loss of sumoylation. No cleavage and reduced transcriptional activity. Ref.24

Mutagenesis

18

1

E → A: Loss of sumoylation. Increased cleavage and enhanced transcriptional activity. Ref.24

Mutagenesis

19

1

K → R: No effect on sumoylation nor on proteolytic cleavage. Ref.24

Mutagenesis

36

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

56

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

59

1

S → A: Loss of phosphorylation. No effect on activated MAPK8-mediated phosphorylation. Similar loss of phosphorylation as by dephosphorylation by PP2AC. Reduced proteolytic processing. Ref.25 Ref.32 Ref.35

Mutagenesis

59

1

S → E: Some association with chromatin, increased phosphorylation levels and decreased glycosylation. Ref.25 Ref.32 Ref.35

Mutagenesis

73

1

S → A: Little effect on activated MAPK8-mediated phosphorylation. Ref.35

Mutagenesis

81

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

85

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

98

1

T → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

101

1

S → A: Significant reduction of phosphorylation on DNA damage. Ref.30 Ref.33

Mutagenesis

101

1

S → D: Increase in phosphorylation on DNA damage. Ref.30 Ref.33

Mutagenesis

117

1

T → A: No effect on activated MAPK8-mediated phosphorylation. Ref.35

Mutagenesis

220

1

S → A: No effect on dephosphorylation by PP2A. Ref.25

Mutagenesis

250

1

T → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

278

1

T → A: Almost complete abolishment of activated MAPK8-mediated phosphorylation and 40% reduction in protein levels during mitosis. Protein levels reduced by 70% during mitosis; when associated with A-739. Ref.35

Mutagenesis

278

1

T → D: Increased protein stability during mitosis; when associated with D-739. Ref.35

Mutagenesis

281

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

291

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

296

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

313

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

351

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

355

1

T → A: No effect on dephosphorylation by PP2A. Ref.16 Ref.25

Mutagenesis

394

1

T → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

427

1

T → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

431

1

S → A: No effect on phosphorylation on DNA damage. Ref.33

Mutagenesis

453

1

T → A: Abolishes MAPK-mediated phosphorylation, 50% reduction in MAPK1/MAPK3-mediated activity on VEGF promoter and no effect on dephosphorylation by PP2A. Greatly reduced MAPK1-mediated activity on VEGF promoter; when associated with A-739. Ref.16 Ref.20 Ref.25

Mutagenesis

491

1

S → A: Loss of O-glycosylation. Increase in transcriptional activity. Ref.11 Ref.15

Mutagenesis

612

1

S → A: Diminished glycosylation. Inhibits transcriptional activity; when associated with A-640; A-641; A-698 and A-702. Ref.31

Mutagenesis

640

1

T → A: Diminished glycosylation. Inhibits transcriptional activity; when associated with A-612; A-641; A-698 and A-702. Ref.31

Mutagenesis

641

1

S → A: Abolishes PRKCzeta-mediated phosphorylation. Diminished glycosylation. Inhibits transcriptional activity; when associated with A-612; A-640; A-641 and A-702. Ref.27 Ref.31

Mutagenesis

651

1

T → A: No effect on dephosphorylation by PP2A. Ref.25

Mutagenesis

668

1

T → A: Abolishes PRKCzeta-mediated but not PKCdelta-mediated phosphorylation. No effect on DNA binding; when associated with A-670 and A-681. Ref.34

Mutagenesis

670

1

S → A: Abolishes PRKCzeta-mediated but not PKCdelta-mediated phosphorylation. No effect on DNA binding; when associated with A-668 and A-681. Ref.34

Mutagenesis

681

1

T → A: Abolishes PRKCzeta-mediated but not PKCdelta-mediated phosphorylation. Some effect on dephosphorylation by PP2A. No effect on DNA binding; when associated with A-668 and A-681. Ref.25 Ref.34

Mutagenesis

698

1

S → A: Diminished glycosylation. Inhibits transcriptional activity; when associated with A-612; A-640; A-641 and A-702. Ref.31

Mutagenesis

702

1

S → A: Diminished glycosylation. Inhibits transcriptional activity; when associated with A-612; A-640; A-641 and A-698. Ref.31

Mutagenesis

703

1

K → A: Abolishes acetylation. Increases recruitment of p300 to the promoter and enhances gene transcription. Ref.26

Mutagenesis

728

1

S → A: Exhibits attenuated endoproteolytic cleavage; when associated with A-732. Ref.32

Mutagenesis

732

1

S → A: Exhibits attenuated endoproteolytic cleavage; when associated with A-728. Ref.32

Mutagenesis

739

1

T → A: Abolishes MAPK-mediated phosphorylation. 50% reduction in MAPK1/MAPK3-mediated activity on VEGF promoter, 40% reduction in protein levels during mitosis and no effect on dephosphorylation by PP2A. Greatly reduced MAPK1-mediated activity on VEGF promoter; when associated with A-453. Protein levels during mitosis reduced by 70%; when associated with A-278. Ref.16 Ref.20 Ref.25 Ref.35

Mutagenesis

739

1

T → D: Increased protein stability during mitosis; when associated with D-278. Ref.16 Ref.20 Ref.25 Ref.35

Sequence conflict

366

1

D → G AA sequence Ref.4

Sequence conflict

670

1

S → F AA sequence Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

785

Helix Strand Turn

Details...

Beta strand

620 – 622

3

Beta strand

636 – 638

3

Helix

640 – 651

12

Turn

661 – 663

3

Beta strand

666 – 668

3

Helix

670 – 677

8

Turn

678 – 680

3

Turn

689 – 692

4

Helix

699 – 706

8

Helix

707 – 709

3

Sequences

	Sequence		Length	Mass (Da)
	P08047 [UniParc]. Last modified April 27, 2001. Version 3. Checksum: 43893DBF6518B9EA	FASTA	785	80,693
	10 20 30 40 50 60 MSDQDHSMDE MTAVVKIEKG VGGNNGGNGN GGGAFSQARS SSTGSSSSTG GGGQESQPSP 70 80 90 100 110 120 LALLAATCSR IESPNENSNN SQGPSQSGGT GELDLTATQL SQGANGWQII SSSSGATPTS 130 140 150 160 170 180 KEQSGSSTNG SNGSESSKNR TVSGGQYVVA AAPNLQNQQV LTGLPGVMPN IQYQVIPQFQ 190 200 210 220 230 240 TVDGQQLQFA ATGAQVQQDG SGQIQIIPGA NQQIITNRGS GGNIIAAMPN LLQQAVPLQG 250 260 270 280 290 300 LANNVLSGQT QYVTNVPVAL NGNITLLPVN SVSAATLTPS SQAVTISSSG SQESGSQPVT 310 320 330 340 350 360 SGTTISSASL VSSQASSSSF FTNANSYSTT TTTSNMGIMN FTTSGSSGTN SQGQTPQRVS 370 380 390 400 410 420 GLQGSDALNI QQNQTSGGSL QAGQQKEGEQ NQQTQQQQIL IQPQLVQGGQ ALQALQAAPL 430 440 450 460 470 480 SGQTFTTQAI SQETLQNLQL QAVPNSGPII IRTPTVGPNG QVSWQTLQLQ NLQVQNPQAQ 490 500 510 520 530 540 TITLAPMQGV SLGQTSSSNT TLTPIASAAS IPAGTVTVNA AQLSSMPGLQ TINLSALGTS 550 560 570 580 590 600 GIQVHPIQGL PLAIANAPGD HGAQLGLHGA GGDGIHDDTA GGEEGENSPD AQPQAGRRTR 610 620 630 640 650 660 REACTCPYCK DSEGRGSGDP GKKKQHICHI QGCGKVYGKT SHLRAHLRWH TGERPFMCTW 670 680 690 700 710 720 SYCGKRFTRS DELQRHKRTH TGEKKFACPE CPKRFMRSDH LSKHIKTHQN KKGGPGVALS 730 740 750 760 770 780 VGTLPLDSGA GSEGSGTATP SALITTNMVA MEAICPEGIA RLANSGINVM QVADLQSINI SGNGF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Brain and Testis.
[2]	Haggart M.H., Ladurner A.G. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-785. Tissue: Cervix carcinoma.
[3]	"Heterogeneous Sp1 mRNAs in human HepG2 cells include a product of homotypic trans-splicing." Takahara T., Kanazu S., Yanagisawa S., Akanuma H. J. Biol. Chem. 275:38067-38072(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-558, TRANS-SPLICING.
[4]	"Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain." Kadonaga J.T., Carner K.R., Masiarz F.R., Tjian R. Cell 51:1079-1090(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 90-785, PROTEIN SEQUENCE OF 359-375 AND 670-675.
[5]	"Expression of transcription factor Sp1 mRNA in mammalian cells." Nicolas M., Noe V., Ciudad C.J. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-109.
[6]	"Sequencing of the 5' end of human transcription factor SP1 mRNA." Handschug K., Huebner A. Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-98.
[7]	"O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation." Jackson S.P., Tjian R. Cell 55:125-133(1988) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION.
[8]	"Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif." Courey A.J., Tjian R. Cell 55:887-898(1988) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSACTIVATION DOMAINS.
[9]	"Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Sp1 and trans-activation of viral long terminal repeat." Wang L., Mukherjee S., Jia F., Narayan O., Zhao L.J. J. Biol. Chem. 270:25564-25569(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV-1 VPR.
[10]	"The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1." Parks C.L., Shenk T. J. Biol. Chem. 271:4417-4430(1996) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF SEROTONIN 1A RECEPTOR PROMOTER BINDING SITES.
[11]	"O glycosylation of an Sp1-derived peptide blocks known Sp1 protein interactions." Roos M.D., Su K., Baker J.R., Kudlow J.E. Mol. Cell. Biol. 17:6472-6480(1997) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT SER-491, MUTAGENESIS OF SER-491, IDENTIFICATION BY MASS SPECTROMETRY.
[12]	"The SV40 capsid protein VP3 cooperates with the cellular transcription factor Sp1 in DNA-binding and in regulating viral promoter activity." Gordon-Shaag A., Ben-Nun-Shaul O., Kasamatsu H., Oppenheim A.B., Oppenheim A. J. Mol. Biol. 275:187-195(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SV40 VP2/3.
[13]	"Functional interactions between Sp1 or Sp3 and the helicase-like transcription factor mediate basal expression from the human plasminogen activator inhibitor-1 gene." Ding H., Benotmane A.M., Suske G., Collen D., Belayew A. J. Biol. Chem. 274:19573-19580(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HLTF.
[14]	"A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening." Gunther M., Laithier M., Brison O. Mol. Cell. Biochem. 210:131-142(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ATF7IP; PHC2; POGZ AND HCFC1. Tissue: Colon.
[15]	"O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits its transcriptional capability." Yang X., Su K., Roos M.D., Chang Q., Paterson A.J., Kudlow J.E. Proc. Natl. Acad. Sci. U.S.A. 98:6611-6616(2001) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT SER-491, FUNCTION, MUTAGENESIS OF SER-491.
[16]	"Identification of two Sp1 phosphorylation sites for p42/p44 mitogen-activated protein kinases: their implication in vascular endothelial growth factor gene transcription." Milanini-Mongiat J., Pouyssegur J., Pages G. J. Biol. Chem. 277:20631-20639(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-453 AND THR-739, FUNCTION, MUTAGENESIS OF THR-355; THR-453 AND THR-739.
[17]	"Cellular transcription factor Sp1 recruits simian virus 40 capsid proteins to the viral packaging signal, ses." Gordon-Shaag A., Ben-Nun-Shaul O., Roitman V., Yosef Y., Oppenheim A. J. Virol. 76:5915-5924(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SV40 VP1.
[18]	"Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter." Di Padova M., Bruno T., De Nicola F., Iezzi S., D'Angelo C., Gallo R., Nicosia D., Corbi N., Biroccio A., Floridi A., Passananti C., Fanciulli M. J. Biol. Chem. 278:36496-36504(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AATF.
[19]	"Interaction between the varicella zoster virus IE62 major transactivator and cellular transcription factor Sp1." Peng H., He H., Hay J., Ruyechan W.T. J. Biol. Chem. 278:38068-38075(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VARICELLA-ZOSTER VIRUS IE62 PROTEIN.
[20]	"Fibroblast growth factor-2 represses platelet-derived growth factor receptor-alpha (PDGFR-alpha) transcription via ERK1/2-dependent Sp1 phosphorylation and an atypical cis-acting element in the proximal PDGFR-alpha promoter." Bonello M.R., Khachigian L.M. J. Biol. Chem. 279:2377-2382(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-453 AND THR-739, FUNCTION, MUTAGENESIS OF THR-453 AND THR-739.
[21]	"Transcriptional repression and heterochromatin formation by MBD1 and MCAF/AM family proteins." Ichimura T., Watanabe S., Sakamoto Y., Aoto T., Fujita N., Nakao M. J. Biol. Chem. 280:13928-13935(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ATF7IP AND ATF7IP2.
[22]	"Insulin dynamically regulates calmodulin gene expression by sequential O-glycosylation and phosphorylation of SP1 and its subcellular compartmentalization in liver cells." Majumdar G., Harrington A., Hungerford J., Martinez-Hernandez A., Gerling I.C., Raghow R., Solomon S. J. Biol. Chem. 281:3642-3650(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT SER-612; THR-640; SER-641; SER-698 AND SER-702, PHOSPHORYLATION, INDUCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[23]	"HER-2/neu represses the metastasis suppressor RECK via ERK and Sp transcription factors to promote cell invasion." Hsu M.C., Chang H.C., Hung W.C. J. Biol. Chem. 281:4718-4725(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-453 AND THR-739, FUNCTION.
[24]	"Sumoylation inhibits cleavage of Sp1 N-terminal negative regulatory domain and inhibits Sp1-dependent transcription." Spengler M.L., Brattain M.G. J. Biol. Chem. 281:5567-5574(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-16, PROTEOLYTIC PROCESSING, MUTAGENESIS OF LYS-16; GLU-18 AND LYS-19.
[25]	"Increased chromatin association of Sp1 in interphase cells by PP2A-mediated dephosphorylations." Vicart A., Lefebvre T., Imbert J., Fernandez A., Kahn-Perles B. J. Mol. Biol. 364:897-908(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-59 AND THR-681, DEPHOSPHORYLATION, GLYCOSYLATION, FUNCTION, MUTAGENESIS OF SER-59; SER-220; THR-355; THR-453; THR-651; THR-681 AND THR-739.
[26]	"Sp1 deacetylation induced by phorbol ester recruits p300 to activate 12(S)-lipoxygenase gene transcription." Hung J.J., Wang Y.T., Chang W.C. Mol. Cell. Biol. 26:1770-1785(2006) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-703, INTERACTION WITH HDAC1; EP300 AND JUN, FUNCTION, MUTAGENESIS OF LYS-703.
[27]	"Phosphatidylinositol 3-kinase/protein kinase Czeta-induced phosphorylation of Sp1 and p107 repressor release have a critical role in histone deacetylase inhibitor-mediated derepression of transcription of the luteinizing hormone receptor gene." Zhang Y., Liao M., Dufau M.L. Mol. Cell. Biol. 26:6748-6761(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-641, FUNCTION, MUTAGENESIS OF SER-641.
[28]	Erratum Zhang Y., Liao M., Dufau M.L. Mol. Cell. Biol. 26:8214-8214(2006)
[29]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-59, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[30]	"Phosphorylation of Sp1 in response to DNA damage by ataxia telangiectasia-mutated kinase." Olofsson B.A., Kelly C.M., Kim J., Hornsby S.M., Azizkhan-Clifford J. Mol. Cancer Res. 5:1319-1330(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-101, FUNCTION, MUTAGENESIS OF SER-101.
[31]	"Activation of PPARgamma negatively regulates O-GlcNAcylation of Sp1." Chung S.S., Kim J.H., Park H.S., Choi H.H., Lee K.W., Cho Y.M., Lee H.K., Park K.S. Biochem. Biophys. Res. Commun. 372:713-718(2008) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, FUNCTION, MUTAGENESIS OF SER-612; THR-640; SER-641; SER-698 AND SER-702.
[32]	"Phosphorylation mediates Sp1 coupled activities of proteolytic processing, desumoylation and degradation." Spengler M.L., Guo L.W., Brattain M.G. Cell Cycle 7:623-630(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-7 AND SER-59, SUMOYLATION AT LYS-16, PROTEOLYTIC PROCESSING, UBIQUITINATION, FUNCTION, MUTAGENESIS OF SER-7; SER-59; SER-728 AND SER-732.
[33]	"Identification of phosphorylation sites on transcription factor Sp1 in response to DNA damage and its accumulation at damaged sites." Iwahori S., Yasui Y., Kudoh A., Sato Y., Nakayama S., Murata T., Isomura H., Tsurumi T. Cell. Signal. 20:1795-1803(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-101, FUNCTION, MUTAGENESIS OF SER-36; SER-56; SER-81; SER-85; THR-98; SER-101; THR-250; SER-281; SER-291; SER-296; SER-313; SER-351; THR-394; THR-427 AND SER-431.
[34]	"Angiotensin II-inducible platelet-derived growth factor-D transcription requires specific Ser/Thr residues in the second zinc finger region of Sp1." Tan N.Y., Midgley V.C., Kavurma M.M., Santiago F.S., Luo X., Peden R., Fahmy R.G., Berndt M.C., Molloy M.P., Khachigian L.M. Circ. Res. 102:38-51(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-668; SER-670 AND THR-681, MUTAGENESIS OF THR-668; SER-670 AND THR-681.
[35]	"Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis." Chuang J.-Y., Wang Y.-T., Yeh S.-H., Liu Y.-W., Chang W.-C., Hung J.-J. Mol. Biol. Cell 19:1139-1151(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-59, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-59; SER-73; THR-117; THR-278 AND THR-739.
[36]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-651, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[37]	"O-GlcNAc inhibits interaction between Sp1 and Elf-1 transcription factors." Lim K., Chang H.I. Biochem. Biophys. Res. Commun. 380:569-574(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, INTERACTION WITH ELF1.
[38]	"O-GlcNAcylation of Sp1 interrupts Sp1 interaction with NF-Y." Lim K., Chang H.I. Biochem. Biophys. Res. Commun. 382:593-597(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, INTERACTION WITH NFYA.
[39]	"MCAF1/AM is involved in Sp1-mediated maintenance of cancer-associated telomerase activity." Liu L., Ishihara K., Ichimura T., Fujita N., Hino S., Tomita S., Watanabe S., Saitoh N., Ito T., Nakao M. J. Biol. Chem. 284:5165-5174(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ATF7IP AND TBP.
[40]	"O-linked N-acetylglucosaminylation of Sp1 inhibits the human immunodeficiency virus type 1 promoter." Jochmann R., Thurau M., Jung S., Hofmann C., Naschberger E., Kremmer E., Harrer T., Miller M., Schaft N., Stuerzl M. J. Virol. 83:3704-3718(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, FUNCTION.
[41]	"Human BAHD1 promotes heterochromatic gene silencing." Bierne H., Tham T.N., Batsche E., Dumay A., Leguillou M., Kerneis-Golsteyn S., Regnault B., Seeler J.S., Muchardt C., Feunteun J., Cossart P. Proc. Natl. Acad. Sci. U.S.A. 106:13826-13831(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BAHD1.
[42]	"Snail associates with EGR-1 and SP-1 to upregulate transcriptional activation of p15INK4b." Hu C.T., Chang T.Y., Cheng C.C., Liu C.S., Wu J.R., Li M.C., Wu W.S. FEBS J. 277:1202-1218(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EGR1.
[43]	"Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1." Yu H.T., Chan W.W., Chai K.H., Lee C.W., Chang R.C., Yu M.S., McLoughlin D.M., Miller C.C., Lau K.F. J. Cell. Biochem. 109:782-793(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[44]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND SER-7, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE. Tissue: Cervix carcinoma.
[45]	"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].
[46]	"Cooperative transcriptional activation by Klf4, Meis2, and Pbx1." Bjerke G.A., Hyman-Walsh C., Wotton D. Mol. Cell. Biol. 31:3723-3733(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MEIS2 AND PBX1.
[47]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, MASS SPECTROMETRY.
[48]	"Structures of zinc finger domains from transcription factor Sp1. Insights into sequence-specific protein-DNA recognition." Narayan V.A., Kriwacki R.W., Caradonna J.P. J. Biol. Chem. 272:7801-7809(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 654-684 AND 684-712.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BC043224 mRNA. Translation: AAH43224.1. Different initiation.
BC062539 mRNA. Translation: AAH62539.1.
AF252284 mRNA. Translation: AAF67726.1.
AB039286 Genomic DNA. Translation: BAB13476.1.
J03133 mRNA. Translation: AAA61154.1.
AF255682 mRNA. Translation: AAF78781.1.
AJ272134 mRNA. Translation: CAB75345.1.

IPI

IPI00465152.

PIR

A29635.

RefSeq

NP_001238754.1. NM_001251825.1.
NP_003100.1. NM_003109.1.
NP_612482.2. NM_138473.2.

UniGene

Hs.620754.
Hs.649191.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SP1	NMR	-	A	684-712	[»]
1SP2	NMR	-	A	654-684	[»]
1VA1	NMR	-	A	619-654	[»]
1VA2	NMR	-	A	654-684	[»]
1VA3	NMR	-	A	684-712	[»]

DisProt

DP00378.

ProteinModelPortal

P08047.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-36N.

IntAct

P08047. 55 interactions.

MINT

MINT-98326.

STRING

9606.ENSP00000329357.

PTM databases

GlycoSuiteDB

P08047.

PhosphoSite

P08047.

Polymorphism databases

DMDM

13638437.

Proteomic databases

PaxDb

P08047.

PeptideAtlas

P08047.

PRIDE

P08047.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000327443; ENSP00000329357; ENSG00000185591.

GeneID

6667.

KEGG

hsa:6667.

UCSC

uc001scw.3. human.

Organism-specific databases

CTD

6667.

GeneCards

GC12P053773.

HGNC

HGNC:11205. SP1.

HPA

CAB000330.
HPA001853.
HPA012292.

MIM

189906. gene.

neXtProt

NX_P08047.

PharmGKB

PA36042.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5048.

HOGENOM

HOG000234295.

HOVERGEN

HBG008933.

InParanoid

P08047.

KO

K04684.

OMA

GEQNQQT.

OrthoDB

EOG4QFWCX.

PhylomeDB

P08047.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3apathway. FOXA1 transcription factor network.
hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
foxm1pathway. FOXM1 transcription factor network.
hif1_tfpathway. HIF-1-alpha transcription factor network.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il4_2pathway. IL4-mediated signaling events.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
telomerasepathway. Regulation of Telomerase.

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P08047.

Bgee

P08047.

CleanEx

HS_SP1.

Genevestigator

P08047.

GermOnline

ENSG00000185591. Homo sapiens.

Family and domain databases

Gene3D

3.30.160.60. 3 hits.

InterPro

IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]

Pfam

PF00096. zf-C2H2. 1 hit.
[Graphical view]

SMART

SM00355. ZnF_C2H2. 3 hits.
[Graphical view]

PROSITE

PS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL6103.

ChiTaRS

SP1. human.

EvolutionaryTrace

P08047.

GenomeRNAi

6667.

NextBio

25995.

PMAP-CutDB

P08047.

SOURCE

Search...

Entry information

Entry name

SP1_HUMAN

Accession

Primary (citable) accession number: P08047
Secondary accession number(s): Q86TN8 , Q9H3Q5, Q9NR51, Q9NY21, Q9NYE7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	April 27, 2001
Last modified:	May 1, 2013
This is version 169 of the entry and version 3 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.