O89090 (SP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified June 11, 2014. Version 130. History...
Names and origin
|Protein names||Recommended name:|
Transcription factor Sp1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||784 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 By similarity.
Interacts with ATF7IP, ATF7IP2, BAHD1, POGZ, HCFC1, AATF and PHC2. 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. Interacts with ATF7IP and TBP. Interacts with MEIS2 isoform 4and PBX1 isoform PBX1a Interacts with EGR1 By similarity.
Nucleus. Cytoplasm By similarity. Note: Nuclear location is governed by glycosylated/phosphorylated states. Insulin promotes nuclear location, while glucagon favors cytoplasmic location By similarity.
Phosphorylated on multiple serine and threonine residues. Phosphorylation is coupled to ubiquitination, sumoylation and proteolytic processing. Phosphorylation on Ser-61 enhances proteolytic cleavage. Phosphorylation on Ser-7 enhances ubiquitination and protein degradation. Hyperphosphorylation on Ser-103 in response to DNA damage has no effect on transcriptional activity. MAPK1/MAPK3-mediated phosphorylation on Thr-455 and Thr-738 enhances VEGF transcription but, represses FGF2-triggered PDGFR-alpha transcription. Also implicated in the repression of RECK by ERBB2. Hyperphosphorylated on Thr-280 and Thr-738 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-642 by PKCzeta is critical for TSA-activated LHR gene expression through release of its repressor, p107. Phosphorylation on Thr-669, Ser-671 and Thr-682 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-61 and Thr-682 can both be dephosphorylated by PP2A during cell-cycle interphase. Dephosphorylation on Ser-61 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 By similarity.
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 By similarity.
Ubiquitinated. Ubiquitination occurs on the C-terminal proteolytically-cleaved peptide and is triggered by phosphorylation By similarity.
Sumoylated with SUMO1. Sumoylation modulates proteolytic cleavage of the N-terminal repressor domain. Sumoylation levels are attenuated during tumorigenesis. Phosphorylation mediates SP1 desumoylation By similarity.
Proteolytic cleavage in the N-terminal repressor domain is prevented by sumoylation. The C-terminal cleaved product is susceptible to degradation By similarity.
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. Inhibited by peroxisomome proliferator receptor gamma (PPARgamma) By similarity.
Belongs to the Sp1 C2H2-type zinc-finger protein family.
Contains 3 C2H2-type zinc fingers.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: O89090-1) |
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: O89090-2) |
Also known as: Sp1-S;
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed Ref.5|
|Chain||2 – 784||783||Transcription factor Sp1||PRO_0000047138|
|Zinc finger||627 – 656||30||C2H2-type 1|
|Zinc finger||657 – 686||30||C2H2-type 2|
|Zinc finger||687 – 714||28||C2H2-type 3|
|Region||2 – 84||83||Repressor domain By similarity|
|Region||148 – 253||106||Transactivation domain A (Gln-rich) By similarity|
|Region||263 – 497||235||Transactivation domain B (Gln-rich) By similarity|
|Region||498 – 611||114||Transactivation domain C (highly charged) By similarity|
|Region||620 – 784||165||VZV IE62-binding By similarity|
|Region||709 – 784||76||Domain D By similarity|
|Compositional bias||37 – 145||109||Ser/Thr-rich|
|Compositional bias||273 – 381||109||Ser/Thr-rich|
|Site||65 – 66||2||Cleavage By similarity|
Amino acid modifications
|Modified residue||2||1||N-acetylserine Ref.5|
|Modified residue||2||1||Phosphoserine By similarity|
|Modified residue||7||1||Phosphoserine By similarity|
|Modified residue||61||1||Phosphoserine By similarity|
|Modified residue||103||1||Phosphoserine; by ATM By similarity|
|Modified residue||280||1||Phosphothreonine; by MAPK8 By similarity|
|Modified residue||455||1||Phosphothreonine; by MAPK1 AND MAPK3 By similarity|
|Modified residue||613||1||Phosphoserine; alternate By similarity|
|Modified residue||641||1||Phosphothreonine; alternate By similarity|
|Modified residue||642||1||Phosphoserine; by PKC/PRKCZ; alternate By similarity|
|Modified residue||652||1||Phosphothreonine; by PKC/PRKCZ By similarity|
|Modified residue||669||1||Phosphothreonine By similarity|
|Modified residue||671||1||Phosphoserine; by PKC/PRKCZ By similarity|
|Modified residue||682||1||Phosphothreonine; by PKC/PRKCZ By similarity|
|Modified residue||703||1||Phosphoserine; alternate By similarity|
|Modified residue||704||1||N6-acetyllysine By similarity|
|Modified residue||738||1||Phosphothreonine; by MAPK1, MAPK3 AND MAPK8 By similarity|
|Glycosylation||493||1||O-linked (GlcNAc) By similarity|
|Glycosylation||613||1||O-linked (GlcNAc); alternate By similarity|
|Glycosylation||641||1||O-linked (GlcNAc); alternate By similarity|
|Glycosylation||642||1||O-linked (GlcNAc); alternate By similarity|
|Glycosylation||699||1||O-linked (GlcNAc) By similarity|
|Glycosylation||703||1||O-linked (GlcNAc); alternate By similarity|
|Cross-link||16||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Alternative sequence||56 – 372||317||Missing in isoform 2.||VSP_007376|
|Sequence conflict||100||1||T → A in AAC16484. Ref.1|
|Sequence conflict||131 – 133||3||Missing in AAC16484. Ref.1|
|Sequence conflict||220||1||R → E in AAC08527. Ref.3|
|Sequence conflict||462||1||G → V in AAC16484. Ref.1|
|||"Sp family transcription factors regulate expression of rat D2 dopamine receptor gene."|
Yajima S., Lee S.H., Minowa T., Mouradian M.M.
DNA Cell Biol. 17:471-479(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
|||"An alternatively spliced form of the transcription factor Sp1 containing only a single glutamine-rich transactivation domain."|
Persengiev S.P., Saffer J.D., Kilpatrick D.L.
Proc. Natl. Acad. Sci. U.S.A. 92:9107-9111(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
|||"Isolation of cDNA encoding transcription factor sp1 containing two glutamine-rich transactivation domain."|
Park E.J., Kim J.H., Kim C.G., Park S.D., Hong S.S.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
|||"Difference in the genomic organizations of the related transcription factors Sp1 and Krox-20; possible evolutionary significance."|
Chestier A., Charnay P.
DNA Seq. 2:325-327(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 684-784.
|||"Large-scale phosphorylation analysis of mouse liver."|
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
|+||Additional computationally mapped references.|
|AF062566 mRNA. Translation: AAC16484.1.|
S79832 mRNA. Translation: AAB35321.1.
AF022363 mRNA. Translation: AAC08527.1.
X60136 Genomic DNA. Translation: CAA42721.1.
|RefSeq||NP_038700.2. NM_013672.2. |
3D structure databases
|SMR||O89090. Positions 583-713. |
Protein-protein interaction databases
|BioGrid||203414. 26 interactions.|
|IntAct||O89090. 8 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000163709; ENSMUSP00000130747; ENSMUSG00000001280. [O89090-2]|
|UCSC||uc012aab.1. mouse. [O89090-2]|
|MGI||MGI:98372. Sp1. |
Gene expression databases
Family and domain databases
|Gene3D||18.104.22.168. 3 hits. |
|InterPro||IPR007087. Znf_C2H2. |
|SMART||SM00355. ZnF_C2H2. 3 hits. |
|PROSITE||PS00028. ZINC_FINGER_C2H2_1. 3 hits. |
PS50157. ZINC_FINGER_C2H2_2. 3 hits.
|Accession||Primary (citable) accession number: O89090|
Secondary accession number(s): O89087, Q62251, Q64167
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|