Specificity protein gene transcriptions

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Editor-In-Chief: Henry A. Hoff

File:Ashwagandha.jpg
Withania somnifera produces Withaferin A, a sterodial lactone known to inhibit Sp1 transcription factor. Credit: Hari Prasad Nadig from Bangalore, India.{{free media}}

Specificity protein 1 is Sp1.

Sp1 has been used as a control protein to compare with when studying the increase or decrease of the aryl hydrocarbon receptor and/or the estrogen receptor, since it binds to both and generally remains at a relatively constant level.[1]

Withaferin A, a sterodial lactone from Withania somnifera is known to inhibit Sp1 transcription factor.[2]

Consensus sequences

SP1 belongs to the Sp/KLF family of transcription factors. The protein is 785 amino acids long, with a molecular weight of 81 kDA. The SP1 transcription factor contains a zinc finger motif, by which it binds directly to DNA and enhances gene transcription. Its zinc fingers are of the Cys2/His2 type and bind the consensus sequence 5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3' (GC box).

Sp1-box 1 (GGGGCT) and Sp1-box 2 (CTGCCC).[3]

"Sp3 has been shown to repress transcriptional activity of Sp1 [9]."[3]

Sp-1 (CCGCCCC).[4]

Sp1 (GCGGC).[5]

An apparent consensus sequences for Sp1 (GGGGCT), (CTGCCC) or (CCGCCCC) is 3'-(C/G)(C/G/T)G(C/G)C(C/T)-5'. Or, each must be considered separately.

Human genes

GeneID: 6667 is SP1 Sp1 transcription factor. "The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. Post-translational modifications such as phosphorylation, acetylation, glycosylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor. Three transcript variants encoding different isoforms have been found for this gene."[6]

  1. NP_612482.2 transcription factor Sp1 isoform a.
  2. NP_003100.1 transcription factor Sp1 isoform b.
  3. NP_001238754.1 transcription factor Sp1 isoform c.

GeneID: 6668 is SP2 Sp2 transcription factor. "This gene encodes a member of the Sp subfamily of Sp/XKLF transcription factors. Sp family proteins are sequence-specific DNA-binding proteins characterized by an amino-terminal trans-activation domain and three carboxy-terminal zinc finger motifs. This protein contains the least conserved DNA-binding domain within the Sp subfamily of proteins, and its DNA sequence specificity differs from the other Sp proteins. It localizes primarily within subnuclear foci associated with the nuclear matrix, and can activate or in some cases repress expression from different promoters."[7]

  1. NP_003101.3 transcription factor Sp2.

Gene ID: 6670 is SP3 Sp3 transcription factor. "This gene belongs to a family of Sp1 related genes that encode transcription factors that regulate transcription by binding to consensus GC- and GT-box regulatory elements in target genes. This protein contains a zinc finger DNA-binding domain and several transactivation domains, and has been reported to function as a bifunctional transcription factor that either stimulates or represses the transcription of numerous genes. Transcript variants encoding different isoforms have been described for this gene, and one has been reported to initiate translation from a non-AUG (AUA) start codon. Additional isoforms, resulting from the use of alternate downstream translation initiation sites, have also been noted. A related pseudogene has been identified on chromosome 13."[8]

  1. NP_003102.1 transcription factor Sp3 isoform 1.
  2. NP_001017371.3 transcription factor Sp3 isoform 2.
  3. NP_001166183.1 transcription factor Sp3 isoform 3.

GeneID: 6671 is SP4 Sp4 transcription factor. "The protein encoded by this gene is a transcription factor that can bind to the GC promoter region of a variety of genes, including those of the photoreceptor signal transduction system. The encoded protein binds to the same sites in promoter CpG islands as does the transcription factor SP1, although its expression is much more restricted compared to that of SP1. This gene may be involved in bipolar disorder and schizophrenia."[9]

  1. NP_003103.2 transcription factor Sp4 isoform 1.
  2. NP_001313471.1 transcription factor Sp4 isoform 2.
  3. NP_001313472.1 transcription factor Sp4 isoform 3.
  4. NR_137166.1 RNA Sequence non-coding (variant 4).

GeneID: 389058 is SP5 Sp5 transcription factor.

  1. NP_001003845.1 transcription factor Sp5.

GeneID: 80320 is SP6 Sp6 transcription factor (aka KLF14). "SP6 belongs to a family of transcription factors that contain 3 classical zinc finger DNA-binding domains consisting of a zinc atom tetrahedrally coordinated by 2 cysteines and 2 histidines (C2H2 motif). These transcription factors bind to GC-rich sequences and related GT and CACCC boxes."[10]

  1. NP_001245177.1 transcription factor Sp6 (variant 1).
  2. NP_954871.1 transcription factor Sp6 (variant 2).

GeneID: 121340 is SP7 Sp7 transcription factor. "This gene encodes a member of the Sp subfamily of Sp/XKLF transcription factors. Sp family proteins are sequence-specific DNA-binding proteins characterized by an amino-terminal trans-activation domain and three carboxy-terminal zinc finger motifs. This protein is a bone specific transcription factor and is required for osteoblast differentiation and bone formation."[11]

  1. NP_001166938.1 transcription factor Sp7 isoform a.
  2. NP_690599.1 transcription factor Sp7 isoform a.
  3. NP_001287766.1 transcription factor Sp7 isoform b.

GeneID: 221833 is SP8 Sp8 transcription factor. "The protein encoded by this gene is an SP family transcription factor that in mouse has been shown to be essential for proper limb development. Two transcript variants encoding different isoforms have been found for this gene."[12]

  1. NP_874359.2 transcription factor Sp8 isoform 1.
  2. NP_945194.1 transcription factor Sp8 isoform 2.

GeneID: 100131390 is SP9 Sp9 transcription factor.

Sp/KLF family

The Sp/KLF family (specificity protein/Krüppel-like factor) is a family of transcription factors,[13] including the Kruppel-like factors as well as Sp1 transcription factor, Sp2 transcription factor, Sp3 transcription factor,[14][15] Sp4 transcription factor,[16] Sp8 transcription factor,[17] Sp9;[18] and possibly Sp5[19] and Sp7 transcription factor.[17] KLF14 is also designated Sp6.[20]

Sp1-box 1 (Motojima) Samplings

Copying the apparent consensus sequences for Sp1 (GGGGCT)and putting each sequence in "⌘F" finds none located between ZSCAN22 and A1BG and four between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence GGGGCT (starting with SuccessablesSP1M.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for GGGGCT, 0.
  2. positive strand, negative direction, looking for GGGGCT, 1, GGGGCT at 3039.
  3. positive strand, positive direction, looking for GGGGCT, 1, GGGGCT at 576.
  4. negative strand, positive direction, looking for GGGGCT, 4, GGGGCT at 3983, GGGGCT at 1029, GGGGCT at 415, GGGGCT at 262.
  5. complement, negative strand, negative direction, looking for CCCCGA, 1, CCCCGA at 3039.
  6. complement, positive strand, negative direction, looking for CCCCGA, 0.
  7. complement, positive strand, positive direction, looking for CCCCGA, 4, CCCCGA at 3983, CCCCGA at 1029, CCCCGA at 415, CCCCGA at 262.
  8. complement, negative strand, positive direction, looking for CCCCGA, 1, CCCCGA at 576.
  9. inverse complement, negative strand, negative direction, looking for AGCCCC, 1, AGCCCC at 3037.
  10. inverse complement, positive strand, negative direction, looking for AGCCCC, 0.
  11. inverse complement, positive strand, positive direction, looking for AGCCCC, 6, AGCCCC at 4426, AGCCCC at 4411, AGCCCC at 1955, AGCCCC at 1866, AGCCCC at 349, AGCCCC at 279.
  12. inverse complement, negative strand, positive direction, looking for AGCCCC, 1, AGCCCC at 4218.
  13. inverse negative strand, negative direction, looking for CTGGGG, 0.
  14. inverse positive strand, negative direction, looking for CTGGGG, 1, CTGGGG at 3037.
  15. inverse positive strand, positive direction, looking for CTGGGG, 1, CTGGGG at 4218.
  16. inverse negative strand, positive direction, looking for CTGGGG, 6, CTGGGG at 4426, CTGGGG at 4411, CTGGGG at 1955, CTGGGG at 1866, CTGGGG at 349, CTGGGG at 279.

SP1M UTRs

Negative strand, negative direction: AGCCCC at 3037.

Positive strand, negative direction: GGGGCT at 3039.

SP1M core promoters

Positive strand, positive direction: AGCCCC at 4426, AGCCCC at 4411.

SP1M proximal promoters

Negative strand, positive direction: AGCCCC at 4218.

SP1M distal promoters

Negative strand, positive direction: GGGGCT at 3983, GGGGCT at 1029, GGGGCT at 415, GGGGCT at 262.

Positive strand, positive direction: AGCCCC at 1955, AGCCCC at 1866, GGGGCT at 576, AGCCCC at 349, AGCCCC at 279.

Sp1-box 2 (Motojima) Samplings

Copying a responsive elements consensus sequence CTGCCC and putting the sequence in "⌘F" finds two between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence CTGCCC (starting with SuccessablesSP1M2.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for CTGCCC, 0.
  2. positive strand, negative direction, looking for CTGCCC, 1, CTGCCC at 3853.
  3. positive strand, positive direction, looking for CTGCCC, 1, CTGCCC at 412.
  4. negative strand, positive direction, looking for CTGCCC, 2, CTGCCC at 4233, CTGCCC at 741.
  5. complement, negative strand, negative direction, looking for GACGGG, 1, GACGGG at 3853.
  6. complement, positive strand, negative direction, looking for GACGGG, 0.
  7. complement, positive strand, positive direction, looking for GACGGG, 2, GACGGG at 4233, GACGGG at 74.
  8. complement, negative strand, positive direction, looking for GACGGG, 1, GACGGG at 412.
  9. inverse complement, negative strand, negative direction, looking for GGGCAG, 2, GGGCAG at 1510, GGGCAG at 753.
  10. inverse complement, positive strand, negative direction, looking for GGGCAG, 1, GGGCAG at 1822.
  11. inverse complement, positive strand, positive direction, looking for GGGCAG, 1, GGGCAG at 3202.
  12. inverse complement, negative strand, positive direction, looking for GGGCAG, 3, GGGCAG at 3472, GGGCAG at 2895, GGGCAG at 2295.
  13. inverse negative strand, negative direction, looking for CCCGTC, 1, CCCGTC at 1822.
  14. inverse positive strand, negative direction, looking for CCCGTC, 2, CCCGTC at 1510, CCCGTC at 753.
  15. inverse positive strand, positive direction, looking for CCCGTC, 3, CCCGTC at 3472, CCCGTC at 2895, CCCGTC at 2295.
  16. inverse negative strand, positive direction, looking for CCCGTC, 1, CCCGTC at 3202.

SP1M2 UTRs

Positive strand, negative direction: CTGCCC at 3853.

SP1M2 proximal promoters

Negative strand, positive direction: CTGCCC at 4233.

SP1M2 distal promoters

Negative strand, negative direction: GGGCAG at 1510, GGGCAG at 753.

Positive strand, negative direction: GGGCAG at 1822.

Negative strand, positive direction: GGGCAG at 3472, GGGCAG at 2895, GGGCAG at 2295, CTGCCC at 741.

Positive strand, positive direction: GGGCAG at 3202, CTGCCC at 412.

Sp-1 (Sato) samplings

Copying a responsive elements consensus sequence CCGCCCC and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence CCGCCCC (starting with SuccessablesSP1S.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for CCGCCCC, 0.
  2. positive strand, negative direction, looking for CCGCCCC, 0.
  3. positive strand, positive direction, looking for CCGCCCC, 1, CCGCCCC at 1027.
  4. negative strand, positive direction, looking for CCGCCCC, 0.
  5. complement, negative strand, negative direction, looking for GGCGGGG, 0.
  6. complement, positive strand, negative direction, looking for GGCGGGG, 0.
  7. complement, positive strand, positive direction, looking for GGCGGGG, 0.
  8. complement, negative strand, positive direction, looking for GGCGGGG, GGCGGGG at 1027.
  9. inverse complement, negative strand, negative direction, looking for GGGGCGG, 0.
  10. inverse complement, positive strand, negative direction, looking for GGGGCGG, 0.
  11. inverse complement, positive strand, positive direction, looking for GGGGCGG, 1, GGGGCGG at 4238.
  12. inverse complement, negative strand, positive direction, looking for GGGGCGG, 4, GGGGCGG at 4439, GGGGCGG at 4429, GGGGCGG at 1793, GGGGCGG at 353.
  13. inverse negative strand, negative direction, looking for CCCCGCC, 0.
  14. inverse positive strand, negative direction, looking for CCCCGCC, 0.
  15. inverse positive strand, positive direction, looking for CCCCGCC, 4, CCCCGCC at 4439, CCCCGCC at 4429, CCCCGCC at 1793, CCCCGCC at 353.
  16. inverse negative strand, positive direction, looking for CCCCGCC, 1, CCCCGCC at 4238.

SP1S core promoters

Negative strand, positive direction: GGGGCGG at 4439, GGGGCGG at 4429.

SP1S proximal promoters

Positive strand, positive direction: GGGGCGG at 4238.

SP1S distal promoters

Negative strand, positive direction: GGGGCGG at 1793, GGGGCGG at 353.

Positive strand, positive direction: CCGCCCC at 1027.

Sp1 (Yao) samplings

Copying a responsive elements consensus sequence GCGGC and putting the sequence in "⌘F" finds 21 between ZNF497 and A1BG or one between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence GCGGC (starting with SuccessablesSP1Y.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for AAAAAAAA, 0.
  2. positive strand, negative direction, looking for AAAAAAAA, 0.
  3. positive strand, positive direction, looking for AAAAAAAA, 0.
  4. negative strand, positive direction, looking for AAAAAAAA, 0.
  5. complement, negative strand, negative direction, looking for TTTTTTTT, 0.
  6. complement, positive strand, negative direction, looking for TTTTTTTT, 0.
  7. complement, positive strand, positive direction, looking for TTTTTTTT, 0.
  8. complement, negative strand, positive direction, looking for TTTTTTTT, 0.
  9. inverse complement, negative strand, negative direction, looking for TTTTTTTT, 0.
  10. inverse complement, positive strand, negative direction, looking for TTTTTTTT, 0.
  11. inverse complement, positive strand, positive direction, looking for TTTTTTTT, 0.
  12. inverse complement, negative strand, positive direction, looking for TTTTTTTT, 0.
  13. inverse negative strand, negative direction, looking for AAAAAAAA, 0.
  14. inverse positive strand, negative direction, looking for AAAAAAAA, 0.
  15. inverse positive strand, positive direction, looking for AAAAAAAA, 0.
  16. inverse negative strand, positive direction, looking for AAAAAAAA, 0.

SP1Y UTRs

SP1Y core promoters

SP1Y proximal promoters

SP1Y distal promoters

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

Initial content for this page in some instances came from Wikiversity.

See also

References

  1. Wormke M, Stoner M, Saville B, Walker K, Abdelrahim M, Burghardt R, Safe S (March 2003). "The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes". Mol. Cell. Biol. 23 (6): 1843–55. doi:10.1128/MCB.23.6.1843-1855.2003. PMC 149455. PMID 12612060.
  2. Prasanna KS, Shilpa P, Salimath BP (2009). "Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription" (PDF). Current Trends in Biotechnology and Pharmacy. 3 (2): 138–148.
  3. 3.0 3.1 Masaru Motojima, Takao Ando and Toshimasa Yoshioka (10 July 2000). "Sp1-like activity mediates angiotensin-II-induced plasminogen-activator inhibitor type-1 (PAI-1) gene expression in mesangial cells" (PDF). Biomedical Journal. 349 (2): 435–441. doi:10.1042/0264-6021:3490435. PMID 10880342. Retrieved 13 August 2020.
  4. Hiroshi Sato, Megumi Kita, and Motoharu Seiki (5 November 1993). "v-Src Activates the Expression of 92-kDa Type IV Collagenase Gene through the AP-1 Site and the GT Box Homologous to Retinoblastoma Control Elements" (PDF). The Journal of Biological Chemistry. 268 (31): 23460–8. PMID 8226872. Retrieved 13 August 2020.
  5. D. W. Yao, J. Luo, Q. Y. He, J. Li, H. Wang, H. B. Shi, H. F. Xu, M. Wang and J. J. Loor (May 2016). "Characterization of the liver X receptor-dependent regulatory mechanism of goat stearoyl-coenzyme A desaturase 1 gene by linoleic acid". Journal of Dairy Science. 99 (5): 3945–3957. doi:10.3168/jds.2015-10601. PMID 26947306. Retrieved 5 September 2020.
  6. RefSeq (November 2014). SP1 Sp1 transcription factor [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 16 November 2018.
  7. RefSeq (July 2008). SP2 Sp2 transcription factor [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 16 November 2018.
  8. RefSeq (February 2010). SP3 Sp3 transcription factor [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 16 November 2018.
  9. RefSeq (May 2016). SP4 Sp4 transcription factor [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 16 November 2018.
  10. OMIM (March 2008). SP6 Sp6 transcription factor [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 16 November 2018.
  11. RefSeq (July 2010). SP7 Sp7 transcription factor [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 16 November 2018.
  12. RefSeq (June 2011). SP8 Sp8 transcription factor [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 16 November 2018.
  13. Fernandez-Zapico ME, Lomberk GA, Tsuji S, Demars CJ, Bardsley MR, Lin YH, Almada L, Han JJ, Mukhopadhyay D, Ordog T, Buttar NS, Urrutia R (December 2010). "A Functional Family-Wide Screening of SP/KLF Proteins Identifies a Subset of Suppressors of KRAS-Mediated Cell Growth". Biochem J. 435 (2): 529–37. doi:10.1042/BJ20100773. PMC 3130109. PMID 21171965.
  14. EntrezGene 6670
  15. Essafi-Benkhadir K; Grosso S; Puissant A; Robert G; Essafi M; Deckert M; Chamorey E; Dassonville O; Milano G; Auberger P; Pag?s G (2009). "Dual role of Sp3 transcription factor as an inducer of apoptosis and a marker of tumour aggressiveness". PLoS ONE. 4 (2): e4478. doi:10.1371/journal.pone.0004478. PMC 2636865. PMID 19212434.
  16. EntrezGene 6671
  17. 17.0 17.1 EntrezGene 170574
  18. EntrezGene 381373
  19. EntrezGene 64406
  20. EntrezGene 83395

External links