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Protein

Transcription factor Sp3

Gene

SP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional factor that can act as an activator or repressor depending on isoform and/or post-translational modifications. Binds to GT and GC boxes promoter elements. Competes with SP1 for the GC-box promoters. Weak activator of transcription but can activate a number of genes involved in different processes such as cell-cycle regulation, hormone-induction and house-keeping.12 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri621 – 645C2H2-type 1PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri651 – 675C2H2-type 2PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri681 – 703C2H2-type 3PROSITE-ProRule annotationAdd BLAST23

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000172845-MONOMER.
ReactomeiR-HSA-3232118. SUMOylation of transcription factors.
SignaLinkiQ02447.
SIGNORiQ02447.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor Sp3
Alternative name(s):
SPR-2
Gene namesi
Name:SP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:11208. SP3.

Subcellular locationi

  • Nucleus
  • NucleusPML body

  • Note: Localizes to the nuclear periphery and in nuclear dots when sumoylated. Some localization in PML nuclear bodies.

GO - Cellular componenti

  • cytoplasm Source: HPA
  • Golgi apparatus Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: HPA
  • PML body Source: UniProtKB-SubCell
  • transcriptional repressor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi120K → R: Some loss of sumoylation. Slight increase in transcriptional activity. Large increase in transcriptional activity; when associated with R-551. 1 Publication1
Mutagenesisi551 – 553KEE → AAA: Increases transcriptional activity. 1 Publication3
Mutagenesisi551 – 553KEE → REA: 200-fold increase in transcriptional activation. 1 Publication3
Mutagenesisi551 – 553KEE → RED: 200-fold increase in transcriptional activation. 1 Publication3
Mutagenesisi551 – 552KE → RA: 200-fold increase in transcriptional activation. 2
Mutagenesisi551 – 552KE → RD: 200-fold increase in transcriptional activation. 2
Mutagenesisi551K → Q: A decreased interaction with HDAC1 and deacetylation of SP3. Increase of about 4.5% of activity of the TERT promoter. Decreased recruitment of HDAC1 and increased binding of RNA polymerase II with promoter DNA. 3 Publications1
Mutagenesisi551K → R: Great loss of sumoylation, 20-fold increase in transcriptional activity and diffuse nuclear localization. Further small increase in transcriptional activity; when associated with R-120. Increased interaction with HDAC1 and deacetylation of SP3. About 50% decrease in activity of the TERT promoter. Enhances recruitment of HDAC1 and inhibits binding of RNA polymerase II with promoter DNA. 3 Publications1

Organism-specific databases

DisGeNETi6670.
OpenTargetsiENSG00000172845.
PharmGKBiPA36045.

Polymorphism and mutation databases

BioMutaiSP3.
DMDMi30923147.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000471411 – 781Transcription factor Sp3Add BLAST781

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei73PhosphoserineCombined sources1
Cross-linki120Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei551N6-acetyllysine; alternate2 Publications1
Cross-linki551Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki551Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki551Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei563PhosphoserineCombined sources1
Modified residuei566PhosphoserineBy similarity1
Modified residuei646PhosphoserineCombined sources1

Post-translational modificationi

Not glycosylated.
Acetylated by histone acetyltransferase p300, deacetylated by HDACs. Acetylation/deacetylation states regulate transcriptional activity. Acetylation appears to activate transcription. Alternate sumoylation and acetylation at Lys-551 also control transcriptional activity. Ceramides can also regulate acetylation/deacetylation events through altering the interaction of HDAC with SP3. In vitro, C(18)-ceramides, but not C(16)-ceramides, increase the interaction of HDAC1 with SP3 and enhance the deacetylation of SP3 and the subsequent repression of the TERT promoter.7 Publications
Sumoylated on all isoforms. Sumoylated on 2 sites in longer isoforms with Lys-551 being the major site. Sumoylation at this site promotes nuclear localization to the nuclear periphery, nuclear dots and PML nuclear bodies. Sumoylation on Lys-551 represses the transactivation activity, except for the largest isoform, L-Sp3, which has little effect on transactivation. Alternate sumoylation and acetylation at Lys-551 also control transcriptional activity.7 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ02447.
MaxQBiQ02447.
PaxDbiQ02447.
PeptideAtlasiQ02447.
PRIDEiQ02447.

PTM databases

iPTMnetiQ02447.
PhosphoSitePlusiQ02447.

Miscellaneous databases

PMAP-CutDBQ02447.

Expressioni

Tissue specificityi

Ubiquitously expressed.

Gene expression databases

BgeeiENSG00000172845.
CleanExiHS_SP3.
ExpressionAtlasiQ02447. baseline and differential.
GenevisibleiQ02447. HS.

Organism-specific databases

HPAiCAB004580.
HPA032145.
HPA032146.

Interactioni

Subunit structurei

Interacts with HLTF; the interaction may be required for basal transcriptional activity of HLTF. Interacts with HDAC1; the interaction deacetylates SP3 and regulates its transcriptional activity. Interacts with HDAC2 (preferably the CK2-phosphorylated form); the interaction deacetylates SP3 and regulates its transcriptional activity. Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ESR1P033722EBI-348158,EBI-78473

Protein-protein interaction databases

BioGridi112553. 34 interactors.
IntActiQ02447. 13 interactors.
MINTiMINT-189716.
STRINGi9606.ENSP00000310301.

Structurei

3D structure databases

ProteinModelPortaliQ02447.
SMRiQ02447.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni138 – 237Transactivation domain (Gln-rich)Add BLAST100
Regioni350 – 499Transactivation domain (Gln-rich)Add BLAST150
Regioni534 – 620Repressor domainAdd BLAST87

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi21 – 31Poly-GlyAdd BLAST11
Compositional biasi35 – 39Poly-Gln5
Compositional biasi44 – 100Ala-richAdd BLAST57

Sequence similaritiesi

Contains 3 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri621 – 645C2H2-type 1PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri651 – 675C2H2-type 2PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri681 – 703C2H2-type 3PROSITE-ProRule annotationAdd BLAST23

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00760000118984.
HOVERGENiHBG008933.
InParanoidiQ02447.
KOiK09193.
OMAiPQIQSTD.
OrthoDBiEOG091G0HX6.
PhylomeDBiQ02447.
TreeFamiTF350150.

Family and domain databases

Gene3Di3.30.160.60. 3 hits.
InterProiIPR030450. Sp1_fam.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR23235. PTHR23235. 1 hit.
PfamiPF00096. zf-C2H2. 2 hits.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 3 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 3 hits.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q02447-1) [UniParc]FASTAAdd to basket
Also known as: Large, L-Sp3

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.

« Hide

        10         20         30         40         50
MTAPEKPVKQ EEMAALDVDS GGGGGGGGGH GEYLQQQQQH GNGAVAAAAA
60 70 80 90 100
AQDTQPSPLA LLAATCSKIG PPSPGDDEEE AAAAAGAPAA AGATGDLASA
110 120 130 140 150
QLGGAPNRWE VLSATPTTIK DEAGNLVQIP SAATSSGQYV LPLQNLQNQQ
160 170 180 190 200
IFSVAPGSDS SNGTVSSVQY QVIPQIQSAD GQQVQIGFTG SSDNGGINQE
210 220 230 240 250
SSQIQIIPGS NQTLLASGTP SANIQNLIPQ TGQVQVQGVA IGGSSFPGQT
260 270 280 290 300
QVVANVPLGL PGNITFVPIN SVDLDSLGLS GSSQTMTAGI NADGHLINTG
310 320 330 340 350
QAMDSSDNSE RTGERVSPDI NETNTDTDLF VPTSSSSQLP VTIDSTGILQ
360 370 380 390 400
QNTNSLTTSS GQVHSSDLQG NYIQSPVSEE TQAQNIQVST AQPVVQHLQL
410 420 430 440 450
QESQQPTSQA QIVQGITPQT IHGVQASGQN ISQQALQNLQ LQLNPGTFLI
460 470 480 490 500
QAQTVTPSGQ VTWQTFQVQG VQNLQNLQIQ NTAAQQITLT PVQTLTLGQV
510 520 530 540 550
AAGGAFTSTP VSLSTGQLPN LQTVTVNSID SAGIQLHPGE NADSPADIRI
560 570 580 590 600
KEEEPDPEEW QLSGDSTLNT NDLTHLRVQV VDEEGDQQHQ EGKRLRRVAC
610 620 630 640 650
TCPNCKEGGG RGTNLGKKKQ HICHIPGCGK VYGKTSHLRA HLRWHSGERP
660 670 680 690 700
FVCNWMYCGK RFTRSDELQR HRRTHTGEKK FVCPECSKRF MRSDHLAKHI
710 720 730 740 750
KTHQNKKGIH SSSTVLASVE AARDDTLITA GGTTLILANI QQGSVSGIGT
760 770 780
VNTSATSNQD ILTNTEIPLQ LVTVSGNETM E
Length:781
Mass (Da):81,925
Last modified:May 16, 2003 - v3
Checksum:iDCFD4363509DB49D
GO
Isoform 2 (identifier: Q02447-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: Missing.

Note: Produced by alternative initiation at Met-13 of isoform 1. No experimental confirmation available.
Show »
Length:769
Mass (Da):80,557
Checksum:iC02D0B852BBF9389
GO
Isoform 3 (identifier: Q02447-3) [UniParc]FASTAAdd to basket
Also known as: M1-Sp3

The sequence of this isoform differs from the canonical sequence as follows:
     1-285: Missing.

Note: Produced by alternative initiation at Met-286 of isoform 1. No experimental confirmation available.
Show »
Length:496
Mass (Da):53,715
Checksum:i65658E7F04158661
GO
Isoform 4 (identifier: Q02447-4) [UniParc]FASTAAdd to basket
Also known as: M2-Sp3

The sequence of this isoform differs from the canonical sequence as follows:
     1-302: Missing.

Note: Produced by alternative initiation at Met-303 of isoform 1. No experimental confirmation available.
Show »
Length:479
Mass (Da):52,050
Checksum:iDA04C2A90DFA307A
GO
Isoform 5 (identifier: Q02447-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: MTAPEKPVKQEEMAALDVDSGGGGGGGGGHGEYLQQQQQHGNGAVAAAAAAQDTQPSPLALLAATCSKI → M

Note: Produced by alternative splicing. An AUA codon is translated into Met and used as a translation initiation site (in vitro).
Show »
Length:713
Mass (Da):75,330
Checksum:iB0CF8FC66DA30478
GO
Isoform 6 (identifier: Q02447-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: Missing.
     53-93: Missing.

Note: Produced by alternative splicing.
Show »
Length:728
Mass (Da):76,814
Checksum:iE9D95D6717E9F885
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti69I → M in AAR30505 (PubMed:15474306).Curated1
Sequence conflicti71P → G in AAA36630 (Ref. 7) Curated1
Sequence conflicti739N → K in AAL58086 (PubMed:12297010).Curated1
Sequence conflicti739N → K in AAR30505 (PubMed:15474306).Curated1
Sequence conflicti739N → K in AAR30506 (PubMed:15474306).Curated1
Sequence conflicti739N → K in CAA48562 (PubMed:1341900).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_016123164T → A.3 PublicationsCorresponds to variant rs1047640dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0266981 – 302Missing in isoform 4. CuratedAdd BLAST302
Alternative sequenceiVSP_0266991 – 285Missing in isoform 3. CuratedAdd BLAST285
Alternative sequenceiVSP_0267001 – 69MTAPE…TCSKI → M in isoform 5. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_0267011 – 12Missing in isoform 2 and isoform 6. 2 PublicationsAdd BLAST12
Alternative sequenceiVSP_02670253 – 93Missing in isoform 6. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY070137 mRNA. Translation: AAL58086.1.
AY441957 mRNA. Translation: AAR30505.1.
AY441958 mRNA. Translation: AAR30506.1.
AK304199 mRNA. Translation: BAG65079.1.
BC126414 mRNA. Translation: AAI26415.1.
AF494280 Genomic DNA. Translation: AAM12875.1.
AJ310752 mRNA. Translation: CAC34575.1.
M97191 mRNA. Translation: AAA36630.2.
X68560 mRNA. Translation: CAA48562.1.
CCDSiCCDS2254.1. [Q02447-1]
CCDS46452.1. [Q02447-5]
PIRiB44489.
RefSeqiNP_001017371.3. NM_001017371.4. [Q02447-5]
NP_001166183.1. NM_001172712.1.
NP_003102.1. NM_003111.4. [Q02447-1]
UniGeneiHs.531587.

Genome annotation databases

EnsembliENST00000310015; ENSP00000310301; ENSG00000172845. [Q02447-1]
GeneIDi6670.
KEGGihsa:6670.
UCSCiuc002uig.3. human. [Q02447-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY070137 mRNA. Translation: AAL58086.1.
AY441957 mRNA. Translation: AAR30505.1.
AY441958 mRNA. Translation: AAR30506.1.
AK304199 mRNA. Translation: BAG65079.1.
BC126414 mRNA. Translation: AAI26415.1.
AF494280 Genomic DNA. Translation: AAM12875.1.
AJ310752 mRNA. Translation: CAC34575.1.
M97191 mRNA. Translation: AAA36630.2.
X68560 mRNA. Translation: CAA48562.1.
CCDSiCCDS2254.1. [Q02447-1]
CCDS46452.1. [Q02447-5]
PIRiB44489.
RefSeqiNP_001017371.3. NM_001017371.4. [Q02447-5]
NP_001166183.1. NM_001172712.1.
NP_003102.1. NM_003111.4. [Q02447-1]
UniGeneiHs.531587.

3D structure databases

ProteinModelPortaliQ02447.
SMRiQ02447.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112553. 34 interactors.
IntActiQ02447. 13 interactors.
MINTiMINT-189716.
STRINGi9606.ENSP00000310301.

PTM databases

iPTMnetiQ02447.
PhosphoSitePlusiQ02447.

Polymorphism and mutation databases

BioMutaiSP3.
DMDMi30923147.

Proteomic databases

EPDiQ02447.
MaxQBiQ02447.
PaxDbiQ02447.
PeptideAtlasiQ02447.
PRIDEiQ02447.

Protocols and materials databases

DNASUi6670.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310015; ENSP00000310301; ENSG00000172845. [Q02447-1]
GeneIDi6670.
KEGGihsa:6670.
UCSCiuc002uig.3. human. [Q02447-1]

Organism-specific databases

CTDi6670.
DisGeNETi6670.
GeneCardsiSP3.
HGNCiHGNC:11208. SP3.
HPAiCAB004580.
HPA032145.
HPA032146.
MIMi601804. gene.
neXtProtiNX_Q02447.
OpenTargetsiENSG00000172845.
PharmGKBiPA36045.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00760000118984.
HOVERGENiHBG008933.
InParanoidiQ02447.
KOiK09193.
OMAiPQIQSTD.
OrthoDBiEOG091G0HX6.
PhylomeDBiQ02447.
TreeFamiTF350150.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000172845-MONOMER.
ReactomeiR-HSA-3232118. SUMOylation of transcription factors.
SignaLinkiQ02447.
SIGNORiQ02447.

Miscellaneous databases

ChiTaRSiSP3. human.
GeneWikiiSp3_transcription_factor.
GenomeRNAii6670.
PMAP-CutDBQ02447.
PROiQ02447.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172845.
CleanExiHS_SP3.
ExpressionAtlasiQ02447. baseline and differential.
GenevisibleiQ02447. HS.

Family and domain databases

Gene3Di3.30.160.60. 3 hits.
InterProiIPR030450. Sp1_fam.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR23235. PTHR23235. 1 hit.
PfamiPF00096. zf-C2H2. 2 hits.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 3 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSP3_HUMAN
AccessioniPrimary (citable) accession number: Q02447
Secondary accession number(s): A0AVL9
, B4E2B7, Q69B26, Q69B27, Q8TD56, Q8WWU4, Q9BQR1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: May 16, 2003
Last modified: November 30, 2016
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.