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Protein

Transcription factor Sp3

Gene

SP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000172845.13
HGNCiHGNC:11208 SP3
MIMi601804 gene
neXtProtiNX_Q02447

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
Cross-linki593Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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
ProteomicsDBi58091
58092 [Q02447-2]
58093 [Q02447-3]
58094 [Q02447-4]
58095 [Q02447-5]
58096 [Q02447-6]

PTM databases

iPTMnetiQ02447
PhosphoSitePlusiQ02447

Miscellaneous databases

PMAP-CutDBiQ02447

Expressioni

Tissue specificityi

Ubiquitously expressed.

Gene expression databases

BgeeiENSG00000172845 Expressed in 242 organ(s), highest expression level in amniotic fluid
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, 43 interactors
ELMiQ02447
IntActiQ02447, 13 interactors
MINTiQ02447
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

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
OMAiIAQQTIH
OrthoDBiEOG091G0HX6
PhylomeDBiQ02447
TreeFamiTF350150

Family and domain databases

InterProiView protein in InterPro
IPR030452 SP3
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PANTHERiPTHR23235:SF3 PTHR23235:SF3, 1 hit
PfamiView protein in Pfam
PF00096 zf-C2H2, 3 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 3 hits
SUPFAMiSSF57667 SSF57667, 2 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 3 hits
PS50157 ZINC_FINGER_C2H2_2, 3 hits

Sequences (6+)i

Sequence statusi: Complete.

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

This entry has 6 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y6K5H0Y6K5_HUMAN
Transcription factor Sp3
SP3
713Annotation score:
H0Y7L6H0Y7L6_HUMAN
Transcription factor Sp3
SP3
738Annotation score:

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 → A3 PublicationsCorresponds to variant dbSNP:rs1047640Ensembl.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]
ENST00000640958; ENSP00000492253; ENSG00000172845 [Q02447-5]
GeneIDi6670
KEGGihsa:6670
UCSCiuc002uig.3 human [Q02447-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Similar proteinsi

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, 43 interactors
ELMiQ02447
IntActiQ02447, 13 interactors
MINTiQ02447
STRINGi9606.ENSP00000310301

PTM databases

iPTMnetiQ02447
PhosphoSitePlusiQ02447

Polymorphism and mutation databases

BioMutaiSP3
DMDMi30923147

Proteomic databases

EPDiQ02447
MaxQBiQ02447
PaxDbiQ02447
PeptideAtlasiQ02447
PRIDEiQ02447
ProteomicsDBi58091
58092 [Q02447-2]
58093 [Q02447-3]
58094 [Q02447-4]
58095 [Q02447-5]
58096 [Q02447-6]

Protocols and materials databases

DNASUi6670
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310015; ENSP00000310301; ENSG00000172845 [Q02447-1]
ENST00000640958; ENSP00000492253; ENSG00000172845 [Q02447-5]
GeneIDi6670
KEGGihsa:6670
UCSCiuc002uig.3 human [Q02447-1]

Organism-specific databases

CTDi6670
DisGeNETi6670
EuPathDBiHostDB:ENSG00000172845.13
GeneCardsiSP3
HGNCiHGNC:11208 SP3
HPAiCAB004580
HPA032145
HPA032146
MIMi601804 gene
neXtProtiNX_Q02447
OpenTargetsiENSG00000172845
PharmGKBiPA36045
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00760000118984
HOVERGENiHBG008933
InParanoidiQ02447
KOiK09193
OMAiIAQQTIH
OrthoDBiEOG091G0HX6
PhylomeDBiQ02447
TreeFamiTF350150

Enzyme and pathway databases

ReactomeiR-HSA-3232118 SUMOylation of transcription factors
SignaLinkiQ02447
SIGNORiQ02447

Miscellaneous databases

ChiTaRSiSP3 human
GeneWikiiSp3_transcription_factor
GenomeRNAii6670
PMAP-CutDBiQ02447
PROiPR:Q02447
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172845 Expressed in 242 organ(s), highest expression level in amniotic fluid
CleanExiHS_SP3
ExpressionAtlasiQ02447 baseline and differential
GenevisibleiQ02447 HS

Family and domain databases

InterProiView protein in InterPro
IPR030452 SP3
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PANTHERiPTHR23235:SF3 PTHR23235:SF3, 1 hit
PfamiView protein in Pfam
PF00096 zf-C2H2, 3 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 3 hits
SUPFAMiSSF57667 SSF57667, 2 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 3 hits
PS50157 ZINC_FINGER_C2H2_2, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiSP3_HUMAN
AccessioniPrimary (citable) accession number: Q02447
Secondary accession number(s): A0AVL9
, B4E2B7, Q69B26, Q69B27, Q8TD56, Q8WWU4, Q9BQR1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: May 16, 2003
Last modified: November 7, 2018
This is version 184 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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