SP3

Summary

SP3 (Sp3 transcription factor, HGNC:11208) is a protein-coding gene on chromosome 2q31.1, encoding Transcription factor Sp3 (Q02447). Transcriptional factor that can act as an activator or repressor depending on isoform and/or post-translational modifications.

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.

Source: NCBI Gene 6670 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 114 total
• Transcription factor: yes — 465 downstream targets (CollecTRI)
• MANE Select transcript: NM_003111

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11208
Approved symbol	SP3
Name	Sp3 transcription factor
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	SPR-2
Ensembl gene	ENSG00000172845
Ensembl biotype	protein_coding
OMIM	601804
Entrez	6670

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 4 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000310015, ENST00000416195, ENST00000418194, ENST00000418620, ENST00000462904, ENST00000465379, ENST00000483084, ENST00000490182, ENST00000650743, ENST00000651846, ENST00000652005

RefSeq mRNA: 3 — MANE Select: NM_003111 NM_001017371, NM_001172712, NM_003111

CCDS: CCDS2254, CCDS46452

Canonical transcript exons

ENST00000310015 — 7 exons

Exon	Start	End
ENSE00001192444	173918593	173918785
ENSE00001192448	173913070	173913266
ENSE00001192467	173954873	173956232
ENSE00003539132	173964405	173964553
ENSE00003574266	173965165	173965373
ENSE00003654507	173963761	173963883
ENSE00003847527	173900775	173910257

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 97.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.2132 / max 629.1677, expressed in 1817 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31830	19.3966	1747
31832	5.5197	1665
31837	4.7316	1618
31835	3.3923	1357
31834	1.3092	823
31836	0.7054	369
31833	0.1584	38

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hair follicle	UBERON:0002073	97.95	gold quality
germinal epithelium of ovary	UBERON:0001304	97.52	gold quality
sural nerve	UBERON:0015488	97.52	gold quality
superficial temporal artery	UBERON:0001614	97.16	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.13	gold quality
calcaneal tendon	UBERON:0003701	97.09	gold quality
buccal mucosa cell	CL:0002336	97.00	gold quality
skin of hip	UBERON:0001554	96.99	gold quality
palpebral conjunctiva	UBERON:0001812	96.99	gold quality
ventricular zone	UBERON:0003053	96.91	gold quality
trabecular bone tissue	UBERON:0002483	96.87	gold quality
embryo	UBERON:0000922	96.79	gold quality
amniotic fluid	UBERON:0000173	96.75	gold quality
ganglionic eminence	UBERON:0004023	96.75	gold quality
periodontal ligament	UBERON:0008266	96.65	gold quality
mammary duct	UBERON:0001765	96.62	gold quality
caput epididymis	UBERON:0004358	96.47	gold quality
eye	UBERON:0000970	96.39	gold quality
oral cavity	UBERON:0000167	96.36	gold quality
endometrium	UBERON:0001295	96.32	gold quality
epithelium of mammary gland	UBERON:0003244	96.28	gold quality
corpus epididymis	UBERON:0004359	96.27	gold quality
bone marrow	UBERON:0002371	96.12	gold quality
jejunal mucosa	UBERON:0000399	96.01	gold quality
cauda epididymis	UBERON:0004360	95.90	gold quality
parietal pleura	UBERON:0002400	95.79	gold quality
secondary oocyte	CL:0000655	95.64	gold quality
epithelium of nasopharynx	UBERON:0001951	95.58	gold quality
nasopharynx	UBERON:0001728	95.57	gold quality
bone marrow cell	CL:0002092	95.54	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.46
E-MTAB-6386	no	193.60
E-MTAB-6142	no	89.12
E-GEOD-93593	no	7.45

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

465 targets.

Target	Regulation
ABCA1	Repression
ABCA2	Activation
ABCB1
ABCC1
ABCC3
ABCG2	Unknown
ACE	Unknown
ACHE
ACLY
ACSBG1	Unknown
ACSS2	Activation
ADAM2
ADCY4	Repression
ADGRE5	Activation
ADGRG1
ADH5
ADIPOQ
AEBP1
AFAP1L1
AFM
AGTR1	Unknown
AKAP12	Unknown
AKR1C3	Activation
ALDH7A1
ALOX12	Activation
ALOX15B
ALOX5
ALPL	Activation
ANG	Unknown
ANGPT2

JASPAR motifs

Motif	Name	Family
MA0746.1	SP3	Three-zinc finger Kruppel-related
MA0746.2	SP3	Three-zinc finger Kruppel-related
MA0746.3	SP3	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:23019068

Upstream regulators (CollecTRI, top): AP1, E2F1, ESR1, FOS, FOXC1, JUN, MYB, MYBL2, MYC, NEUROD1, NF1, NFKB, NFYA, NR3C1, SP1, SP3, SP4, SPI1, TCF3, TFAP2A, USF1, VSX2, ZBTB10

miRNA regulators (miRDB)

211 targeting SP3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AA	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 40)

• Transcription factor Sp3 blocked the Sp1 induction of COL2A1 promoter activity (PMID:11447232)
• Sp3- mediated transcriptional repression is due, at least in part, to competition for promoter-specific transcription factors (PMID:11773047)
• role in interferon-gamma mediated suppression of macrophage lipoprotein lipase gene transcription (PMID:11796707)
• role in identifying sterol-indendent regulatory elements in human ATP-binding cassette transporter A1 promoter (PMID:11839742)
• role in regulating 11beta-hydroxysteroid dehydrogenase type 2 promoter (PMID:11850421)
• Role of Sp1 and Sp3 in the nutrient-regulated expression of the human asparagine synthetase gene (PMID:11867623)
• cooperation with hepatocyte nuclear factor-4 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line (PMID:12133007)
• Results suggest that Sp1 and Sp3 associate with the hTERT promoter, recruiting HDAC for the localized deacetylation of nucleosomal histones and transcriptional silencing of the hTERT gene in normal human somatic cells. (PMID:12151407)
• CK2 phosphorylation of HDAC2 recruited by Sp1 or Sp3 could regulate HDAC activity and alter the balance of histone deacetylase and histone acetyltransferase activities and dynamic chromatin remodeling of estrogen-regulated genes. (PMID:12176973)
• TGF-beta1 inhibition of COL2A1 gene transcription in articular chondrocytes is mediated by an increase of the Sp3/Sp1 ratio and by the repression of Sp1 transactivating effects on that gene (PMID:12186868)
• Use of non-AUG (AUA) translation initiation site and alternate downstream start sites, results in multiple SP3 isoforms. (PMID:12297010)
• role of transcription factors Sp1 and Sp3 in the regulation of telomerase activity and human telomerase reverse transcriptase (hTERT) in Jurkat T cells (PMID:12297462)
• This protein plays a role in the identification of regulatory elements in the human adipose most abundant gene transcript-1(apM-1) promoter. (PMID:12378384)
• 5’ UTR of Sp3 transcription factor (PMID:12411611)
• role in regulating vascular endothelial growth factor-A gene transcription by activating two proximal GC-rich promoter elements (PMID:12509426)
• results suggest that oxidized phospholipids inhibit transcription of the thrombomodulin gene in vascular endothelium by inhibiting the binding of retinoic acid receptor beta-retinoid x receptor alpha heterodimer and Sp1 and Sp3 to thrombomodulin promoter (PMID:12576329)
• Regulates leukotreiene C4 synthase gene expression in mononuclear phagocytes. (PMID:12664565)
• This protein and Sp1 are involved in up-regulation of human deoxyribonuclease II transcription during differentiation of HL-60 cells. (PMID:12694199)
• Sp1 and Sp3 regulate human CETP promoter activity through three Sp1/Sp3 binding sites in a distinct manner (PMID:12730302)
• The results indicate that Sp1 is the protein mediating the basal transcription of MGST1. It appears that both the Sp1 and Sp3 proteins are important for the basal expression of PGES (PMID:12818425)
• Acetylation acts as a switch that controls the repressor and activator role of Sp3. (PMID:12837748)
• Sp3 and Sp1 have roles in regulating monoamine oxidase B in human tumor cells (PMID:12855685)
• HNF4-alpha, HNF3-beta and Sp1/Sp3 are important in regulation of prothrombin expression (PMID:12911579)
• TFIIB intewracts with SP1/SP3 at the SP1 site. (PMID:12972613)
• Biotin affects gene expression in Jurkaat cells. (PMID:14608051)
• In conclusion, we provide evidence for AML-1, PU.1, and Sp3 cooperatively and directly mediating BPI-expression during myeloid differentiation. (PMID:14623259)
• E2F and Sp1/Sp3 synergize but are not sufficient to activate the MYCN gene in neuroblastoma (PMID:14645238)
• SP3 acts as a positive regulator on the core promoter of human ZPK gene (PMID:14697235)
• the cooperation of HIF-1 with Sp1/Sp3 confers transcriptional activation under hypoxia to RORalpha4 (PMID:14742449)
• S-nitrosoglutathione increases Sp3 binding to DNA and transcription of CFTR at physiological concentrations, but inhibits Sp3 binding and CFTR transcription at nitrosative stress levels. (PMID:14766015)
• An SP3 binding site in the IGFBP4 gene was identified and the role of SP3 in regulating its promoter activity in CaCo-2 cells was studied. (PMID:14767471)
• Sp3 isoform ratios and activity are controlled at the translational level, which regulates expression of genes during mitosis and has effects on cell cycle regulation and tumorigenesis (PMID:14767558)
• Sp3 binding is regulated by methylation in the core-promoter region of the chondromodulin-I gene (PMID:15107420)
• PPARgamma1 has bifunctional properties in the regulation of KDR gene expression mediated via interaction with both Sp1 and Sp3 (PMID:15111490)
• human secretin gene is controlled by the Sp1/Sp3 transcription factors ratio (PMID:15118068)
• four isoforms derive from alternative translational start sites at positions 1, 37, 856, and 907; the transcriptional activity of all the Sp3 isoforms is regulated by SUMO modification (PMID:15247228)
• Sp1 and Sp3 proteins play a physiologically important role in positively and negatively regulating the 15-LOX2 gene expression, respectively. (PMID:15247906)
• The reduced binding affinity of Sp1/Sp3 to the T allele explain earlier observations of a reduced t-PA release and an increased risk of myocardial infarction in individuals carrying this allele. (PMID:15466927)
• Sp3 isoforms are sumoylated in vivo and this post-translational modification plays an important role in the regulation of Sp3-mediated transcription. (PMID:15494207)
• results show that there are genuine Sp1/Sp3 or Egr-1 controlled genes showing no cross-regulation of Sp1/Sp3 and Egr-1 through the same DNA-binding site (PMID:15523672)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sp3a	ENSDARG00000001549
danio_rerio	sp3b	ENSDARG00000007812
mus_musculus	Sp3	ENSMUSG00000027109
rattus_norvegicus	Sp3	ENSRNOG00000060479

Paralogs (3): SP4 (ENSG00000105866), SP2 (ENSG00000167182), SP1 (ENSG00000185591)

Protein

Protein identifiers

Transcription factor Sp3 — Q02447 (reviewed: Q02447)

Alternative names: SPR-2

All UniProt accessions (6): Q02447, A0A494C070, A0A494C0Z6, A0A494C1G8, H0Y6K5, H0Y7L6

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Subunit / interactions. 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.

Subcellular location. Nucleus. PML body.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. 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. 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.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Miscellaneous. Produced by alternative initiation at Met-13 of isoform 1. Produced by alternative initiation at Met-286 of isoform 1. Produced by alternative initiation at Met-303 of isoform 1. Produced by alternative splicing. An AUA codon is translated into Met and used as a translation initiation site (in vitro). Produced by alternative splicing.

Similarity. Belongs to the Sp1 C2H2-type zinc-finger protein family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q02447-1	1, Large, L-Sp3	yes
Q02447-2	2
Q02447-3	3, M1-Sp3
Q02447-4	4, M2-Sp3
Q02447-5	5
Q02447-6	6

RefSeq proteins (3): NP_001017371, NP_001166183, NP_003102* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (43 total): mutagenesis site 8, region of interest 6, compositionally biased region 5, modified residue 5, cross-link 5, splice variant 5, zinc finger region 3, sequence conflict 3, chain 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02447-F1	38.74	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 73, 551, 563, 566, 646, 120, 551, 551, 551, 593

Mutagenesis-validated functional residues (8):

Position	Phenotype
120	some loss of sumoylation. slight increase in transcriptional activity. large increase in transcriptional activity; when
551–553	increases transcriptional activity.
551–553	200-fold increase in transcriptional activation.
551–552	200-fold increase in transcriptional activation.
551	a decreased interaction with hdac1 and deacetylation of sp3. increase of about 4.5% of activity of the tert promoter. de
551	great loss of sumoylation, 20-fold increase in transcriptional activity and diffuse nuclear localization. further small

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3232118	SUMOylation of transcription factors
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 391 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, E2F_Q4, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, GOBP_MYELOID_CELL_HOMEOSTASIS, PID_TELOMERASE_PATHWAY, E2F4DP1_01, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_B_CELL_ACTIVATION, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, TTTGTAG_MIR520D

GO Biological Process (25): ossification (GO:0001503), natural killer cell differentiation (GO:0001779), trophectodermal cell differentiation (GO:0001829), liver development (GO:0001889), embryonic placenta development (GO:0001892), myeloid progenitor cell differentiation (GO:0002318), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), B cell differentiation (GO:0030183), T cell differentiation (GO:0030217), megakaryocyte differentiation (GO:0030219), monocyte differentiation (GO:0030224), lung development (GO:0030324), granulocyte differentiation (GO:0030851), enucleate erythrocyte differentiation (GO:0043353), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic camera-type eye morphogenesis (GO:0048596), embryonic skeletal system development (GO:0048706), embryonic process involved in female pregnancy (GO:0060136), definitive hemopoiesis (GO:0060216), negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), erythrocyte differentiation (GO:0030218)

GO Molecular Function (14): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), chromatin binding (GO:0003682), zinc ion binding (GO:0008270), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), PML body (GO:0016605), transcription repressor complex (GO:0017053), protein-DNA complex (GO:0032993)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lymphocyte differentiation	3
DNA-templated transcription	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
transcription by RNA polymerase II	2
myeloid leukocyte differentiation	2
regulation of transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
binding	2
DNA binding	2
multicellular organismal process	1
natural killer cell activation	1
blastocyst formation	1
cell differentiation	1
gland development	1
hepaticobiliary system development	1
in utero embryonic development	1
placenta development	1
embryonic organ development	1
hematopoietic progenitor cell differentiation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
B cell activation	1
T cell activation	1
myeloid cell differentiation	1
mononuclear cell differentiation	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
erythrocyte differentiation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
embryonic camera-type eye development	1
embryonic eye morphogenesis	1
camera-type eye morphogenesis	1
skeletal system development	1
chordate embryonic development	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

2444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SP3	NXNL1	Q96CM4	696
SP3	ESR1	P03372	676
SP3	PAX4	O43316	648
SP3	VSX1	Q9NZR4	644
SP3	NFATC2	Q13469	625
SP3	E2F1	Q01094	588
SP3	ACRV1	P26436	572
SP3	EWSR1	Q01844	566
SP3	DYRK1A	Q13627	551
SP3	USF2	Q15853	548
SP3	DYRK2	Q92630	536
SP3	ETS1	P14921	530
SP3	RELA	Q04206	528
SP3	AKR1C3	P42330	519
SP3	CD14	P08571	514

IntAct

59 interactions, top by confidence:

A	B	Type	Score
HTT	SP3	psi-mi:“MI:0915”(physical association)	0.670
SP3	ESR1	psi-mi:“MI:0407”(direct interaction)	0.670
ESR1	SP3	psi-mi:“MI:0407”(direct interaction)	0.670
SP3	CIB3	psi-mi:“MI:0915”(physical association)	0.560
SP3	PHF21A	psi-mi:“MI:0915”(physical association)	0.560
POGZ	SP3	psi-mi:“MI:0915”(physical association)	0.560
SP3	LIN54	psi-mi:“MI:0915”(physical association)	0.560
SP3	SPANXN2	psi-mi:“MI:0915”(physical association)	0.560
SNRPB	SP3	psi-mi:“MI:0915”(physical association)	0.560
SP3	GABPA	psi-mi:“MI:0407”(direct interaction)	0.540
GABPA	SP3	psi-mi:“MI:0915”(physical association)	0.540
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
MBTPS1	CLGN	psi-mi:“MI:0914”(association)	0.530
PDGFRL	ANKRD28	psi-mi:“MI:0914”(association)	0.530
ITLN1	HSPA5	psi-mi:“MI:0914”(association)	0.530
MAP1LC3A	SP3	psi-mi:“MI:0407”(direct interaction)	0.440
SP3		psi-mi:“MI:0915”(physical association)	0.400
	SP3	psi-mi:“MI:0915”(physical association)	0.400
SP3	GCH1	psi-mi:“MI:0915”(physical association)	0.370
GCH1	SP3	psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
	ARID1A	psi-mi:“MI:0914”(association)	0.350
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
GRHL1	POLRMT	psi-mi:“MI:0914”(association)	0.350
PRSS33	SAC3D1	psi-mi:“MI:0914”(association)	0.350

BioGRID (121): SP3 (Reconstituted Complex), SP3 (Affinity Capture-MS), SP3 (Affinity Capture-MS), SP3 (Affinity Capture-MS), SP3 (Affinity Capture-MS), SP3 (Affinity Capture-MS), SP3 (Affinity Capture-MS), SP3 (Affinity Capture-MS), SP3 (Affinity Capture-MS), STK19 (Two-hybrid), SP3 (Affinity Capture-Western), SP1 (Affinity Capture-Western), SUB1 (Affinity Capture-Western), DEAF1 (Affinity Capture-Western), SP3 (Affinity Capture-Western)

ESM2 similar proteins: A6QQW0, B4F7E9, O15391, O43167, O62836, O70230, O70494, P08048, P15337, P17010, P17012, P18846, P20385, P25490, P27699, P36508, P52747, P79145, P81069, P81269, Q00420, Q00899, Q01147, Q01611, Q02447, Q03060, Q03061, Q06547, Q08DA8, Q0V8G2, Q1LYE3, Q1LZH5, Q1RMI3, Q4V8R6, Q52KB5, Q52V16, Q58DZ6, Q5XIU2, Q66K89, Q6B4Z5

Diamond homologs: A5ABV9, O08876, O14901, O70494, O89090, O89091, P08047, P0CG40, P41696, Q01714, Q02446, Q02447, Q0VA40, Q13351, Q22678, Q3SY56, Q5XGT8, Q62445, Q64HY3, Q64HY5, Q6BEB4, Q6NW96, Q6P0J3, Q8BMJ8, Q8IXZ3, Q8K1S5, Q8TDD2, Q8VI67, Q90WR8, Q9ESX2, Q9JHX2, Q9TZ64, O08584, O35738, O35819, O43474, O62259, O75840, O95600, P46099

SIGNOR signaling

22 interactions.

A	Effect	B	Mechanism
MAPK1	up-regulates	SP3	phosphorylation
MAPK3	up-regulates	SP3	phosphorylation
SP3	“up-regulates quantity by expression”	SCNN1A	“transcriptional regulation”
PPP1CA	“down-regulates activity”	SP3	dephosphorylation
SP3	“up-regulates quantity by expression”	ITGA11
SP3	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
SP3	“down-regulates quantity by repression”	MAOB	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	IFITM5	“transcriptional regulation”
SP3	“down-regulates quantity by repression”	LORICRIN	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	CBS	“transcriptional regulation”
SP3	“down-regulates quantity by repression”	SOX18	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	CYP27A1	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	FMR1	“transcriptional regulation”
PP1	“down-regulates activity”	SP3	dephosphorylation
SP3	“up-regulates quantity by expression”	ASNS	“transcriptional regulation”
Gbeta	up-regulates	SP3	phosphorylation
ERK1/2	up-regulates	SP3	phosphorylation
SP3	“up-regulates quantity by expression”	HGF	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	SLC9A3	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	SLC19A3	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	PCYT1A	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	CADM1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

114 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1445 predictions. Top by Δscore:

Variant	Effect	Δscore
2:173910923:T:TA	donor_gain	1.0000
2:173912314:A:C	donor_gain	1.0000
2:173913065:GTAAC:G	donor_loss	1.0000
2:173913066:TAACC:T	donor_loss	1.0000
2:173913068:A:AC	donor_loss	1.0000
2:173913069:C:CG	donor_loss	1.0000
2:173913262:TACCT:T	acceptor_gain	1.0000
2:173913265:CT:C	acceptor_gain	1.0000
2:173913267:C:CC	acceptor_gain	1.0000
2:173918781:AATAT:A	acceptor_gain	1.0000
2:173918782:ATAT:A	acceptor_gain	1.0000
2:173918783:TAT:T	acceptor_gain	1.0000
2:173918784:AT:A	acceptor_gain	1.0000
2:173918786:C:CC	acceptor_gain	1.0000
2:173910094:T:TA	donor_gain	0.9900
2:173910916:CTGAA:C	donor_gain	0.9900
2:173913068:A:C	donor_gain	0.9900
2:173913133:T:TA	donor_gain	0.9900
2:173913263:ACCT:A	acceptor_gain	0.9900
2:173913264:CCTC:C	acceptor_gain	0.9900
2:173913265:CTCTA:C	acceptor_loss	0.9900
2:173913267:CTAAA:C	acceptor_loss	0.9900
2:173918587:GCATA:G	donor_loss	0.9900
2:173918588:CATA:C	donor_loss	0.9900
2:173918589:ATAC:A	donor_loss	0.9900
2:173918590:TACC:T	donor_loss	0.9900
2:173918591:A:G	donor_loss	0.9900
2:173918592:C:T	donor_loss	0.9900
2:173918594:TTCC:T	donor_gain	0.9900
2:173918599:C:CT	donor_gain	0.9900

AlphaMissense

5073 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:173910180:G:C	H703D	1.000
2:173910190:A:C	H699Q	1.000
2:173910190:A:T	H699Q	1.000
2:173910191:T:C	H699R	1.000
2:173910191:T:G	H699P	1.000
2:173910192:G:C	H699D	1.000
2:173910192:G:T	H699N	1.000
2:173910195:T:C	K698E	1.000
2:173910200:A:G	L696P	1.000
2:173910204:G:C	H695D	1.000
2:173910206:T:A	D694V	1.000
2:173910206:T:C	D694G	1.000
2:173910207:C:A	D694Y	1.000
2:173910207:C:G	D694H	1.000
2:173910211:T:A	R692S	1.000
2:173910211:T:G	R692S	1.000
2:173910212:C:A	R692I	1.000
2:173910212:C:G	R692T	1.000
2:173910217:A:C	F690L	1.000
2:173910217:A:T	F690L	1.000
2:173910218:A:C	F690C	1.000
2:173910218:A:G	F690S	1.000
2:173910219:A:G	F690L	1.000
2:173910219:A:T	F690I	1.000
2:173910223:T:A	K688N	1.000
2:173910223:T:G	K688N	1.000
2:173910224:T:A	K688I	1.000
2:173910225:T:C	K688E	1.000
2:173910229:A:C	C686W	1.000
2:173910230:C:G	C686S	1.000

dbSNP variants (sampled 300 via entrez): RS1000051077 (2:173966377 A>G), RS1000059857 (2:173930197 C>A,T), RS1000066620 (2:173903012 T>C), RS1000110143 (2:173930461 C>T), RS1000193471 (2:173905207 A>G), RS1000248411 (2:173931473 A>G), RS1000253099 (2:173935440 G>A), RS1000327301 (2:173941132 A>T), RS1000389279 (2:173957614 G>A), RS1000403727 (2:173962891 A>C), RS1000422968 (2:173901846 C>A,T), RS1000525507 (2:173959108 G>A), RS1000535520 (2:173959397 C>T), RS1000577490 (2:173933786 T>C), RS1000584308 (2:173922134 A>G,T)

Disease associations

OMIM: gene MIM:601804 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002148_1	Otitis media (chronic/recurrent)	2.000000e-08
GCST002182_1	End-stage renal disease in Type 1 diabetics	4.000000e-08
GCST002500_16	QT interval	6.000000e-10
GCST003983_44	Male-pattern baldness	5.000000e-08
GCST004748_73	Lung cancer	6.000000e-06
GCST004863_123	Mosquito bite size	2.000000e-07
GCST007621_5	Sensation seeking	1.000000e-06
GCST010919_8	QT interval	3.000000e-06
GCST90000025_827	Appendicular lean mass	5.000000e-19

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0008378	mosquito bite reaction size measurement
EFO:0006946	behavioural disinhibition measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

72 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	7
trichostatin A	increases expression, affects binding, affects cotreatment, increases reaction	4
mithramycin A	affects binding, increases reaction, decreases expression, decreases reaction, increases activity	3
perfluorooctane sulfonic acid	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Decitabine	affects cotreatment, increases reaction, affects binding	2
Fulvestrant	decreases methylation, affects binding, increases reaction, affects cotreatment	2
Quercetin	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
selenomethylselenocysteine	affects binding, increases reaction	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
homocysteic acid	increases activity, decreases reaction	1
sodium arsenate	decreases expression	1
sodium arsenite	increases expression	1
tetrathiomolybdate	decreases expression	1
hyperoside	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
cordycepin	increases activity	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression, decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1E6	Abcam HCT 116 SP3 KO	Cancer cell line	Male
CVCL_HC94	HEK293 eGFP-SP3	Transformed cell line	Female
CVCL_TQ11	HAP1 SP3 (-) 1	Cancer cell line	Male
CVCL_TQ12	HAP1 SP3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.