SP100

Summary

SP100 (SP100 nuclear body protein, HGNC:11206) is a protein-coding gene on chromosome 2q37.1, encoding Nuclear autoantigen Sp-100 (P23497). Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis.

This gene encodes a subnuclear organelle and major component of the PML (promyelocytic leukemia)-SP100 nuclear bodies. PML and SP100 are covalently modified by the SUMO-1 modifier, which is considered crucial to nuclear body interactions. The encoded protein binds heterochromatin proteins and is thought to play a role in tumorigenesis, immunity, and gene regulation. Alternatively spliced variants have been identified for this gene; one of which encodes a high-mobility group protein.

Source: NCBI Gene 6672 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 166 total
• Druggable target: yes
• MANE Select transcript: NM_001080391

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11206
Approved symbol	SP100
Name	SP100 nuclear body protein
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000067066
Ensembl biotype	protein_coding
OMIM	604585
Entrez	6672

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 18 protein_coding, 8 retained_intron

ENST00000264052, ENST00000340126, ENST00000409112, ENST00000409341, ENST00000409824, ENST00000409897, ENST00000413284, ENST00000427101, ENST00000431952, ENST00000432979, ENST00000452345, ENST00000459786, ENST00000462751, ENST00000466710, ENST00000470940, ENST00000488180, ENST00000492546, ENST00000494508, ENST00000494901, ENST00000884435, ENST00000884436, ENST00000884437, ENST00000884438, ENST00000884439, ENST00000957126, ENST00000957127

RefSeq mRNA: 6 — MANE Select: NM_001080391 NM_001080391, NM_001206701, NM_001206702, NM_001206703, NM_001206704, NM_003113

CCDS: CCDS2477, CCDS42832, CCDS56170, CCDS56171, CCDS56172, CCDS56173

Canonical transcript exons

ENST00000340126 — 29 exons

Exon	Start	End
ENSE00000786632	230506303	230506445
ENSE00000843903	230503066	230503110
ENSE00000843904	230504186	230504290
ENSE00000843907	230507993	230508031
ENSE00000922441	230498461	230498535
ENSE00001908190	230542836	230545606
ENSE00002449057	230469043	230469096
ENSE00002451671	230449088	230449150
ENSE00002453517	230511125	230511166
ENSE00002455099	230446819	230446902
ENSE00002463212	230462435	230462518
ENSE00002493813	230444178	230444346
ENSE00002505223	230470015	230470098
ENSE00002517732	230473324	230473440
ENSE00002518645	230467120	230467215
ENSE00002526619	230442937	230443099
ENSE00002530098	230449561	230449710
ENSE00002530762	230464067	230464150
ENSE00003501720	230450172	230450255
ENSE00003519490	230461262	230461414
ENSE00003573285	230539267	230539382
ENSE00003588497	230541301	230541372
ENSE00003597321	230541892	230542035
ENSE00003624801	230474394	230474447
ENSE00003625457	230540876	230540996
ENSE00003659581	230466301	230466354
ENSE00003664150	230417591	230417665
ENSE00003784126	230494416	230494460
ENSE00003848431	230416201	230416328

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.4847 / max 531.0456, expressed in 1675 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25816	40.1524	1674
25817	1.4835	661
25815	0.8489	558

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.21	gold quality
lymph node	UBERON:0000029	98.08	gold quality
right lung	UBERON:0002167	97.70	gold quality
tendon	UBERON:0000043	97.56	gold quality
spleen	UBERON:0002106	97.53	gold quality
tendon of biceps brachii	UBERON:0008188	97.48	gold quality
gall bladder	UBERON:0002110	97.27	gold quality
monocyte	CL:0000576	97.25	gold quality
mononuclear cell	CL:0000842	97.07	gold quality
leukocyte	CL:0000738	97.04	gold quality
bone marrow cell	CL:0002092	96.91	gold quality
sural nerve	UBERON:0015488	96.89	gold quality
upper lobe of left lung	UBERON:0008952	96.88	gold quality
colonic epithelium	UBERON:0000397	96.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.67	gold quality
tonsil	UBERON:0002372	96.64	gold quality
pericardium	UBERON:0002407	96.64	gold quality
right uterine tube	UBERON:0001302	96.48	gold quality
right coronary artery	UBERON:0001625	96.48	gold quality
upper lobe of lung	UBERON:0008948	96.45	gold quality
tibial nerve	UBERON:0001323	96.42	gold quality
blood	UBERON:0000178	96.39	gold quality
peritoneum	UBERON:0002358	96.35	gold quality
omental fat pad	UBERON:0010414	96.35	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.33	gold quality
vermiform appendix	UBERON:0001154	96.31	gold quality
caecum	UBERON:0001153	96.16	gold quality
endocervix	UBERON:0000458	96.10	gold quality
right adrenal gland	UBERON:0001233	96.07	gold quality
ectocervix	UBERON:0012249	96.06	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	983.95
E-MTAB-7008	yes	64.02
E-MTAB-9221	yes	18.05
E-CURD-112	yes	12.29
E-MTAB-11011	no	2410.18
E-MTAB-7303	no	243.22
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
ETS1	Repression
MMP1	Repression
PLAU	Repression

Upstream regulators (CollecTRI, top): IRF9

miRNA regulators (miRDB)

61 targeting SP100, 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-4776-3P	100.00	68.73	1340
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-26A-5P	99.78	73.52	2303

Literature-anchored findings (GeneRIF, showing 33)

• Sp100 interacts with ETS-1 and stimulates its transcriptional activity. (PMID:11909962)
• a novel function for Sp100 as a coactivator for HIPK2-mediated p53 activation. (PMID:14647468)
• SP100 modulates ETS1-dependent biological processes (PMID:15247905)
• Genes that are negatively regulated by ETS1 and upregulated by SP100 have antimigratory or antiangiogenic properties. (PMID:15592518)
• EBNA-LP interacts with the promyelocytic leukemia nuclear body (PML NB)-associated protein Sp100 and displaces Sp100 and heterochromatin protein 1alpha (HP1alpha) from PML NBs. (PMID:16177824)
• Repressive Sp100 isoforms B, C, and HMG are an essential part of the IFN-beta-mediated suppression of ICP0 expression. (PMID:16873258)
• Sp100 isoforms suppress immediate-early HSV-1 proteins at the promoter level and that IFN changes the splicing pattern of the Sp100 transcript to the suppressing Sp100C isoform. (PMID:19279115)
• During interphase PML-NBs adopt a spherical organization characterized by the assembly of PML and Sp100 proteins into patches within a 50- to 100-nm-thick shell. (PMID:20130140)
• Sp100 has a role in the initiation and progression of tumorgenesis (PMID:20512085)
• SP100 expression reduces malignancy of brain tumors (PMID:21274506)
• Endogenous Sp100 may interact with PhiC31 integrase and inhibit the efficiency of PhiC31 integrase-mediated recombination. (PMID:21383994)
• Sp100 counteract human cytomegalovirus infection via the repression of viral immediate-early gene expression. (PMID:21471311)
• Taken together, these data provide evidence that Sp100 is the first ND10-related factor identified that not only possesses the potential to restrict the initial stage of infection but also inhibits cytomegalovirus replication during the late phase. (PMID:21734036)
• These findings indicate that thehuman herpesvirus 5 IE1-dependent loss of human Sp100 proteins during virus infection may represent an important requirement for efficient viral growth. (PMID:21880768)
• These findings expand our knowledge of both Sp100 and Cdc20 as well as their role in ubiquitination. (PMID:22086178)
• Herpesvirus saimiri tegument protein specifically degraded the cellular ND10 component Sp100. (PMID:22278248)
• SP100 and Adeno-associated virus 2 Rep78 are both located in the nucleolus, which provides the spatial possibility for their interaction. (PMID:22419217)
• Authors conclude that several ND10 components, including Daxx, the promyelocytic leukemia (PML) protein, and Sp100 cooperate in an additive manner to regulate herpes simplex virus type 1 and human cytomegalovirus infection. (PMID:23221561)
• Sp100 is recruited to activated arrays in cells expressing the herpes simplex virus type 1 E3 ubiquitin ligase, ICP0, which degrades all Sp100 isoforms except unsumoylated Sp100A. (PMID:23485562)
• The results suggest that hantavirus infection interferes with DAXX-mediated apoptosis, and expression of interferon-activated Sp100 and ISG-20 proteins may indicate intracellular intrinsic antiviral attempts. (PMID:23830076)
• Two regions within the N-terminal of the herpes simplex virus 1 ICP0 facilitate the degradation and dissociation of host PML and dissociation of Sp100 from ND10. (PMID:24089549)
• Sp100 repressed viral transcription and replication only during the initial stages of viral establishment, suggesting that Sp100 acts as a repressor of incoming human papillomavirus type 18 DNA. (PMID:24194542)
• Sp100 depletion promotes Adenovirus progeny production and early viral protein synthesis. (PMID:24623443)
• PML, hDaxx and Sp100 primarily act as cellular restriction factors during lytic human cytomegalovirus replication and during the dynamic process of reactivation but do not serve as key determinants for the establishment of latency. (PMID:26057166)
• These results suggest that high-risk human papillomavirus 31 target interferon kappa to prevent Sp100 expression and identify Sp100 as an interferon-stimulated gene with anti-human papillomavirus activity. (PMID:26491169)
• Data suggest that nuclear antigen Sp100C is a multifaceted histone H3 methylation and phosphorylation sensor. (PMID:27129259)
• the ND10 bodies become viral replication compartments, and ICP0, a viral E3 ligase, degrades both PML and SP100. The amounts of PML and SP100 and the number of ND10 structures increase in cells exposed to IFN-beta. (PMID:28439026)
• that Sp100 represses viral transcription and replication in differentiated cells (PMID:28968443)
• The cellular nuclear domain 10 (ND10) complex plays an important role in suppressing HHV-6A lytic replication and the silencing of the virus genome in latently infected cells. (PMID:30060604)
• significant genetic predisposition to the sp100 autoantibody, but not the gp210 autoantibody, subphenotype in primary biliary cholangitis patients (PMID:30854688)
• Findings demonstrated that spheroids from pancreatic cancer cells caused circular defects in lymphatic endothelial monolayers. These CCIDs in pancreatic cancer were partly regulated by S100P. (PMID:31180531)
• PML Body Component Sp100A Restricts Wild-Type Herpes Simplex Virus 1 Infection. (PMID:35353002)
• Histone lactylation-boosted ALKBH3 potentiates tumor progression and diminished promyelocytic leukemia protein nuclear condensates by m1A demethylation of SP100A. (PMID:38118002)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubtf	ENSDARG00000035066
danio_rerio	ubtfl	ENSDARG00000038780
		ENSMUSG00000094514
		ENSMUSG00000094915
caenorhabditis_elegans	hmg-3	WBGENE00001973
caenorhabditis_elegans		WBGENE00001974

Paralogs (20): HMGB3 (ENSG00000029993), HMG20B (ENSG00000064961), SMARCE1 (ENSG00000073584), SP140 (ENSG00000079263), TOX4 (ENSG00000092203), HMGXB4 (ENSG00000100281), TOX3 (ENSG00000103460), TFAM (ENSG00000108064), UBTF (ENSG00000108312), HMGB1P1 (ENSG00000124097), TOX2 (ENSG00000124191), SP110 (ENSG00000135899), HMG20A (ENSG00000140382), SSRP1 (ENSG00000149136), HMGB2 (ENSG00000164104), HMGB4 (ENSG00000176256), SP140L (ENSG00000185404), HMGB1 (ENSG00000189403), TOX (ENSG00000198846), UBTFL1 (ENSG00000255009)

Protein

Protein identifiers

Nuclear autoantigen Sp-100 — P23497 (reviewed: P23497)

Alternative names: Nuclear dot-associated Sp100 protein, Speckled 100 kDa

All UniProt accessions (6): P23497, C9JBL0, E9PHV6, H0Y4R8, H7C1G8, H7C4B4

UniProt curated annotations — full annotation on UniProt →

Function. Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation.

Subunit / interactions. Homodimer; isoforms are able to heterodimerize. Interacts with members of the HP1 family of nonhistone chromosomal protein, such as CBX5 and CBX3 via the PxVxL motif. Interacts with ETS1; the interaction is direct and modulates ETS1 transcriptional activity. Interacts with the MRN complex which is composed of two heterodimers RAD50/MRE11 associated with a single NBN; recruits the complex to PML-related bodies. Interacts with HIPK2; positively regulates TP53-dependent transcription. Interacts with CASP8AP2; may negatively regulate CASP8AP2 export from the nucleus to the cytoplasm. Interacts with SUMO1P1/SUMO5. (Microbial infection) Interacts with Epstein-Barr virus EBNA-LP; this interaction is important for EBNA-LP coactivator activity. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL123; may play a role in infection by the virus.

Subcellular location. Nucleus. PML body. Nuclear body. Cytoplasm Nucleus.

Tissue specificity. Widely expressed. Sp100-B is expressed only in spleen, tonsil, thymus, mature B-cell line and some T-cell line, but not in brain, liver, muscle or non-lymphoid cell lines.

Post-translational modifications. Sumoylated. Sumoylation depends on a functional nuclear localization signal but is not necessary for nuclear import or nuclear body targeting. Sumoylated. Sumoylated with SUMO1. Sumoylation depends on a functional nuclear localization signal but is not necessary for nuclear import or nuclear body targeting. Sumoylation may stabilize the interaction with CBX5. (Microbial infection) Immediate early protein IE1 of human cytomegalovirus (HHV-5) interferes with the sumoylation of SP100.

Domain organisation. The HSR domain is important for the nuclear body targeting as well as for the dimerization. Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.

Induction. Up-regulated by interferon, retinoic acid, TNF/TNFA and lipopolysaccharide (at protein level). Up-regulated following heat-shock.

Miscellaneous. The major isoform Sp100-A, has a calculated molecular weight of 54 kDa, but exhibits aberrant electrophoretic mobilities, with an apparent molecular weight of 100 kDa. Major isoform.

Isoforms (7)

UniProt ID	Names	Canonical?
P23497-1	Sp100-HMG, SP100HMG, SpAlt-HMG	yes
P23497-2	Sp100-A, SP100A, SP100
P23497-3	Sp100-B, SP100B, SpAlt-212
P23497-4	Sp100-C, SP100C
P23497-5	SpAlt-C
P23497-6	6
P23497-7	7

RefSeq proteins (6): NP_001073860, NP_001193630, NP_001193631, NP_001193632, NP_001193633, NP_003104 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000770	SAND_dom	Domain
IPR004865	HSR_dom	Domain
IPR009071	HMG_box_dom	Domain
IPR010919	SAND-like_dom_sf	Homologous_superfamily
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR043563	Sp110/Sp140/Sp140L-like	Family

Pfam: PF00505, PF01342, PF03172, PF09011

UniProt features (82 total): modified residue 13, splice variant 10, strand 8, helix 8, compositionally biased region 7, cross-link 7, sequence conflict 6, region of interest 5, short sequence motif 5, sequence variant 3, domain 2, DNA-binding region 2, mutagenesis site 2, turn 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

122 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5PXL	X-RAY DIFFRACTION	1.35
6G5P	X-RAY DIFFRACTION	1.35
9T2I	X-RAY DIFFRACTION	1.35
5PWS	X-RAY DIFFRACTION	1.4
5PXT	X-RAY DIFFRACTION	1.4
5PX2	X-RAY DIFFRACTION	1.43
5PX6	X-RAY DIFFRACTION	1.43
5PXA	X-RAY DIFFRACTION	1.43
5PXN	X-RAY DIFFRACTION	1.43
5PWU	X-RAY DIFFRACTION	1.44
5PY5	X-RAY DIFFRACTION	1.44
5PX4	X-RAY DIFFRACTION	1.45
5PYW	X-RAY DIFFRACTION	1.45
5PWG	X-RAY DIFFRACTION	1.46
5PWR	X-RAY DIFFRACTION	1.46
5PXB	X-RAY DIFFRACTION	1.46
5PWF	X-RAY DIFFRACTION	1.48
5PXS	X-RAY DIFFRACTION	1.49
5PWH	X-RAY DIFFRACTION	1.5
5PWP	X-RAY DIFFRACTION	1.51
5PWQ	X-RAY DIFFRACTION	1.52
5PXC	X-RAY DIFFRACTION	1.52
5PZ8	X-RAY DIFFRACTION	1.52
5PYL	X-RAY DIFFRACTION	1.53
5PWM	X-RAY DIFFRACTION	1.54
5PZ7	X-RAY DIFFRACTION	1.54
5PX0	X-RAY DIFFRACTION	1.55
5PX1	X-RAY DIFFRACTION	1.55
5PXE	X-RAY DIFFRACTION	1.55
5PYA	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23497-F1	57.48	0.14

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 (20): 2, 18, 157, 171, 180, 228, 331, 362, 394, 407, 409, 410, 451, 241, 297, 300, 306, 366, 387, 594

Mutagenesis-validated functional residues (2):

Position	Phenotype
165	prevents cdc20-mediated degradation; when associated with ala-168.
168	prevents cdc20-mediated degradation; when associated with ala-165.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-877300	Interferon gamma signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
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
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 350 (showing top): GOBP_CHROMOSOME_ORGANIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_RESPONSE_TO_PEPTIDE, MODULE_45, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_REGULATION_OF_PROTEIN_EXPORT_FROM_NUCLEUS

GO Biological Process (24): negative regulation of transcription by RNA polymerase II (GO:0000122), telomere maintenance (GO:0000723), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of endothelial cell migration (GO:0010596), DNA damage response, signal transduction by p53 class mediator (GO:0030330), response to retinoic acid (GO:0032526), negative regulation of viral transcription (GO:0032897), response to cytokine (GO:0034097), response to type I interferon (GO:0034340), response to type II interferon (GO:0034341), maintenance of protein location (GO:0045185), regulation of angiogenesis (GO:0045765), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of protein export from nucleus (GO:0046826), retinoic acid receptor signaling pathway (GO:0048384), regulation of viral process (GO:0050792), type II interferon-mediated signaling pathway (GO:0060333), type I interferon-mediated signaling pathway (GO:0060337), regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902041), regulation of Fas signaling pathway (GO:1902044), DNA metabolic process (GO:0006259), defense response (GO:0006952), immune response (GO:0006955)

GO Molecular Function (14): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), transcription corepressor activity (GO:0003714), kinase binding (GO:0019900), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein dimerization activity (GO:0046983), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), chromo shadow domain binding (GO:0070087), protein binding (GO:0005515), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (10): chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), nuclear body (GO:0016604), PML body (GO:0016605), nuclear periphery (GO:0034399), Mre11 complex (GO:0030870), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
Interferon Signaling	1
Immune System	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
protein binding	3
nuclear lumen	3
cellular anatomical structure	3
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
response to cytokine	2
innate immune response	2
interferon-mediated signaling pathway	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
intracellular membraneless organelle	2
DNA metabolic process	1
telomere organization	1
regulation of endothelial cell migration	1
negative regulation of cell migration	1
endothelial cell migration	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
response to lipid	1
response to oxygen-containing compound	1
viral transcription	1
regulation of viral transcription	1
negative regulation of viral process	1
response to peptide	1
intracellular protein localization	1
maintenance of location	1
angiogenesis	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
protein export from nucleus	1
negative regulation of nucleocytoplasmic transport	1
regulation of protein export from nucleus	1
maintenance of protein location in nucleus	1
negative regulation of intracellular protein transport	1
hormone-mediated signaling pathway	1
nuclear receptor-mediated signaling pathway	1

Protein interactions and networks

STRING

1866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SP100	DAXX	Q9UER7	996
SP100	ATRX	P46100	991
SP100	HSPA4	P34932	987
SP100	SUMO1	P55856	983
SP100	PML	P29590	918
SP100	CLPB	Q9H078	870
SP100	DNAJB1	P25685	866
SP100	HSP90AA1	P07900	846
SP100	HSP90AB1	P08238	846
SP100	CALCOCO2	Q13137	826
SP100	NUP210	Q8TEM1	821
SP100	SUMO2	P55855	747
SP100	CLPX	O76031	723
SP100	DLAT	P10515	712
SP100	TP53	P04637	707

IntAct

102 interactions, top by confidence:

A	B	Type	Score
SP100	SUMO1	psi-mi:“MI:0915”(physical association)	0.760
SP100	ACTN2	psi-mi:“MI:0915”(physical association)	0.670
GIPC2	SP100	psi-mi:“MI:0915”(physical association)	0.670
TRAF3IP3	SP100	psi-mi:“MI:0915”(physical association)	0.670
ACTN2	SP100	psi-mi:“MI:0915”(physical association)	0.670
SP100	TRAF3IP3	psi-mi:“MI:0915”(physical association)	0.670
SP100	GIPC2	psi-mi:“MI:0915”(physical association)	0.670
HMGB1	SP100	psi-mi:“MI:0914”(association)	0.670
HMGB1	SP100	psi-mi:“MI:0915”(physical association)	0.670
UL123	SP100	psi-mi:“MI:0915”(physical association)	0.630
SP100	UL123	psi-mi:“MI:0915”(physical association)	0.630
SP100	CASP8AP2	psi-mi:“MI:0915”(physical association)	0.600
CASP8AP2	SP100	psi-mi:“MI:0915”(physical association)	0.600

BioGRID (283): SP100 (Biochemical Activity), SP100 (Biochemical Activity), SP100 (Biochemical Activity), SP100 (Two-hybrid), SP100 (Two-hybrid), SP100 (Two-hybrid), SP100 (Two-hybrid), SUMO1 (Two-hybrid), DYRK2 (Two-hybrid), RBM39 (Two-hybrid), CBX5 (Two-hybrid), ZC2HC1A (Two-hybrid), AMOTL2 (Two-hybrid), GIPC2 (Two-hybrid), TRAF3IP3 (Two-hybrid)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0JMF7, A1L2Y1, A2ALV5, A9JRX0, B2GUZ2, D3ZSP7, F1QB81, O35892, O70608, O75113, P23497, P70347, Q0P5X5, Q13129, Q16533, Q2T9I9, Q3U1D0, Q5CZC0, Q5H9M0, Q5REF4, Q5RHB5, Q5SW75, Q5T4T6, Q5T5J6, Q5XG69, Q5ZLE9, Q60664, Q63HN8, Q7M6U3, Q7Z4H7, Q80VH0, Q8BVK9, Q8C263, Q8CCC3, Q8NA03, Q90WN7, Q92844, Q96QP1

Diamond homologs: A9RA84, B0CM99, B1MTB0, B2RPK0, O01683, O04235, O15347, O15405, O49595, O49596, O49597, O54879, O64702, O94842, O94900, P07156, P07746, P09429, P0CO24, P0CO25, P10103, P11632, P11633, P11873, P12682, P17741, P23497, P26583, P26584, P26585, P26586, P27347, P30681, P40618, P40619, P40620, P40621, P40622, P40623, P40632

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDC20	“down-regulates quantity by destabilization”	SP100	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SUMOylation of transcription factors	5	95.2×	2e-07
SUMOylation of transcription cofactors	5	40.5×	1e-05
SUMOylation of chromatin organization proteins	5	26.4×	4e-05
DNA Repair	6	19.7×	2e-05
Cell Cycle	6	7.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	19
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4763 predictions. Top by Δscore:

Variant	Effect	Δscore
2:230442931:CCCTA:C	acceptor_loss	1.0000
2:230442932:CCTA:C	acceptor_loss	1.0000
2:230442933:CTAG:C	acceptor_loss	1.0000
2:230442934:TA:T	acceptor_loss	1.0000
2:230442935:A:AG	acceptor_gain	1.0000
2:230442935:A:AT	acceptor_loss	1.0000
2:230442936:G:GG	acceptor_gain	1.0000
2:230442936:G:GT	acceptor_loss	1.0000
2:230442936:GGAT:G	acceptor_gain	1.0000
2:230443094:TTTG:T	donor_gain	1.0000
2:230443095:TTGAA:T	donor_gain	1.0000
2:230443096:TGAA:T	donor_gain	1.0000
2:230443097:GAA:G	donor_gain	1.0000
2:230443097:GAAG:G	donor_gain	1.0000
2:230443098:AA:A	donor_gain	1.0000
2:230443098:AAGTA:A	donor_loss	1.0000
2:230443099:AG:A	donor_loss	1.0000
2:230443100:G:GG	donor_gain	1.0000
2:230443101:TAAG:T	donor_loss	1.0000
2:230444304:G:GT	donor_gain	1.0000
2:230444305:A:T	donor_gain	1.0000
2:230446817:A:AG	acceptor_gain	1.0000
2:230446818:G:GA	acceptor_gain	1.0000
2:230446818:GT:G	acceptor_gain	1.0000
2:230446818:GTA:G	acceptor_gain	1.0000
2:230450253:A:T	donor_gain	1.0000
2:230450256:G:GG	donor_gain	1.0000
2:230462433:A:AG	acceptor_gain	1.0000
2:230462434:G:GA	acceptor_gain	1.0000
2:230462434:GTC:G	acceptor_gain	1.0000

AlphaMissense

5945 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:230506395:T:A	W655R	0.998
2:230506395:T:C	W655R	0.998
2:230443028:G:C	A67P	0.997
2:230506359:T:C	F643L	0.997
2:230506360:T:C	F643S	0.997
2:230506361:T:A	F643L	0.997
2:230506361:T:G	F643L	0.997
2:230506397:G:C	W655C	0.997
2:230506397:G:T	W655C	0.997
2:230444236:T:C	L110P	0.996
2:230442999:T:C	F57S	0.995
2:230443043:T:C	F72L	0.995
2:230443045:T:A	F72L	0.995
2:230443045:T:G	F72L	0.995
2:230444317:T:C	L137S	0.995
2:230443050:T:C	F74S	0.994
2:230444245:T:C	L113P	0.994
2:230444281:T:C	L125P	0.993
2:230444283:T:C	F126L	0.993
2:230444284:T:C	F126S	0.993
2:230444285:C:A	F126L	0.993
2:230444285:C:G	F126L	0.993
2:230506364:A:C	E644D	0.993
2:230506364:A:T	E644D	0.993
2:230442998:T:C	F57L	0.992
2:230443000:C:A	F57L	0.992
2:230443000:C:G	F57L	0.992
2:230443012:G:C	K61N	0.992
2:230443012:G:T	K61N	0.992
2:230443065:G:C	R79P	0.992

dbSNP variants (sampled 300 via entrez): RS1000025383 (2:230523304 C>T), RS1000026592 (2:230435462 G>T), RS1000080503 (2:230531706 T>G), RS1000122976 (2:230433765 T>G), RS1000126826 (2:230490803 G>A), RS1000155384 (2:230434121 A>C,G), RS1000164925 (2:230528093 C>T), RS1000170483 (2:230545894 C>T), RS1000201504 (2:230545652 C>A,G), RS1000233017 (2:230484111 T>C), RS1000242006 (2:230537559 A>G), RS1000267911 (2:230429065 G>A), RS1000272475 (2:230503416 T>A,C), RS1000274388 (2:230516667 G>A), RS1000277165 (2:230459915 T>C)

Disease associations

OMIM: gene MIM:604585 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003262_634	Post bronchodilator FEV1	2.000000e-06
GCST003262_635	Post bronchodilator FEV1	2.000000e-06
GCST003264_441	Post bronchodilator FEV1/FVC ratio	6.000000e-07
GCST003264_912	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST003542_13	Night sleep phenotypes	8.000000e-06
GCST005860_3	Cholangiocarcinoma in primary sclerosing cholangitis (time to event)	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066216 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Non-enzymatic BRD containing proteins

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	decreases expression, affects cotreatment, increases expression	4
Acetaminophen	decreases expression, increases expression	3
bisphenol F	increases methylation, affects cotreatment, increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Vorinostat	affects binding, increases reaction, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Estradiol	affects cotreatment, increases expression	2
Nickel	increases expression	2
GSK-J4	increases expression	1
urushiol	increases expression	1
alpha phellandrene	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases expression	1
geraniol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
cobaltous chloride	increases expression	1
nickel chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
monomethylarsonous acid	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
ruxolitinib	decreases reaction, increases expression	1
(+)-JQ1 compound	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5696868	Binding	Inhibition of SP100 in human HL-60 cells assessed as fold change at 5 uM in presence of biotinylated histone peptide by LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1HP	Abcam A-549 SP100 KO	Cancer cell line	Male
CVCL_B2H4	Abcam HeLa SP100 KO	Cancer cell line	Female
CVCL_TQ05	HAP1 SP100 (-) 1	Cancer cell line	Male
CVCL_TQ06	HAP1 SP100 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome