SSRP1

Summary

SSRP1 (structure specific recognition protein 1, HGNC:11327) is a protein-coding gene on chromosome 11q12.1, encoding FACT complex subunit SSRP1 (Q08945). Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

The protein encoded by this gene is a subunit of a heterodimer that, along with SUPT16H, forms chromatin transcriptional elongation factor FACT. FACT interacts specifically with histones H2A/H2B to effect nucleosome disassembly and transcription elongation. FACT and cisplatin-damaged DNA may be crucial to the anticancer mechanism of cisplatin. This encoded protein contains a high mobility group box which most likely constitutes the structure recognition element for cisplatin-modified DNA. This protein also functions as a co-activator of the transcriptional activator p63. An alternatively spliced transcript variant of this gene has been described, but its full-length nature is not known.

Source: NCBI Gene 6749 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 83 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• Transcription factor: yes — 156 downstream targets (CollecTRI)
• MANE Select transcript: NM_003146

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11327
Approved symbol	SSRP1
Name	structure specific recognition protein 1
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	FACT80
Ensembl gene	ENSG00000149136
Ensembl biotype	protein_coding
OMIM	604328
Entrez	6749

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 retained_intron

ENST00000278412, ENST00000293880, ENST00000526696, ENST00000529002, ENST00000635721, ENST00000857851, ENST00000857852, ENST00000857853, ENST00000857854, ENST00000857855, ENST00000857856, ENST00000857857, ENST00000857858, ENST00000857859, ENST00000939970, ENST00000939971, ENST00000939972, ENST00000939973, ENST00000939974, ENST00000939975, ENST00000939976, ENST00000939977, ENST00000939978

RefSeq mRNA: 1 — MANE Select: NM_003146 NM_003146

CCDS: CCDS7952

Canonical transcript exons

ENST00000278412 — 17 exons

Exon	Start	End
ENSE00000988946	57332959	57333149
ENSE00000988947	57332625	57332855
ENSE00000988951	57330855	57330927
ENSE00000988952	57330291	57330429
ENSE00000988953	57330093	57330138
ENSE00000988954	57328297	57328426
ENSE00000988956	57327426	57327514
ENSE00000988957	57326703	57326889
ENSE00001027126	57335068	57335240
ENSE00001027128	57335730	57335892
ENSE00001745097	57325988	57326478
ENSE00003549319	57334463	57334648
ENSE00003573574	57327712	57327882
ENSE00003632331	57332383	57332486
ENSE00003645712	57333435	57333540
ENSE00003657755	57331668	57331889
ENSE00003669342	57332152	57332280

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.9300 / max 315.6811, expressed in 1817 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119731	43.6897	1817
119730	0.9087	603
119729	0.3013	119
119728	0.0304	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.73	gold quality
ganglionic eminence	UBERON:0004023	98.62	gold quality
tendon of biceps brachii	UBERON:0008188	98.51	gold quality
embryo	UBERON:0000922	98.00	gold quality
cortical plate	UBERON:0005343	97.74	gold quality
gastrocnemius	UBERON:0001388	96.88	gold quality
tendon	UBERON:0000043	96.70	gold quality
calcaneal tendon	UBERON:0003701	96.64	gold quality
islet of Langerhans	UBERON:0000006	96.61	gold quality
body of pancreas	UBERON:0001150	96.53	gold quality
muscle of leg	UBERON:0001383	96.46	gold quality
left ovary	UBERON:0002119	96.38	gold quality
body of uterus	UBERON:0009853	96.25	gold quality
mucosa of transverse colon	UBERON:0004991	96.21	gold quality
right ovary	UBERON:0002118	96.18	gold quality
rectum	UBERON:0001052	96.13	gold quality
ectocervix	UBERON:0012249	96.05	gold quality
adenohypophysis	UBERON:0002196	96.01	gold quality
skin of leg	UBERON:0001511	95.92	gold quality
right uterine tube	UBERON:0001302	95.91	gold quality
pancreas	UBERON:0001264	95.88	gold quality
body of stomach	UBERON:0001161	95.79	gold quality
left uterine tube	UBERON:0001303	95.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.74	gold quality
lower esophagus	UBERON:0013473	95.72	gold quality
stromal cell of endometrium	CL:0002255	95.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.64	gold quality
sural nerve	UBERON:0015488	95.61	gold quality
endocervix	UBERON:0000458	95.59	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.94
E-MTAB-10553	yes	8.12
E-MTAB-10596	no	110.01
E-CURD-88	no	3.85

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

156 targets.

Target	Regulation
ABCB1
ACHE
ADAM2
ADAMTS7
AGTR2
ALB
ALDOB
AMY2A
ANKRD1
ANKRD2
APOA5
BCL2
BCL2L1
BDNF
BDNF-AS
C4BPA
CASP1
CCNB1
CCND1
CCNE1
CD1A
CD74
CD83
CDAN1
CDH17
CDKL5
CDKN1A
CDKN1B
CDKN1C
CDKN2A

miRNA regulators (miRDB)

43 targeting SSRP1, 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-3646	100.00	73.56	5283
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-4784	99.15	67.41	1733

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• SSRP1 stimulates p63 activity by associating with this activator at the promoter (PMID:12374749)
• CK2 regulates the DNA-binding ability of SSRP1 and that this regulation may be responsive to specific cell stresses. (PMID:15659405)
• These results demonstrate that SSRP1 degradation during apoptosis is a two-step process coupling caspase cleavage and ubiquitin-dependent proteolysis. (PMID:16498457)
• SSRP1 has Spt16-dependent and -independent roles in regulating gene transcription in human cells. (PMID:17209051)
• occurrence of an unusual TG 3’ splice site in intron 1 (PMID:17672918)
• CENP-H-containing complex facilitates deposition of newly synthesized CENP-A into centromeric chromatin in cooperation with FACT and CHD1. (PMID:19625449)
• SSRP1 may play a role in the DNA damage response mediated by homologous recombination; SSRP1 physically interacts with a key recombination repair protein, Rad54 (PMID:19639603)
• These results indicate that SSRP1 is a novel cellular protein involved in LANA-dependent DNA replication. (PMID:19710137)
• results demonstrate that SSRP1 is crucial for microtubule growth and spindle assembly during mitosis. (PMID:19995907)
• Studies suggest that that even though FACT has rapid chromatin-binding activity, the binding pattern of FACT on chromatin changes after origin licensing, which may contribute to the establishment of its functional link to the DNA replication machinery. (PMID:21232560)
• The histone chaperone FACT: structural insights and mechanisms for nucleosome reorganization. (PMID:21454601)
• DNA-PK and FACT both play roles in DNA repair. Therefore both are putative targets for therapeutic inhibition. (PMID:21679440)
• specific FACT subunits synchronize interactions with various target sites on individual nucleosomes to generate a high affinity binding event and promote reorganization. (PMID:21969370)
• The HSF1-RPA complex leads to preloading of RNA polymerase II and opens the chromatin structure by recruiting a histone chaperone, FACT (PMID:22940245)
• SETD2 activity modulates FACT recruitment and nucleosome dynamics, thereby repressing cryptic transcription initiation. (PMID:23325844)
• hFACT-H2A/H2B interactions play a key role in overcoming the nucleosomal barrier by Pol II and promoting nucleosome survival during transcription (PMID:23610384)
• In the absence of FACT complex, SSRP1 and SPT16 mRNAs are unstable and inefficiently translated, making reactivation of FACT function unlikely in normal cells. (PMID:23839038)
• A primary role for FACT in RNF20 recruitment chromatin remodeling for initiation of homologous recombination repair. (PMID:24357716)
• EEF1A1, SSRP1, and XRCC6 are novel interacting partners of the mineralocorticoid receptor (PMID:25000480)
• FACT, NF-kappaB, and cell-cycle progression are inhibited by quinacrine, which overcomes resistance to erlotinib in non-small cell lung cancer (PMID:25028470)
• Our studies facilitate the understanding of SSRP1 and provide insights into the molecular mechanisms of interaction with DNA and histones of the FACT complex. (PMID:26687053)
• Results show that SSRP1 upregulation contributed to hepatocellular carcinoma development and the tumor-suppressive miR-497 served as its negative regulator. (PMID:26755331)
• FACT is required for TOP1 binding to H3K4me3 at non-B DNA containing chromatin for the site-specific cleavage. (PMID:26842758)
• AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome (PMID:26966247)
• These data uncover a previously unknown role for SSRP1 in promoting the activation of the Wnt signaling pathway activity during cellular differentiation. (PMID:27146025)
• The association of LEDGF proteins with the FACT complex and give further support to a role of SSRP1 in HIV-1 infection. (PMID:27216501)
• FACT chaperone stabilizes the soluble CENP-T/-W complex in the cell and promotes dynamics of exchange, enabling CENP-T/-W deposition at centromeres. (PMID:27284163)
• High FACT expression is associated with glioblastoma. (PMID:27370399)
• This discloses a novel property of FACT wherein it has a co-remodeling activity and strongly enhances the remodeling capacity of the chromatin remodelers. Altogether, our data suggest that FACT may acts in concert with RSC to facilitate excision of DNA lesions during the initial step of BER. (PMID:27467129)
• SSRP1/Ets-1/Pim-3 signalling is tightly associated with the proliferation, apoptosis, autophagy, invasion and clonogenicity of nasopharyngeal carcinoma cells, and blockage of this signalling facilitates chemosensitivity of the cells to docetaxel. (PMID:27525970)
• we propose that FACT is both a marker and a target of aggressive breast cancer cells, whose inhibition results in their death or conversion a less aggressive subtype (PMID:28423528)
• Data revealed that SSRP1 is highly overexpressed in glioma tissues at both the mRNA and protein levels and correlated with tumor grade. Further analysis demonstrated that that SSRP1 regulates the proliferation and metastasis of glioma cells via the MAPK signaling pathway. (PMID:29048646)
• Intrinsic DNA-bending activity therefore favors nucleosome assembly by FACT over nucleosome reorganization, but excessive activity impairs FACT release, suggesting a quality control checkpoint during nucleosome assembly (PMID:29514976)
• regulation of SSRP1 by homodimerization (PMID:29764934)
• Findings provide mechanistic insights by which the two subunits of FACT coordinate with each other to fulfill its functions and suggest that FACT may play essential roles in preserving the original histones with epigenetic identity during transcription or DNA replication. (PMID:30029006)
• It has been demonstrated that FACT potentiates H2A.X-dependent signaling of DNA damage. (PMID:30344095)
• Authors confirm that inhibition of FACT at release from quiescence suppressed the p27 degradation capacity resulting in an increased mVenus-p27K(-) signal. FACT plays an important role in promoting the transition from G0 to the proliferative state. (PMID:30548853)
• Long noncoding RNA LOC101927746 interacts with miR-584-3p which targets SSRP1. LOC101927746/miR-584-3p/SSRP1 pathway modulates colorectal cancer progression. (PMID:30616889)
• FACT subunit Spt16 controls UVSSA recruitment to lesion-stalled RNA Pol II and stimulates transcription-coupled nucleotide excision repair. (PMID:30715484)
• FACT complex is essential for the expeditious hepatocellular carcinoma oxidative stress response and is a potential therapeutic target for HCC treatment. (PMID:31439637)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ssrp1b	ENSDARG00000016994
danio_rerio	ssrp1a	ENSDARG00000037397
mus_musculus	Ssrp1	ENSMUSG00000027067
rattus_norvegicus	Ssrp1	ENSRNOG00000008825
drosophila_melanogaster	Hmg-2	FBGN0026582
caenorhabditis_elegans		WBGENE00008081

Paralogs (20): HMGB3 (ENSG00000029993), HMG20B (ENSG00000064961), SP100 (ENSG00000067066), SMARCE1 (ENSG00000073584), SP140 (ENSG00000079263), TOX4 (ENSG00000092203), HMGXB4 (ENSG00000100281), TOX3 (ENSG00000103460), TFAM (ENSG00000108064), UBTF (ENSG00000108312), HMGB1P1 (ENSG00000124097), TOX2 (ENSG00000124191), SP110 (ENSG00000135899), HMG20A (ENSG00000140382), HMGB2 (ENSG00000164104), HMGB4 (ENSG00000176256), SP140L (ENSG00000185404), HMGB1 (ENSG00000189403), TOX (ENSG00000198846), UBTFL1 (ENSG00000255009)

Protein

Protein identifiers

FACT complex subunit SSRP1 — Q08945 (reviewed: Q08945)

Alternative names: Chromatin-specific transcription elongation factor 80 kDa subunit, Facilitates chromatin transcription complex 80 kDa subunit, Facilitates chromatin transcription complex subunit SSRP1, Recombination signal sequence recognition protein 1, Structure-specific recognition protein 1, T160

All UniProt accessions (4): Q08945, A0A0U1RRK2, E9PMD4, E9PPZ7

UniProt curated annotations — full annotation on UniProt →

Function. Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of ‘Ser-392’ of p53/TP53 via its association with CK2 (casein kinase II). Binds specifically to double-stranded DNA and at low levels to DNA modified by the antitumor agent cisplatin. May potentiate cisplatin-induced cell death by blocking replication and repair of modified DNA. Also acts as a transcriptional coactivator for p63/TP63.

Subunit / interactions. Interacts with MYOG (via C-terminal region). Component of the FACT complex, a stable heterodimer of SSRP1 and SUPT16H. Also a component of a CK2-SPT16-SSRP1 complex which forms following UV irradiation, composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B. Binds to histone H3-H4 tetramers, but not to intact nucleosomes. Identified in a centromere complex containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1. Interacts with isoform gamma of TP63. Interacts with FYTTD1/UIF. Interacts with SRF. Interacts with NEK9. (Microbial infection) Interacts with Herpes simplex virus 1 (HHV-1) protein ICP22; this interaction relocalizes the FACT complex to viral genomes in infected cells.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Post-translational modifications. Phosphorylated by CK2 following UV but not gamma irradiation. Phosphorylation inhibits its DNA-binding activity. Ubiquitinated. Polyubiquitinated following caspase cleavage resulting in degradation of the N-terminal ubiquitinated part of the cleaved protein. Sumoylated.

Domain organisation. The HMG box DNA-binding domain mediates DNA-binding. It has both affinity and specificity for DNA damaged globally with cisplatin.

Miscellaneous. Autoantibodies against SSRP1 are present in sera from patients with systemic lupus erythematosus, but not other rheumatic diseases.

Similarity. Belongs to the SSRP1 family.

RefSeq proteins (1): NP_003137* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000969	SSRP1/POB3	Family
IPR009071	HMG_box_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013719	RTT106/SPT16-like_middle_dom	Domain
IPR024954	SSRP1_DD	Domain
IPR035417	SSRP1/POB3_N	Domain
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR038167	SSRP1_sf	Homologous_superfamily
IPR048985	SSRP1_C	Domain
IPR048993	SSRP1-like_PH1	Domain
IPR050454	RTT106/SSRP1_HistChap/FACT	Family

Pfam: PF00505, PF03531, PF08512, PF17292, PF21092, PF21103

UniProt features (79 total): strand 25, modified residue 19, helix 12, compositionally biased region 8, mutagenesis site 4, cross-link 3, sequence variant 2, initiator methionine 1, chain 1, site 1, DNA-binding region 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
5UMR	X-RAY DIFFRACTION	1.5
5UMS	X-RAY DIFFRACTION	1.57
6L1R	X-RAY DIFFRACTION	1.8
4IFS	X-RAY DIFFRACTION	1.93
6L34	X-RAY DIFFRACTION	2
6L1E	X-RAY DIFFRACTION	2.09
9EH2	ELECTRON MICROSCOPY	3.1
6UPK	ELECTRON MICROSCOPY	4.9
9S3G	ELECTRON MICROSCOPY	6.4
6UPL	ELECTRON MICROSCOPY	7.4
5VWE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08945-F1	74.87	0.28

Functional residue map

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

Catalytic / active sites (1): 450–451 (cleavage; by caspase-3 and/or caspase-7)

Post-translational modifications (22): 2, 170, 233, 413, 437, 441, 444, 452, 471, 510, 542, 657, 659, 667, 668, 671, 672, 673, 688, 90 …

Mutagenesis-validated functional residues (4):

Position	Phenotype
450	abolishes cleavage by caspase.
510	unable to bind dna; when associated with a-657 and a-688.
657	unable to bind dna; when associated with a-510 and a-688. still able to bind dna; when associated with a-688.
688	unable to bind dna; when associated with a-510 and a-657. still able to bind dna; when associated with a-657.

Function

Pathways and Gene Ontology

Reactome pathways

26 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-9943411	CHD1 and CHD2 subfamily
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-167169	HIV Transcription Elongation
R-HSA-167172	Transcription of the HIV genome
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 210 (showing top): MORF_DNMT1, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, MORF_ESPL1, BASSO_B_LYMPHOCYTE_NETWORK, GGGNRMNNYCAT_UNKNOWN, MORF_RRM1, MORF_CDK2, MORF_HDAC2, GNF2_MCM5, KAUFFMANN_DNA_REPAIR_GENES, GNF2_RRM1, PUJANA_CHEK2_PCC_NETWORK, REACTOME_HIV_INFECTION, GNF2_SMC4L1, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN

GO Biological Process (6): DNA replication (GO:0006260), DNA repair (GO:0006281), nucleosome assembly (GO:0006334), nucleosome disassembly (GO:0006337), regulation of chromatin organization (GO:1902275), DNA damage response (GO:0006974)

GO Molecular Function (6): DNA binding (GO:0003677), RNA binding (GO:0003723), nucleosome binding (GO:0031491), histone binding (GO:0042393), chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), FACT complex (GO:0035101), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Transcription of the HIV genome	6
RNA Polymerase II Transcription	3
RNA Polymerase II Transcription Elongation	1
Tat-mediated elongation of the HIV-1 transcript	1
HIV Transcription Elongation	1
Transcriptional Regulation by TP53	1
Regulation of TP53 Activity	1
CHD chromatin remodelers	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Late Phase of HIV Life Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
chromatin organization	2
nucleosome organization	2
nucleic acid binding	2
binding	2
nuclear lumen	2
intracellular membraneless organelle	2
DNA biosynthetic process	1
DNA damage response	1
protein-DNA complex assembly	1
protein-DNA complex disassembly	1
regulation of cellular component organization	1
cellular response to stress	1
chromatin binding	1
protein-containing complex binding	1
protein binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
chromatin	1
transcription elongation factor complex	1

Protein interactions and networks

STRING

3566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSRP1	SUPT16H	Q9Y5B9	999
SSRP1	SUPT6H	Q7KZ85	891
SSRP1	DDX21	Q9NR30	871
SSRP1	SUPT5H	O00267	828
SSRP1	H2BC21	Q16778	828
SSRP1	DHX9	Q08211	823
SSRP1	H2AC19	P20670	820
SSRP1	H2AC20	Q16777	820
SSRP1	HNRNPC	P07910	747
SSRP1	POLR2A	P24928	716
SSRP1	H3C1	P02295	668
SSRP1	H3-3A	P06351	651
SSRP1	H3C14	Q71DI3	648
SSRP1	H3-4	Q16695	646
SSRP1	H3-7	Q5TEC6	646
SSRP1	H3-5	Q6NXT2	646

IntAct

243 interactions, top by confidence:

A	B	Type	Score
SUPT16H	SSRP1	psi-mi:“MI:0915”(physical association)	0.910
MCM2	MCM4	psi-mi:“MI:0914”(association)	0.830
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
CSNK2A1	SSRP1	psi-mi:“MI:0217”(phosphorylation reaction)	0.760
DDX21	HNRNPC	psi-mi:“MI:0915”(physical association)	0.750
RPA4	RPA1	psi-mi:“MI:0914”(association)	0.740
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
BMAL2	CLOCK	psi-mi:“MI:0914”(association)	0.670
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
COMMD6	VPS26C	psi-mi:“MI:0914”(association)	0.640
MACROD1	PARP1	psi-mi:“MI:0914”(association)	0.620
SSRP1	H3C1	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SSRP1	H2BC21	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (966): TONSL (Co-localization), SSRP1 (Synthetic Growth Defect), SSRP1 (Co-localization), SSRP1 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS), SSRP1 (Biochemical Activity), SSRP1 (Reconstituted Complex), SSRP1 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS)

ESM2 similar proteins: A8WWU0, O01683, O02328, O04235, O94267, P0CQ22, P0CQ23, P0CR74, P0CR75, P27692, P32558, P41848, Q00976, Q04636, Q04678, Q04931, Q05153, Q05344, Q08943, Q08945, Q19753, Q293F6, Q2UBF1, Q4H2R2, Q4P647, Q54G78, Q54LA1, Q54S43, Q54X97, Q5A1D5, Q5B2X8, Q61E63, Q65WY8, Q6BS60, Q6BXE5, Q6C7V4, Q6C931, Q6CHJ8, Q6CWD7, Q6CWW9

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

3 interactions.

A	Effect	B	Mechanism
CSNK2A1	“down-regulates activity”	SSRP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 230 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
Activation of the pre-replicative complex	7	13.8×	8e-06
Deposition of new CENPA-containing nucleosomes at the centromere	14	13.5×	6e-10
SIRT1 negatively regulates rRNA expression	13	13.4×	2e-09
RNA Polymerase I Promoter Opening	12	13.4×	5e-09
Packaging Of Telomere Ends	10	13.3×	8e-08
B-WICH complex positively regulates rRNA expression	18	13.2×	9e-13
Inhibition of DNA recombination at telomere	13	13.2×	2e-09
DNA methylation	12	13.0×	7e-09

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	10	18.5×	8e-08
heterochromatin formation	12	14.8×	3e-08
double-strand break repair via nonhomologous end joining	6	12.2×	1e-03
mRNA transport	8	10.2×	3e-04
DNA replication	12	9.6×	2e-06
nucleosome assembly	14	9.5×	1e-07
positive regulation of interferon-beta production	5	9.5×	1e-02
telomere maintenance	6	7.8×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2943 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57326692:T:TA	donor_gain	1.0000
11:57326794:AGCTG:A	donor_gain	1.0000
11:57326795:G:C	donor_gain	1.0000
11:57326889:CCTG:C	acceptor_gain	1.0000
11:57327421:CTCA:C	donor_loss	1.0000
11:57327422:TCA:T	donor_loss	1.0000
11:57327423:CA:C	donor_loss	1.0000
11:57327424:A:AC	donor_gain	1.0000
11:57327424:ACCTC:A	donor_loss	1.0000
11:57327425:C:CC	donor_gain	1.0000
11:57327425:C:CT	donor_loss	1.0000
11:57327425:CCT:C	donor_gain	1.0000
11:57327512:CTC:C	acceptor_gain	1.0000
11:57327513:TC:T	acceptor_gain	1.0000
11:57327514:CC:C	acceptor_gain	1.0000
11:57327515:C:CC	acceptor_gain	1.0000
11:57327516:T:C	acceptor_loss	1.0000
11:57327521:C:CT	acceptor_gain	1.0000
11:57327523:C:CT	acceptor_gain	1.0000
11:57327525:C:CT	acceptor_gain	1.0000
11:57327527:C:CT	acceptor_gain	1.0000
11:57327528:A:T	acceptor_gain	1.0000
11:57327708:TCA:T	donor_loss	1.0000
11:57327709:CA:C	donor_loss	1.0000
11:57327710:A:AC	donor_gain	1.0000
11:57327710:AC:A	donor_gain	1.0000
11:57327710:ACCT:A	donor_gain	1.0000
11:57327711:C:CT	donor_gain	1.0000
11:57327711:CC:C	donor_gain	1.0000
11:57327711:CCT:C	donor_gain	1.0000

AlphaMissense

4741 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:57327511:A:G	W596R	1.000
11:57327511:A:T	W596R	1.000
11:57327739:C:A	W585C	1.000
11:57327739:C:G	W585C	1.000
11:57327741:A:G	W585R	1.000
11:57327741:A:T	W585R	1.000
11:57327749:C:T	G582D	1.000
11:57327752:G:T	A581E	1.000
11:57327809:C:G	R562P	1.000
11:57327821:A:G	L558P	1.000
11:57327825:A:G	W557R	1.000
11:57327825:A:T	W557R	1.000
11:57327834:A:C	Y554D	1.000
11:57330898:A:T	V418D	1.000
11:57330910:A:G	L414P	1.000
11:57330927:C:A	R408S	1.000
11:57330927:C:G	R408S	1.000
11:57331668:C:A	R408M	1.000
11:57331668:C:G	R408T	1.000
11:57331674:A:T	I406N	1.000
11:57331676:G:C	S405R	1.000
11:57331676:G:T	S405R	1.000
11:57331678:T:G	S405R	1.000
11:57331683:A:G	F403S	1.000
11:57331722:T:A	D390V	1.000
11:57331722:T:C	D390G	1.000
11:57331723:C:G	D390H	1.000
11:57331724:A:C	F389L	1.000
11:57331724:A:T	F389L	1.000
11:57331725:A:G	F389S	1.000

dbSNP variants (sampled 300 via entrez): RS1000044629 (11:57333601 G>A,C), RS1000078696 (11:57333835 A>T), RS1000723699 (11:57333289 C>T), RS1001663300 (11:57326551 G>A,C,T), RS1002078591 (11:57327981 G>A), RS1002380059 (11:57328289 G>C), RS1002395137 (11:57334804 CAG>C), RS1003693614 (11:57331285 A>G), RS1003951237 (11:57330713 G>A), RS1004001843 (11:57331007 G>A), RS1004020912 (11:57331648 T>C), RS1004519041 (11:57331362 A>C), RS1004740011 (11:57336039 G>C), RS1005640576 (11:57334867 G>A), RS1005952557 (11:57335853 C>A,G,T)

Disease associations

OMIM: gene MIM:604328 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725086 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 6 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.65	Kd	2.228	nM	CHEMBL3752910
8.65	ED50	2.228	nM	CHEMBL3752910
7.09	Kd	82	nM	MOLIBRESIB
7.00	IC50	100	nM	MOLIBRESIB
5.44	Kd	3605	nM	CHEMBL5653589
5.44	ED50	3605	nM	CHEMBL5653589

PubChem BioAssay actives

4 with measured affinity, of 11 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149501: Binding affinity to human SSRP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0022	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179136: Binding affinity against SSRP1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0820	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149501: Binding affinity to human SSRP1 incubated for 45 mins by Kinobead based pull down assay	kd	3.6050	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases abundance	2
Arsenic	increases abundance, affects expression, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Bortezomib	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Coumestrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652543	Binding	Binding affinity to human SSRP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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