HTATSF1

Summary

HTATSF1 (HIV-1 Tat specific factor 1, HGNC:5276) is a protein-coding gene on chromosome Xq26.3, encoding 17S U2 SnRNP complex component HTATSF1 (O43719). Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs. It is a common-essential gene (DepMap: required in 91.8% of cancer cell lines).

The protein encoded by this gene functions as a cofactor for the stimulation of transcriptional elongation by HIV-1 Tat, which binds to the HIV-1 promoter through Tat-TAR interaction. This protein may also serve as a dual-function factor to couple transcription and splicing and to facilitate their reciprocal activation. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 27336 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 141 total
• GTEx eGene: eQTL in 10 tissues, sQTL in 1 (q < 0.05)
• Cancer dependency (DepMap): dependent in 91.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_014500
• Notable: 141 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5276
Approved symbol	HTATSF1
Name	HIV-1 Tat specific factor 1
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	TAT-SF1
Ensembl gene	ENSG00000102241
Ensembl biotype	protein_coding
OMIM	300346
Entrez	27336

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 4 nonsense_mediated_decay

MANE Select: ENST00000218364

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 5: 1

ENST00000218364, ENST00000425695, ENST00000448450, ENST00000535601, ENST00000866995, ENST00000866996, ENST00000866997, ENST00000866998, ENST00000866999, ENST00000928616, ENST00000928617, ENST00000959448, ENST00000959449, ENST00000959450, ENST00000959451, ENST00001037790, ENST00001037791, ENST00001037792, ENST00001088313, ENST00001105937, ENST00001112883, ENST00001121708, ENST00001135545

RefSeq mRNA: 2 — MANE Select: NM_014500 NM_001163280, NM_014500

CCDS: CCDS14657

Canonical transcript exons

ENST00000218364 — 9 exons

Exon	Start	End
ENSE00000677003	136499598	136499778
ENSE00000677004	136500158	136500205
ENSE00000677005	136500664	136500818
ENSE00000677007	136504364	136504463
ENSE00000677008	136509091	136509180
ENSE00000677009	136510082	136510219
ENSE00001305625	136510808	136512346
ENSE00001932076	136497592	136497870
ENSE00003785219	136502778	136502941

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.3777 / max 485.9157, expressed in 1813 samples.

Highest expression (Bgee): sural nerve, skeletal muscle tissue of rectus abdominis, pituitary gland, germinal epithelium of ovary, medial globus pallidus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

HTATSF1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	2.6e-10	+0.13	X:136498293:G:T
Testis	eqtl	5.7e-09	+0.21	X:136505077:G:C
Adipose Subcutaneous	eqtl	1.8e-07	+0.54	X:136421828:A:G
Skin Sun Exposed Lower leg	eqtl	4.1e-04	+0.09	X:136217452:T:C
Brain Putamen basal ganglia	eqtl	1.5e-03	+0.56	X:136000921:G:A
Pancreas	eqtl	8.0e-03	+0.69	X:136822393:G:A
Adrenal Gland	eqtl	9.5e-03	+0.40	X:135584027:C:T
Breast Mammary Tissue	eqtl	1.6e-02	+0.95	X:136556197:A:G
Adipose Visceral Omentum	eqtl	1.9e-02	-0.71	X:136076609:C:T
Spleen	eqtl	3.3e-02	+0.40	X:136297616:C:T
Brain Caudate basal ganglia	sqtl	4.4e-02	-1.06	X:136146510:GT:G

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
197693	26.5144	1810
197699	2.0582	660
197698	1.5529	829
197697	1.1956	625
197694	0.5352	242
197696	0.3949	198
197695	0.1266	36

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	99.41	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.30	gold quality
pituitary gland	UBERON:0000007	98.17	gold quality
germinal epithelium of ovary	UBERON:0001304	97.97	gold quality
medial globus pallidus	UBERON:0002477	97.91	gold quality
epithelium of nasopharynx	UBERON:0001951	97.76	gold quality
ganglionic eminence	UBERON:0004023	97.75	gold quality
nasopharynx	UBERON:0001728	97.74	gold quality
globus pallidus	UBERON:0001875	97.72	gold quality
tendon of biceps brachii	UBERON:0008188	97.69	gold quality
vastus lateralis	UBERON:0001379	97.67	gold quality
adenohypophysis	UBERON:0002196	97.67	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.65	gold quality
oocyte	CL:0000023	97.55	gold quality
biceps brachii	UBERON:0001507	97.49	gold quality
superior vestibular nucleus	UBERON:0007227	97.37	gold quality
medulla oblongata	UBERON:0001896	97.26	gold quality
subthalamic nucleus	UBERON:0001906	97.24	gold quality
lateral globus pallidus	UBERON:0002476	97.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.19	gold quality
embryo	UBERON:0000922	97.15	gold quality
amniotic fluid	UBERON:0000173	97.08	gold quality
tendon	UBERON:0000043	97.04	gold quality
synovial joint	UBERON:0002217	97.02	gold quality
muscle of leg	UBERON:0001383	96.91	gold quality
cortical plate	UBERON:0005343	96.90	gold quality
gastrocnemius	UBERON:0001388	96.89	gold quality
skeletal muscle organ	UBERON:0014892	96.88	gold quality
muscle organ	UBERON:0001630	96.87	gold quality
inferior vagus X ganglion	UBERON:0005363	96.86	gold quality
quadriceps femoris	UBERON:0001377	96.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.82	gold quality
substantia nigra pars compacta	UBERON:0001965	96.65	gold quality
skeletal muscle tissue	UBERON:0001134	96.61	gold quality
parietal pleura	UBERON:0002400	96.61	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.58	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.52	gold quality
ventral tegmental area	UBERON:0002691	96.51	gold quality
palpebral conjunctiva	UBERON:0001812	96.50	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.42	gold quality
pons	UBERON:0000988	96.39	gold quality
spinal cord	UBERON:0002240	96.31	gold quality
hypothalamus	UBERON:0001898	96.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.30	gold quality
eye	UBERON:0000970	96.29	gold quality
calcaneal tendon	UBERON:0003701	96.28	gold quality
blood vessel layer	UBERON:0004797	96.25	gold quality
cranial nerve II	UBERON:0000941	96.23	gold quality
midbrain	UBERON:0001891	96.19	gold quality
substantia nigra	UBERON:0002038	96.14	gold quality
pleura	UBERON:0000977	96.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.01	gold quality
body of tongue	UBERON:0011876	95.97	gold quality
renal medulla	UBERON:0000362	95.95	gold quality
secondary oocyte	CL:0000655	95.92	gold quality
inferior olivary complex	UBERON:0002127	95.83	gold quality
amygdala	UBERON:0001876	95.77	gold quality
gluteal muscle	UBERON:0002000	95.74	gold quality
muscle tissue	UBERON:0002385	95.63	gold quality
tibia	UBERON:0000979	95.61	gold quality
nucleus accumbens	UBERON:0001882	95.60	gold quality
putamen	UBERON:0001874	95.58	gold quality
ventricular zone	UBERON:0003053	95.57	gold quality
pigmented layer of retina	UBERON:0001782	95.56	gold quality
retina	UBERON:0000966	95.54	gold quality
tongue	UBERON:0001723	95.45	gold quality
visceral pleura	UBERON:0002401	95.37	gold quality
deltoid	UBERON:0001476	95.32	gold quality
islet of Langerhans	UBERON:0000006	95.20	gold quality
caudate nucleus	UBERON:0001873	95.20	gold quality
central nervous system	UBERON:0001017	95.13	gold quality
corpus callosum	UBERON:0002336	95.13	gold quality
paraflocculus	UBERON:0005351	95.13	gold quality
brain	UBERON:0000955	95.09	gold quality
forebrain	UBERON:0001890	95.08	gold quality
occipital lobe	UBERON:0002021	95.08	gold quality
urethra	UBERON:0000057	94.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.91	gold quality
seminal vesicle	UBERON:0000998	94.90	gold quality
Ammon’s horn	UBERON:0001954	94.90	gold quality
superior surface of tongue	UBERON:0007371	94.86	gold quality
diaphragm	UBERON:0001103	94.84	gold quality
primary visual cortex	UBERON:0002436	94.84	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.77	gold quality
right ovary	UBERON:0002118	94.76	gold quality
ovary	UBERON:0000992	94.74	gold quality
endometrium	UBERON:0001295	94.73	gold quality
cerebellum	UBERON:0002037	94.71	gold quality
cerebellar cortex	UBERON:0002129	94.70	gold quality
cerebellar hemisphere	UBERON:0002245	94.70	gold quality
trigeminal ganglion	UBERON:0001675	94.69	gold quality
telencephalon	UBERON:0001893	94.69	gold quality
cingulate cortex	UBERON:0003027	94.52	gold quality
penis	UBERON:0000989	94.48	gold quality
temporal lobe	UBERON:0001871	94.45	gold quality
anterior cingulate cortex	UBERON:0009835	94.44	gold quality
esophagus squamous epithelium	UBERON:0006920	94.42	gold quality
prefrontal cortex	UBERON:0000451	94.40	gold quality
gingival epithelium	UBERON:0001949	94.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	no	2.26
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	170.3	high
Pituitary gland	tissue	140.7
Tongue	tissue	101.9
Adrenal gland	tissue	94.2	high
Heart muscle	tissue	61.2	high
Epididymis	tissue	55.8	high
Retina	tissue	52.0
Bone marrow	tissue	51.6	high
Ovary	tissue	51.4	high
Caudate putamen	tissue	49.8
Parathyroid gland	tissue	49.6	high
Frontal cortex	tissue	45.6
Locus coeruleus	tissue	45.6
Postcentral gyrus	tissue	45.4
Thyroid gland	tissue	44.6	high
Corpus callosum	tissue	44.4
Hippocampus	tissue	44.0	high
Nucleus accumbens	tissue	43.9
Kidney	tissue	40.5	high
Thymus	tissue	40.1
Testis	tissue	38.8	high
Seminal vesicle	tissue	37.4	high
Endometrium 1	tissue	36.8	high
Adipose tissue	tissue	36.5	high
Hypothalamus	tissue	35.2
Midbrain	tissue	34.9
Spinal cord	tissue	34.8
Placenta	tissue	34.2	high
Choroid plexus	tissue	33.6
Pons	tissue	33.5
Breast	tissue	33.4	high
Tonsil	tissue	33.4	high
Rectum	tissue	33.2	high
Thalamus	tissue	33.2
Substantia nigra	tissue	33.2
Skin 1	tissue	33.1	high
Prostate	tissue	33.1	high
Fallopian tube	tissue	33.0	high
Urinary bladder	tissue	32.8	high
Colon	tissue	32.6	high
Medulla oblongata	tissue	32.4
Lymph node	tissue	32.3	high
Smooth muscle	tissue	32.3	high
Cervix	tissue	31.4	high
Periaqueductal gray	tissue	31.1
Stomach 1	tissue	30.7	high
Putamen	tissue	30.7
Septum	tissue	30.4
Superior colliculi	tissue	30.0
Ventral forebrain	tissue	30.0
Appendix	tissue	29.2	high
Liver	tissue	28.8	high
Esophagus	tissue	28.5	high
Hippocampal formation	tissue	27.7
Vagina	tissue	27.2	high
Spleen	tissue	26.9	high
Gallbladder	tissue	26.8	high
Salivary gland	tissue	26.7	high
Pancreas	tissue	26.1	high
Cerebral cortex	tissue	25.4	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventromedial nucleus (104.4), Arcuate nucleus (93.0), Paraventricular nucleus (65.3), Inferior olive (64.9), Supraoptic nucleus (62.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting HTATSF1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

22 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-5586-5P	96.29	68.02	685

Functional genomics

Regional missense constraint (gnomAD)

ENST00000218364 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
X:136,497,685–136,499,758	89 / 92.3	0.96	no
X:136,499,759–136,510,970	117 / 222.2	0.53	no
X:136,510,971–136,512,010	246 / 245.3	1.00	no
DepMap (CRISPR cell-line fitness): dependent in 91.8% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): DK-MG (-1.634), DB (-1.625), Set-2 (-1.505), A-172 (-1.454), MEL-HO (-1.444), SK-N-MC (-1.439), TUHR10TKB (-1.425), LS123 (-1.407), Calu-6 (-1.349), MG-63 (-1.339), THP-1 (-1.337), SU.86.86 (-1.282), S-117 (-1.257), KLE (-1.246), RERF-GC-1B (-1.244).

Literature-anchored findings (GeneRIF, showing 7)

• These results support the notion that Tat-induced neuropathogenesis is mediated by multiple mechanisms involving both intracellular and extracellular Tat protein. (PMID:15050687)
• phosphorylated by P-TEFb kinase during HIV-1 transcription in Tat/TAR dependent manner (PMID:15564463)
• Intracellular HIV-1 Tat protein represses constitutive LMP2 transcription increasing proteasome activity by interfering with the binding of IRF-1 to STAT1 (PMID:16512786)
• Tat-SF1 is not required for regulating HIV-1 transcription, but is required for maintaining the ratios of different classes of HIV-1 transcripts. (PMID:19479034)
• these findings suggest that Tat-SF1 functions independently in transcription and splicing of cellular genes. (PMID:21282347)
• This study validates Tat-SF1 as an HDF in CD4+ T cell-derived SupT1 cells. (PMID:23153325)
• Human Tat-specific factor 1 binds the HIV-1 genome and selectively transports HIV-1 RNAs. (PMID:32016635)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	htatsf1	ENSDARG00000056649
mus_musculus	Htatsf1	ENSMUSG00000067873
rattus_norvegicus	Htatsf1	ENSRNOG00000027761
drosophila_melanogaster	barc	FBGN0037081
caenorhabditis_elegans	cus-2	WBGENE00022025

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919709) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal pluripotent precursor cell morphology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RB63	97.7%	Diamond
Arabidopsis thaliana	Q9S709	85.5%	Diamond
Oryza sativa Japonica Group	Q9ZQW8	71.0%	Diamond
Saccharomyces cerevisiae S288C	P53830	34.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC00892	ncRNA	100128420
VGLL1	protein-coding	51442
BRS3	protein-coding	680
MIR934	ncRNA	100126324
CD40LG	protein-coding	959
ADGRG4	protein-coding	139378
MAP7D3	protein-coding	79649

Protein

Protein identifiers

17S U2 SnRNP complex component HTATSF1 — O43719 (reviewed: O43719)

Alternative names: HIV Tat-specific factor 1

All UniProt accessions (3): O43719, Q5H918, Q5H919

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs. The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing. Within the 17S U2 SnRNP complex, HTATSF1 is required to stabilize the branchpoint-interacting stem loop. HTATSF1 is displaced from the 17S U2 SnRNP complex before the stable addition of the 17S U2 SnRNP complex to the spliceosome, destabilizing the branchpoint-interacting stem loop and allowing to probe intron branch site sequences. Also acts as a regulator of transcriptional elongation, possibly by mediating the reciprocal stimulatory effect of splicing on transcriptional elongation. Involved in double-strand break (DSB) repair via homologous recombination in S-phase by promoting the recruitment of TOPBP1 to DNA damage sites. Mechanistically, HTATSF1 is (1) recruited to DNA damage sites in S-phase via interaction with poly-ADP-ribosylated RPA1 and (2) phosphorylated by CK2, promoting recruitment of TOPBP1, thereby facilitating RAD51 nucleofilaments formation and RPA displacement, followed by homologous recombination. (Microbial infection) In case of infection by HIV-1, it is up-regulated by the HIV-1 proteins NEF and gp120, acts as a cofactor required for the Tat-enhanced transcription of the virus.

Subunit / interactions. Component of the 17S U2 SnRNP complex, a ribonucleoprotein complex that contains small nuclear RNA (snRNA) U2 and a number of specific proteins. Within the 17S U2 SnRNP complex, interacts (via UHM region) directly with SF3B1. Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. Interacts with GTF2F2/RAP30 and POLR2A. Interacts with TCERG1/CA150. Interacts with (poly-ADP-ribosylated) RPA1; promoting HTATSF1 recruitment to DNA damage sites. Interacts (when phosphorylated) with TOPBP1; promoting recruitment of TOPBP1 to DNA damage sites during S-phase.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylation at Ser-748 by CK2 during S-phase in response to DNA damage promotes interaction with TOPBP1 and double-strand break (DSB) repair via homologous recombination.

Domain organisation. The RRM domains mediate interaction with U snRNPs. The RRM domains specifically bind poly-ADP-ribosylated RPA1.

Similarity. Belongs to the HTATSF1 family.

RefSeq proteins (2): NP_001156752, NP_055315* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034392	TatSF1-like_RRM1	Domain
IPR034393	TatSF1-like	Family
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (84 total): modified residue 31, compositionally biased region 14, strand 9, helix 7, region of interest 6, mutagenesis site 4, sequence variant 3, domain 2, cross-link 2, sequence conflict 2, turn 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

11 structures by resolution:

PDB	Title	Method	Resolution (Å)
6N3D	Structure of HIV Tat-specific factor 1 U2AF Homology Motif (APO-State)	X-RAY DIFFRACTION	1.13
6N3E	Structure of HIV Tat-specific factor 1 U2AF Homology Motif bound to U2AF ligand motif 4	X-RAY DIFFRACTION	1.89
6NSX	Yeast Hsh155 Ligand bound to Human Tat-SF1 Motif	X-RAY DIFFRACTION	2
6N3F	Structure of HIV Tat-specific factor 1 U2AF Homology Motif bound to SF3b1 ULM5	X-RAY DIFFRACTION	2.1
7Q3L	Human 17S U2 snRNP 5’ domain	ELECTRON MICROSCOPY	2.21
7EVO	The cryo-EM structure of the human 17S U2 snRNP	ELECTRON MICROSCOPY	2.5
8HK1	The cryo-EM structure of human pre-17S U2 snRNP	ELECTRON MICROSCOPY	2.7
6Y50	5’domain of human 17S U2 snRNP	ELECTRON MICROSCOPY	4.1
6Y53	human 17S U2 snRNP low resolution part	ELECTRON MICROSCOPY	7.1
6Y5Q	human 17S U2 snRNP	ELECTRON MICROSCOPY	7.1
2DIT	Solution structure of the RRM_1 domain of HIV TAT specific factor 1 variant	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43719-F1	59.95	0.18

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH supported · IF enhanced

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 (33)

Type	Positions
N-acetylserine	2
N6-acetyllysine	297
Phosphoserine	387, 403, 407, 409, 445, 452, 453, 481, 485, 494, 498, 521, 529, 557, 561, 579, 597, 600, 607, 616, 624, 642, 676, 702, 713, 714, 721, 748
Phosphothreonine	633
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	429, 430

Mutagenesis-validated functional residues (4)

Position	Phenotype
136	loss of interaction with u snrnps.
155–156	in 4a mutant; abolished binding to poly-adp-ribosylated rpa1 and recruitment to dna damage sites; when associated with 297-a-a-298.
297–298	in 4a mutant; abolished binding to poly-adp-ribosylated rpa1 and recruitment to dna damage sites; when associated with 155-a-a-156.
748	impaired phosphorylation by ck2, leading to abolish interaction with topbp1.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9770562	mRNA Polyadenylation	curated
R-HSA-72163	mRNA Splicing - Major Pathway	curated
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA	—
R-HSA-72172	mRNA Splicing	—

MSigDB gene sets: 150 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, CHEOK_RESPONSE_TO_MERCAPTOPURINE_AND_LD_MTX_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_RAD21, TGACCTY_ERR1_Q2, MORF_PSMC2, MORF_RAF1, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME, WTGAAAT_UNKNOWN

GO Biological Process (10): mRNA splicing, via spliceosome (GO:0000398), double-strand break repair via homologous recombination (GO:0000724), DNA-templated transcription (GO:0006351), U2-type prespliceosome assembly (GO:1903241), protein localization to site of double-strand break (GO:1990166), DNA repair (GO:0006281), chromatin organization (GO:0006325), mRNA processing (GO:0006397), DNA damage response (GO:0006974), RNA splicing (GO:0008380)

GO Molecular Function (5): RNA binding (GO:0003723), chromatin-protein adaptor activity (GO:0140463), poly-ADP-D-ribose modification-dependent protein binding (GO:0160004), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), U2-type spliceosomal complex (GO:0005684), U2 snRNP (GO:0005686), site of double-strand break (GO:0035861), spliceosomal complex (GO:0005681), chromosome (GO:0005694)

Reactome top-level categories

4 top-level categories:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

29 GO namespaces:

Category	Terms
RNA processing	2
binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
recombinational repair	1
double-strand break repair	1
gene expression	1
RNA biosynthetic process	1
spliceosomal complex assembly	1
protein localization to chromosome	1
DNA metabolic process	1
DNA damage response	1
cellular component organization	1
mRNA metabolic process	1
cellular response to stress	1
nucleic acid binding	1
chromatin binding	1
chromatin organization	1
protein-macromolecule adaptor activity	1
ADP-D-ribose modification-dependent protein binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
spliceosomal complex	1
spliceosomal snRNP complex	1
site of DNA damage	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
U2-type prespliceosome assembly	BP	direct assay
double-strand break repair via homologous recombination	BP	direct assay
mRNA splicing, via spliceosome	BP	direct assay
protein localization to site of double-strand break	BP	direct assay
U2-type spliceosomal complex	CC	direct assay
nucleoplasm	CC	direct assay
site of double-strand break	CC	direct assay
RNA binding	MF	high-throughput assay
chromatin-protein adaptor activity	MF	direct assay
poly-ADP-D-ribose modification-dependent protein binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,248 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTATSF1	CDK9	P50750	840
HTATSF1	CCNT1	O60563	832
HTATSF1	LSM2	Q9Y333	804
HTATSF1	BRD4	O60885	775
HTATSF1	HEXIM1	O94992	764
HTATSF1	RPS2	P15880	723
HTATSF1	RBM8A	Q9Y5S9	703
HTATSF1	DDX46	Q7L014	702
HTATSF1	CCNT2	O60583	651
HTATSF1	PAK1IP1	Q9NWT1	617
HTATSF1	POLR2A	P24928	596
HTATSF1	CDC40	O60508	573
HTATSF1	SUPT5H	O00267	571
HTATSF1	CDK7	P50613	563
HTATSF1	SF3B2	Q13435	547

IntAct

Human interaction partners of HTATSF1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

20 partners by confidence:

Partner	Interaction type	MIscore	Records
SF3B1	direct interaction	0.650	6
SNRPA1	association	0.640	3
SF3A2	physical association	0.560	1
RBM7	association	0.530	2
TCEANC2	association	0.530	1
CSNK2A1	phosphorylation reaction	0.440	1
MAP1LC3A	direct interaction	0.440	1
FLYWCH1	physical association	0.400	1
NP	physical association	0.400	1
CCP110	physical association	0.370	1
SRSF4	physical association	0.370	1
ZNF512B	physical association	0.370	1
NGEF	association	0.350	1
RNF25	association	0.350	1
SF3B2	association	0.350	1
SF3B6	association	0.350	1
EEF1D	physical association	0.000	1
FEZ1	physical association	0.000	1
SNRPB	physical association	0.000	1
SNRPN	physical association	0.000	1

BioGRID (192 interactions; top human partners by supporting records): HDAC6 (Two-hybrid; 4 records), RBM7 (Affinity Capture-MS; 3 records), SF3A2 (Affinity Capture-Western; 3 records), SNRPA1 (Affinity Capture-MS; 3 records), SNRPB (Affinity Capture-MS; 3 records), SNRPF (Affinity Capture-MS; 3 records), SUPT5H (Affinity Capture-Western; 3 records), AP3D1 (Co-fractionation; 2 records), BRD4 (Affinity Capture-MS; 2 records), GTF2F2 (Affinity Capture-Western; 2 records), POLK (Proximity Label-MS; 2 records), POLR2A (Affinity Capture-Western; 2 records), PYHIN1 (Affinity Capture-MS; 2 records), SF3B1 (Affinity Capture-MS; 2 records), SNRPB2 (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
HTATSF1	“form complex”	“U2 snRNP complex”	binding

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
Spliceosome, E complex	129	RBM17, DDX39A, GEMIN2, NCBP2, PRPF31, SART3, SF3A2, SNRPA, SRSF7, DDX39B, DHX15, GEMIN5, SCAF4, SMARCB1, SNRPD3, SYNCRIP, U2AF2, HNRNPC, SF3B2, SMARCC2, SFSWAP, USP39, GEMIN6, HNRNPK, RBM42, SF3B1, SF3B4, SNRPG, SRSF6, BCAS2, SMN1, CPSF7, SMARCE1, SRSF8, ARID1A, LSM4, SNRPC, CHD8, FUS, SNRNP70, SRSF11, NUDT21, PBRM1, SNRPB2, SNRPD1, YBX1, SF1, SNRPD2, SRSF2, SRSF5, PPIH, SRSF3, DDX20, SART1, SRSF1, SRSF4, PRPF19, RBM39, RBMXL2, SREK1, PRPF3, SMARCA2, U2AF1, SF3B6, SMARCA1, CPSF1, DDX23, DHX9, RUVBL1, SNRPF, SRRM2, ALYREF, HNRNPA0, HNRNPH1, PCBP2, RBM10, SF3B3, STRAP, HNRNPR, RBM25, ACTBL2, CHERP, SNRPA1, ACTL6A, DDX46, HNRNPL, RBM7, CPSF6, ARID2, DNAJC8, EFTUD2, KHSRP, RUVBL2, SMARCA4, PCBP1, SNRNP40, SNRPE, PRPF4, PRPF8, SF3A1, SF3A3, SNRNP200, ZCCHC8, DDX5, LUC7L3, SMARCC1, HNRNPA2B1, HNRNPD, HTATSF1, LUC7L2, PHF5A, PRPF6, SMARCD1, SNRPB, GEMIN8, U2SURP, NCBP1, GEMIN4, HNRNPU, MTREX, ARID1B, CHD4, HNRNPM, PRPF40A, HNRNPF, SRRT, DDX17, HNRNPA1, PUF60
Spliceosome, A complex	112	RBM39, SAP30BP, CDK11A, CHERP, HNRNPA1, HNRNPK, HNRNPR, HNRNPU, RBM25, SF3A1, DDX46, HNRNPA3, RNPS1, SART1, SF1, SF3A2, SF3B4, SNRPB, ACIN1, CCAR2, DHX9, ELAVL1, ILF2, SF3B3, SRSF5, HNRNPA2B1, CD2BP2, DDX5, PUF60, RBM17, SNRPA1, TCERG1, ZC3H18, SNRPD1, SRSF2, SYNCRIP, ZNF207, CTNNBL1, HSPA8, NCBP2, SF3B2, TRA2B, YBX1, RBM10, SF3A3, SRRM1, SRSF6, SRSF7, SUGP1, DDX42, DNAJC8, EFTUD2, PRCC, SF3B5, SMNDC1, SNRNP200, WBP11, CDC5L, PPP1R8, PRPF6, BCAS2, NCBP1, PRPF19, PRPF3, SNRPD3, SRSF4, U2AF2, HNRNPUL1, NRIP2, PHF5A, RBM5, RBMX, SNRPA, SRRM2, U2AF1, CCAR1, CFAP20, CIRBP, DDX23, SF3B1, SF3B6, SNRPB2, SNRPE, BUB3, DHX15, PCBP1, PPP1CA, PQBP1, SNRNP70, SRSF1, U2SURP, DDX17, SNRPC, SNRPD2, SNRPF, SNRPG, SRRT, SRSF3, SRSF9, AGGF1, FUS, HNRNPC, HTATSF1, ILF3, PLRG1, SEC31B, TRIR, CWC15, HNRNPAB, PNN, PRPF40A, PRPF8
RNA pol II containing coactivator complex Tat-SF	5	CDK9, HTATSF1, NCL, POLR2A, SUPT5H

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 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
mRNA Splicing	8	54.9×	3e-11
CHD1 and CHD2 subfamily	7	47.6×	7e-10
mRNA Polyadenylation	8	43.9×	7e-11
Processing of Capped Intron-Containing Pre-mRNA	8	41.1×	9e-11
mRNA Splicing - Major Pathway	9	30.7×	7e-11
Dengue Virus-Host Interactions	8	22.8×	7e-09
Metabolism of RNA	8	20.8×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	6	197.1×	3e-11
mRNA splicing, via spliceosome	7	33.7×	4e-08
RNA splicing	6	27.9×	2e-06

Disease & clinical

Genetic variants

Variant evidence for HTATSF1: 141 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	5
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 681):

Position(s)	Effect	Δscore	Sites
X:136497871–136497872	donor_loss	1.0000	5
X:136498454	donor_gain	1.0000
X:136499779	donor_loss	1.0000
X:136500656–136500658	acceptor_gain	1.0000	2
X:136500662–136500663	acceptor_loss	1.0000	6
X:136500819–136500820	donor_loss	1.0000	5
X:136502769	acceptor_gain	1.0000
X:136502773–136502776	acceptor_gain	1.0000	3
X:136502776–136502777	acceptor_loss	1.0000	4
X:136502943	donor_gain	1.0000

AlphaMissense

1,468 missense substitutions predicted likely pathogenic (of 5,102 scored), across 286 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M153	9	0.970	0.999
M271	9	0.851	0.993
D183	8	0.997	0.999
F218	8	0.995	1.000
D308	8	0.988	0.995
F272	8	0.987	0.999
D175	8	0.985	0.999
F149	8	0.984	1.000
D202	8	0.981	0.997
F337	8	0.981	0.999
F60	8	0.979	0.999
F67	8	0.978	0.999
D290	8	0.978	0.993
F125	8	0.976	0.999
F277	8	0.974	0.996
F307	8	0.969	0.999
D143	8	0.967	0.994
N132	8	0.961	0.997
D248	8	0.960	0.992
H310	8	0.960	0.996

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.33e-07
Glioblastoma Multiforme (validation)	favorable	0.0004

Disease associations

OMIM: gene MIM:300346 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, decreases methylation	3
methylmercuric chloride	increases expression	2
bisphenol A	decreases expression, affects cotreatment, increases expression	2
trichostatin A	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Tretinoin	decreases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
coumarin	affects phosphorylation	1
1-UFT protocol	decreases response to substance	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
fenpyroximate	decreases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
MT19c compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases response to substance	1
Vorinostat	decreases expression	1
Arbutin	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.