SERTAD1

Summary

SERTAD1 (SERTA domain containing 1, HGNC:17932) is a protein-coding gene on chromosome 19q13.2, encoding SERTA domain-containing protein 1 (Q9UHV2). Acts at E2F-responsive promoters as coregulator to integrate signals provided by PHD- and/or bromodomain-containing transcription factors.

Predicted to enable transcription coactivator activity. Acts upstream of or within negative regulation of cell growth. Located in cytoplasm and nucleus.

Source: NCBI Gene 29950 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_013376

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17932
Approved symbol	SERTAD1
Name	SERTA domain containing 1
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	SEI1, TRIP-Br1
Ensembl gene	ENSG00000197019
Ensembl biotype	protein_coding
OMIM	617850
Entrez	29950

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000357949, ENST00000869921, ENST00000869922, ENST00000933429

RefSeq mRNA: 1 — MANE Select: NM_013376 NM_013376

CCDS: CCDS12557

Canonical transcript exons

ENST00000357949 — 2 exons

Exon	Start	End
ENSE00001417932	40421589	40423546
ENSE00001429761	40425867	40425992

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 94.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6534 / max 1278.8803, expressed in 1809 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180989	22.6534	1809

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	94.09	gold quality
amniotic fluid	UBERON:0000173	93.77	gold quality
lower lobe of lung	UBERON:0008949	93.66	gold quality
ileal mucosa	UBERON:0000331	92.65	gold quality
saphenous vein	UBERON:0007318	92.58	gold quality
trachea	UBERON:0003126	92.02	gold quality
pharyngeal mucosa	UBERON:0000355	90.73	gold quality
tibialis anterior	UBERON:0001385	90.33	silver quality
epithelial cell of pancreas	CL:0000083	89.86	silver quality
mucosa of stomach	UBERON:0001199	89.70	gold quality
pericardium	UBERON:0002407	89.08	gold quality
epithelium of nasopharynx	UBERON:0001951	88.27	silver quality
nipple	UBERON:0002030	88.03	gold quality
cartilage tissue	UBERON:0002418	88.00	gold quality
lower esophagus mucosa	UBERON:0035834	87.87	gold quality
esophagus squamous epithelium	UBERON:0006920	87.79	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.77	gold quality
decidua	UBERON:0002450	87.69	gold quality
epithelium of mammary gland	UBERON:0003244	87.60	gold quality
palpebral conjunctiva	UBERON:0001812	87.58	gold quality
upper arm skin	UBERON:0004263	87.51	silver quality
mammary duct	UBERON:0001765	87.50	gold quality
kidney epithelium	UBERON:0004819	87.17	silver quality
left uterine tube	UBERON:0001303	86.94	gold quality
gingival epithelium	UBERON:0001949	86.64	gold quality
nasal cavity epithelium	UBERON:0005384	86.63	silver quality
right lung	UBERON:0002167	86.44	gold quality
granulocyte	CL:0000094	86.39	gold quality
omental fat pad	UBERON:0010414	86.38	gold quality
peritoneum	UBERON:0002358	86.34	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	474.53
E-MTAB-10137	no	5.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SET	Activation

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

25 targeting SERTAD1, 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-4775	99.98	75.00	6394
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-6884-3P	98.05	65.32	750
HSA-MIR-6779-3P	97.51	65.82	789
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-3131	95.33	65.74	102
HSA-MIR-6732-5P	93.97	64.65	422
HSA-MIR-611	93.79	64.24	81

Literature-anchored findings (GeneRIF, showing 18)

• p34SEI-1 strongly suppressed CREB-mediated transcription, and this suppression was overcome by excess amount of CBP (PMID:12736710)
• interacts with low- and high-risk HPV11 and HPV16 E6 proteins in yeast, in vitro and in mammalian cell cultures (PMID:14675634)
• p34SEI1 fragment 30-160 can bind, activate, and inhibit cyclin-dependent kinase CDK4; fragment 30-132 binds and activates but does not inhibit CDK4, while fragment 30-88 cannot bind, activate, or inhibit but retains LexA-mediated transactivation activity. (PMID:15065884)
• p34(SEI-1) and p16(INK4A) have different roles in development of squamous cell carcinoma of the head and neck (PMID:16201750)
• Translocation of small amount of NM23H1 into the nucleus induced by the overexpressions of SEI1/SET could increase the frequency of sister chromatid exchangein esophageal cancers. (PMID:20570897)
• study shows that the p34SE1-1 expression level was not changed after H2O2 treatment at either protein or transcriptional levels (PMID:21344158)
• These results suggest that p34 (SEI-1) inhibits ROS-induced cell death through by indirectly inducing ubiquitination of ASK1. (PMID:21725208)
• High SERTAD1 expression is associated with breast cancer. (PMID:23970032)
• Data demonstrate that p34SEI-1 induces the activation of either AKT or ILK signaling on HER2/neu expression status. (PMID:24789658)
• TRIP-Br1 confers resistance to serum starvation-induced cell deaths by stabilizing the XIAP protein and inhibiting cellular ROS production. (PMID:26334958)
• Findings provide evidence that TRIP-Br1 functions as an oncogenic protein by providing cancer cells resistance to the hypoxia-induced cell death of breast cancer cells. (PMID:27035851)
• SEI1 up-regulation induces genomic instability by inhibiting DNA damage response in ovarian cancer cells. (PMID:27697611)
• Here, the authors show that transcriptional regulator interacting with the PHD-bromodomain 1 (TRIP-Br1, Sertad1), a newly identified protein with poorly characterized functions, acts as an adaptor that bridges the interaction of multiple Adenylyl cyclase isoforms with X-linked inhibitor of apoptosis protein (XIAP), a RING-domain E3 ubiquitin ligase. (PMID:28656888)
• NEDD4-1 recognizes SERTA domain containing proline rich region of p34SEI-1. Residues of NEDD4-1 responsible for direct interaction with p34SEI-1 are identified by NMR titration experiments. (PMID:28666866)
• Sertad1 could antagonize iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells when iASPP was in the stage of overproduction. (PMID:29179704)
• In human PCa tumor tissues, Sertad1 expression is positively correlated with AR expression and the Gleason score. Taken together, this report is the first to show that Sertad1 is a novel AR-LBD-binding protein, and DHT-liganded AR-LBD inhibits Sertad1 degradation. (PMID:30230528)
• Inhibitory Role of TRIP-Br1/XIAP in Necroptosis under Nutrient/Serum Starvation. (PMID:32050753)
• SERTAD1 initiates NLRP3-mediated inflammasome activation through restricting NLRP3 polyubiquitination. (PMID:38341852)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sertad1	ENSMUSG00000008384
rattus_norvegicus	Sertad1	ENSRNOG00000024363

Paralogs (1): SERTAD3 (ENSG00000167565)

Protein

Protein identifiers

SERTA domain-containing protein 1 — Q9UHV2 (reviewed: Q9UHV2)

Alternative names: CDK4-binding protein p34SEI1, Transcriptional regulator interacting with the PHD-bromodomain 1

All UniProt accessions (2): Q53GC0, Q9UHV2

UniProt curated annotations — full annotation on UniProt →

Function. Acts at E2F-responsive promoters as coregulator to integrate signals provided by PHD- and/or bromodomain-containing transcription factors. Stimulates E2F1/TFDP1 transcriptional activity. Renders the activity of cyclin D1/CDK4 resistant to the inhibitory effects of CDKN2A/p16INK4A.

Subunit / interactions. Interacts with the PHD-bromodomain of TIF1, TRIM28/TIF1B and p300/CBP. Interacts with E2F1 and TFDP1; modulates transactivation activity of TFDP1/E2F complexes. Also interacts with CDK4.

Post-translational modifications. Polyubiquitinated, which promotes proteasomal degradation.

RefSeq proteins (1): NP_037508* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009263	SERTA_dom	Domain
IPR052262	E2F-SERTA_domain_protein	Family

Pfam: PF06031

UniProt features (6 total): region of interest 2, chain 1, domain 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHV2-F1	63.69	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 210 (showing top): RNGTGGGC_UNKNOWN, AP1_01, GOBP_REGULATION_OF_PHOSPHORYLATION, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, FOSTER_TOLERANT_MACROPHAGE_UP, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_IL3RA, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, INGRAM_SHH_TARGETS_DN, BACH2_01, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, TGANTCA_AP1_C, TTGGAGA_MIR5155P_MIR519E

GO Biological Process (5): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), positive regulation of cell population proliferation (GO:0008284), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of cell growth (GO:0030308), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (2): transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), sarcoplasm (GO:0016528)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	2
cyclin-dependent protein serine/threonine kinase activity	1
regulation of protein serine/threonine kinase activity	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

742 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERTAD1	CDCA4	Q9BXL8	890
SERTAD1	RPA2	P15927	763
SERTAD1	STN1	Q9H668	761
SERTAD1	CDK4	P11802	749
SERTAD1	SERTAD4	Q9NUC0	700
SERTAD1	CCNA1	P78396	687
SERTAD1	CCNA2	P20248	641
SERTAD1	E2F1	Q01094	583
SERTAD1	SERTAD2	Q14140	573
SERTAD1	CDKN2A	P42771	527
SERTAD1	DCTN6	O00399	525
SERTAD1	TRIM24	O15164	484
SERTAD1	SEC61G	P38384	479
SERTAD1	EP300	Q09472	447
SERTAD1	FOXO1	Q12778	434

IntAct

132 interactions, top by confidence:

A	B	Type	Score
KLHL42	SERTAD1	psi-mi:“MI:0915”(physical association)	0.670
SERTAD1	KLHL42	psi-mi:“MI:0915”(physical association)	0.670
E6	SERTAD1	psi-mi:“MI:0407”(direct interaction)	0.590
E6	SERTAD1	psi-mi:“MI:0915”(physical association)	0.590
SERTAD1	TOM20	psi-mi:“MI:0915”(physical association)	0.560
SERTAD1	HGH1	psi-mi:“MI:0915”(physical association)	0.560
HGH1	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
TOM20	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
ZNF410	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
KAT14	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
FAAP20	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
SSX7	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
SERTAD1	PSORS1C2	psi-mi:“MI:0915”(physical association)	0.560
CINP	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
AIRIM	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
KLC4	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
ATG12	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
SERTAD1	CKS1B	psi-mi:“MI:0915”(physical association)	0.560
FNDC11	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
CIB3	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (92): SERTAD1 (Two-hybrid), SERTAD1 (Two-hybrid), ROPN1 (Two-hybrid), ZNF410 (Two-hybrid), EGLN3 (Two-hybrid), CIB3 (Two-hybrid), PATE1 (Two-hybrid), P4HA3 (Two-hybrid), KLHL42 (Two-hybrid), SERTAD1 (Affinity Capture-Western), SERTAD1 (Affinity Capture-Western), ADCY1 (Reconstituted Complex), SERTAD1 (Reconstituted Complex), XIAP (Reconstituted Complex), ADCY1 (Biochemical Activity)

ESM2 similar proteins: A0A1B0GUS0, A0A5F9ZHS7, A7E346, A7MB34, A8MZG2, B2RU40, D4A9R4, O08574, O75593, P0C1Z6, P0CG20, Q0VG99, Q0ZCJ7, Q17QH7, Q29RM2, Q2KIS6, Q2M2S6, Q2M3G4, Q2NL68, Q32LE6, Q3U1J1, Q5JXC2, Q5R815, Q5SW24, Q61660, Q63247, Q6NZ36, Q6PBC9, Q6ZN01, Q6ZRI6, Q7TN08, Q7Z591, Q80VF6, Q86WR7, Q8BG26, Q8BP99, Q8BXQ8, Q8IYS4, Q8N9Y4, Q8NAV2

Diamond homologs: Q14140, Q9BXL8, Q9JJG5, Q9JL10, Q9UHV2, Q9ERC3, Q9UJW9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

334 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40423547:C:CC	acceptor_gain	1.0000
19:40425863:ATACC:A	donor_loss	1.0000
19:40425864:TAC:T	donor_loss	1.0000
19:40425865:A:AT	donor_loss	1.0000
19:40423542:AGCAT:A	acceptor_gain	0.9900
19:40423543:GCAT:G	acceptor_gain	0.9900
19:40423544:CAT:C	acceptor_gain	0.9900
19:40423544:CATC:C	acceptor_gain	0.9900
19:40423545:AT:A	acceptor_gain	0.9900
19:40423546:TCT:T	acceptor_loss	0.9900
19:40423548:T:A	acceptor_loss	0.9900
19:40425028:A:AC	donor_gain	0.9900
19:40425029:C:CC	donor_gain	0.9900
19:40425866:CCTTG:C	donor_gain	0.9900
19:40423557:C:CT	acceptor_gain	0.9800
19:40425865:A:AC	donor_gain	0.9800
19:40425866:C:CC	donor_gain	0.9800
19:40423550:C:CT	acceptor_gain	0.9700
19:40423558:A:T	acceptor_gain	0.9700
19:40425041:A:AC	donor_gain	0.9700
19:40425042:C:CC	donor_gain	0.9700
19:40425508:C:A	donor_gain	0.9700
19:40425602:T:TA	donor_gain	0.9700
19:40423551:A:T	acceptor_gain	0.9600
19:40425507:G:GA	donor_gain	0.9600
19:40425528:T:TA	donor_gain	0.9600
19:40425865:AC:A	donor_gain	0.9600
19:40425866:CC:C	donor_gain	0.9600
19:40424885:AT:A	donor_gain	0.9400
19:40425515:T:TA	donor_gain	0.9400

AlphaMissense

1510 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40423391:C:A	K52N	0.990
19:40423391:C:G	K52N	0.990
19:40423332:T:A	N72I	0.989
19:40423331:G:C	N72K	0.987
19:40423331:G:T	N72K	0.987
19:40423326:A:G	L74P	0.986
19:40423338:A:T	V70D	0.986
19:40423341:A:G	L69P	0.984
19:40423526:C:A	K7N	0.983
19:40423526:C:G	K7N	0.983
19:40423389:A:G	L53P	0.982
19:40423393:T:C	K52E	0.980
19:40423344:A:T	V68E	0.978
19:40423026:A:G	F174S	0.977
19:40423025:A:C	F174L	0.976
19:40423025:A:T	F174L	0.976
19:40423027:A:G	F174L	0.976
19:40423021:C:G	D176H	0.973
19:40423317:A:G	I77T	0.972
19:40423026:A:C	F174C	0.967
19:40423323:C:G	R75P	0.966
19:40423356:A:G	L64P	0.965
19:40423017:A:T	I177N	0.964
19:40423333:T:A	N72Y	0.962
19:40422894:A:T	L218H	0.961
19:40423020:T:A	D176V	0.961
19:40423014:T:A	D178V	0.960
19:40423333:T:C	N72D	0.960
19:40423347:A:G	L67P	0.959
19:40423020:T:G	D176A	0.958

dbSNP variants (sampled 300 via entrez): RS1000462710 (19:40427297 G>A), RS1000563814 (19:40427013 C>G), RS1000932809 (19:40425627 G>A,C), RS1001006398 (19:40425803 C>A,G), RS1001132506 (19:40425100 G>T), RS1002147130 (19:40424861 G>A), RS1002253033 (19:40426146 C>G,T), RS1003067393 (19:40426900 T>C), RS1003117897 (19:40426523 G>A), RS1003127742 (19:40426267 C>G,T), RS1003141350 (19:40427202 C>T), RS1003327934 (19:40421391 G>T), RS1003407193 (19:40421956 G>C), RS1003453704 (19:40425613 A>G), RS1003702062 (19:40421665 G>A,T)

Disease associations

OMIM: gene MIM:617850 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003827_4	Otitis media	2.000000e-07
GCST003828_1	Otitis media (chronic)	3.000000e-08
GCST003829_4	Otitis media (recurrent)	1.000000e-07
GCST90002394_558	Monocyte percentage of white cells	8.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, increases expression	8
Benzo(a)pyrene	increases expression	6
Aflatoxin B1	increases expression, affects expression	5
Cadmium Chloride	increases abundance, increases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
(+)-JQ1 compound	increases expression	3
Air Pollutants	increases expression, affects expression, increases abundance, decreases expression	3
Fluorouracil	affects reaction, increases expression	3
Formaldehyde	increases expression	3
Tobacco Smoke Pollution	increases expression	3
Acetaminophen	increases expression	2
Copper	increases expression, affects binding, decreases expression	2
Tretinoin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
Cyclosporine	affects expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
urushiol	decreases expression	1
chloroacetaldehyde	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
quercitrin	increases expression	1
diethyl maleate	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1

Clinical trials (associated diseases)

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