UBTD1

Summary

UBTD1 (ubiquitin domain containing 1, HGNC:25683) is a protein-coding gene on chromosome 10q24.1-q24.2, encoding Ubiquitin domain-containing protein 1 (Q9HAC8). May be involved in the regulation of cellular senescence through a positive feedback loop with TP53.

The degradation of many proteins is carried out by the ubiquitin pathway in which proteins are targeted for degradation by covalent conjugation of the polypeptide ubiquitin. This gene encodes a protein that belongs to the ubiquitin family of proteins. The encoded protein is thought to regulate E2 ubiquitin conjugating enzymes belonging to the UBE2D family.

Source: NCBI Gene 80019 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_024954

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25683
Approved symbol	UBTD1
Name	ubiquitin domain containing 1
Location	10q24.1-q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11807
Ensembl gene	ENSG00000165886
Ensembl biotype	protein_coding
OMIM	616388
Entrez	80019

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000370664, ENST00000923989, ENST00000958439

RefSeq mRNA: 1 — MANE Select: NM_024954 NM_024954

CCDS: CCDS7465

Canonical transcript exons

ENST00000370664 — 3 exons

Exon	Start	End
ENSE00001097699	97567914	97568141
ENSE00001453263	97570138	97571206
ENSE00001453269	97498924	97499273

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 94.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8439 / max 520.6183, expressed in 1732 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106437	18.2165	1717
106438	3.6274	1272

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.10	gold quality
right testis	UBERON:0004534	93.99	gold quality
apex of heart	UBERON:0002098	92.16	gold quality
skin of leg	UBERON:0001511	91.33	gold quality
testis	UBERON:0000473	90.85	gold quality
skin of abdomen	UBERON:0001416	90.85	gold quality
right lung	UBERON:0002167	90.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.77	gold quality
gastrocnemius	UBERON:0001388	88.39	gold quality
upper lobe of left lung	UBERON:0008952	88.34	gold quality
heart left ventricle	UBERON:0002084	87.78	gold quality
right atrium auricular region	UBERON:0006631	87.74	gold quality
metanephros cortex	UBERON:0010533	87.62	gold quality
upper lobe of lung	UBERON:0008948	87.52	gold quality
zone of skin	UBERON:0000014	87.28	gold quality
cardiac ventricle	UBERON:0002082	87.20	gold quality
stromal cell of endometrium	CL:0002255	87.06	gold quality
muscle of leg	UBERON:0001383	86.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.88	gold quality
ascending aorta	UBERON:0001496	85.30	gold quality
thoracic aorta	UBERON:0001515	85.16	gold quality
cardiac atrium	UBERON:0002081	85.08	gold quality
adenohypophysis	UBERON:0002196	84.45	gold quality
heart	UBERON:0000948	84.38	gold quality
descending thoracic aorta	UBERON:0002345	84.22	gold quality
omental fat pad	UBERON:0010414	83.82	gold quality
peritoneum	UBERON:0002358	83.77	gold quality
ectocervix	UBERON:0012249	83.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.45	gold quality
endocervix	UBERON:0000458	83.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting UBTD1, 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-4283	100.00	66.42	2097
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-301A-5P	96.88	68.07	931

Literature-anchored findings (GeneRIF, showing 7)

• Biochemical characterization of recombinant UBTD1 and UBE2D demonstrated that the two proteins form a stable, stoichiometric complex that can be purified to near homogeneity. (PMID:24211586)
• Establish UBTD1 as a regulator of cellular senescence that mediates p53 function, and provide insights into the mechanism of Mdm2 inhibition that impacts p53 dynamics during cellular senescence and tumourigenesis. (PMID:25382750)
• low levels of UBTD1 are associated with poor patient survival, suggesting that biological functions of UBTD1 could be beneficial in limiting cancer progression. (PMID:30804013)
• CXCR4 mediates matrix stiffness-induced downregulation of UBTD1 driving hepatocellular carcinoma progression via YAP signaling pathway. (PMID:32483419)
• UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFR signaling. (PMID:33884955)
• The ubiquitin-like protein UBTD1 promotes colorectal cancer progression by stabilizing c-Myc to upregulate glycolysis. (PMID:39003255)
• UBTD1 is a potential prognostic biomarker in colorectal cancer. (PMID:39095643)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubtd1a	ENSDARG00000007382
danio_rerio	ubtd1b	ENSDARG00000079623
mus_musculus	Ubtd1	ENSMUSG00000025171
rattus_norvegicus	Ubtd1	ENSRNOG00000013813
drosophila_melanogaster	CG1172	FBGN0264712

Paralogs (1): UBTD2 (ENSG00000168246)

Protein

Protein identifiers

Ubiquitin domain-containing protein 1 — Q9HAC8 (reviewed: Q9HAC8)

All UniProt accessions (1): Q9HAC8

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the regulation of cellular senescence through a positive feedback loop with TP53. Is a TP53 downstream target gene that increases the stability of TP53 protein by promoting the ubiquitination and degradation of MDM2.

Subunit / interactions. Interacts with UBTD1.

Induction. Induced by cytotoxic agents, it is also increased during premature senescence. the induction seems to be mediated by TP53.

RefSeq proteins (1): NP_079230* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR019956	Ubiquitin_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR032752	DC-UbP/UBTD2_N	Domain
IPR038169	DC-UbP/UBTD2_N_sf	Homologous_superfamily
IPR039869	UBTD1/2	Family

Pfam: PF00240, PF16455

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAC8-F1	74.78	0.11

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, PARENT_MTOR_SIGNALING_UP, CHEN_METABOLIC_SYNDROM_NETWORK, LINSLEY_MIR16_TARGETS, CCACACA_MIR147, FORTSCHEGGER_PHF8_TARGETS_DN, CRX_DN.V1_UP, FEV_TARGET_GENES, SFMBT1_TARGET_GENES, SIPA1_TARGET_GENES, ZNF2_TARGET_GENES, ZNF282_TARGET_GENES, ZNF407_TARGET_GENES, ZNF524_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBTD1	BRD10	Q5HYC2	447
UBTD1	CLPSL2	Q6UWE3	437
UBTD1	FRMPD2	Q68DX3	434
UBTD1	TMEM222	Q9H0R3	418
UBTD1	THUMPD2	Q9BTF0	411
UBTD1	ZNF550	Q7Z398	400
UBTD1	FNDC9	Q8TBE3	372
UBTD1	ZDHHC16	Q969W1	364
UBTD1	VWA3A	A6NCI4	355
UBTD1	TMUB1	Q9BVT8	350
UBTD1	POU2AF2	Q8IXP5	321
UBTD1	MMS19	Q96T76	319
UBTD1	RSKR	Q96LW2	311
UBTD1	UBL5	Q9BZL1	309
UBTD1	CTNNB1	P35222	309

IntAct

86 interactions, top by confidence:

A	B	Type	Score
MID1	UBTD1	psi-mi:“MI:0915”(physical association)	0.720
UBTD1	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.720
MRFAP1L1	UBTD1	psi-mi:“MI:0915”(physical association)	0.720
TRIM39	UBTD1	psi-mi:“MI:0915”(physical association)	0.670
UBTD1	TRIM39	psi-mi:“MI:0915”(physical association)	0.670
UBTD1	UBE2D4	psi-mi:“MI:0915”(physical association)	0.670
UBE2D2	UBTD1	psi-mi:“MI:0915”(physical association)	0.670
MID2	UBTD1	psi-mi:“MI:0915”(physical association)	0.560
RNF5	UBTD1	psi-mi:“MI:0915”(physical association)	0.560
TRIM50	UBTD1	psi-mi:“MI:0915”(physical association)	0.560
WWP2	UBTD1	psi-mi:“MI:0915”(physical association)	0.560
UBTD1	TRIM39	psi-mi:“MI:0915”(physical association)	0.560
TP53BP2	UBTD1	psi-mi:“MI:0915”(physical association)	0.560
UBTD1	TRAF6	psi-mi:“MI:0915”(physical association)	0.560
UBE2D3	UBTD1	psi-mi:“MI:0915”(physical association)	0.560
UBE2D1	UBTD1	psi-mi:“MI:0915”(physical association)	0.560
UBTD1	MRFAP1	psi-mi:“MI:0915”(physical association)	0.560
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530

BioGRID (62): UBTD1 (Two-hybrid), UBTD1 (Two-hybrid), UBTD1 (Two-hybrid), MRFAP1L1 (Two-hybrid), UBTD1 (Two-hybrid), UBTD1 (Affinity Capture-MS), UBTD1 (Affinity Capture-MS), CTNNB1 (Affinity Capture-Western), CTNNB1 (Proximity Label-MS), CTNNB1 (Co-fractionation), CTNNB1 (Co-localization), UBTD1 (Affinity Capture-Western), YAP1 (Affinity Capture-Western), BTRC (Affinity Capture-Western), UBE2D3 (Affinity Capture-Western)

ESM2 similar proteins: A1Z3X3, A4GWN3, A5PKE4, B0KWT6, B1MTV8, B2GV38, B2KIK3, B5X9S9, B5XFI8, B7NZQ9, C1BGZ8, C1BHN7, C1BXU5, C3KHF2, O09172, P0CL18, P11441, P21126, P48507, P48508, P54731, Q2HJD0, Q2KIJ6, Q2T9Y6, Q3TDN2, Q3ZBQ1, Q5E9L7, Q5EAE3, Q5R4T1, Q5RAC9, Q5VZK9, Q640W6, Q676U5, Q68FV8, Q6DG43, Q6DLV9, Q6EDY6, Q6PGH0, Q7ZWB2, Q8C0J2

Diamond homologs: P0C032, Q05120, Q3ZBQ1, Q4V8W7, Q54XV3, Q5EAE3, Q640W6, Q68FV8, Q6DG43, Q6GL38, Q6PGH0, Q8WUN7, Q91WB7, Q9HAC8, Q9HDW4, Q03919, Q8RUC6, P29595, Q15843, Q54L35, Q71UE8, Q93725

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
Antigen processing: Ubiquitination & Proteasome degradation	6	9.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein K48-linked ubiquitination	6	38.9×	2e-06
ubiquitin-dependent protein catabolic process	5	14.3×	1e-03
protein ubiquitination	5	8.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

481 predictions. Top by Δscore:

Variant	Effect	Δscore
10:97567902:T:TA	acceptor_gain	1.0000
10:97567907:T:A	acceptor_gain	1.0000
10:97567909:CCCA:C	acceptor_loss	1.0000
10:97567910:CCAG:C	acceptor_loss	1.0000
10:97567911:CAG:C	acceptor_loss	1.0000
10:97567912:A:AG	acceptor_gain	1.0000
10:97567912:AG:A	acceptor_gain	1.0000
10:97567912:AGGAC:A	acceptor_gain	1.0000
10:97567913:G:A	acceptor_gain	1.0000
10:97567913:G:GT	acceptor_gain	1.0000
10:97567913:GGA:G	acceptor_gain	1.0000
10:97567913:GGAC:G	acceptor_gain	1.0000
10:97567913:GGACG:G	acceptor_gain	1.0000
10:97568137:TCATG:T	donor_gain	1.0000
10:97568138:CATG:C	donor_gain	1.0000
10:97568139:ATG:A	donor_gain	1.0000
10:97568140:TG:T	donor_gain	1.0000
10:97568140:TGGTA:T	donor_loss	1.0000
10:97568141:GG:G	donor_gain	1.0000
10:97568142:G:GG	donor_gain	1.0000
10:97568142:GTAA:G	donor_loss	1.0000
10:97570134:A:AG	acceptor_gain	1.0000
10:97570136:A:AG	acceptor_gain	1.0000
10:97570136:AG:A	acceptor_gain	1.0000
10:97570137:G:GA	acceptor_gain	1.0000
10:97570137:GG:G	acceptor_gain	1.0000
10:97570137:GGC:G	acceptor_gain	1.0000
10:97570137:GGCA:G	acceptor_gain	1.0000
10:97570137:GGCAC:G	acceptor_gain	1.0000
10:97499270:GCAG:G	donor_gain	0.9900

AlphaMissense

1470 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:97567949:T:A	W36R	1.000
10:97567949:T:C	W36R	1.000
10:97567951:G:C	W36C	1.000
10:97567951:G:T	W36C	1.000
10:97567983:T:C	L47P	1.000
10:97567993:A:C	K50N	1.000
10:97567993:A:T	K50N	1.000
10:97567995:G:C	R51P	1.000
10:97568003:T:C	F54L	1.000
10:97568004:T:C	F54S	1.000
10:97568005:C:A	F54L	1.000
10:97568005:C:G	F54L	1.000
10:97568006:T:A	W55R	1.000
10:97568006:T:C	W55R	1.000
10:97568007:G:C	W55S	1.000
10:97568008:G:C	W55C	1.000
10:97568008:G:T	W55C	1.000
10:97568024:T:C	F61L	1.000
10:97568026:C:A	F61L	1.000
10:97568026:C:G	F61L	1.000
10:97568030:G:C	G63R	1.000
10:97568045:T:A	W68R	1.000
10:97568045:T:C	W68R	1.000
10:97568046:G:C	W68S	1.000
10:97568047:G:C	W68C	1.000
10:97568047:G:T	W68C	1.000
10:97568055:T:A	L71H	1.000
10:97568055:T:C	L71P	1.000
10:97568064:C:A	A74D	1.000
10:97568100:C:A	A86D	1.000

dbSNP variants (sampled 300 via entrez): RS1000014381 (10:97544609 A>T), RS1000021802 (10:97511064 C>T), RS1000051311 (10:97511460 C>T), RS1000054157 (10:97552704 A>G), RS1000088745 (10:97562806 C>T), RS1000148982 (10:97527079 G>A), RS1000182053 (10:97526834 G>A,C), RS1000256687 (10:97564843 C>A), RS1000295590 (10:97530995 C>A,T), RS1000304628 (10:97570965 C>T), RS1000333184 (10:97533425 C>G,T), RS1000362212 (10:97571155 C>T), RS1000366371 (10:97517572 C>A,T), RS1000472038 (10:97564586 G>A), RS1000534769 (10:97520437 A>C)

Disease associations

OMIM: gene MIM:616388 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_678	Obesity-related traits	7.000000e-06
GCST003264_97	Post bronchodilator FEV1/FVC ratio	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005134	amino acid measurement
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	3
Lead	affects methylation, affects expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	decreases methylation	1
trichostatin A	affects expression	1
benzo(e)pyrene	increases methylation	1
ICG 001	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Arsenic	decreases expression, increases abundance	1
Aspirin	increases expression	1
Atrazine	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Methapyrilene	increases methylation	1
Ozone	increases abundance, affects expression	1
Phthalic Acids	increases methylation	1
Testosterone	affects cotreatment, increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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