UBL5

Summary

UBL5 (ubiquitin like 5, HGNC:13736) is a protein-coding gene on chromosome 19p13.2, encoding Ubiquitin-like protein 5 (Q9BZL1). Ubiquitin-like protein that plays a role in cell proliferation and sister chromatid cohesion by associating with spliceosomal proteins. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a member of a group of proteins similar to ubiquitin. The encoded protein is not thought to degrade proteins like ubiquitin but to affect their function through being bound to target proteins by an isopeptide bond. The gene product has been studied as a link to predisposition to obesity based on its expression in Psammomys obesus, the fat sand rat, which is an animal model for obesity studies. Variation in this gene was found to be significantly associated with some metabolic traits (PMID: 15331561) but not associated with childhood obesity (PMID: 19189687). Pseudogenes of this gene are located on chromosomes 3, 5 and 17. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 59286 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 16 total
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001048241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13736
Approved symbol	UBL5
Name	ubiquitin like 5
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198258
Ensembl biotype	protein_coding
OMIM	606849
Entrez	59286

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000358666, ENST00000586895, ENST00000588141, ENST00000588595, ENST00000589372, ENST00000589960, ENST00000590068, ENST00000593087, ENST00000883416, ENST00000883417, ENST00000883418, ENST00000883419, ENST00000936833, ENST00000936834, ENST00000936835, ENST00000936836, ENST00000936837, ENST00000936838, ENST00000936839, ENST00000936840

RefSeq mRNA: 2 — MANE Select: NM_001048241 NM_001048241, NM_024292

CCDS: CCDS12219

Canonical transcript exons

ENST00000586895 — 5 exons

Exon	Start	End
ENSE00002786125	9827918	9827984
ENSE00003481251	9828592	9828675
ENSE00003522706	9828327	9828393
ENSE00003543384	9828837	9828874
ENSE00003663734	9829965	9830115

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 138.2786 / max 754.7523, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173707	138.2786	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	99.56	gold quality
right testis	UBERON:0004534	99.53	gold quality
left testis	UBERON:0004533	99.48	gold quality
right adrenal gland	UBERON:0001233	99.46	gold quality
mucosa of transverse colon	UBERON:0004991	99.45	gold quality
left adrenal gland cortex	UBERON:0035825	99.43	gold quality
left adrenal gland	UBERON:0001234	99.42	gold quality
right adrenal gland cortex	UBERON:0035827	99.42	gold quality
pituitary gland	UBERON:0000007	99.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.41	gold quality
cingulate cortex	UBERON:0003027	99.40	gold quality
anterior cingulate cortex	UBERON:0009835	99.40	gold quality
monocyte	CL:0000576	99.37	gold quality
left lobe of thyroid gland	UBERON:0001120	99.34	gold quality
right frontal lobe	UBERON:0002810	99.34	gold quality
right atrium auricular region	UBERON:0006631	99.34	gold quality
metanephros cortex	UBERON:0010533	99.34	gold quality
right lobe of thyroid gland	UBERON:0001119	99.33	gold quality
left coronary artery	UBERON:0001626	99.33	gold quality
right uterine tube	UBERON:0001302	99.32	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.31	gold quality
granulocyte	CL:0000094	99.30	gold quality
islet of Langerhans	UBERON:0000006	99.30	gold quality
prefrontal cortex	UBERON:0000451	99.30	gold quality
lower esophagus	UBERON:0013473	99.30	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.29	gold quality
ascending aorta	UBERON:0001496	99.28	gold quality
thoracic aorta	UBERON:0001515	99.28	gold quality
ganglionic eminence	UBERON:0004023	99.28	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	7.47
E-ENAD-20	no	585.18
E-MTAB-7008	no	445.94
E-HCAD-5	no	31.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting UBL5, 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-3605-5P	99.96	67.12	932
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-744-5P	93.78	65.29	230
HSA-MIR-10396A-5P	93.49	65.54	172

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• The UBL5 gene is unlikely to play a major role in the genetic susceptibility to early-onset obesity. (PMID:19189687)
• Results suggest that UBL5 could be targeted to Cajal bodies (CBs) via its interaction with coilin. (PMID:23726919)
• our results show that UBL5 plays an evolutionary conserved role in pre-mRNA splicing, the integrity of which is essential for the fidelity of chromosome segregation. (PMID:25092792)
• Findings establish UBL5 as a factor that promotes the functionality of the FA DNA repair pathway. (PMID:25862789)
• Moonlighting functions of the ubiquitin-like protein, Hub1/UBL-5. (PMID:37453225)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ubl5	ENSMUSG00000084786
drosophila_melanogaster	ubl	FBGN0022224
caenorhabditis_elegans	ubl-5	WBGENE00006726

Protein

Protein identifiers

Ubiquitin-like protein 5 — Q9BZL1 (reviewed: Q9BZL1)

All UniProt accessions (3): A0A024R7B0, Q9BZL1, K7EQ43

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-like protein that plays a role in cell proliferation and sister chromatid cohesion by associating with spliceosomal proteins. Participates thereby in pre-mRNA splicing by maintaining spliceosome integrity. Promotes the functional integrity of the Fanconi anemia DNA repair pathway by interacting with FANCI component and subsequently mediating the formation of FANCI homodimers. Also plays a protective role against ER stress-induced apoptosis.

Subunit / interactions. Interacts with CLK1, CLK3 and CLK4. Interacts with coilin/COIL. Interacts with spliceosome components SART1 and EFTUD2. Interacts with FANCI; this interaction promotes FANCI dimerization.

Subcellular location. Cytoplasm. Nucleus. Cajal body.

Tissue specificity. Ubiquitous. Highest level of expression in heart, skeletal muscle, kidney, liver, iris and lymphoblasts.

Induction. Depleted by ER stress-induced mediated by the ubiquitin-independent proteasome system independent of transcriptional regulation and downstream of PERK activation.

RefSeq proteins (2): NP_001041706, NP_077268 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR039732	Hub1/Ubl5	Family

Pfam: PF00240

UniProt features (11 total): strand 4, turn 2, helix 2, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
4PYU	X-RAY DIFFRACTION	2
8H6K	ELECTRON MICROSCOPY	2.7
8Q7N	ELECTRON MICROSCOPY	3.1
9R3D	ELECTRON MICROSCOPY	3.12
6AHD	ELECTRON MICROSCOPY	3.8
7ABF	ELECTRON MICROSCOPY	3.9
7AAV	ELECTRON MICROSCOPY	4.2
8QO9	ELECTRON MICROSCOPY	5.29
7ABG	ELECTRON MICROSCOPY	7.8
7ABI	ELECTRON MICROSCOPY	8
9R8V	ELECTRON MICROSCOPY	8.5
1P0R	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZL1-F1	91.63	0.77

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
22	does not impair binding to sart1 nor its pre-mrna splicing function.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway

MSigDB gene sets: 152 (showing top): MODULE_151, GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, MARTINEZ_RB1_TARGETS_UP, GGAANCGGAANY_UNKNOWN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOBP_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, REACTOME_MRNA_SPLICING, TIEN_INTESTINE_PROBIOTICS_24HR_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, GOBP_PROTEIN_TARGETING_TO_MITOCHONDRION, GOBP_POSITIVE_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_PROTEIN_TARGETING

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), obsolete positive regulation of protein targeting to mitochondrion (GO:1903955), protein modification process (GO:0036211)

GO Molecular Function (2): protein tag activity (GO:0031386), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Cajal body (GO:0015030)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
protein metabolic process	1
macromolecule modification	1
molecular tag activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1376 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBL5	UBL3	O95164	929
UBL5	NEDD8	Q15843	822
UBL5	SART1	O43290	786
UBL5	SUMO1	P55856	659
UBL5	PRPF38A	Q8NAV1	612
UBL5	MFAP1	P55081	571
UBL5	CLPP	Q16740	564
UBL5	URM1	Q9BTM9	534
UBL5	DDX46	Q7L014	513
UBL5	CLK1	P49759	490
UBL5	FANCI	Q9NVI1	485
UBL5	UFM1	P61960	467
UBL5	BOLA1	Q9Y3E2	458
UBL5	FBXL12	Q9NXK8	455
UBL5	HSPA9	P30036	448

IntAct

142 interactions, top by confidence:

A	B	Type	Score
UBL5	SART1	psi-mi:“MI:0914”(association)	0.670
SART1	UBL5	psi-mi:“MI:0915”(physical association)	0.670
UBL5	SERTAD3	psi-mi:“MI:0915”(physical association)	0.600
SERTAD3	UBL5	psi-mi:“MI:0915”(physical association)	0.600
CTAG1A	UBL5	psi-mi:“MI:0915”(physical association)	0.560
HID1	UBL5	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	UBL5	psi-mi:“MI:0915”(physical association)	0.560
BEND7	UBL5	psi-mi:“MI:0915”(physical association)	0.560
CERCAM	UBL5	psi-mi:“MI:0915”(physical association)	0.560
SMCP	UBL5	psi-mi:“MI:0915”(physical association)	0.560
UBL5	TRIM39	psi-mi:“MI:0915”(physical association)	0.560
UBL5	HESX1	psi-mi:“MI:0915”(physical association)	0.560
ZNF618	UBL5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	UBL5	psi-mi:“MI:0915”(physical association)	0.560
NFYA	UBL5	psi-mi:“MI:0915”(physical association)	0.560
TLE5	UBL5	psi-mi:“MI:0915”(physical association)	0.560
LENG1	UBL5	psi-mi:“MI:0915”(physical association)	0.560
C1QTNF1	UBL5	psi-mi:“MI:0915”(physical association)	0.560
UBL5	SPATC1L	psi-mi:“MI:0915”(physical association)	0.560
UBL5	SPANXB1	psi-mi:“MI:0915”(physical association)	0.560
PAX4	UBL5	psi-mi:“MI:0915”(physical association)	0.560
SF1	UBL5	psi-mi:“MI:0915”(physical association)	0.560
TEX35	UBL5	psi-mi:“MI:0915”(physical association)	0.560
CCDC196	UBL5	psi-mi:“MI:0915”(physical association)	0.560
CCDC28B	UBL5	psi-mi:“MI:0915”(physical association)	0.560
UBL5	PRMT8	psi-mi:“MI:0915”(physical association)	0.560
ZFP41	UBL5	psi-mi:“MI:0915”(physical association)	0.560
MBD3L1	UBL5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (108): SART1 (Two-hybrid), SART1 (Affinity Capture-Western), UBL5 (Reconstituted Complex), COIL (Co-fractionation), UBL5 (Affinity Capture-MS), UBL5 (Co-fractionation), UBL5 (Co-fractionation), TRIM27 (Two-hybrid), UBL5 (Affinity Capture-MS), UBL5 (Affinity Capture-MS), UBL5 (Affinity Capture-MS), FANCI (Affinity Capture-Western), UBL5 (Affinity Capture-Western), UBL5 (Reconstituted Complex), WAPAL (Synthetic Lethality)

ESM2 similar proteins: A7WLH8, G0SEV9, O57686, O80840, O94650, P18669, P25113, P42678, P55853, P63165, P63166, P91302, Q28BL6, Q2EF74, Q3KRA6, Q3SZ62, Q3T0Z3, Q5E9D1, Q5EAX4, Q5I0H3, Q5R6J4, Q5RFB8, Q5VQ78, Q5ZLN1, Q6BUP7, Q6CU12, Q6DEP7, Q6EGX7, Q6FIX7, Q6GML7, Q6H8D5, Q6H8D6, Q6Q546, Q6Z8K4, Q756X3, Q791B0, Q7SXF2, Q7SZR5, Q8L828, Q8QGH2

Diamond homologs: O94650, P91302, Q3T0Z3, Q54Q03, Q6BUP7, Q6CU12, Q6EGX7, Q6FIX7, Q6Q546, Q756X3, Q791B0, Q7SXF2, Q9BZL1, Q9EPV8, Q9FGZ9, Q9V998

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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 - Major Pathway	9	17.0×	3e-07
Processing of Capped Intron-Containing Pre-mRNA	5	14.2×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	8	14.7×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

631 predictions. Top by Δscore:

Variant	Effect	Δscore
19:9828557:A:AG	acceptor_gain	1.0000
19:9828557:ACC:A	acceptor_gain	1.0000
19:9828559:C:A	acceptor_gain	1.0000
19:9828566:ATTT:A	acceptor_gain	1.0000
19:9828673:GTG:G	donor_gain	1.0000
19:9828558:C:G	acceptor_gain	0.9900
19:9828566:A:AG	acceptor_gain	0.9900
19:9828567:T:G	acceptor_gain	0.9900
19:9828569:T:TA	acceptor_gain	0.9900
19:9828575:A:AG	acceptor_gain	0.9900
19:9828575:AACT:A	acceptor_gain	0.9900
19:9828576:A:G	acceptor_gain	0.9900
19:9828578:T:A	acceptor_gain	0.9900
19:9827983:AGGTG:A	donor_loss	0.9800
19:9827984:GGT:G	donor_loss	0.9800
19:9827985:G:A	donor_loss	0.9800
19:9827986:T:A	donor_loss	0.9800
19:9828583:T:TA	acceptor_gain	0.9800
19:9828585:C:CA	acceptor_gain	0.9800
19:9828676:G:GA	donor_loss	0.9800
19:9828676:G:GG	donor_gain	0.9800
19:9828677:TGAG:T	donor_loss	0.9800
19:9828678:G:GG	donor_loss	0.9800
19:9828899:G:GT	donor_gain	0.9800
19:9828576:ACT:A	acceptor_gain	0.9700
19:9828590:A:AG	acceptor_gain	0.9700
19:9828591:G:GG	acceptor_gain	0.9700
19:9828591:GCAC:G	acceptor_gain	0.9700
19:9828670:G:GT	donor_gain	0.9700
19:9827987:G:GT	donor_loss	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000120252 (19:9828281 G>A), RS1000471366 (19:9827992 G>T), RS1001152534 (19:9827005 G>A), RS1001458129 (19:9826696 C>T), RS1002194505 (19:9829483 G>A), RS1003015215 (19:9829280 T>C,G), RS1003110022 (19:9829580 C>G), RS1003342801 (19:9830573 G>A), RS1003635484 (19:9826503 G>A), RS1003918301 (19:9827686 T>A,C), RS1005624677 (19:9827366 T>G), RS1005643453 (19:9829246 C>T), RS1005969566 (19:9830426 G>A), RS1007060084 (19:9827320 G>A), RS1007809337 (19:9828458 A>G,T)

Disease associations

OMIM: gene MIM:606849 | 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
GCST001859_12	Thiazide-induced adverse metabolic effects in hypertensive patients	3.000000e-06
GCST006914_15	Sleep duration	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	3
Tretinoin	increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
potassium perchlorate	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
cadmium acetate	increases expression	1
beta-methylcholine	affects expression	1
CD 437	decreases expression	1
K 7174	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Metribolone	affects splicing	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1

Clinical trials (associated diseases)

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