UBAC1

Summary

UBAC1 (UBA domain containing 1, HGNC:30221) is a protein-coding gene on chromosome 9q34.3, encoding Ubiquitin-associated domain-containing protein 1 (Q9BSL1). Non-catalytic component of the KPC complex, a E3 ubiquitin-protein ligase complex that mediates polyubiquitination of target proteins, such as CDKN1B and NFKB1.

Enables polyubiquitin modification-dependent protein binding activity and proteasome binding activity. Involved in protein maturation and protein ubiquitination. Located in Golgi apparatus; cytosol; and plasma membrane.

Source: NCBI Gene 10422 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_016172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30221
Approved symbol	UBAC1
Name	UBA domain containing 1
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	GBDR1, KPC2
Ensembl gene	ENSG00000130560
Ensembl biotype	protein_coding
OMIM	608129
Entrez	10422

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000371756, ENST00000465873, ENST00000471163, ENST00000478485, ENST00000486258, ENST00000489050, ENST00000906557, ENST00000906558, ENST00000906559, ENST00000941598, ENST00000941599, ENST00000941600, ENST00000941601, ENST00000941602, ENST00000941603

RefSeq mRNA: 1 — MANE Select: NM_016172 NM_016172

CCDS: CCDS35177

Canonical transcript exons

ENST00000371756 — 10 exons

Exon	Start	End
ENSE00000895010	135947798	135947905
ENSE00001456024	135932969	135933515
ENSE00001456025	135961025	135961373
ENSE00003479386	135946269	135946371
ENSE00003488250	135938222	135938360
ENSE00003492410	135939673	135939759
ENSE00003523866	135945889	135945997
ENSE00003558326	135953680	135953753
ENSE00003594974	135945028	135945250
ENSE00003649861	135955295	135955415

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.0339 / max 715.1812, expressed in 1812 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103112	13.1727	1769
103113	11.6134	1784
103111	0.7449	116
103110	0.2909	73
103114	0.2120	82

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.21	gold quality
muscle of leg	UBERON:0001383	98.18	gold quality
muscle organ	UBERON:0001630	98.00	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.77	gold quality
apex of heart	UBERON:0002098	97.67	gold quality
skeletal muscle tissue	UBERON:0001134	97.63	gold quality
biceps brachii	UBERON:0001507	97.55	gold quality
triceps brachii	UBERON:0001509	97.55	gold quality
vastus lateralis	UBERON:0001379	97.47	gold quality
quadriceps femoris	UBERON:0001377	97.44	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.25	gold quality
gluteal muscle	UBERON:0002000	97.15	gold quality
diaphragm	UBERON:0001103	96.99	gold quality
deltoid	UBERON:0001476	96.87	gold quality
body of tongue	UBERON:0011876	96.67	gold quality
muscle tissue	UBERON:0002385	96.40	gold quality
bronchial epithelial cell	CL:0002328	96.39	gold quality
epithelium of bronchus	UBERON:0002031	96.31	gold quality
oocyte	CL:0000023	96.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.28	gold quality
heart left ventricle	UBERON:0002084	96.24	gold quality
tibialis anterior	UBERON:0001385	96.19	gold quality
cardiac ventricle	UBERON:0002082	96.14	gold quality
bronchus	UBERON:0002185	95.94	gold quality
skin of leg	UBERON:0001511	95.84	gold quality
skin of abdomen	UBERON:0001416	95.77	gold quality
trabecular bone tissue	UBERON:0002483	95.24	gold quality
mucosa of transverse colon	UBERON:0004991	95.11	gold quality
left testis	UBERON:0004533	94.94	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	387.43
E-HCAD-4	yes	144.78
E-CURD-112	yes	45.66
E-MTAB-10042	yes	32.31
E-CURD-122	yes	19.33
E-ANND-3	yes	9.72
E-MTAB-9388	yes	8.14
E-HCAD-9	yes	5.87
E-CURD-10	no	109.79
E-MTAB-9067	no	3.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting UBAC1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
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-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-1236-5P	96.62	66.38	856
HSA-MIR-365A-5P	94.91	63.72	471
HSA-MIR-365B-5P	94.91	63.79	470

Literature-anchored findings (GeneRIF, showing 3)

• AIRE interacts with multiple components of the transcription complex including a novel interaction with the UBA domain protein, GBDR1. (PMID:16310047)
• our experiments support that PPP1CB and KPC2 together inhibit the activity of HOXA2 by activating its nuclear export, but favored HOXA2 de-ubiquitination and stabilization thereby establishing a store of HOXA2 in the cytoplasm. (PMID:31323436)
• UBAC1/KPC2 Regulates TLR3 Signaling in Human Keratinocytes through Functional Interaction with the CARD14/CARMA2sh-TANK Complex. (PMID:33316896)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubac1	ENSDARG00000059722
mus_musculus	Ubac1	ENSMUSG00000036352
rattus_norvegicus	Ubac1	ENSRNOG00000017983

Paralogs (5): TNRC6C (ENSG00000078687), TNRC6A (ENSG00000090905), TNRC6B (ENSG00000100354), UBXN4 (ENSG00000144224), UBXN1 (ENSG00000162191)

Protein

Protein identifiers

Ubiquitin-associated domain-containing protein 1 — Q9BSL1 (reviewed: Q9BSL1)

Alternative names: Glialblastoma cell differentiation-related protein 1, Kip1 ubiquitination-promoting complex protein 2

All UniProt accessions (2): Q9BSL1, A0A140VK64

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic component of the KPC complex, a E3 ubiquitin-protein ligase complex that mediates polyubiquitination of target proteins, such as CDKN1B and NFKB1. The KPC complex catalyzes polyubiquitination and proteasome-mediated degradation of CDKN1B during G1 phase of the cell cycle. The KPC complex also acts as a key regulator of the NF-kappa-B signaling by promoting maturation of the NFKB1 component of NF-kappa-B by catalyzing ubiquitination of the NFKB1 p105 precursor. Within the KPC complex, UBAC1 acts as an adapter that promotes the transfer of target proteins that have been polyubiquitinated by RNF123/KPC1 to the 26S proteasome.

Subunit / interactions. Component of the KPC complex composed of RNF123/KPC1 and UBAC1/KPC2. Interacts (via ubiquitin-like domain) with RNF123. Interacts (via ubiquitin-like and UBA domains) with the proteasome via its N-terminal domain.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous.

Domain organisation. The UBA domains recognize and bind polyubiquitinated proteins.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BSL1-1	1	yes
Q9BSL1-2	2

RefSeq proteins (1): NP_057256* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006636	STI1_HS-bd	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR015940	UBA	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR041926	UBA1_UBAC1	Domain
IPR041927	UBA2_UBAC1	Domain
IPR052476	UBAC1	Family
IPR057650	UBL_UBAC1	Domain

Pfam: PF22562, PF23326

UniProt features (21 total): domain 4, helix 4, sequence conflict 2, modified residue 2, region of interest 2, compositionally biased region 2, chain 1, splice variant 1, sequence variant 1, strand 1, initiator methionine 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DAI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSL1-F1	75.29	0.17

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 (2): 2, 1

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 165 (showing top): GNF2_PRDX2, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, RORA1_01, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_HDAC1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, TGACCTY_ERR1_Q2, GNF2_ANK1, GOBP_PROTEIN_MATURATION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (2): protein ubiquitination (GO:0016567), protein maturation (GO:0051604)

GO Molecular Function (3): polyubiquitin modification-dependent protein binding (GO:0031593), proteasome binding (GO:0070628), protein binding (GO:0005515)

GO Cellular Component (6): ubiquitin ligase complex (GO:0000151), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
protein modification by small protein conjugation	1
gene expression	1
protein metabolic process	1
modification-dependent protein binding	1
protein-containing complex binding	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

789 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBAC1	RNF123	Q5XPI4	993
UBAC1	CD248	Q9HCU0	875
UBAC1	VIM	P08670	874
UBAC1	IPO8	O15397	728
UBAC1	OXA1L	Q15070	716
UBAC1	PPT1	P50897	696
UBAC1	NR3C2	P08235	658
UBAC1	APEH	P13798	608
UBAC1	ST20	Q9HBF5	581
UBAC1	MDH2	P40926	518
UBAC1	SRC	P12931	507
UBAC1	OPRD1	P41143	506
UBAC1	UBL7	Q96S82	478
UBAC1	NUB1	Q9Y5A7	459
UBAC1	SEC61A1	P38378	449

IntAct

244 interactions, top by confidence:

A	B	Type	Score
UBAC1	DAZAP2	psi-mi:“MI:0915”(physical association)	0.780
UBAC1	TRIM2	psi-mi:“MI:0915”(physical association)	0.780
DAZAP2	UBAC1	psi-mi:“MI:0915”(physical association)	0.780
UBAC1	UBB	psi-mi:“MI:0914”(association)	0.740
UBB	UBAC1	psi-mi:“MI:0915”(physical association)	0.740
HTT	UBAC1	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (187): UBAC1 (Two-hybrid), TRIM2 (Two-hybrid), TRIM39 (Two-hybrid), UBAC1 (Two-hybrid), UBAC1 (Biochemical Activity), UBAC1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS)

ESM2 similar proteins: A1CDT9, A1DCU5, A3KMV2, F4JPR7, G5EFF7, O17453, O48726, O74803, P32628, P48510, P54725, P54726, P54727, P54728, P55035, Q0CJ13, Q0U3Y6, Q10169, Q1DNB9, Q1EBV4, Q28DG7, Q29RK4, Q2H085, Q2KIS3, Q2USD7, Q40742, Q4KMA2, Q4WGS4, Q54LV1, Q5AY89, Q5XIR9, Q5ZJI9, Q6NXA9, Q6NYI0, Q7K2G1, Q7S906, Q7ZXQ3, Q84L30, Q84L31, Q84L32

Diamond homologs: E1BMF7, E1BY77, F1QFS9, P34631, P38237, P45974, P54201, P56399, P57075, Q04323, Q11119, Q28DG7, Q32KW2, Q3V3E1, Q3ZBU9, Q499N6, Q5BKP2, Q5HZY0, Q5R407, Q5R4I3, Q5XIR9, Q5ZJI9, Q6GL77, Q6GLV4, Q6IP50, Q6NXA9, Q7YTB0, Q8BGG7, Q8L6Y1, Q8TF42, Q8VCH8, Q8VDI7, Q922Y1, Q92575, Q92995, Q9BSL1, Q9BZV1, Q9TXH9, Q9VCE9, Q8H0T4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UBAC1	“form complex”	KPC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1918 predictions. Top by Δscore:

Variant	Effect	Δscore
9:135933513:ATG:A	acceptor_gain	1.0000
9:135933514:TG:T	acceptor_gain	1.0000
9:135933514:TGC:T	acceptor_loss	1.0000
9:135933515:GC:G	acceptor_loss	1.0000
9:135933516:C:CC	acceptor_gain	1.0000
9:135933516:CT:C	acceptor_loss	1.0000
9:135933517:T:A	acceptor_loss	1.0000
9:135938218:ATAC:A	donor_loss	1.0000
9:135938219:TACCT:T	donor_loss	1.0000
9:135938220:A:AC	donor_gain	1.0000
9:135938220:ACCTA:A	donor_loss	1.0000
9:135938221:C:CC	donor_gain	1.0000
9:135938221:CCTAG:C	donor_gain	1.0000
9:135938357:CGCA:C	acceptor_gain	1.0000
9:135938358:GCA:G	acceptor_gain	1.0000
9:135938359:CA:C	acceptor_gain	1.0000
9:135938359:CAC:C	acceptor_gain	1.0000
9:135938359:CACTG:C	acceptor_loss	1.0000
9:135938360:ACTG:A	acceptor_loss	1.0000
9:135938361:C:CA	acceptor_loss	1.0000
9:135938361:C:CC	acceptor_gain	1.0000
9:135938362:T:A	acceptor_loss	1.0000
9:135938370:C:CT	acceptor_gain	1.0000
9:135938370:C:T	acceptor_gain	1.0000
9:135939672:CCG:C	donor_gain	1.0000
9:135939756:CGGC:C	acceptor_gain	1.0000
9:135945048:C:CA	donor_gain	1.0000
9:135945887:A:AC	donor_gain	1.0000
9:135945888:C:CC	donor_gain	1.0000
9:135945995:TTG:T	acceptor_gain	1.0000

AlphaMissense

2678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:135938245:A:G	L360P	0.999
9:135938275:A:T	I350N	0.999
9:135938350:A:G	L325P	0.999
9:135939704:A:G	L311P	0.999
9:135939730:G:C	F302L	0.999
9:135939730:G:T	F302L	0.999
9:135939732:A:G	F302L	0.999
9:135945221:A:G	L228P	0.999
9:135945234:C:G	A224P	0.999
9:135945901:A:G	L214P	0.999
9:135945927:A:C	F205L	0.999
9:135945927:A:T	F205L	0.999
9:135945928:A:G	F205S	0.999
9:135945929:A:G	F205L	0.999
9:135945943:A:G	L200P	0.999
9:135946337:A:G	L159P	0.999
9:135933446:A:T	V391D	0.998
9:135938354:A:G	W324R	0.998
9:135938354:A:T	W324R	0.998
9:135939708:C:G	A310P	0.998
9:135939731:A:G	F302S	0.998
9:135939746:A:G	L297P	0.998
9:135945913:G:T	A210D	0.998
9:135945943:A:T	L200H	0.998
9:135946326:C:G	A163P	0.998
9:135946346:A:G	L156P	0.998
9:135946349:A:T	I155K	0.998
9:135946358:A:G	L152P	0.998
9:135933434:A:C	I395S	0.997
9:135933434:A:T	I395N	0.997

dbSNP variants (sampled 300 via entrez): RS1000058990 (9:135944413 C>T), RS1000119925 (9:135962386 C>T), RS1000159982 (9:135960480 C>A,G,T), RS1000210734 (9:135954924 A>G), RS1000268510 (9:135957810 T>C), RS1000321395 (9:135957510 G>C), RS1000333107 (9:135957608 C>G,T), RS1000408670 (9:135944566 G>A), RS1000464285 (9:135947747 C>A,T), RS1000765067 (9:135953529 A>C,G), RS1000788378 (9:135953055 C>A,T), RS1000918696 (9:135933591 C>A,T), RS1001058727 (9:135944048 G>A), RS1001075051 (9:135952855 G>A), RS1001079558 (9:135938122 C>T)

Disease associations

OMIM: gene MIM:608129 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004131_21	Inflammatory bowel disease	5.000000e-36
GCST004132_11	Crohn’s disease	6.000000e-30
GCST004133_17	Ulcerative colitis	2.000000e-16
GCST011177_4	Lung adenocarcinoma (survival time) in never smokers	6.000000e-07
GCST90002405_478	Reticulocyte count	3.000000e-10
GCST90002406_291	Reticulocyte fraction of red cells	3.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0000714	survival time
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
bisphenol A	decreases expression, decreases methylation	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Arsenic	decreases expression, increases abundance, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
K 7174	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	increases expression	1
Acetaminophen	affects response to substance	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Copper	affects binding, decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TV41	HAP1 UBAC1 (-) 1	Cancer cell line	Male
CVCL_TV42	HAP1 UBAC1 (-) 2	Cancer cell line	Male
CVCL_TV43	HAP1 UBAC1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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