UBASH3B

Summary

UBASH3B (ubiquitin associated and SH3 domain containing B, HGNC:29884) is a protein-coding gene on chromosome 11q24.1, encoding Ubiquitin-associated and SH3 domain-containing protein B (Q8TF42). Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases.

This gene encodes a protein that contains a ubiquitin associated domain at the N-terminus, an SH3 domain, and a C-terminal domain with similarities to the catalytic motif of phosphoglycerate mutase. The encoded protein was found to inhibit endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor.

Source: NCBI Gene 84959 — RefSeq curated summary.

At a glance

• GWAS associations: 25 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 89 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 20 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 0.58 (moderately constrained)
• MANE Select transcript: NM_032873
• Notable: 89 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29884
Approved symbol	UBASH3B
Name	ubiquitin associated and SH3 domain containing B
Location	11q24.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1959, STS-1, TULA2, TULA-2
Ensembl gene	ENSG00000154127
Ensembl biotype	protein_coding
OMIM	609201
Entrez	84959

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 retained_intron, 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000284273

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 2, TSL 4: 3, TSL 5: 1

ENST00000284273, ENST00000525711, ENST00000526386, ENST00000526493, ENST00000529998, ENST00000530578, ENST00000530917, ENST00000533451, ENST00001056511, ENST00001130415

RefSeq mRNA: 2 — MANE Select: NM_032873 NM_001363365, NM_032873

CCDS: CCDS31694

Canonical transcript exons

ENST00000284273 — 14 exons

Exon	Start	End
ENSE00001014157	122794702	122794834
ENSE00001014158	122798942	122799034
ENSE00001014161	122806410	122806516
ENSE00001014162	122801188	122801332
ENSE00001014168	122808067	122808176
ENSE00001014170	122796911	122797033
ENSE00001268639	122655722	122656210
ENSE00001399355	122809749	122814473
ENSE00003479909	122776219	122776272
ENSE00003493787	122783053	122783222
ENSE00003554082	122777024	122777210
ENSE00003560675	122789100	122789308
ENSE00003596886	122779497	122779695
ENSE00003603574	122796156	122796276

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 90.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5217 / max 418.5821, expressed in 1546 samples.

Highest expression (Bgee): pons, cerebellum, cerebellar cortex, cerebellar hemisphere, cerebellar vermis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

UBASH3B is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	3.1e-45	-0.87	11:122654259:A:G
Whole Blood	eqtl	4.0e-19	-0.27	11:122638529:A:G
Adipose Subcutaneous	eqtl	8.9e-11	+0.31	11:122654033:G:A
Esophagus Muscularis	eqtl	2.2e-10	+0.34	11:122649820:G:C
Adipose Visceral Omentum	eqtl	6.1e-09	+0.28	11:122654033:G:A
Cells Cultured fibroblasts	eqtl	1.6e-08	-0.09	11:122633969:A:AG
Thyroid	eqtl	6.1e-08	+0.14	11:122735508:G:C
Breast Mammary Tissue	eqtl	1.1e-07	+0.33	11:122648573:T:G
Colon Sigmoid	eqtl	5.2e-07	+0.48	11:122725489:C:T
Esophagus Gastroesophageal Junction	eqtl	6.9e-07	+0.41	11:122654033:G:A
Uterus	eqtl	7.8e-07	+0.78	11:122654033:G:A
Nerve Tibial	eqtl	1.5e-06	+0.28	11:122656504:G:C
Skin Sun Exposed Lower leg	eqtl	4.0e-04	-0.10	11:122706265:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.2e-03	-0.10	11:122725886:G:A
Heart Atrial Appendage	eqtl	1.2e-03	-0.17	11:122739114:C:G
Heart Left Ventricle	eqtl	6.0e-03	+0.24	11:122629727:C:T
Brain Cortex	eqtl	8.6e-03	+0.14	11:122635300:G:T
Adrenal Gland	eqtl	2.1e-02	+0.19	11:122730911:T:C
Liver	eqtl	2.8e-02	-0.56	11:123613331:A:G
Artery Tibial	eqtl	4.9e-02	+0.10	11:121986044:C:A

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
117237	7.9197	1507
117255	0.3741	168
117240	0.2984	151
117239	0.2897	150
117253	0.2721	85
117238	0.0964	29
117252	0.0941	52
206480	0.0940	25
117251	0.0831	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	90.05	gold quality
cerebellum	UBERON:0002037	87.41	gold quality
cerebellar cortex	UBERON:0002129	87.07	gold quality
cerebellar hemisphere	UBERON:0002245	86.96	gold quality
cerebellar vermis	UBERON:0004720	86.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.91	gold quality
stromal cell of endometrium	CL:0002255	85.55	gold quality
decidua	UBERON:0002450	83.67	gold quality
blood	UBERON:0000178	82.38	gold quality
spleen	UBERON:0002106	82.36	gold quality
monocyte	CL:0000576	82.08	gold quality
leukocyte	CL:0000738	82.05	gold quality
bone marrow cell	CL:0002092	80.97	gold quality
bone marrow	UBERON:0002371	80.50	gold quality
placenta	UBERON:0001987	80.09	gold quality
amniotic fluid	UBERON:0000173	79.57	gold quality
substantia nigra pars compacta	UBERON:0001965	79.08	gold quality
thymus	UBERON:0002370	77.84	gold quality
cardiac muscle of right atrium	UBERON:0003379	77.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.79	gold quality
left ventricle myocardium	UBERON:0006566	77.75	gold quality
islet of Langerhans	UBERON:0000006	77.57	gold quality
buccal mucosa cell	CL:0002336	77.28	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.02	gold quality
cortical plate	UBERON:0005343	76.74	gold quality
granulocyte	CL:0000094	76.19	gold quality
vermiform appendix	UBERON:0001154	75.75	gold quality
dorsal root ganglion	UBERON:0000044	75.44	gold quality
ventricular zone	UBERON:0003053	75.02	gold quality
upper lobe of left lung	UBERON:0008952	74.45	gold quality
kidney epithelium	UBERON:0004819	74.28	gold quality
superficial temporal artery	UBERON:0001614	74.14	silver quality
upper lobe of lung	UBERON:0008948	74.04	gold quality
lung	UBERON:0002048	73.79	gold quality
pancreatic ductal cell	CL:0002079	73.52	silver quality
trabecular bone tissue	UBERON:0002483	73.45	gold quality
substantia nigra pars reticulata	UBERON:0001966	73.11	gold quality
right lung	UBERON:0002167	72.17	gold quality
skin of leg	UBERON:0001511	72.06	gold quality
lymph node	UBERON:0000029	72.03	gold quality
prefrontal cortex	UBERON:0000451	71.57	gold quality
embryo	UBERON:0000922	71.34	gold quality
ganglionic eminence	UBERON:0004023	71.34	gold quality
gingival epithelium	UBERON:0001949	71.13	silver quality
lower lobe of lung	UBERON:0008949	70.30	gold quality
endothelial cell	CL:0000115	69.97	silver quality
zone of skin	UBERON:0000014	69.56	gold quality
caecum	UBERON:0001153	69.25	gold quality
adrenal tissue	UBERON:0018303	69.19	gold quality
superior vestibular nucleus	UBERON:0007227	69.14	gold quality
substantia nigra	UBERON:0002038	68.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.91	gold quality
skin of abdomen	UBERON:0001416	68.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	68.55	gold quality
midbrain	UBERON:0001891	68.26	gold quality
neocortex	UBERON:0001950	68.16	gold quality
smooth muscle tissue	UBERON:0001135	68.09	gold quality
frontal cortex	UBERON:0001870	67.96	gold quality
gall bladder	UBERON:0002110	67.93	gold quality
anterior cingulate cortex	UBERON:0009835	67.91	gold quality
gingiva	UBERON:0001828	67.76	silver quality
tonsil	UBERON:0002372	67.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.49	gold quality
middle temporal gyrus	UBERON:0002771	67.37	silver quality
nasal cavity mucosa	UBERON:0001826	67.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.94	gold quality
sural nerve	UBERON:0015488	66.59	gold quality
palpebral conjunctiva	UBERON:0001812	66.45	gold quality
cerebral cortex	UBERON:0000956	66.44	gold quality
urinary bladder	UBERON:0001255	66.26	gold quality
esophagus squamous epithelium	UBERON:0006920	65.98	silver quality
primary visual cortex	UBERON:0002436	65.91	gold quality
brain	UBERON:0000955	65.87	gold quality
rectum	UBERON:0001052	65.87	gold quality
colonic epithelium	UBERON:0000397	65.68	gold quality
omental fat pad	UBERON:0010414	65.66	gold quality
peritoneum	UBERON:0002358	65.60	gold quality
right frontal lobe	UBERON:0002810	65.42	gold quality
tibialis anterior	UBERON:0001385	65.28	silver quality
secondary oocyte	CL:0000655	65.19	gold quality
adipose tissue of abdominal region	UBERON:0007808	65.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	65.00	gold quality
trigeminal ganglion	UBERON:0001675	64.96	gold quality
superior frontal gyrus	UBERON:0002661	64.90	gold quality
hypothalamus	UBERON:0001898	64.81	gold quality
pancreas	UBERON:0001264	64.39	gold quality
Brodmann (1909) area 23	UBERON:0013554	64.01	silver quality
anatomical system	UBERON:0000467	63.89	gold quality
upper leg skin	UBERON:0004262	63.72	gold quality
small intestine	UBERON:0002108	63.65	gold quality
multicellular organism	UBERON:0000468	63.55	gold quality
material anatomical entity	UBERON:0000465	63.54	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.48	gold quality
postcentral gyrus	UBERON:0002581	63.47	gold quality
endometrium	UBERON:0001295	63.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	63.42	gold quality
esophagus mucosa	UBERON:0002469	63.12	gold quality
metanephros	UBERON:0000081	63.07	gold quality
calcaneal tendon	UBERON:0003701	62.93	gold quality
visceral pleura	UBERON:0002401	62.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-11	yes	174.87
E-ANND-3	yes	5.51

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	44.7	high
Olfactory bulb	tissue	17.5
Pons	tissue	16.7
Cerebral cortex	tissue	15.0	low
Somatosensory cortex	tissue	15.0
Spleen	tissue	14.7	high
Thymus	tissue	14.1
Occipital cortex	tissue	14.0
Placenta	tissue	12.9	high
Motor cortex	tissue	12.6
Hippocampal formation	tissue	12.2
Entorhinal cortex	tissue	11.7
Frontal cortex	tissue	11.5
Retrosplenial and cingulate cortex	tissue	11.5
Temporal cortex	tissue	11.5
Prefrontal cortex	tissue	11.2
Locus coeruleus	tissue	11.0
Amygdala	tissue	10.9
Insular cortex	tissue	10.8
Substantia nigra	tissue	10.6
Retrosplenial cortex	tissue	10.6
Caudate putamen	tissue	10.1
Medulla oblongata	tissue	8.6
Hypothalamus	tissue	8.6
Spinal cord	tissue	7.3
Midbrain	tissue	7.1
Thalamus	tissue	7.0
Periaqueductal gray	tissue	7.0
Septum	tissue	7.0
Ventral forebrain	tissue	6.9
Superior colliculi	tissue	6.8
Putamen	tissue	6.4
Bone marrow	tissue	6.3	low
Basal ganglia	tissue	6.2	medium
Lymph node	tissue	5.4	high
Postcentral gyrus	tissue	5.2
Appendix	tissue	4.5	high
Lung	tissue	4.3	high
Urinary bladder	tissue	4.1	medium
Hippocampus	tissue	3.5	low
Adipose tissue	tissue	3.2	not detected
Tonsil	tissue	3.0	high
Cervix	tissue	2.8	low
Nucleus accumbens	tissue	2.8
Corpus callosum	tissue	2.6
Skin 1	tissue	2.5	medium
Thyroid gland	tissue	2.2	high
Retina	tissue	1.8
Smooth muscle	tissue	1.8	not detected
Gallbladder	tissue	1.8	medium
Small intestine	tissue	1.5	medium
Stomach 1	tissue	1.3	medium
Rectum	tissue	1.3	medium
Duodenum	tissue	1.3	medium
Colon	tissue	1.2	medium
Choroid plexus	tissue	1.2
Liver	tissue	1.2	medium
Breast	tissue	1.1	medium
Testis	tissue	1.1	medium
Endometrium 1	tissue	0.9	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Cerebellar cortex (32.3), Vermis (28.7), Flocculonodular lobe (25.0), Nucleus raphe magnus (22.2), Pontine nuclei (21.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting UBASH3B by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 208 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420

Functional genomics

gnomAD constraint: pLI 0.0185, LOEUF 0.58, missense Z 2.24 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000284273 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:122,656,050–122,656,199	78 / 68.4	1.14	no
11:122,656,200–122,776,249	6 / 19.9	0.30	yes (p 1.8e-03)
11:122,776,250–122,809,883	573 / 739.0	0.78	no

Literature-anchored findings (GeneRIF, showing 19)

• Sts-1 and Sts-2 bind to Cbl and inhibit endocytosis of receptor tyrosine kinases (PMID:15159412)
• hsp70 inhibits apoptosis upstream and downstream of the mitochondria and is a promising therapeutic target for reversing drug-resistance in chronic myeloid leukemia-blast crisis and acute myeloid leukemia cells. (PMID:15388581)
• TULA proteins TULA and TULA-2 regulate activity of the protein tyrosine kinase Syk (PMID:18189269)
• Ablation of TULA-2 resulted in hyperphosphorylation of Syk and its downstream effector phospholipase C-gamma2 as well as enhanced GPVI-mediated platelet functional responses. (PMID:20585042)
• UBASH3B is a functional target of anti-invasive microRNA200a that is down-regulated in triple negative breast cancer. Importantly, the oncogenic potential of UBASH3B is dependent on its tyrosine phosphatase activity. (PMID:23784775)
• Data suggest that Sts1 (suppressor of T-cell receptor signaling-1) negatively regulates TCR (T-cell receptor) signaling in activated T-lymphocytes via dephosphorylation of ZAP70. (PMID:24256567)
• This recovery involves the phosphorylation of p70 independent of mTOR. (PMID:25271148)
• results demonstrate the importance of STS-1 in regulating IFN-alpha-induced autophagy in B cells (PMID:25959715)
• The study reveals a role of CBL in restricting myeloid proliferation of human AML1-ETOinduced leukemia, and identifies UBASH3B as a potential target for pharmaceutical intervention. (PMID:26449661)
• These results show that TULA-2 is a target of miR-148a-3p (PMID:26516227)
• targeting Aurora B to microtubules by UBASH3B is necessary for the timing and fidelity of chromosome segregation in human cells (PMID:26766443)
• The results show that the interaction between STS-1 and ShcA is regulated in response to EGF receptor activation. (PMID:28690151)
• UBASH3A/STS-2/TULA exhibits substantial homology to UBASH3B/STS-1/TULA-2, but possesses only a small fraction of phosphatase activity of UBASH3B/STS-1/TULA-2, and thus, its regulatory effect may be based also on the phosphatase-independent mechanisms. Critical physiologic effects of these proteins have been demonstrated in T lymphocytes, platelets, stem cells, and other important cell types. (PMID:30076707)
• the UBASH3B gene rs4936742 (T > C) polymorphism is associated with an increased risk of Behcet’s disease, especially non-ocular BD, in Iranian population. We could not find any susceptibility role of this genetic locus for posterior uveitis in Behcet’s disease. (PMID:30289285)
• Sts-1 is a negative regulator. (PMID:30962580)
• These studies help define a critical role of Ubash3b in leukemia (PMID:31399640)
• An unexpected 2-histidine phosphoesterase activity of suppressor of T-cell receptor signaling protein 1 contributes to the suppression of cell signaling. (PMID:32371395)
• Ubash3b promotes TPA-mediated suppression of leukemogenesis through accelerated downregulation of PKCdelta protein. (PMID:33556471)
• FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression. (PMID:38461240)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubash3ba	ENSDARG00000061243
danio_rerio	ubash3bb	ENSDARG00000077399
mus_musculus	Ubash3b	ENSMUSG00000032020
rattus_norvegicus	Ubash3b	ENSRNOG00000008187
drosophila_melanogaster	Epp	FBGN0039137
caenorhabditis_elegans		WBGENE00020321

Paralogs (1): UBASH3A (ENSG00000160185)

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
Bos taurus	Q32KW2	91.9%	Diamond
Xenopus laevis	Q6GLV4	87.8%	Diamond
Xenopus tropicalis	Q6GL77	87.6%	Diamond
Schizosaccharomyces pombe 972h-	Q11119	53.7%	Diamond
Dictyostelium discoideum	P54201	51.2%	Diamond
Bombyx mori	Q7YTB0	50.0%	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
BSX	protein-coding	390259
CRTAM	protein-coding	56253
JHY	protein-coding	79864
TRK-TTT2-1	tRNA	100189294

Protein

Protein identifiers

Ubiquitin-associated and SH3 domain-containing protein B — Q8TF42 (reviewed: Q8TF42)

Alternative names: Cbl-interacting protein p70, Suppressor of T-cell receptor signaling 1, T-cell ubiquitin ligand 2, Tyrosine-protein phosphatase STS1/TULA2

All UniProt accessions (1): Q8TF42

UniProt curated annotations — full annotation on UniProt →

Function. Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. Exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP70. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination.

Subunit / interactions. Homodimer. Interacts with JAK2 (in vitro). Interacts with CBL. Part of a complex containing CBL and activated EGFR. Interacts with ubiquitin and with mono-ubiquitinated proteins. Interacts with ZAP70 (ubiquitinated form).

Subcellular location. Cytoplasm. Nucleus.

RefSeq proteins (2): NP_001350294, NP_116262* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR013078	His_Pase_superF_clade-1	Family
IPR015940	UBA	Domain
IPR029033	His_PPase_superfam	Homologous_superfamily
IPR035632	UBASH3B_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR051710	Phosphatase_SH3-domain	Family

Pfam: PF00300, PF14604, PF22562

Catalyzed reactions (Rhea)

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (57 total): helix 23, strand 16, turn 6, active site 3, domain 2, sequence variant 2, modified residue 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
5VR6	Structure of Human Sts-1 histidine phosphatase domain with sulfate bound	X-RAY DIFFRACTION	1.87
8U5M	Structure of Sts-1 HP domain with rebamipide	X-RAY DIFFRACTION	2.46
5W5G	Structure of Human Sts-1 histidine phosphatase domain	X-RAY DIFFRACTION	2.48
8U7E	Structure of Sts-1 HP domain with rebamipide derivative	X-RAY DIFFRACTION	2.63
2CPW	Solution structure of RSGI RUH-031, a UBA domain from human cDNA	SOLUTION NMR
2E5K	Solution structure of SH3 domain in Suppressor of T-cell receptor signaling 1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF42-F1	85.15	0.71

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nuclear bodies; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

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

Catalytic / active sites (3)

Position	Role
390
391	tele-phosphohistidine intermediate
576

Post-translational modifications (2)

Type	Positions
Phosphoserine	20
Phosphothreonine	23

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 327 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, GOBP_NEGATIVE_REGULATION_OF_PLATELET_ACTIVATION, GOBP_PLATELET_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_MONOATOMIC_CATION_TRANSPORT, PAX2_01, GOBP_NEGATIVE_REGULATION_OF_COAGULATION, GOBP_WOUND_HEALING, GOBP_CELL_CELL_ADHESION

GO Biological Process (6): negative regulation of signal transduction (GO:0009968), collagen-activated tyrosine kinase receptor signaling pathway (GO:0038063), regulation of osteoclast differentiation (GO:0045670), negative regulation of bone resorption (GO:0045779), regulation of release of sequestered calcium ion into cytosol (GO:0051279), platelet aggregation (GO:0070527)

GO Molecular Function (7): protein tyrosine phosphatase activity (GO:0004725), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), phosphoprotein binding (GO:0051219), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

26 GO namespaces:

Category	Terms
protein binding	2
signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
cell surface receptor protein tyrosine kinase signaling pathway	1
collagen-activated signaling pathway	1
regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of bone resorption	1
bone resorption	1
negative regulation of bone remodeling	1
release of sequestered calcium ion into cytosol	1
regulation of calcium ion transmembrane transport	1
platelet activation	1
homotypic cell-cell adhesion	1
phosphoprotein phosphatase activity	1
ubiquitin-like protein ligase binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 18 of 1,084 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBASH3B	LCP2	Q13094	804
UBASH3B	PGAM4	Q8N0Y7	782
UBASH3B	PGAM1	P18669	780
UBASH3B	ZAP70	P43403	774
UBASH3B	EGFR	P00533	561
UBASH3B	CCDC180	Q9P1Z9	465
UBASH3B	TBC1D9	Q6ZT07	445
UBASH3B	UBAC2	Q8NBM4	441
UBASH3B	CBL	P22681	429
UBASH3B	SYK	P43405	420
UBASH3B	JAK2	O60674	389
UBASH3B	DOLPP1	Q86YN1	389
UBASH3B	SLC17A7	Q9P2U7	370
UBASH3B	SLC8A2	Q9UPR5	370
UBASH3B	KCNH3	Q9ULD8	370
UBASH3B	ITPKA	P23677	370
UBASH3B	EPHB6	O15197	370
UBASH3B	KCNAB3	O43448	370

IntAct

Human interaction partners of UBASH3B in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 42 partners by confidence:

Partner	Interaction type	MIscore	Records
DOC2A	physical association	0.800	4
CBLB	physical association	0.780	6
RCHY1	physical association	0.780	6
DAZAP2	physical association	0.720	6
VPS37B	physical association	0.720	6
EGFR	association	0.690	2
FAM168A	physical association	0.670	4
FAM209A	physical association	0.590	2
KPRP	physical association	0.560	5
BBC3	physical association	0.560	3
CCDC74B	physical association	0.560	3
DISC1	physical association	0.560	3
DLGAP2	physical association	0.560	3
DMRT3	physical association	0.560	3
DTX3	physical association	0.560	3
EFS	physical association	0.560	3
HOXB2	physical association	0.560	3
INCA1	physical association	0.560	3
KAT5	physical association	0.560	3
KDM1A	physical association	0.560	3
LMO2	physical association	0.560	3
LZTS2	physical association	0.560	3
PIAS2	physical association	0.560	3
PRR35	physical association	0.560	3
PSMB1	physical association	0.560	3
PTPN21	physical association	0.560	3
REL	physical association	0.560	3
RNF216	physical association	0.560	3
SLC25A48	physical association	0.560	3
SPRY2	physical association	0.560	3

BioGRID (254 interactions; top human partners by supporting records): EGFR (Affinity Capture-Western; 10 records), CBL (Negative Genetic; 7 records), UBC (Reconstituted Complex; 7 records), DOC2A (Affinity Capture-MS; 5 records), SYK (Affinity Capture-MS; 5 records), AURKB (Affinity Capture-Western; 4 records), RCHY1 (Two-hybrid; 4 records), ABL1 (Affinity Capture-MS; 3 records), FAM209A (Affinity Capture-MS; 3 records), GRB2 (Affinity Capture-MS; 3 records), SHC1 (Affinity Capture-MS; 3 records), ACTB (Affinity Capture-MS; 2 records), CBLB (Two-hybrid; 2 records), CCDC33 (Affinity Capture-MS; 2 records), CRK (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
UBASH3B	down-regulates	CBL	binding

Ligand–receptor pairs (CellPhoneDB) (3)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

3 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
PPARA	ligand	Signaling by Dehydroepiandrosterone
NR1I2	ligand	Signaling by Dehydroepiandrosterone
ESR1	ligand	Signaling by Dehydroepiandrosterone

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 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
Activation of NF-kappaB in B cells	5	37.9×	7e-05
CLEC7A (Dectin-1) signaling	5	27.4×	2e-04
Antigen processing: Ubiquitination & Proteasome degradation	5	7.2×	7e-03

Disease & clinical

Genetic variants

Variant evidence for UBASH3B: 89 ClinVar records (0 pathogenic / likely pathogenic); 25 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	5
Benign	5

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 1,300):

Position(s)	Effect	Δscore	Sites
11:122777023	acceptor_loss	1.0000	2
11:122777156	donor_gain	1.0000
11:122777211–122777212	donor_loss	1.0000	4
11:122783051–122783052	acceptor_loss	1.0000	6
11:122783163	donor_gain	1.0000
11:122789098–122789099	acceptor_loss	1.0000	6
11:122796154–122796155	acceptor_loss	1.0000	6
11:122796242	donor_gain	1.0000
11:122796277–122796278	donor_loss	1.0000	4
11:122796909–122796910	acceptor_loss	1.0000	5

AlphaMissense

1,955 missense substitutions predicted likely pathogenic (of 4,251 scored), across 447 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
M47	9	0.905	0.996
M421	9	0.893	0.993
H212	8	0.999	1.000
H576	8	0.999	1.000
H126	8	0.998	1.000
H391	8	0.998	0.999
F176	8	0.996	1.000
D396	8	0.996	0.999
N118	8	0.994	0.999
H76	8	0.993	1.000
D79	8	0.993	0.998
H121	8	0.993	0.998
D438	8	0.993	0.999
D250	8	0.992	0.999
F49	8	0.990	1.000
F133	8	0.989	0.999
F172	8	0.984	1.000
N420	8	0.984	1.000
F132	8	0.979	1.000
F219	8	0.977	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000144

Disease associations

OMIM: gene MIM:609201 | disease phenotypes:

GWAS associations

25 associations:

Study	Trait	p-value
GCST010242_34	HDL cholesterol levels	7e-39
GCST010241_28	Apolipoprotein A1 levels	1e-24
GCST004235_45	Total cholesterol levels	5e-15
GCST006627_7	Diastolic blood pressure	6e-15
GCST002223_66	HDL cholesterol	1e-14
GCST002221_19	Cholesterol, total	2e-14
GCST010204_18	Low density lipoprotein cholesterol levels	3e-13
GCST006585_885	Blood protein levels	1e-11
GCST007267_213	Systolic blood pressure	1e-11
GCST90011899_129	Aspartate aminotransferase levels	1e-11
GCST007576_309	Chronotype	2e-11
GCST90013406_32	Liver enzyme levels (alkaline phosphatase)	8e-11
GCST000760_47	Cholesterol, total	2e-10
GCST010245_57	LDL cholesterol levels	7e-10
GCST90002386_216	High light scatter reticulocyte percentage of red cells	1e-9
GCST002896_38	Cholesterol, total	4e-9
GCST010146_14	Serum immune biomarker levels	6e-9
GCST011348_60	High density lipoprotein cholesterol levels	7e-9
GCST006503_1	Eye length	8e-9
GCST000755_17	HDL cholesterol	3e-8
GCST006584_2	Pemphigus vulgaris	3e-8
GCST008062_40	Blood urea nitrogen levels	3e-8
GCST002987_21	Stroke	9e-7
GCST010397_103	Gut microbiota (bacterial taxa, rank normal transformation method)	5e-6
GCST007124_6	Multiple sclerosis and HDL levels (pleiotropy)	8e-6

EFO canonical traits (from GWAS)

12 canonical traits:

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0004458	C-reactive protein measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0007874	gut microbiome measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725045 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,790 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1697771	REBAMIPIDE	3	3,790

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM
Rebamipide	IC50	3000 nM

ChEMBL bioactivities

7 potent at pChembl≥5 of 7 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.24	Kd	578	nM	CHEMBL5653589
5.93	ED50	1172	nM	CHEMBL5653589
5.70	Ki	2000	nM	REBAMIPIDE
5.52	IC50	3000	nM	REBAMIPIDE
5.43	IC50	3700	nM	REBAMIPIDE

PubChem BioAssay actives

6 with measured affinity, of 35 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149706: Binding affinity to human UBASH3B incubated for 45 mins by Kinobead based pull down assay	kd	0.5780	uM
2-[(4-chlorobenzoyl)amino]-3-(2-oxo-1H-quinolin-4-yl)propanoic acid	2099342: Competitive inhibition of human STS-1 HP domain (369 to 636 residues) phosphatase activity expressed in Escherichia coli BL21 (DE3) using pNPP as substrate assessed as inhibition constant preincubated for 20 mins followed by substrate addition by Lineweaver-Burk plot analysis	ki	2.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	9
Benzo(a)pyrene	increases expression, increases methylation	5
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Air Pollutants	increases expression, increases abundance	3
Aflatoxin B1	affects expression, increases expression	3
entinostat	affects cotreatment, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Doxorubicin	increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	increases abundance, increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
lead acetate	increases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
trichostatin A	increases expression	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cupric chloride	increases expression	1
1-nitropyrene	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5541097	Binding	Inhibition of human STS-1 HP domain (369 to 636 residues) phosphatase activity expressed in Escherichia coli BL21 (DE3) using pNPP as substrate preincubated for 20 mins followed by substrate addition by absorbance based spectrophotometric a	Rebamipide and Derivatives are Potent, Selective Inhibitors of Histidine Phosphatase Activity of the Suppressor of T Cell Receptor Signaling Proteins. — *J Med Chem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for UBASH3B across ~30M SureChEMBL compounds — explore on Sugi Predict.