AJUBA

Summary

AJUBA (ajuba LIM protein, HGNC:20250) is a protein-coding gene on chromosome 14q11.2, encoding LIM domain-containing protein ajuba (Q96IF1). Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiat….

Enables alpha-catenin binding activity and transcription corepressor activity. Involved in several processes, including miRNA-mediated gene silencing by inhibition of translation; negative regulation of hippo signaling; and regulation of cellular response to hypoxia. Acts upstream of or within miRNA-mediated post-transcriptional gene silencing and positive regulation of protein-containing complex assembly. Located in several cellular components, including Golgi apparatus; P-body; and nucleoplasm.

Source: NCBI Gene 84962 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 72 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_032876

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20250
Approved symbol	AJUBA
Name	ajuba LIM protein
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC15563
Ensembl gene	ENSG00000129474
Ensembl biotype	protein_coding
OMIM	609066
Entrez	84962

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000262713, ENST00000397388, ENST00000553592, ENST00000553736, ENST00000553911, ENST00000555479, ENST00000556731, ENST00000921862

RefSeq mRNA: 3 — MANE Select: NM_032876 NM_001289097, NM_032876, NM_198086

CCDS: CCDS9581, CCDS9582

Canonical transcript exons

ENST00000262713 — 8 exons

Exon	Start	End
ENSE00000889186	22974839	22974890
ENSE00001323590	22971177	22973568
ENSE00001794620	22978344	22978445
ENSE00002284099	22981261	22982551
ENSE00003470923	22976645	22976712
ENSE00003482706	22974974	22975104
ENSE00003522791	22976456	22976518
ENSE00003788388	22974047	22974115

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 97.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8727 / max 280.7085, expressed in 1386 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142283	5.9888	1149
142284	2.7938	989
142285	2.2081	959
142282	1.9070	752
142286	1.1289	706
142287	0.6374	390
142280	0.4358	222
142278	0.3266	69
142279	0.2142	95
142281	0.1805	99

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	97.40	gold quality
upper arm skin	UBERON:0004263	96.23	gold quality
ventricular zone	UBERON:0003053	95.84	gold quality
esophagus squamous epithelium	UBERON:0006920	95.53	gold quality
gingival epithelium	UBERON:0001949	95.43	gold quality
gingiva	UBERON:0001828	94.32	gold quality
upper leg skin	UBERON:0004262	92.99	gold quality
zone of skin	UBERON:0000014	91.54	gold quality
skin of leg	UBERON:0001511	91.49	gold quality
skin of abdomen	UBERON:0001416	91.02	gold quality
amniotic fluid	UBERON:0000173	90.85	gold quality
lower esophagus mucosa	UBERON:0035834	90.69	gold quality
metanephros cortex	UBERON:0010533	90.64	gold quality
kidney epithelium	UBERON:0004819	90.37	gold quality
skin of hip	UBERON:0001554	90.20	gold quality
stromal cell of endometrium	CL:0002255	89.69	gold quality
esophagus mucosa	UBERON:0002469	88.17	gold quality
metanephros	UBERON:0000081	88.13	gold quality
visceral pleura	UBERON:0002401	88.02	gold quality
seminal vesicle	UBERON:0000998	87.76	gold quality
ectocervix	UBERON:0012249	87.76	gold quality
lower lobe of lung	UBERON:0008949	87.71	gold quality
mammalian vulva	UBERON:0000997	87.57	gold quality
penis	UBERON:0000989	87.46	gold quality
vagina	UBERON:0000996	87.30	gold quality
parietal pleura	UBERON:0002400	86.37	gold quality
kidney	UBERON:0002113	86.33	gold quality
liver	UBERON:0002107	86.32	gold quality
placenta	UBERON:0001987	86.21	gold quality
body of uterus	UBERON:0009853	85.75	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.11
E-MTAB-6386	no	14.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting AJUBA, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-4303	98.01	68.13	2304

Literature-anchored findings (GeneRIF, showing 33)

• Ajuba contributes to the bridging of the cadherin adhesive complexes to the actin cytoskeleton and as such contribute to the formation or strengthening of cadherin-mediated cell-cell adhesion. (PMID:12417594)
• in addition to its effects upon Rac activity, Ajuba can also influence cell migration through regulation of PI(4,5)P2 synthesis through direct activation of PIPKIalpha enzyme activity (PMID:15870270)
• Ajuba is a new cytosolic component of the IL-1 signaling pathway modulating IL-1-induced NF-kappaB activation by influencing the assembly and activity of the aPKC/p62/TRAF6 multiprotein signaling complex (PMID:15870274)
• Ajuba promoted GSK-3beta-mediated phosphorylation of beta-catenin by reinforcing the association between beta-catenin and GSK-3beta. (PMID:17621269)
• Ajuba is a microtubule-associated protein that collaborates with Aurora B and BUBR1 at the metaphase-anaphase transition and this may be important to ensure proper chromosome segregation. (PMID:18710370)
• Ajuba is utilized as a corepressor selectively on Gfi1 target genes (PMID:18805794)
• Ajuba contains functional nuclear-receptor interacting motifs and selectively interacts with retinoic acid receptors and rexinoid receptor subtypes. (PMID:20133701)
• A Rac-PAK1-Ajuba feedback loop integrates spatiotemporal signaling with actin remodeling at cell-cell contacts and stabilizes preassembled cadherin complexes. (PMID:22105346)
• AJUBA negatively regulates YAP activity through the LATS family, and inactivation of AJUBA is a novel key mechanism in malignant mesothelioma cell proliferation (PMID:24336325)
• the LIM protein JUB serves as a tumor-promoting gene in colorectal cancer by promoting epithelial-mesenchymal transition, a critical process of metastasis. (PMID:24673742)
• The LIM domain of Ajuba can competitively bind to the N-terminal of Aurora-A, and inhibited the interaction between N-terminal and C-terminal of Aurora A. (PMID:24680704)
• The results in this study uncovered that JUB was a regulator involved in proliferation of glioma cells, and it could be used as a potential therapeutic target for glioma. (PMID:26406867)
• Data show that AJUBA upregulated MMP10 and MMP13 expression in esophageal squamous cell carcinoma (ESCC). (PMID:27172796)
• mitotic phosphorylation of Ajuba is sufficient to promote cell proliferation and anchorage-independent growth in vitro and tumorigenesis in vivo (PMID:27226586)
• Mechanistic investigations reveal that AJUBA specifically binds the FERM domain of JAK1 to dissociate JAK1 from the IFNgamma recepter, resulting in an inhibition of STAT1 phosporylation and concomitantly its nuclear translocation. Clinically, the level of AJUBA in CRC specimens is negatively correlated with the levels of IFIT2 and pSTAT1 (PMID:27893714)
• Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinomas to treatment with PLK1 inhibitors. (PMID:28126323)
• AJUBA is a LIM domain protein and contributes to the formation and stability of cadherin-mediated cell-cell adhesion. Loss of AJUBA enhances Prostate cancer cell migration and downregulation of AJUBA expression is observed in metastatic Prostate cancer. (PMID:28422308)
• we unveil a unique participation of Ajuba in maintaining CdGAP in an inactivated status to modulate Rac1 activity and stabilize junctions. (PMID:28835688)
• High AJUBA level enhances cervical cancer cells. (PMID:29126926)
• We show that all three mammalian Ajuba family proteins - AJUBA, LIMD1 and WTIP - exhibit tension-dependent localization to adherens junctions, and that both LATS family proteins, LATS1 and LATS2, exhibit an overlapping tension-dependent junctional localization (PMID:29440237)
• LIM Protein Ajuba associates with the RPA complex through direct cell cycle-dependent interaction with the RPA70 subunit (PMID:29934626)
• It is an oncogene in CRC oncogenesis and development. (PMID:30395690)
• data demonstrate that Ajuba functions as a novel co-activator of ERalpha and that Ajuba/DBC1/CBP/p300 ternary complex may be a new target for developing therapeutics to treat breast cancer (PMID:30597111)
• Ajuba functions as a co-activator of SP1 to induce its target gene, and that Ajuba itself is a target genes of SP1. Ajuba/SP1 complex could form a feed forward loop to drive SP1 target gene transcription and promote cell proliferation of pancreatic cancer cells. (PMID:31101117)
• Ajuba: An emerging signal transducer in oncogenesis. (PMID:31740385)
• Hsa_circ_0128846 promotes tumorigenesis of colorectal cancer by sponging hsa-miR-1184 and releasing AJUBA and inactivating Hippo/YAP signalling. (PMID:32681581)
• Super-enhancer-driven AJUBA is activated by TCF4 and involved in epithelial-mesenchymal transition in the progression of Hepatocellular Carcinoma. (PMID:32802179)
• Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells. (PMID:33640888)
• Ajuba transactivates N-cadherin expression in colorectal cancer cells through interaction with Twist. (PMID:34173718)
• miR-433-3p Targets AJUBA to Inhibit Malignant Progression of Glioma. (PMID:34518486)
• Mitophagy antagonism by ZIKV reveals Ajuba as a regulator of PINK1 signaling, PKR-dependent inflammation, and viral invasion of tissues. (PMID:34706234)
• Ajuba Overexpression Promotes Breast Cancer Chemoresistance and Glucose Uptake through TAZ-GLUT3/Survivin Pathway. (PMID:35178446)
• LIM domain-containing protein Ajuba inhibits chemotherapy-induced apoptosis by negatively regulating p53 stability in colorectal cancer cells. (PMID:36931700)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ajuba	ENSDARG00000077842
mus_musculus	Ajuba	ENSMUSG00000022178
rattus_norvegicus	Ajuba	ENSRNOG00000012791

Paralogs (2): WTIP (ENSG00000142279), LIMD1 (ENSG00000144791)

Protein

Protein identifiers

LIM domain-containing protein ajuba — Q96IF1 (reviewed: Q96IF1)

All UniProt accessions (4): Q96IF1, G3V481, G3V5F5, H0YJL9

UniProt curated annotations — full annotation on UniProt →

Function. Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration. Contributes to the linking and/or strengthening of epithelia cell-cell junctions in part by linking adhesive receptors to the actin cytoskeleton. May be involved in signal transduction from cell adhesion sites to the nucleus. Plays an important role in regulation of the kinase activity of AURKA for mitotic commitment. Also a component of the IL-1 signaling pathway modulating IL-1-induced NFKB1 activation by influencing the assembly and activity of the PRKCZ-SQSTM1-TRAF6 multiprotein signaling complex. Functions as an HDAC-dependent corepressor for a subset of GFI1 target genes. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1.

Subunit / interactions. Interacts with GRB2, PIP5K1B and SLC1A2. Interacts with AURKA; the interaction occurs during mitosis and both proteins are phosphorylated as they form a complex. Interacts with CTNNA1 and with F-actin. Interacts with LATS2; the interaction occurs during mitosis and the complex regulates organization of the spindle apparatus through recruitment of TUBG to the centrosome. Forms a complex with SQSTM1, PRKCZ and TRAF6. Component of the GFI1-AJUBA-HDAC1 repressor complex. Interacts directly (via the LIM domains) with GFI1; the interaction results in the HDAC-dependent corepression of a subset of GFI1 target genes, and is independent of the GFI1 SNAG domain. Interacts with HDAC1, HDAC2 and HDAC3. Interacts with SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain). Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1, LATS2, SAV1, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM domains) with isoform 1 and isoform 3 of VHL. Interacts (via LIM domains) with SNAI1 (via SNAG domain).

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane. Cell junction. Nucleus. Microtubule organizing center. Centrosome. P-body.

Post-translational modifications. Phosphorylated by LATS2 during mitosis. Phosphorylated by AURKA.

Domain organisation. LIM region interacts with CTNNA1. The preLIM region binds directly actin filaments. LIM-2 and LIM-3 domains mediate the interaction with the N-terminal region of AURKA. The association between LATS2 and AJUBA required the second LIM domain of AJUBA.

Miscellaneous. ‘Ajuba’ means ‘curiosity’ in Urdu, an Indian dialect.

Similarity. Belongs to the zyxin/ajuba family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96IF1-1	1	yes
Q96IF1-2	2

RefSeq proteins (3): NP_001276026, NP_116265, NP_932352 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR047172	Ajuba-like	Family
IPR047245	Ajuba-like_LIM1	Domain
IPR047247	Ajuba-like_LIM2	Domain
IPR047248	Ajuba-like_LIM3	Domain

Pfam: PF00412

UniProt features (17 total): modified residue 5, domain 3, compositionally biased region 3, region of interest 3, chain 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IF1-F1	58.01	0.03

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 (5): 79, 119, 133, 175, 263

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-1234174	Cellular response to hypoxia
R-HSA-1266738	Developmental Biology
R-HSA-1640170	Cell Cycle
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-2262752	Cellular responses to stress
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5619507	Activation of HOX genes during differentiation
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 322 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, AHRARNT_01, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, AREB6_03, GOZGIT_ESR1_TARGETS_DN, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_HIPPO_SIGNALING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03

GO Biological Process (20): negative regulation of transcription by RNA polymerase II (GO:0000122), response to hypoxia (GO:0001666), regulation of DNA-templated transcription (GO:0006355), cytoskeleton organization (GO:0007010), intracellular protein localization (GO:0008104), positive regulation of biosynthetic process (GO:0009891), calcium-dependent cell-cell adhesion (GO:0016339), lamellipodium assembly (GO:0030032), regulation of cell migration (GO:0030334), positive regulation of protein-containing complex assembly (GO:0031334), miRNA-mediated post-transcriptional gene silencing (GO:0035195), miRNA-mediated gene silencing by inhibition of translation (GO:0035278), wound healing, spreading of epidermal cells (GO:0035313), negative regulation of hippo signaling (GO:0035331), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), glycerophospholipid biosynthetic process (GO:0046474), focal adhesion assembly (GO:0048041), regulation of cellular response to hypoxia (GO:1900037), cell adhesion (GO:0007155), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (7): chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), protein kinase activator activity (GO:0030295), alpha-catenin binding (GO:0045294), metal ion binding (GO:0046872), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (16): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), focal adhesion (GO:0005925), lamellipodium (GO:0030027), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cellular response to hypoxia	1
G2/M Transition	1
Activation of HOX genes during differentiation	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Cellular responses to stress	1
Gene expression (Transcription)	1
Cellular responses to stimuli	1
Cell Cycle, Mitotic	1
Developmental Biology	1
Mitotic G2-G2/M phases	1
Cell Cycle	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of DNA-templated transcription	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
response to stress	1
response to decreased oxygen levels	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
organelle organization	1
macromolecule localization	1
biosynthetic process	1
regulation of biosynthetic process	1
positive regulation of metabolic process	1
cell-cell adhesion	1
lamellipodium organization	1
plasma membrane bounded cell projection assembly	1
cell migration	1
regulation of cell motility	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
regulatory ncRNA-mediated post-transcriptional gene silencing	1
negative regulation of translation	1
miRNA-mediated post-transcriptional gene silencing	1
wound healing, spreading of cells	1
hippo signaling	1
regulation of hippo signaling	1
negative regulation of intracellular signal transduction	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
glycerophospholipid metabolic process	1
phospholipid biosynthetic process	1
glycerolipid biosynthetic process	1
cell-substrate junction assembly	1

Protein interactions and networks

STRING

822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AJUBA	RPH3AL	Q9UNE2	737
AJUBA	BORA	Q6PGQ7	660
AJUBA	AURKA	O14965	617
AJUBA	LATS1	O95835	580
AJUBA	RPH3A	Q9Y2J0	567
AJUBA	NEDD9	Q14511	541
AJUBA	PDLIM2	Q96JY6	525
AJUBA	HDAC6	Q9UBN7	490
AJUBA	CDH1	P12830	470
AJUBA	TPX2	Q9ULW0	457
AJUBA	NDEL1	Q9GZM8	453
AJUBA	PLK1	P53350	445
AJUBA	RAB3A	P20336	441
AJUBA	MAP2K7	O14733	429
AJUBA	LIN28A	Q9H9Z2	426

IntAct

87 interactions, top by confidence:

A	B	Type	Score
AJUBA	LATS2	psi-mi:“MI:0915”(physical association)	0.710
LATS2	AJUBA	psi-mi:“MI:0915”(physical association)	0.710
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.690
AJUBA	TSG101	psi-mi:“MI:0915”(physical association)	0.680
TSG101	AJUBA	psi-mi:“MI:0407”(direct interaction)	0.680
SNAI1	HDAC1	psi-mi:“MI:0914”(association)	0.640
ZNF576	ZBED1	psi-mi:“MI:0914”(association)	0.640
PPP2R3A	WTIP	psi-mi:“MI:0914”(association)	0.640
SNAI1	AJUBA	psi-mi:“MI:0915”(physical association)	0.560
CATSPER1	AJUBA	psi-mi:“MI:0915”(physical association)	0.560
TFAP4	AJUBA	psi-mi:“MI:0915”(physical association)	0.560
AJUBA	ZNF512B	psi-mi:“MI:0915”(physical association)	0.560
LGALS14	AJUBA	psi-mi:“MI:0915”(physical association)	0.560
AJUBA	ZNF541	psi-mi:“MI:0915”(physical association)	0.560
CREB5	AJUBA	psi-mi:“MI:0915”(physical association)	0.560
FARS2	AJUBA	psi-mi:“MI:0915”(physical association)	0.560
PIN1	AJUBA	psi-mi:“MI:0915”(physical association)	0.560
AJUBA	TEKT3	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	WTIP	psi-mi:“MI:0914”(association)	0.530
SFN	AJUBA	psi-mi:“MI:0915”(physical association)	0.520
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (121): AJUBA (Affinity Capture-MS), AJUBA (Affinity Capture-Western), AJUBA (Affinity Capture-Western), AJUBA (Affinity Capture-Western), AJUBA (Affinity Capture-MS), AJUBA (Affinity Capture-Western), AJUBA (Affinity Capture-MS), AJUBA (Affinity Capture-MS), AJUBA (Affinity Capture-MS), AJUBA (Affinity Capture-MS), AJUBA (Affinity Capture-MS), AJUBA (Affinity Capture-MS), AJUBA (Affinity Capture-Western), RNF146 (Affinity Capture-Western), AJUBA (Affinity Capture-Luminescence)

ESM2 similar proteins: A2A288, A2A699, A2AEV7, A2ARS0, A5PKW4, A6NIX2, A8MVW0, B2RXF5, C9JTQ0, D3ZG83, E1BKA3, F1MUS9, O09039, O14559, O43900, O75427, P98077, Q02779, Q16584, Q18PE0, Q1JQB5, Q2M3V2, Q3U0S6, Q53LP3, Q5BJT1, Q5U2Z2, Q5U651, Q66HA1, Q66L42, Q6NY19, Q6ZUM4, Q7TQJ8, Q80VL3, Q80VM4, Q80XI6, Q8BLS7, Q8NCA9, Q91XC0, Q96FS4, Q96HB5

Diamond homologs: A1ZA47, A2ALU4, A5H447, D4A702, E1BKA3, O00151, O14639, O43294, O60711, O70209, O70400, O75112, O94929, P20271, P48059, P49023, P49024, P50464, P52944, Q09476, Q0WSN2, Q13796, Q15942, Q1JQB5, Q2KJ33, Q2TCH4, Q2YDK0, Q3MHZ4, Q3SX26, Q3SX40, Q3SYZ8, Q3T0X8, Q3TJD7, Q55BI0, Q5F464, Q5R7I1, Q5RCF7, Q5TD97, Q5U2Z2, Q5XI07

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PAK1	“up-regulates activity”	AJUBA	phosphorylation

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
FOXO-mediated transcription	5	41.0×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein dephosphorylation	5	20.5×	3e-03
negative regulation of canonical Wnt signaling pathway	5	10.9×	9e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — HNSC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1102 predictions. Top by Δscore:

Variant	Effect	Δscore
14:22974042:CTCA:C	donor_loss	1.0000
14:22974043:TCAC:T	donor_loss	1.0000
14:22974044:CAC:C	donor_loss	1.0000
14:22974045:A:C	donor_loss	1.0000
14:22974111:CAGCC:C	acceptor_gain	1.0000
14:22974888:TTT:T	acceptor_gain	1.0000
14:22974889:TT:T	acceptor_gain	1.0000
14:22974891:C:CC	acceptor_gain	1.0000
14:22974972:A:AC	donor_gain	1.0000
14:22974973:C:CC	donor_gain	1.0000
14:22975111:CA:C	acceptor_gain	1.0000
14:22976516:AAAC:A	acceptor_loss	1.0000
14:22976519:C:CC	acceptor_gain	1.0000
14:22974039:ACACT:A	donor_loss	0.9900
14:22974040:CACTC:C	donor_loss	0.9900
14:22974041:ACTC:A	donor_loss	0.9900
14:22974041:ACTCA:A	donor_loss	0.9900
14:22974044:CA:C	donor_loss	0.9900
14:22974046:C:A	donor_loss	0.9900
14:22974114:CC:C	acceptor_gain	0.9900
14:22974115:CC:C	acceptor_gain	0.9900
14:22974116:C:A	acceptor_loss	0.9900
14:22974116:C:CC	acceptor_gain	0.9900
14:22974117:T:C	acceptor_loss	0.9900
14:22974117:T:G	acceptor_loss	0.9900
14:22974122:CA:C	acceptor_gain	0.9900
14:22974123:A:AC	acceptor_gain	0.9900
14:22974134:C:CT	acceptor_gain	0.9900
14:22974134:C:T	acceptor_gain	0.9900
14:22974833:A:AC	donor_gain	0.9900

AlphaMissense

3446 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:22973491:G:C	C523W	1.000
14:22973492:C:G	C523S	1.000
14:22973492:C:T	C523Y	1.000
14:22973493:A:G	C523R	1.000
14:22973493:A:T	C523S	1.000
14:22973500:G:C	C520W	1.000
14:22973501:C:A	C520F	1.000
14:22973501:C:G	C520S	1.000
14:22973501:C:T	C520Y	1.000
14:22973502:A:G	C520R	1.000
14:22973502:A:T	C520S	1.000
14:22973504:A:G	L519P	1.000
14:22973507:A:G	L518S	1.000
14:22973524:G:C	F512L	1.000
14:22973524:G:T	F512L	1.000
14:22973526:A:G	F512L	1.000
14:22973527:A:C	C511W	1.000
14:22973529:A:G	C511R	1.000
14:22973552:A:G	L503P	1.000
14:22973552:A:T	L503Q	1.000
14:22973563:G:C	C499W	1.000
14:22973564:C:G	C499S	1.000
14:22973564:C:T	C499Y	1.000
14:22973565:A:G	C499R	1.000
14:22973565:A:T	C499S	1.000
14:22974050:A:C	C496W	1.000
14:22974051:C:A	C496F	1.000
14:22974051:C:G	C496S	1.000
14:22974051:C:T	C496Y	1.000
14:22974052:A:G	C496R	1.000

dbSNP variants (sampled 300 via entrez): RS1000329378 (14:22973266 C>A,G), RS1000331319 (14:22979519 T>C,G), RS1000807294 (14:22979914 T>A), RS1000870961 (14:22974475 A>G), RS1001070161 (14:22980930 A>C,G), RS1001177850 (14:22975677 A>G), RS1002004230 (14:22975883 G>C), RS1002337538 (14:22982572 C>G,T), RS1002853106 (14:22977375 C>T), RS1002885463 (14:22977608 A>G), RS1003186141 (14:22979039 G>A,C), RS1003217695 (14:22979317 C>A,T), RS1003241628 (14:22971148 G>C), RS1004236301 (14:22976373 A>G), RS1004391210 (14:22982785 A>C,G)

Disease associations

OMIM: gene MIM:609066 | 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
GCST002030_8	Primary tooth development (time to first tooth eruption)	7.000000e-06
GCST002031_8	Primary tooth development (number of teeth)	3.000000e-08
GCST006976_70	Macular thickness	7.000000e-10
GCST009186_9	Insular cortex volume	6.000000e-06
GCST009306_20	Spatial processing	2.000000e-08
GCST010396_261	Gut microbiota (bacterial taxa, hurdle binary method)	3.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008354	cognitive function measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
entinostat	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Air Pollutants	increases abundance, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects expression	1
deoxynivalenol	decreases phosphorylation	1
glycidyl methacrylate	increases expression	1
3,4-dichloroaniline	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
cupric oxide	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
polyhexamethyleneguanidine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-phenylbutyric acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1Q3	HAP1 AJUBA (-) 2	Cancer cell line	Male
CVCL_JL62	VU-SCC-040	Cancer cell line	Female
CVCL_XL15	HAP1 AJUBA (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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