PSMD10

Summary

PSMD10 (proteasome 26S subunit, non-ATPase 10, HGNC:9555) is a protein-coding gene on chromosome Xq22.3, encoding 26S proteasome non-ATPase regulatory subunit 10 (O75832). Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC).

This gene encodes a subunit of the PA700/19S complex, which is the regulatory component of the 26S proteasome. The 26S proteosome complex is required for ubiquitin-dependent protein degradation. This protein is a non-ATPase subunit that may be involved in protein-protein interactions. Aberrant expression of this gene may paly a role in tumorigenesis. Two transcripts encoding different isoforms have been described. Pseudogenes have been identified on chromosomes 3 and 20.

Source: NCBI Gene 5716 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 68 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9555
Approved symbol	PSMD10
Name	proteasome 26S subunit, non-ATPase 10
Location	Xq22.3
Locus type	gene with protein product
Status	Approved
Aliases	p28
Ensembl gene	ENSG00000101843
Ensembl biotype	protein_coding
OMIM	300880
Entrez	5716

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 retained_intron

ENST00000217958, ENST00000338548, ENST00000340200, ENST00000361815, ENST00000372295, ENST00000372296, ENST00000553388, ENST00000853188, ENST00000923416, ENST00000923417, ENST00000946898

RefSeq mRNA: 2 — MANE Select: NM_002814 NM_002814, NM_170750

CCDS: CCDS14536, CCDS14537

Canonical transcript exons

ENST00000217958 — 5 exons

Exon	Start	End
ENSE00000674381	108087953	108088099
ENSE00001388624	108091407	108091542
ENSE00001423035	108087686	108087852
ENSE00001764642	108084207	108085127
ENSE00003627870	108088752	108088850

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 97.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.3523 / max 1152.3094, expressed in 1800 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200087	27.6718	1800
200088	1.6805	1139

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	97.64	gold quality
nasopharynx	UBERON:0001728	97.63	gold quality
ventricular zone	UBERON:0003053	96.80	gold quality
hypothalamus	UBERON:0001898	96.54	gold quality
islet of Langerhans	UBERON:0000006	96.46	gold quality
palpebral conjunctiva	UBERON:0001812	96.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.19	gold quality
tibia	UBERON:0000979	96.01	gold quality
bronchial epithelial cell	CL:0002328	95.81	gold quality
spinal cord	UBERON:0002240	95.80	gold quality
ganglionic eminence	UBERON:0004023	95.72	gold quality
germinal epithelium of ovary	UBERON:0001304	95.71	gold quality
cortical plate	UBERON:0005343	95.55	gold quality
adrenal tissue	UBERON:0018303	95.42	gold quality
corpus callosum	UBERON:0002336	95.41	gold quality
substantia nigra	UBERON:0002038	95.30	gold quality
corpus epididymis	UBERON:0004359	95.29	gold quality
pons	UBERON:0000988	95.17	gold quality
secondary oocyte	CL:0000655	95.16	gold quality
prefrontal cortex	UBERON:0000451	95.06	gold quality
embryo	UBERON:0000922	94.99	gold quality
midbrain	UBERON:0001891	94.94	gold quality
epithelium of bronchus	UBERON:0002031	94.93	gold quality
choroid plexus epithelium	UBERON:0003911	94.93	gold quality
amygdala	UBERON:0001876	94.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.80	gold quality
esophagus squamous epithelium	UBERON:0006920	94.78	gold quality
cingulate cortex	UBERON:0003027	94.73	gold quality
nucleus accumbens	UBERON:0001882	94.66	gold quality
anterior cingulate cortex	UBERON:0009835	94.66	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.42
E-GEOD-100618	no	694.95
E-HCAD-5	no	2.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, MYC, NR1H4, PEG3, TBX15

miRNA regulators (miRDB)

56 targeting PSMD10, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-6868-5P	99.06	65.69	1284

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of p28/gankyrin in HCC plays an important role and contributes to the metastasis potential in the process of carcinogenesis. (PMID:12174370)
• MAGE-A4 binds to gankyrin and suppresses its oncogenic activity. (PMID:12525503)
• gankyrin interactions with partner proteins are mediated by residues situated on its concave surface (PMID:14573599)
• X-ray structure of gankyrin. (PMID:14997555)
• The hepatocytic staining for p28(GANK) is clearly useful in differentiating hepatocyte-originated carcinoma from non-HCC. p28(GANK) may be used as an ancillary marker for the diagnosis of HCC. (PMID:15221469)
• Structural comparison with p16(INK4A) identified several residues of gankyrin that are potentially important for CDK4 binding (PMID:15379554)
• role of p28GANK as a highly expressed oncoprotein in hepatocellular carcinoma by in situ examination (PMID:15910504)
• Results allow the dissection of the “protein-protein binding” and “CDK4 inhibition” functions of P16, show that the difference between tumor suppressing and oncogenic functions of P16 and gankyrin, respectively, mainly resides in a single residue. (PMID:17881001)
• Results suggest that gankyrin binds to NF-kappaB and suppresses its activity at the transcription level by modulating acetylation via SIRT1. (PMID:17904523)
• Gankyrin oncoprotein has a role in progression of esophageal squamous cell carcinoma (PMID:17935131)
• These results suggest that overexpression of p28(GANK) prevents the nuclear localization and inhibits the activity of NF-kappaB/RelA. (PMID:18040287)
• gankyrin plays an oncogenic role mainly at the early stages of human hepatocarcinogenesis. (PMID:18161051)
• Rb antagonizes gankyrin to inhibit MDM2-mediate p53 ubiquitination in cancer cells and suggest that the status of both p53 and Rb is important for efficacy of cancer chemotherapy. (PMID:18332869)
• p28GANK knockdown-derived reactive oxygen species induces apoptosis through mitochondrial dysfunction mediated by p38 (PMID:18813787)
• Overexpression of a new gene P28GANK confers multidrug resistance of gastric cancer cells. (PMID:19235584)
• The results of this study demonstrate that gankyrin overexpression downregulates p53 expression and promotes cell proliferation in a zebrafish model. (PMID:19287195)
• The overexpression of multidrug resistance-associated proteins and gankyrin contribute to arsenic trioxide resistance in liver and gastric cancer cells. (PMID:19513507)
• p28GANK-knockdown induces the generation of reactive oxygen species (ROS), which in turn activates p38. (PMID:19729910)
• p28(GANK) has potential implications for hepatocellular carcinoma progression under the endoplasmic reticulum stress conditions (PMID:19736567)
• Gankyrin was overexpressed in colorectal cancer tissues and cell lines compared to controls, and gankyrin expression was correlated with TNM stages and metastasis of CRC. (PMID:19901563)
• analysis of how gankyrin unfolds under force via multiple distinct pathways (PMID:20371329)
• Gankyrin could enhance pancreatic cancer cell proliferation by promoting cell cycle progression and p53 degradation. (PMID:20483533)
• Gankyrin is a key regulator of Ras-mediated activation of Akt through inhibition of the downstream RhoA/ROCK pathway and thus plays an essential role in Ras-induced tumorigenesis. (PMID:20628200)
• we detected a significant correlation between p28(GANK) expression and p-AKT levels in a cohort of hepatocellular carcinoma biopsies, and the combination of these two parameters is a more powerful predictor of poor prognosis. (PMID:21254169)
• these findings suggest that down-regulation of P28GANK gene expression could sensitize osteosarcoma cells to chemotherapeutic drugs by down-regulation of the MDR-1 and Bcl-2 and up-regulation of Bax gene expression. (PMID:21287809)
• Upregulation of p28(GANK) expression subsequently enhanced the transcription activity of beta-catenin. (PMID:21691299)
• Gankyrin overexpression is a prevalent event in human oral cancer and occurs during the early stages of oral carcinogenesis, thus being a viable therapeutic or chemopreventive target in oral cancer (PMID:21868508)
• Knockdown of HURP inhibits the proliferation of hepacellular carcinoma cells via downregulation of gankyrin and accumulation of p53. (PMID:22230478)
• findings suggest that Gankyrin is crucial for breast cancer metastasis (PMID:22890318)
• the roles and underlying mechanisms by which gankyrin is involved in tumorigenesis and cancer metastasis (PMID:22913272)
• Increased expression of p28GANK is correlated with glioma. (PMID:22913315)
• Data indicate that miR-214 down-regulated the expression of PSMD10 (gankyrin) and ASF1B, and gankyrin inhibition induced an increase of P53 mRNA levels. (PMID:23100276)
• gankyrin was identified in normal breasts and overexpressed in invasive breast cancers. The overexpression of gankyrin was associated with extensive intraductal carcinoma and ErbB2 expression in breast cancer. (PMID:23276718)
• In colorectal cancer development, gankyrin would control stem cell behavior by regulating the expression of stemness factors. (PMID:23508981)
• Activation of the interleukin (IL)-8 signaling pathway by Gankyrin. (PMID:23576566)
• Gankyrin is crucial for cholangiocarcinoma carcinogenesis and metastasis by activating IL-6/STAT3 signaling pathway through down-regulating Rb protein. (PMID:24037855)
• Gankyrin deletion abrogated the increased metastatic potential of breast cancer cells under hypoxic conditions partly through regulating Ecadherin. (PMID:24337075)
• The intensity of gankyrin expression was ‘positive’ in two cases (20%) and ‘strongly positive’ in eight cases (80%). (PMID:24460153)
• Gankyrin may be functional in cervical carcinogenesis and metastasis. (PMID:24751719)
• Gankyrin is aberrantly expressed beginning at the initiation stage and plays an important role in the initiation, promotion, and progression of hepatocarcinogenesis. (PMID:24999092)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd10	ENSDARG00000015628
mus_musculus	Psmd10	ENSMUSG00000031429
rattus_norvegicus	Psmd10	ENSRNOG00000051669

Paralogs (1): DTHD1 (ENSG00000197057)

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 10 — O75832 (reviewed: O75832)

Alternative names: 26S proteasome regulatory subunit p28, Gankyrin, p28(GANK)

All UniProt accessions (4): O75832, B1AJY5, B1AJY6, B1AJY7

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis. Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export.

Subunit / interactions. Part of transient complex containing PSMD10, PSMC4, PSMC5 and PAAF1 formed during the assembly of the 26S proteasome. Stays associated throughout the assembly of the PA700/19S RC and is released upon association with the 20S core. Interacts with PSMC4. Interacts with RB1. Interacts with CDK4. Interacts with MDM2. Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine kinase complex. Interacts with ARHGDIA and increases the interaction between ARHGDIA and RHOA, hence promotes ARHGDIA inactivation of RHOA and ROCK.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Tends to be up-regulated in cancer cells with RAS mutations, including lung cancers and adenocarconimas (at protein level).

Isoforms (2)

UniProt ID	Names	Canonical?
O75832-1	1	yes
O75832-2	2

RefSeq proteins (2): NP_002805, NP_736606 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR051637	Ank_repeat_dom-contain_49	Family

Pfam: PF00023, PF12796

UniProt features (33 total): helix 15, repeat 7, region of interest 4, strand 2, chain 1, splice variant 1, mutagenesis site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
7VO6	X-RAY DIFFRACTION	1.71
1UOH	X-RAY DIFFRACTION	2
7VXW	X-RAY DIFFRACTION	2.22
7VY4	X-RAY DIFFRACTION	2.22
7VXV	X-RAY DIFFRACTION	2.23
7VY7	X-RAY DIFFRACTION	2.23
4NIK	X-RAY DIFFRACTION	2.5
1QYM	X-RAY DIFFRACTION	2.8
5VHF	ELECTRON MICROSCOPY	5.7
5VHH	ELECTRON MICROSCOPY	6.1
5VHI	ELECTRON MICROSCOPY	6.8
5VHN	ELECTRON MICROSCOPY	7.3
5VHR	ELECTRON MICROSCOPY	7.7
5VHP	ELECTRON MICROSCOPY	7.9
5VHM	ELECTRON MICROSCOPY	8.3
5VHO	ELECTRON MICROSCOPY	8.3
5VHJ	ELECTRON MICROSCOPY	8.5
5VHQ	ELECTRON MICROSCOPY	8.9
1TR4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75832-F1	95.57	0.96

Antibody-complex structures (SAbDab): 1 — 4NIK

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
182	abolishes interaction with rb1.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9907900	Proteasome assembly

MSigDB gene sets: 212 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, MODULE_151, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_PROTEASOME_ASSEMBLY, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, WONG_PROTEASOME_GENE_MODULE, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, PATIL_LIVER_CANCER

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), positive regulation of cell growth (GO:0030307), positive regulation of protein ubiquitination (GO:0031398), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), negative regulation of apoptotic process (GO:0043066), negative regulation of MAPK cascade (GO:0043409), negative regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043518), positive regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0045737), proteasome regulatory particle assembly (GO:0070682), negative regulation of release of cytochrome c from mitochondria (GO:0090201)

GO Molecular Function (2): RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515)

GO Cellular Component (13): proteasome complex (GO:0000502), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), perinuclear theca (GO:0033011), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), ciliary tip (GO:0097542), sperm glycocalyx (GO:0120238), proteasome regulatory particle, base subcomplex (GO:0008540)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
transcription by RNA polymerase II	2
cytoskeleton	2
sperm flagellum	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of DNA damage response, signal transduction by p53 class mediator	1
negative regulation of signal transduction by p53 class mediator	1
regulation of cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein serine/threonine kinase activity	1
positive regulation of cell cycle	1
positive regulation of protein serine/threonine kinase activity	1
positive regulation of cyclin-dependent protein kinase activity	1
proteasome assembly	1
release of cytochrome c from mitochondria	1
negative regulation of organelle organization	1
regulation of release of cytochrome c from mitochondria	1
negative regulation of apoptotic signaling pathway	1

Protein interactions and networks

STRING

2577 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD10	MDM2	Q00987	965
PSMD10	PSMD13	Q9UNM6	956
PSMD10	PSMC1	P49014	951
PSMD10	CDK4	P11802	942
PSMD10	PSMC4	P43686	931
PSMD10	PSMD9	O00233	769
PSMD10	PAAF1	Q9BRP4	762
PSMD10	PSMD1	Q99460	726
PSMD10	PSMD6	Q15008	712
PSMD10	CEBPA	P49715	711
PSMD10	TP53	P04637	707
PSMD10	ADRM1	Q16186	686
PSMD10	UBFD1	O14562	654
PSMD10	PSMD12	O00232	624
PSMD10	PSMA2	P25787	614

IntAct

167 interactions, top by confidence:

A	B	Type	Score
PSMC4	PSMD10	psi-mi:“MI:0915”(physical association)	0.970
PSMD10	PSMC4	psi-mi:“MI:0915”(physical association)	0.970
PSMD10	PSMC4	psi-mi:“MI:0914”(association)	0.970
PSMD10	PSMC4	psi-mi:“MI:0407”(direct interaction)	0.970
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
PSMC5	PSMD10	psi-mi:“MI:0914”(association)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
UCHL5	PSMD12	psi-mi:“MI:0914”(association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD4	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMC6	PSMD10	psi-mi:“MI:0914”(association)	0.740
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC1	PSMD12	psi-mi:“MI:0914”(association)	0.730

BioGRID (397): HSPA4 (Affinity Capture-Western), HSP90AA1 (Affinity Capture-Western), CLIC1 (Affinity Capture-Western), GRSF1 (Affinity Capture-Western), DDAH1 (Affinity Capture-Western), MAP2K1 (Affinity Capture-Western), HSPA4 (Reconstituted Complex), CLIC1 (Reconstituted Complex), NCK2 (Reconstituted Complex), GRSF1 (Reconstituted Complex), PSMD10 (Two-hybrid), PSMD10 (Affinity Capture-MS), PSMD10 (Affinity Capture-MS), PSMD10 (Affinity Capture-MS), PSMD10 (Affinity Capture-MS)

ESM2 similar proteins: A2AS55, B2RXR6, O15084, O75832, P0C927, Q08DV6, Q0P5B9, Q29RM5, Q2TB02, Q3SX45, Q495B1, Q499M5, Q4V890, Q502K3, Q505D1, Q53RE8, Q5F478, Q5RFS1, Q5U2S6, Q5ZLC8, Q6GPE5, Q6P6B7, Q6P9Z4, Q70X92, Q7T3P8, Q810B6, Q8BTI7, Q8C0T1, Q8C6Y6, Q8K0L0, Q8N8A2, Q8NB46, Q8NI38, Q8WXH4, Q91ZT8, Q96AX9, Q96DX5, Q96NS5, Q96Q27, Q9BSK4

Diamond homologs: D3Z7P3, O75832, O94925, P13264, P28492, Q10311, Q54GC8, Q571F8, Q9BXX2, Q9UI32, Q9Z2X2, Q9Z2X3, A6QR20, Q54HW1, Q9BQI6, O14593, Q13625, Q8CG79

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
Regulation of activated PAK-2p34 by proteasome mediated degradation	17	68.6×	5e-26
Regulation of ornithine decarboxylase (ODC)	17	67.0×	5e-26
Vpu mediated degradation of CD4	17	65.4×	5e-26
Autodegradation of the E3 ubiquitin ligase COP1	17	65.4×	5e-26
Ubiquitin-dependent degradation of Cyclin D	17	65.4×	5e-26
AUF1 (hnRNP D0) binds and destabilizes mRNA	18	64.8×	6e-27
Cross-presentation of soluble exogenous antigens (endosomes)	17	62.5×	1e-25
Vif-mediated degradation of APOBEC3G	17	62.5×	1e-25

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	20	13.7×	7e-15
Ras protein signal transduction	5	13.5×	5e-03
ubiquitin-dependent protein catabolic process	8	7.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
443504	GRCh37/hg19 Xp21.2-q28(chrX:31088082-155233731)x1	Pathogenic

SpliceAI

632 predictions. Top by Δscore:

Variant	Effect	Δscore
X:108087684:A:AC	donor_gain	1.0000
X:108087685:C:CC	donor_gain	1.0000
X:108087848:GCGAT:G	acceptor_gain	1.0000
X:108087849:CGAT:C	acceptor_gain	1.0000
X:108087849:CGATC:C	acceptor_gain	1.0000
X:108087852:TCTGG:T	acceptor_loss	1.0000
X:108087853:C:CC	acceptor_gain	1.0000
X:108087861:A:AC	acceptor_gain	1.0000
X:108087861:A:C	acceptor_gain	1.0000
X:108087947:CCATA:C	donor_loss	1.0000
X:108087948:CATA:C	donor_loss	1.0000
X:108087949:ATAC:A	donor_loss	1.0000
X:108087950:TA:T	donor_loss	1.0000
X:108087951:A:T	donor_loss	1.0000
X:108087952:C:CA	donor_loss	1.0000
X:108088750:A:AC	donor_gain	1.0000
X:108088751:C:CC	donor_gain	1.0000
X:108088751:CAT:C	donor_gain	1.0000
X:108091450:T:A	donor_gain	1.0000
X:108087669:TGC:T	donor_gain	0.9900
X:108087676:TGTC:T	donor_gain	0.9900
X:108087680:ACTTA:A	donor_loss	0.9900
X:108087681:CTTAC:C	donor_loss	0.9900
X:108087682:TTACA:T	donor_loss	0.9900
X:108087683:T:TG	donor_loss	0.9900
X:108087684:A:C	donor_loss	0.9900
X:108087685:CAG:C	donor_gain	0.9900
X:108087685:CAGA:C	donor_gain	0.9900
X:108087685:CAGAG:C	donor_gain	0.9900
X:108087697:AC:A	donor_gain	0.9900

AlphaMissense

1474 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:108088821:G:C	C48W	0.998
X:108087839:A:G	L125S	0.997
X:108085093:C:G	A188P	0.996
X:108087806:T:A	D136V	0.996
X:108087807:C:G	D136H	0.996
X:108087836:A:G	L126P	0.996
X:108088823:A:G	C48R	0.996
X:108087779:C:G	R145P	0.995
X:108088822:C:T	C48Y	0.995
X:108085083:A:G	L191P	0.994
X:108087806:T:G	D136A	0.994
X:108087976:C:G	A113P	0.993
X:108088757:C:G	D70H	0.993
X:108087740:A:G	L158P	0.992
X:108087774:C:G	A147P	0.992
X:108087777:C:G	A146P	0.992
X:108088074:G:T	A80E	0.992
X:108085086:A:G	L190P	0.991
X:108085117:A:G	C180R	0.991
X:108087708:C:G	D169H	0.991
X:108087805:G:C	D136E	0.991
X:108087805:G:T	D136E	0.991
X:108087848:G:T	A122D	0.991
X:108088071:G:T	A81D	0.991
X:108088810:T:G	H52P	0.991
X:108087807:C:A	D136Y	0.990
X:108087970:A:G	S115P	0.990
X:108087972:G:T	A114D	0.990
X:108087973:C:G	A114P	0.990
X:108087975:G:T	A113E	0.990

dbSNP variants (sampled 300 via entrez): RS1000644680 (X:108088478 C>A), RS1000939435 (X:108092957 T>A), RS1001432182 (X:108083961 A>G), RS1002425451 (X:108089436 T>C), RS1002472904 (X:108089011 G>A), RS1003192248 (X:108093258 C>CT), RS1003427338 (X:108091549 C>G,T), RS1004548170 (X:108092004 G>C), RS1004600751 (X:108091596 A>C), RS1004797884 (X:108083721 T>C), RS1005354806 (X:108087575 A>G), RS1007896990 (X:108083858 G>A), RS1008457689 (X:108085235 T>C), RS1008903273 (X:108089968 T>A), RS1008955563 (X:108089607 G>A)

Disease associations

OMIM: gene MIM:300880 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2331054 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.27	Kd	532	nM	CHEMBL4642394
6.24	Kd	580	nM	CHEMBL4642394

PubChem BioAssay actives

2 with measured affinity, of 87 total; 1 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
methyl 4-[4-[3-(4-methylphenyl)sulfonyloxypropyl]triazol-1-yl]benzoate	1869642: Binding affinity to gankyrin (unknown origin) expressed in Escherichia coli BL21 (DE3) expression system assessed as dissociation constant at 1:1 protein to compound concentration by isothermal titration calorimetry	kd	0.5320	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, decreases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
decabromobiphenyl ether	increases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
microcystin RR	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	increases expression	1
bisphenol AF	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases response to substance	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Rotenone	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2345828	Binding	Inhibition of P28 (unknown origin) at 1 uM	Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. — ACS Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2CG	Abcam HeLa PSMD10 KO	Cancer cell line	Female
CVCL_E2I4	HAP1 PSMD10 (-) 1	Cancer cell line	Male
CVCL_E2I5	HAP1 PSMD10 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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