POTEE

Summary

POTEE (POTE ankyrin domain family member E, HGNC:33895) is a protein-coding gene on chromosome 2q21.1, encoding POTE ankyrin domain family member E (Q6S8J3).

Predicted to enable protein kinase binding activity. Predicted to be a structural constituent of postsynaptic actin cytoskeleton. Involved in substantia nigra development. Located in blood microparticle and extracellular exosome.

Source: NCBI Gene 445582 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 7 total
• Druggable target: yes
• MANE Select transcript: NM_001083538

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33895
Approved symbol	POTEE
Name	POTE ankyrin domain family member E
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Aliases	POTE2, POTE-2, A26C1, POTE2gamma, CT104.2
Ensembl gene	ENSG00000188219
Ensembl biotype	protein_coding
OMIM	608914
Entrez	445582

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 nonsense_mediated_decay

ENST00000356920, ENST00000358087, ENST00000514256, ENST00000626191, ENST00000683005

RefSeq mRNA: 1 — MANE Select: NM_001083538 NM_001083538

CCDS: CCDS46414

Canonical transcript exons

ENST00000683005 — 18 exons

Exon	Start	End
ENSE00002432382	131236732	131236802
ENSE00002460408	131263355	131265278
ENSE00003459420	131245407	131245477
ENSE00003461019	131239278	131239444
ENSE00003525391	131250778	131250848
ENSE00003549213	131252918	131253099
ENSE00003556437	131238194	131238238
ENSE00003565611	131252526	131252570
ENSE00003627539	131261726	131261846
ENSE00003713919	131226823	131226929
ENSE00003714255	131228244	131228381
ENSE00003731777	131223870	131224043
ENSE00003733989	131223596	131223710
ENSE00003738635	131230836	131230906
ENSE00003917957	131218310	131218923
ENSE00003918046	131211028	131211183
ENSE00003918609	131209536	131209819
ENSE00003920604	131217589	131217683

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 88.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3668 / max 62.5457, expressed in 144 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22545	0.3668	144

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.46	gold quality
testis	UBERON:0000473	54.08	gold quality
ganglionic eminence	UBERON:0004023	50.63	silver quality
left testis	UBERON:0004533	49.62	gold quality
placenta	UBERON:0001987	49.58	gold quality
right testis	UBERON:0004534	49.42	gold quality
prostate gland	UBERON:0002367	45.76	gold quality
cortical plate	UBERON:0005343	45.09	gold quality
ventricular zone	UBERON:0003053	43.44	gold quality
bone marrow cell	CL:0002092	43.18	gold quality
stromal cell of endometrium	CL:0002255	41.47	silver quality
bone marrow	UBERON:0002371	40.87	gold quality
skeletal muscle tissue	UBERON:0001134	39.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	38.74	gold quality
blood	UBERON:0000178	37.96	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
lower esophagus mucosa	UBERON:0035834	36.85	gold quality
leukocyte	CL:0000738	36.37	gold quality
tibial artery	UBERON:0007610	36.19	silver quality
popliteal artery	UBERON:0002250	36.12	silver quality
monocyte	CL:0000576	35.94	gold quality
muscle tissue	UBERON:0002385	35.42	gold quality
sural nerve	UBERON:0015488	35.13	gold quality
tonsil	UBERON:0002372	32.07	gold quality
corpus callosum	UBERON:0002336	31.57	gold quality
mucosa of stomach	UBERON:0001199	31.49	gold quality
left uterine tube	UBERON:0001303	31.10	gold quality
ascending aorta	UBERON:0001496	31.01	silver quality
adrenal tissue	UBERON:0018303	30.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	26.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting POTEE, 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-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-192-3P	97.52	67.66	1001
HSA-MIR-937-5P	97.43	68.39	667
HSA-MIR-6872-3P	97.08	66.99	750

Literature-anchored findings (GeneRIF, showing 8)

• The POTE paralogs that are expressed in ES cells may have a specific function during lineage-specific differentiation of ES cells. (PMID:18447647)
• POTE gene family encodes a new family of proapoptotic proteins. (PMID:19669888)
• Data show that HPX, POTEE and ApoA1 are deregulated in breast tumors suggesting un important role in breast tumorigenesis. (PMID:24969553)
• POTEE interaction with HIV-1 Nef regulates mTORC2 activation in macrophages. (PMID:30391463)
• In TAMs, POTEE was involved differential protein-protein interaction with mTOR, RICTOR, and Rad51 indicating its biological role in cell invasion through mTORC2 activation. (PMID:30420269)
• POTEE drives colorectal cancer development via regulating SPHK1/p65 signaling. (PMID:31723122)
• POTEE promotes colorectal carcinoma progression via activating the Rac1/Cdc42 pathway. (PMID:32142855)
• POTEE stimulates the proliferation of pancreatic cancer by activating the PI3K/Akt/GSK-3beta/beta-catenin signaling. (PMID:32589786)

Cross-species orthologs

0 orthologs

Paralogs (16): BCL3 (ENSG00000069399), NFKBIE (ENSG00000146232), POTED (ENSG00000166351), POTEC (ENSG00000183206), POTEG (ENSG00000187537), POTEA (ENSG00000188877), POTEF (ENSG00000196604), POTEI (ENSG00000196834), POTEH (ENSG00000198062), POTEM (ENSG00000222036), POTEJ (ENSG00000222038), POTEB2 (ENSG00000230031), POTEB (ENSG00000233917), (ENSG00000276760), (ENSG00000277630), POTEB3 (ENSG00000278522)

Protein

Protein identifiers

POTE ankyrin domain family member E — Q6S8J3 (reviewed: Q6S8J3)

Alternative names: ANKRD26-like family C member 1A, Prostate, ovary, testis-expressed protein on chromosome 2

All UniProt accessions (1): Q6S8J3

UniProt curated annotations — full annotation on UniProt →

Similarity. In the N-terminal section; belongs to the POTE family. In the C-terminal section; belongs to the actin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6S8J3-1	1, POTE2A	yes
Q6S8J3-2	2, POTE2B
Q6S8J3-3	3, POTE2C, POTE2D

RefSeq proteins (1): NP_001077007* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR004000	Actin	Family
IPR004001	Actin_CS	Conserved_site
IPR020902	Actin/actin-like_CS	Conserved_site
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR039497	CC144C-like_CC_dom	Domain
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00022, PF12796, PF14915

UniProt features (26 total): repeat 5, compositionally biased region 5, splice variant 5, sequence conflict 5, region of interest 3, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6S8J3-F1	70.63	0.45

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9035034	RHOF GTPase cycle

MSigDB gene sets: 54 (showing top): GOBP_NEUROGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_NEURAL_NUCLEUS_DEVELOPMENT, GOBP_SUBSTANTIA_NIGRA_DEVELOPMENT, GOBP_MIDBRAIN_DEVELOPMENT, GOBP_HEAD_DEVELOPMENT, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_H4_HISTONE_ACETYLTRANSFERASE_COMPLEX, GOCC_TRANSFERASE_COMPLEX, GOCC_BLOOD_MICROPARTICLE, GOCC_SYNAPSE, GOCC_AXON, GOMF_KINASE_BINDING

GO Biological Process (4): axonogenesis (GO:0007409), substantia nigra development (GO:0021762), cell motility (GO:0048870), postsynaptic actin cytoskeleton organization (GO:0098974)

GO Molecular Function (3): protein kinase binding (GO:0019901), structural constituent of postsynaptic actin cytoskeleton (GO:0098973), protein binding (GO:0005515)

GO Cellular Component (10): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), actin filament (GO:0005884), actin cytoskeleton (GO:0015629), membrane (GO:0016020), axon (GO:0030424), NuA4 histone acetyltransferase complex (GO:0035267), synapse (GO:0045202), extracellular exosome (GO:0070062), blood microparticle (GO:0072562)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
midbrain development	1
neural nucleus development	1
cellular process	1
actin cytoskeleton organization	1
postsynaptic cytoskeleton organization	1
kinase binding	1
structural constituent of cytoskeleton	1
postsynaptic actin cytoskeleton	1
postsynaptic actin cytoskeleton organization	1
structural constituent of postsynapse	1
binding	1
intracellular anatomical structure	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
neuron projection	1
H4/H2A histone acetyltransferase complex	1
cell junction	1
extracellular vesicle	1
extracellular region	1

Protein interactions and networks

STRING

2110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POTEE	NCKAP1	Q9Y2A7	477
POTEE	PSMC1	P49014	439
POTEE	SEC13	P55735	420
POTEE	TAB2	Q9NYJ8	387
POTEE	ANK1	P16157	372
POTEE	ANK2	Q01484	372
POTEE	ANK3	Q12955	371
POTEE	TEX13D	A0A0J9YY54	370
POTEE	ANKRD30A	Q9BXX3	345
POTEE	TEKTL1	Q8IYK2	321
POTEE	AGAP4	Q96P64	308
POTEE	OR5H2	Q8NGV7	303
POTEE	CCDC183	Q5T5S1	299
POTEE	EFCAB8	A8MWE9	299
POTEE	ANKRD26	Q9UPS8	290

IntAct

98 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
HMGB1	SP100	psi-mi:“MI:0914”(association)	0.670
CHST14	CANX	psi-mi:“MI:0914”(association)	0.640
CINP	KIF7	psi-mi:“MI:0914”(association)	0.640
CCR2	POTEE	psi-mi:“MI:0915”(physical association)	0.590
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
PMM1	PMM2	psi-mi:“MI:0914”(association)	0.530
DEFA6	EXTL3	psi-mi:“MI:0914”(association)	0.530
HMOX2	PRAF2	psi-mi:“MI:0914”(association)	0.530
TGDS	GABARAP	psi-mi:“MI:0914”(association)	0.530
GPR35	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
ACP1	ACTB	psi-mi:“MI:0914”(association)	0.530
TMEM186	POTEE	psi-mi:“MI:0914”(association)	0.530
PDGFD	DCTN6	psi-mi:“MI:0914”(association)	0.530
IL27RA	B4GALT5	psi-mi:“MI:0914”(association)	0.530
CINP	CHMP2A	psi-mi:“MI:0914”(association)	0.530
CST7	CTSL	psi-mi:“MI:0914”(association)	0.530
GPR35	LGALS3	psi-mi:“MI:0914”(association)	0.530
MOGAT1	POTEE	psi-mi:“MI:0915”(physical association)	0.400
TUBA1A	CAPZB	psi-mi:“MI:0914”(association)	0.350
TUBA1A	KIF2A	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (205): POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS), POTEE (Affinity Capture-MS)

ESM2 similar proteins: A0A072TK64, A0A072ULZ1, A0A6P8HC43, A2PYL6, A2PYL7, A2PYL8, A2XE45, A2XEA0, A2Y6J9, A5A3E0, B5DUH6, E9Q0N2, F4HWL4, F4JCB2, O04309, O08528, O24521, O95744, P0CG38, P0CG39, P25071, P27881, P28316, P29127, P35753, P37842, P52789, Q1W674, Q29428, Q6S8J3, Q70SU7, Q70SU8, Q75II4, Q84JE8, Q8L727, Q8LRK8, Q8RXK2, Q8VC49, Q90WJ7, Q93Y92

Diamond homologs: A0A0A6YYL3, A0JP26, A0PJZ0, A2A2Z9, A2RUR9, A5A3E0, A6NC57, A6NI47, A7E2S9, B2RU33, H3BUK9, P0CG38, P0CG39, Q3MJ40, Q4R3S3, Q4UJ75, Q5CZ79, Q5JPF3, Q5SQ80, Q5TYW2, Q5VUR7, Q6NSI1, Q6S545, Q6S5H5, Q6S8J3, Q6S8J7, Q811D2, Q86YR6, Q8IYA2, Q92527, Q9BXX2, Q9BXX3, Q9D504, Q9H560, Q9UPS8, Q8IVF6, A6QL64, Q8N2N9, Q8NF67, Q96IX9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Gap junction trafficking and regulation	5	26.1×	4e-04
Gap junction trafficking	5	26.1×	4e-04
RHO GTPases activate IQGAPs	5	19.0×	8e-04
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	12.8×	8e-04
Recycling pathway of L1	5	12.3×	5e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	11.9×	4e-04
COPI-independent Golgi-to-ER retrograde traffic	5	11.4×	5e-03
MHC class II antigen presentation	8	7.8×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1789 predictions. Top by Δscore:

Variant	Effect	Δscore
2:131218921:GAG:G	donor_gain	1.0000
2:131223594:A:AG	acceptor_gain	1.0000
2:131223595:G:GG	acceptor_gain	1.0000
2:131223595:GGACT:G	acceptor_gain	1.0000
2:131223853:T:TA	acceptor_gain	1.0000
2:131223859:A:AG	acceptor_gain	1.0000
2:131223860:A:G	acceptor_gain	1.0000
2:131223861:T:G	acceptor_gain	1.0000
2:131223862:A:AG	acceptor_gain	1.0000
2:131223862:ACT:A	acceptor_gain	1.0000
2:131223863:C:G	acceptor_gain	1.0000
2:131223864:T:A	acceptor_gain	1.0000
2:131223866:ACAG:A	acceptor_loss	1.0000
2:131223867:CAGGC:C	acceptor_loss	1.0000
2:131224040:CAAG:C	donor_loss	1.0000
2:131224041:AAG:A	donor_loss	1.0000
2:131224042:AGG:A	donor_loss	1.0000
2:131224043:GGTA:G	donor_loss	1.0000
2:131224045:T:A	donor_loss	1.0000
2:131226821:A:AG	acceptor_gain	1.0000
2:131226821:AGCAT:A	acceptor_gain	1.0000
2:131226822:G:GG	acceptor_gain	1.0000
2:131226822:GC:G	acceptor_gain	1.0000
2:131226822:GCAT:G	acceptor_gain	1.0000
2:131226822:GCATG:G	acceptor_gain	1.0000
2:131226927:A:T	donor_gain	1.0000
2:131228239:TTTAG:T	acceptor_loss	1.0000
2:131228240:TTAGG:T	acceptor_loss	1.0000
2:131228241:TAGG:T	acceptor_loss	1.0000
2:131228242:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000083927 (2:131232730 A>G), RS1000116647 (2:131232100 T>G), RS1000300416 (2:131259577 T>C,G), RS1000384220 (2:131224805 G>A), RS1000558067 (2:131248168 T>C,G), RS1000629603 (2:131260356 C>T), RS1000934984 (2:131253315 G>A), RS1001038064 (2:131246092 A>G), RS1001094914 (2:131219356 T>C), RS1001257719 (2:131219794 T>C), RS1001310071 (2:131219686 G>A), RS1001435759 (2:131225748 A>C,G,T), RS1001443428 (2:131211851 C>G,T), RS1001460718 (2:131225088 G>A), RS1001489083 (2:131233272 T>C)

Disease associations

OMIM: gene MIM:608914 | 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): CHEMBL6066368 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.99	Kd	1036	nM	CHEMBL5653589
5.61	ED50	2447	nM	CHEMBL5653589
5.30	Kd	4955	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 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	2149038: Binding affinity to human POTEE incubated for 45 mins by Kinobead based pull down assay	kd	1.0359	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149038: Binding affinity to human POTEE incubated for 45 mins by Kinobead based pull down assay	kd	4.9552	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression	1
taxifolin	affects binding	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
butyraldehyde	increases expression	1
epigallocatechin gallate	decreases expression	1
matairesinol	affects binding	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Acetaminophen	decreases expression	1
Caffeine	decreases expression	1
Calcitriol	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	increases expression	1
Estradiol	increases expression	1
Hematoxylin	affects binding	1
Quercetin	affects binding	1
Retinoids	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Asbestos, Crocidolite	increases methylation	1
Acrylamide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652080	Binding	Binding affinity to human POTEE incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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