PABPC1

Summary

PABPC1 (poly(A) binding protein cytoplasmic 1, HGNC:8554) is a protein-coding gene on chromosome 8q22.3, encoding Polyadenylate-binding protein 1 (P11940). Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability. It is a common-essential gene (DepMap: required in 90.3% of cancer cell lines).

This gene encodes a poly(A) binding protein. The protein shuttles between the nucleus and cytoplasm and binds to the 3’ poly(A) tail of eukaryotic messenger RNAs via RNA-recognition motifs. The binding of this protein to poly(A) promotes ribosome recruitment and translation initiation; it is also required for poly(A) shortening which is the first step in mRNA decay. The gene is part of a small gene family including three protein-coding genes and several pseudogenes.

Source: NCBI Gene 26986 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 104 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 7 cancer types
• Cancer dependency (DepMap): dependent in 90.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_002568

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8554
Approved symbol	PABPC1
Name	poly(A) binding protein cytoplasmic 1
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Aliases	PABP1, PABPL1
Ensembl gene	ENSG00000070756
Ensembl biotype	protein_coding
OMIM	604679
Entrez	26986

Gene structure

Transcript identifiers

Ensembl transcripts: 59 — 44 protein_coding, 10 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000318607, ENST00000517403, ENST00000517921, ENST00000517990, ENST00000518196, ENST00000518293, ENST00000518716, ENST00000519004, ENST00000519100, ENST00000519363, ENST00000519596, ENST00000519622, ENST00000519848, ENST00000520142, ENST00000520804, ENST00000520868, ENST00000521067, ENST00000521865, ENST00000522387, ENST00000522658, ENST00000522720, ENST00000523555, ENST00000523636, ENST00000610907, ENST00000676655, ENST00000676662, ENST00000676976, ENST00000677140, ENST00000677285, ENST00000677380, ENST00000677478, ENST00000677765, ENST00000677775, ENST00000677787, ENST00000677892, ENST00000678290, ENST00000678709, ENST00000678822, ENST00000678954, ENST00000679197, ENST00000900763, ENST00000900764, ENST00000900765, ENST00000900766, ENST00000900767, ENST00000900768, ENST00000900769, ENST00000900770, ENST00000900771, ENST00000900772, ENST00000900773, ENST00000900774, ENST00000938879, ENST00000938880, ENST00000938881, ENST00000938882, ENST00000951436, ENST00000951437, ENST00000951438

RefSeq mRNA: 1 — MANE Select: NM_002568 NM_002568

CCDS: CCDS6289

Canonical transcript exons

ENST00000318607 — 15 exons

Exon	Start	End
ENSE00001088711	100717773	100717888
ENSE00001378950	100702916	100703359
ENSE00002107718	100721391	100722088
ENSE00003465118	100704926	100705056
ENSE00003491167	100715462	100715601
ENSE00003509544	100705589	100705673
ENSE00003520268	100706887	100706997
ENSE00003526154	100704297	100704390
ENSE00003577658	100713087	100713181
ENSE00003599167	100712652	100712789
ENSE00003611249	100712362	100712457
ENSE00003620327	100709133	100709223
ENSE00003785590	100709459	100709731
ENSE00003790242	100718087	100718280
ENSE00003791060	100706651	100706805

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 749.3177 / max 8991.6482, expressed in 1828 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94175	721.4863	1828
94173	6.0123	1655
94172	4.4809	1484
94170	2.4510	1169
94158	1.8195	1073
94166	1.6407	859
94159	1.5919	912
94174	1.5332	950
94165	1.3596	592
94161	1.3073	851

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.97	gold quality
pylorus	UBERON:0001166	99.86	gold quality
esophagus squamous epithelium	UBERON:0006920	99.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.82	gold quality
amniotic fluid	UBERON:0000173	99.80	gold quality
epithelium of esophagus	UBERON:0001976	99.80	gold quality
mammalian vulva	UBERON:0000997	99.79	gold quality
monocyte	CL:0000576	99.78	gold quality
mononuclear cell	CL:0000842	99.78	gold quality
nipple	UBERON:0002030	99.78	gold quality
tonsil	UBERON:0002372	99.78	gold quality
trabecular bone tissue	UBERON:0002483	99.78	gold quality
leukocyte	CL:0000738	99.77	gold quality
oral cavity	UBERON:0000167	99.77	gold quality
squamous epithelium	UBERON:0006914	99.77	gold quality
cervix squamous epithelium	UBERON:0006922	99.77	gold quality
urethra	UBERON:0000057	99.76	gold quality
upper leg skin	UBERON:0004262	99.76	gold quality
mammary duct	UBERON:0001765	99.75	gold quality
pharyngeal mucosa	UBERON:0000355	99.74	gold quality
colonic epithelium	UBERON:0000397	99.74	gold quality
cortical plate	UBERON:0005343	99.74	gold quality
cardia of stomach	UBERON:0001162	99.73	gold quality
left testis	UBERON:0004533	99.73	gold quality
tongue squamous epithelium	UBERON:0006919	99.73	gold quality
lower esophagus mucosa	UBERON:0035834	99.73	gold quality
stromal cell of endometrium	CL:0002255	99.72	gold quality
epithelium of nasopharynx	UBERON:0001951	99.72	gold quality
penis	UBERON:0000989	99.71	gold quality
right testis	UBERON:0004534	99.71	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	4861.62
E-HCAD-8	yes	4639.39
E-HCAD-4	yes	2822.16
E-GEOD-125970	yes	998.17
E-CURD-122	yes	78.49
E-MTAB-9467	yes	78.02
E-CURD-88	yes	56.81
E-MTAB-8142	yes	54.72
E-GEOD-84465	yes	39.49
E-MTAB-8410	yes	36.69
E-MTAB-10553	yes	34.36
E-HCAD-31	yes	29.19
E-MTAB-6701	yes	27.16
E-MTAB-9543	yes	27.16
E-GEOD-134144	yes	26.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YBX1

miRNA regulators (miRDB)

53 targeting PABPC1, 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-3163	100.00	77.23	8605
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-451B	99.55	68.28	1380

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Methylated in vivo by CARM1. Methylated region is mapped. (PMID:11850402)
• Paip1 interacts with poly(A) binding protein through two independent binding motifs. (PMID:11997512)
• PABP1 is a potential substrate in MAPKAP kinase 2-induced mRNA stabilization. (PMID:12565831)
• targeted degradation of PABP contributes to translation inhibition in apoptotic cells (PMID:14739600)
• PABP1 associates with paxillin in order to be efficiently transported from the nucleus to the cytoplasm; this event is necessary for cells to remodel their focal adhesions during cell migration. (PMID:15831480)
• a novel signaling pathway involving MKK-2 and ERK1/2 may down-regulate the activity of PABP and eIF4E by controlling their phosphorylation and compensates for the effect of excess cellular PABP (PMID:16332685)
• In esophageal cancer, reduced expression of PABPC1 was correlated with local tumor progression and poor prognosis after surgery. (PMID:16465428)
• PABP interacts with HHV-8 K10/10.1 protein in infected primary effusion lymphoma (PEL) cell lines. (PMID:16716377)
• poly(A)-binding protein 1 (PABP) as a novel BRCA1-interacting protein. (PMID:16782705)
• Structural study of the A-rich repeats in the 5’-untranslated region of PABP. (PMID:17150895)
• We have further characterized the interaction between PABP and IMP1 with the 3’ end of the adenine-rich autoregulatory sequence (PMID:17212783)
• the poly(A) nuclease interacts with the C-terminal domain of polyadenylate-binding protein domain from poly(A)-binding protein (PMID:17595167)
• Data show that TOB enhances mRNA deadenylation in vivo, and that interaction with PABPC1 is necessary for TOB’s deadenylation-enhancing effect. (PMID:17785442)
• Nonsense-mediated decay-sensitive mRNA can be stabilized by tethering the cytoplasmic poly(A) binding protein 1, PABPC1, at a premature termination codon-proximal position. (PMID:18230761)
• RUBVgp2 capsid protein inhibits genetic translation by sequestration of poly(a)-binding protein (PMID:18305028)
• The results further elucidate complex mechanisms where multiple inherent PABP conformations and protein and RNA interactions both serve to differentially regulate PABP cleavage by 3CD, 3C(pro) and 2A(pro). (PMID:18321554)
• Findings suggest several levels of functional antagonism between TTP and PABP1 that have implications for regulation of unstable mRNAs like TNF. (PMID:18467502)
• poly(A)-binding protein cleavage by poliovirus 3C proteinase inhibits viral internal ribosome entry site-mediated translation (PMID:18632855)
• Basophilic inclusions from patients with adult-onset atypical motor neuron disease were distinctly labeled with the antibodies against poly(A)-binding protein 1, T cell intracellular antigen 1, and ribosomal protein S6. (PMID:18642007)
• We show here that PABP-C1 evicted from eIF4G by NSP3 accumulates in the nucleus of rotavirus-infected cells. (PMID:18799579)
• The authors demonstrate that inhibition of HIV expression by Sam68DeltaC is correlated with a loss of PABP1 binding with no attendant change in polyadenosine tail length of the affected RNAs. (PMID:18957126)
• Bunyamwera virus triggers nuclear retention of PABP in mammalian cells. (PMID:19193790)
• Data show that reduced levels of eIF4B, eIF4H, or polyA-binding protein, also trigger SG formation. (PMID:19369421)
• Poly(A)-binding protein modulates mRNA susceptibility to cap-dependent miRNA-mediated repression. (PMID:19934229)
• HIV- 1 protease inhibits Cap- and poly(A)-dependent translation upon eIF4GI and PABP cleavage (PMID:19956697)
• The cytoplasmic poly (A)-binding protein (PABP) plays a crucial role in regulating both translation and stability of eukaryotic mRNA. (PMID:20009508)
• The side chain of the invariant MLLE residue K580 of poly(A)-binding protein forms hydrogen bonds with the backbone of PAM2 residues 5 and 7. (PMID:20096703)
• The authors show that a conserved motif in the human GW182 paralog TNRC6C interacts with the C-terminal domain of polyadenylate binding protein 1 (PABC) and present the crystal structure of the complex. (PMID:20098421)
• Structural basis of binding of P-body-associated proteins GW182 and ataxin-2 by the Mlle domain of poly(A)-binding protein.( (PMID:20181956)
• crystal structures of the MLLE domain from PABPC1 in complex with the two PAM2 regions of eRF3 (PMID:20418951)
• Data show that in addition to PP2Ac, alpha4 interacts with EDD and PABP, suggesting its involvement in multiple steps in the mTOR pathway that leads to translation initiation and cell-cycle progression. (PMID:20544796)
• PABP relocalization in infection was found to be independent of the viral protein ICP27. (PMID:20573819)
• Tob interactions with Caf1 and a C-terminal domain of PABPC1 (PMID:20595394)
• Cytoplasmic PABP accumulation is translationally controlled in human cytomegalovirus-infected cells. (PMID:20980505)
• These findings reveal that despite species-specific differences in the relative strength of the PABPC1-binding sites, the interaction between GW182 proteins and PABPC1 is critical for miRNA-mediated silencing in animal cells. (PMID:21063388)
• LARP4 activity is integrated with other PAM2 protein activities by PABP as part of mRNA homeostasis. (PMID:21098120)
• these results suggest that depletion of PABP prevents protein synthesis and consequently leads to cell death through apoptosis. (PMID:21521633)
• in the absence of PABP, the glycolytic enzyme GAPDH translocated to the cell nucleus and activated the GAPDH mediated apoptotic pathway by enhancing acetylation and serine 46 phosphorylation of p53. (PMID:21539808)
• The present study has characterized DDX3 as a pivotal SG-nucleating factor and illustrates co-ordinative roles for DDX3, eIF4E and PABP1 in integrating environmental stress with translational regulation. (PMID:21883093)
• Nuclear relocalisation of cytoplasmic poly(A)-binding proteins PABP1 and PABP4 in response to UV irradiation reveals mRNA-dependent export (PMID:21940797)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pabpc6	ENSMUSG00000046173
mus_musculus	Pabpc2	ENSMUSG00000051732
rattus_norvegicus	Pabpc2	ENSRNOG00000014527
rattus_norvegicus	Pabpc6	ENSRNOG00000017367

Paralogs (24): ELAVL1 (ENSG00000066044), RBMS2 (ENSG00000076067), PABPC4 (ENSG00000090621), PABPC1L (ENSG00000101104), ELAVL2 (ENSG00000107105), RBM24 (ENSG00000112183), TARDBP (ENSG00000120948), HNRNPR (ENSG00000125944), RBM38 (ENSG00000132819), SYNCRIP (ENSG00000135316), SF3B4 (ENSG00000143368), RBMS3 (ENSG00000144642), PABPC3 (ENSG00000151846), RBMS1 (ENSG00000153250), RBM45 (ENSG00000155636), ELAVL4 (ENSG00000162374), PABPC5 (ENSG00000174740), PUF60 (ENSG00000179950), PABPC1L2B (ENSG00000184388), PABPC1L2A (ENSG00000186288), RBM34 (ENSG00000188739), ELAVL3 (ENSG00000196361), RBM14 (ENSG00000239306), PABPC4L (ENSG00000254535)

Protein

Protein identifiers

Polyadenylate-binding protein 1 — P11940 (reviewed: P11940)

All UniProt accessions (26): P11940, A0A087WTT1, A0A7I2V3J9, A0A7I2V4N4, A0A7I2V649, A0A7I2YQ88, A0A7I2YQ90, A0A7I2YQE4, E5RFD8, E5RGC4, E5RGH3, E5RH24, E5RHG7, E5RJB9, E5RJM8, E7EQV3, E7ERJ7, H0YAP2, H0YAR2, H0YAS6, H0YAS7, H0YAW6, H0YB75, H0YB86, H0YBN4, H0YC10

UniProt curated annotations — full annotation on UniProt →

Function. Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability. Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs. Involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed. By binding to long poly(A) tails, may protect them from uridylation by ZCCHC6/ZCCHC11 and hence contribute to mRNA stability. (Microbial infection) Positively regulates the replication of dengue virus (DENV).

Subunit / interactions. May form homodimers. Component of a multisubunit autoregulatory ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1. Directly interacts with IGF2BP1; the interaction is enhanced by SEPIN14P20 peptide RBPR. Part of a complex associated with the FOS mCRD domain and consisting of HNRPD, SYNCRIP, PAIP1 and CSDE1/UNR. Interacts with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1 and PAIP2. Interacts with PAIP1 with a 1:1 stoichiometry and with PAIP2 with a 1:2 stoichiometry. The interaction with CSDE1 is direct and RNA-independent. Found in a mRNP complex with YBX2. Interacts with TENT2/GLD2. Identified in the spliceosome C complex. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. The interaction with DDX3X is direct and RNA-independent. This interaction increases in stressed cells and decreases during cell recovery. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with NXF1/TAP. Interacts with PIWIL1. Interacts with AGO1, AGO2, GSPT1 and GSPT2 (PubMed:17932509, PubMed:18447585, Ref.66). Interacts with LARP4B (Ref.68). Interacts (via the second and third RRM domains and the C-terminus) with PAIP2B (via central acidic portion and C-terminus). Forms a complex with LARP1 and SHFL. Interacts with LARP4. Interacts with ZFC3H1 in a RNase-sensitive manner. Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner. Interacts with TENT5C; the interaction has no effect on TENT5C poly(A) polymerase function. Interacts with G3BP1 and G3BP2. Interacts with ENDOV; the interaction is RNA-dependent and stimulates ENDOV activity. Interacts with UPF1; the interaction is RNA-dependent. Interacts with IGF2BP2 and IGF2BP3. May interact with SETX. Interacts with RBM46. Interacts with PAN3 isoform 1/Pan3L and isoform 3/Pan3S (via N-terminus); interaction with isoform 1 is less efficient than with isoform 3. Interacts with HELZ (via the PAM2 motif). (Microbial infection) Interacts (via C-terminus) with human cytomegalovirus/HHV-5 protein UL69. (Microbial infection) Interacts (via C-terminus) with human respiratory syncytial virus (HRSV) M2-1 protein. (Microbial infection) Interacts with human herpesvirus 8 protein MTA/ORF57.

Subcellular location. Cytoplasm. Stress granule. Nucleus. Cell projection. Lamellipodium.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by MAPKAPK2. Methylated by CARM1. Arg-493 is dimethylated, probably to asymmetric dimethylarginine.

Domain organisation. The RNA-binding domains RRM1 and RRM2 and the C-terminus (last 138 amino acids) regions interact with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1, respectively. The RNA-binding domains RRM2 and RRM3 and the C-terminus (last 138 amino acids) regions interact with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP2, respectively.

Miscellaneous. Many viruses shutoff host mRNA translational machinery by inhibiting cellular PABPC1 activity using different mechanisms. Picornaviruses, caliciviruses or lentiviruses encode proteases that cleave PABPC1 at several defined sites in the proline-rich linker region between RRMs and the C-terminal domain. Rotaviruses, gammherpesviruses and bunyamwera virus relocalize PABPC1 from the cytoplasm to the nucleus thus altering its function. Many of these viruses translate their mRNA in a PABPC1-independent manner and are unaffected by host PABPC1 inhibition.

Similarity. Belongs to the polyadenylate-binding protein type-1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P11940-1	1	yes
P11940-2	2

RefSeq proteins (1): NP_002559* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002004	PABP_HYD_C	Domain
IPR003954	RRM_euk-type	Domain
IPR006515	PABP_1234	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034364	PABP_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036053	PABP-dom	Homologous_superfamily
IPR045305	RRM2_I_PABPs	Domain

Pfam: PF00076, PF00658

UniProt features (59 total): modified residue 18, helix 14, strand 10, domain 5, sequence conflict 3, turn 3, mutagenesis site 2, region of interest 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
3KUJ	X-RAY DIFFRACTION	1.4
3KUS	X-RAY DIFFRACTION	1.4
2X04	X-RAY DIFFRACTION	1.49
3KTP	X-RAY DIFFRACTION	1.5
3KUT	X-RAY DIFFRACTION	1.5
3KTR	X-RAY DIFFRACTION	1.7
3PTH	X-RAY DIFFRACTION	1.7
3PKN	X-RAY DIFFRACTION	1.8
4F25	X-RAY DIFFRACTION	1.9
5DX1	X-RAY DIFFRACTION	1.93
7BN3	X-RAY DIFFRACTION	1.93
5DX8	X-RAY DIFFRACTION	1.94
4F02	X-RAY DIFFRACTION	2
4F26	X-RAY DIFFRACTION	2
5LGR	X-RAY DIFFRACTION	2
5LGP	X-RAY DIFFRACTION	2.04
5DXA	X-RAY DIFFRACTION	2.07
5LGS	X-RAY DIFFRACTION	2.1
5LGQ	X-RAY DIFFRACTION	2.11
3KUI	X-RAY DIFFRACTION	2.3
3KUR	X-RAY DIFFRACTION	2.5
1CVJ	X-RAY DIFFRACTION	2.6
8SMO	X-RAY DIFFRACTION	3
1G9L	SOLUTION NMR
1JGN	SOLUTION NMR
1JH4	SOLUTION NMR
2D9P	SOLUTION NMR
2K8G	SOLUTION NMR
2RQG	SOLUTION NMR
2RQH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11940-F1	77.90	0.50

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 (18): 315, 319, 385, 419, 432, 436, 455, 460, 475, 481, 493, 493, 493, 506, 512, 518, 1, 299

Mutagenesis-validated functional residues (2):

Position	Phenotype
455	greatly reduces methylation by carm1 (in vitro); when associated with a-460.
460	greatly reduces methylation by carm1 (in vitro); when associated with a-455.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-429947	Deadenylation of mRNA
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-72649	Translation initiation complex formation
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors
R-HSA-9820865	Z-decay: degradation of maternal mRNAs by zygotically expressed factors
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 372 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, AHRARNT_01, GOBP_CYTOPLASMIC_TRANSLATION, GGGACCA_MIR133A_MIR133B, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, PAX4_01, TGCGCANK_UNKNOWN, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, CMYB_01, SP3_Q3, MORF_UBE2I, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION

GO Biological Process (13): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), mRNA splicing, via spliceosome (GO:0000398), regulatory ncRNA-mediated gene silencing (GO:0031047), positive regulation of viral genome replication (GO:0045070), mRNA stabilization (GO:0048255), positive regulation of nuclear-transcribed mRNA poly(A) tail shortening (GO:0060213), CRD-mediated mRNA stabilization (GO:0070934), negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900152), positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900153), negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:2000623), positive regulation of cytoplasmic translation (GO:2000767), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (8): RNA binding (GO:0003723), mRNA binding (GO:0003729), mRNA 3’-UTR binding (GO:0003730), poly(A) binding (GO:0008143), poly(U) RNA binding (GO:0008266), translation activator activity (GO:0008494), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (15): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), lamellipodium (GO:0030027), cell leading edge (GO:0031252), cytoplasmic ribonucleoprotein granule (GO:0036464), extracellular exosome (GO:0070062), catalytic step 2 spliceosome (GO:0071013), mCRD-mediated mRNA stability complex (GO:0106002), ribonucleoprotein complex (GO:1990904), spliceosomal complex (GO:0005681), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Nonsense-Mediated Decay (NMD)	2
Maternal to zygotic transition (MZT)	2
Eukaryotic Translation Initiation	1
Deadenylation-dependent mRNA decay	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Signaling by ROBO receptors	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
negative regulation of mRNA catabolic process	3
positive regulation of mRNA catabolic process	2
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	2
regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	2
positive regulation of translation	2
RNA processing	2
binding	2
cytoplasm	2
protein-containing complex	2
nuclear-transcribed mRNA catabolic process	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
negative regulation of gene expression	1
viral genome replication	1
regulation of viral genome replication	1
positive regulation of viral process	1
regulation of mRNA stability	1
RNA stabilization	1
nuclear-transcribed mRNA poly(A) tail shortening	1
regulation of nuclear-transcribed mRNA poly(A) tail shortening	1
mRNA stabilization	1
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
cytoplasmic translation	1
regulation of cytoplasmic translation	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
mRNA binding	1
poly-purine tract binding	1
poly-pyrimidine tract binding	1
translation regulator activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cell-substrate junction	1
cytoplasmic ribonucleoprotein granule	1
cell leading edge	1
plasma membrane bounded cell projection	1
ribonucleoprotein granule	1

Protein interactions and networks

STRING

3817 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PABPC1	EIF4G1	Q04637	999
PABPC1	EIF4A1	P04765	998
PABPC1	PAIP1	Q9H074	998
PABPC1	EIF4E	P06730	998
PABPC1	EIF4A2	Q14240	998
PABPC1	EIF4B	P23588	993
PABPC1	TNRC6A	Q8NDV7	985
PABPC1	EIF4G3	O43432	984
PABPC1	PAIP2	Q9BPZ3	977
PABPC1	G3BP1	Q13283	975
PABPC1	CSDE1	O75534	956
PABPC1	PABPN1	Q86U42	923
PABPC1	TIA1	P31483	920
PABPC1	DDX6	P26196	908
PABPC1	LARP4	Q71RC2	903

IntAct

575 interactions, top by confidence:

A	B	Type	Score
PAIP1	PABPC1	psi-mi:“MI:0914”(association)	0.970
PABPC1	PAIP1	psi-mi:“MI:0407”(direct interaction)	0.970
TNRC6C	PABPC1	psi-mi:“MI:0407”(direct interaction)	0.910
EIF4G1	PABPC1	psi-mi:“MI:0407”(direct interaction)	0.840
YBX1	SSB	psi-mi:“MI:0914”(association)	0.710
TNRC6C	PABPC1	psi-mi:“MI:0915”(physical association)	0.670
TNRC6C	PABPC1	psi-mi:“MI:0407”(direct interaction)	0.670
NCBP1	PABPC1	psi-mi:“MI:0914”(association)	0.660
NCBP1	PABPC1	psi-mi:“MI:0915”(physical association)	0.660
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
PLEKHA7	CTNND1	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
EIF4E	PABPC1	psi-mi:“MI:0914”(association)	0.560
PABPC1	EIF4E	psi-mi:“MI:0915”(physical association)	0.560
PABPC1	EIF4E	psi-mi:“MI:0914”(association)	0.560
ATXN2	PABPC1	psi-mi:“MI:0915”(physical association)	0.560
APP	PABPC1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1131): PABPC1 (Affinity Capture-MS), PABPC1 (Affinity Capture-Western), PABPC1 (Affinity Capture-Western), PABPC1 (Reconstituted Complex), PABPC1 (Affinity Capture-Western), PABPC1 (Affinity Capture-Western), PABPC1 (Affinity Capture-Western), PABPC1 (Affinity Capture-Western), PABPC1 (Affinity Capture-MS), PABPC1 (Affinity Capture-Western), PABPC1 (Affinity Capture-MS), PABPC1 (Affinity Capture-MS), PABPC1 (Affinity Capture-MS), PABPC1 (Affinity Capture-Western), PABPC1 (Affinity Capture-Western)

ESM2 similar proteins: A0A8M1NHK4, A0AV96, O22173, O60506, P11940, P21187, P29341, P61286, Q13310, Q15233, Q1LZD9, Q32NN2, Q4KLH4, Q4R4J1, Q4V7D7, Q5R469, Q5R5P4, Q5R8F7, Q5R9H4, Q5RFL9, Q5W9D5, Q5W9D6, Q5W9D7, Q5YD48, Q5ZM16, Q66H68, Q6DEY7, Q6GR16, Q6IP09, Q6IRN2, Q6P0D0, Q7JJZ8, Q7TMK9, Q7TP47, Q8BHS3, Q8R326, Q8WXF1, Q91WT8, Q91XU1, Q923K9

Diamond homologs: A0A0D1C8Z4, A1A5R1, A2A5N3, A3LXL0, A4F5G6, A5A6M3, A5DW14, A6NFN3, A6QPR6, F1QB54, F4HT49, O04319, O13845, O35698, O43251, O93235, P0CB38, P11940, P19682, P19683, P19684, P20965, P28644, P29341, P38159, P42731, P49313, P49314, P60824, P60825, P60826, P61286, P62995, P62996, P62997, Q04836, Q08935, Q08937, Q09511, Q0VD23

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
NFX1	“up-regulates activity”	PABPC1	binding
LARP4B	“up-regulates activity”	PABPC1	binding
PABPC1	“up-regulates activity”	eIF4F_complex	binding
PABPC1	“up-regulates activity”	EIF4E	binding
PABPC1	“up-regulates activity”	NFX1	binding
PABPC1	“up-regulates quantity by stabilization”	“messenger RNA”	binding
DDX3X	“up-regulates activity”	PABPC1	binding
MKRN1	“up-regulates activity”	PABPC1	ubiquitination
MKRN3	“down-regulates activity”	PABPC1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 168 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 RUNX1 Expression and Activity	5	27.5×	1e-04
Regulation of MITF-M-dependent genes involved in apoptosis	5	26.0×	1e-04
M-decay: degradation of maternal mRNAs by maternally stored factors	7	18.7×	3e-05
Deadenylation of mRNA	5	18.0×	3e-04
Dengue Virus Genome Translation and Replication	6	15.6×	2e-04
Regulation of MECP2 expression and activity	5	15.1×	7e-04
Nuclear events stimulated by ALK signaling in cancer	5	13.4×	1e-03
MTOR signalling	6	13.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
miRNA-mediated gene silencing by inhibition of translation	7	44.0×	7e-08
positive regulation of cytoplasmic translation	6	42.2×	8e-07
translational initiation	10	25.4×	6e-09
mRNA stabilization	8	20.8×	8e-07
regulation of translational initiation	6	19.9×	6e-05
intrinsic apoptotic signaling pathway	6	15.3×	2e-04
negative regulation of translation	10	13.9×	8e-07
G1/S transition of mitotic cell cycle	8	11.4×	6e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 7 cancer types — BCC, DLBCLNOS, HCC, LUSC, PCM, UTUC, WDTC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	23
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1696850	NM_002568.4(PABPC1):c.1685T>C (p.Leu562Ser)	Pathogenic
3897613	NM_002568.4(PABPC1):c.134A>G (p.Asp45Gly)	Likely pathogenic

SpliceAI

1931 predictions. Top by Δscore:

Variant	Effect	Δscore
8:100704295:A:AC	donor_gain	1.0000
8:100704296:C:CC	donor_gain	1.0000
8:100704298:TTAA:T	donor_gain	1.0000
8:100704386:TCAAC:T	acceptor_gain	1.0000
8:100704387:CAAC:C	acceptor_gain	1.0000
8:100704387:CAACC:C	acceptor_gain	1.0000
8:100704388:AAC:A	acceptor_gain	1.0000
8:100704389:AC:A	acceptor_gain	1.0000
8:100704390:CC:C	acceptor_gain	1.0000
8:100704391:C:CC	acceptor_gain	1.0000
8:100704921:ATCAC:A	donor_loss	1.0000
8:100704922:TCACC:T	donor_loss	1.0000
8:100704923:CA:C	donor_loss	1.0000
8:100704924:A:AT	donor_loss	1.0000
8:100705054:CAC:C	acceptor_gain	1.0000
8:100705055:ACCTA:A	acceptor_loss	1.0000
8:100705057:C:CC	acceptor_gain	1.0000
8:100705057:C:CG	acceptor_loss	1.0000
8:100705064:C:CT	acceptor_gain	1.0000
8:100705670:CAGG:C	acceptor_gain	1.0000
8:100705674:C:CC	acceptor_gain	1.0000
8:100706645:CCATA:C	donor_loss	1.0000
8:100706646:CATA:C	donor_loss	1.0000
8:100706648:TACCT:T	donor_loss	1.0000
8:100706649:A:AC	donor_gain	1.0000
8:100706650:C:CC	donor_gain	1.0000
8:100706801:GTTAG:G	acceptor_gain	1.0000
8:100706802:TTAG:T	acceptor_gain	1.0000
8:100706803:TAG:T	acceptor_gain	1.0000
8:100706804:AG:A	acceptor_gain	1.0000

AlphaMissense

4202 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:100704360:G:C	H617D	1.000
8:100704363:C:G	A616P	1.000
8:100704365:T:G	Q615P	1.000
8:100704368:A:G	L614P	1.000
8:100704368:A:T	L614Q	1.000
8:100704371:A:G	V613A	1.000
8:100704371:A:T	V613E	1.000
8:100704375:C:G	A612P	1.000
8:100704380:G:A	A610V	1.000
8:100704380:G:T	A610D	1.000
8:100704381:C:G	A610P	1.000
8:100704381:C:T	A610T	1.000
8:100704382:T:A	E609D	1.000
8:100704382:T:G	E609D	1.000
8:100704383:T:A	E609V	1.000
8:100704384:C:T	E609K	1.000
8:100704926:C:A	K606N	1.000
8:100704926:C:G	K606N	1.000
8:100704928:T:C	K606E	1.000
8:100704936:A:G	L603P	1.000
8:100704936:A:T	L603H	1.000
8:100704949:A:G	S599P	1.000
8:100704954:A:G	L597P	1.000
8:100704954:A:T	L597H	1.000
8:100704957:A:C	M596R	1.000
8:100704957:A:T	M596K	1.000
8:100704963:A:G	L594P	1.000
8:100704963:A:T	L594H	1.000
8:100704966:A:G	L593P	1.000
8:100704966:A:T	L593H	1.000

dbSNP variants (sampled 300 via entrez): RS1000024118 (8:100721823 G>A), RS1000115942 (8:100710596 A>C,G), RS1000541945 (8:100713931 A>AT), RS1000629943 (8:100720512 G>A,C,T), RS1000648181 (8:100719494 T>C), RS1000776250 (8:100722783 A>G), RS1000843658 (8:100703365 A>G), RS1000918618 (8:100702780 T>G), RS1001080739 (8:100708550 T>C), RS1001095289 (8:100704516 C>A,T), RS1001274738 (8:100704233 C>A,T), RS1001325973 (8:100715945 C>T), RS1001375363 (8:100705208 G>A,C), RS1001433069 (8:100710372 G>A,C), RS1001443895 (8:100704499 G>C,T)

Disease associations

OMIM: gene MIM:604679 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (4): teratoma (MONDO:0002601), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), CIC-rearranged sarcoma (MONDO:0956989)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005951_63	Body mass index	2.000000e-08
GCST010396_271	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-07
GCST90002385_365	High light scatter reticulocyte count	1.000000e-16
GCST90002386_485	High light scatter reticulocyte percentage of red cells	3.000000e-17
GCST90002390_609	Mean corpuscular hemoglobin	2.000000e-09
GCST90002405_516	Reticulocyte count	1.000000e-14
GCST90002406_306	Reticulocyte fraction of red cells	9.000000e-18

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007874	gut microbiome measurement
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D013724	Teratoma	C04.557.465.910

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293286 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 272,757 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1068	OXCARBAZEPINE	4	16,118
CHEMBL1200938	METHYSERGIDE MALEATE	4	4
CHEMBL810	TEMOZOLOMIDE	4	97,713
CHEMBL284328	HOMIDIUM BROMIDE	2	147,818
CHEMBL43482	MITONAFIDE	2	8,660
CHEMBL46874	PINAFIDE	2	2,444

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

Binding affinities (BindingDB)

209 measured of 397 human assays (428 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-sulfanylidene-1,3-dithiole-4,5-dicarboxylic acid dimethyl ester	EC50	0.00847 nM
(3R,4S,5S)-2-(6,8-dimethyl-1-pyrrolo[2,3-g]quinolinyl)oxane-3,4,5-triol;hydrochloride	IC50	23 nM
1-(2-furanyl)-2-(5-methyl-1,3,4-thiadiazol-2-yl)-1H-[1]benzopyrano[2,3-c]pyrrole-3,9-dione	IC50	50.1 nM
MLS001008494	IC50	1030 nM
MLS001212885	IC50	1080 nM
cid_6603239	IC50	1300 nM
(8S)-7-(4-chlorobenzoyl)-3-(3-methacrylamidophenyl)-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	IC50	1540 nM
2-{(E)-2-[3-Methoxy-4-(o-tolylcarbamoyl-methoxy)-phenyl]-vinyl}-1-methyl-pyridinium	IC50	1560 nM
3-[6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-5-phenyl-pentanoic acid	IC50	1610 nM
MLS000117135	EC50	2020 nM
MLS000037873	IC50	2020 nM
1-(1-cyclohex-3-enylmethoxy)-3-(3-ethyl-2-methyl-1-benzimidazol-1-iumyl)-2-propanol;iodide	IC50	2120 nM
N-(3,4-dimethylphenyl)-2-[[5-[3-(4-methoxyphenyl)propyl]-1,3,4-oxadiazol-2-yl]sulfanyl]ethanamide	IC50	2180 nM
(5Z)-3-(3-chlorophenyl)-5-(4-hydroxy-3-methoxy-5-nitro-benzylidene)thiazolidine-2,4-quinone	IC50	2210 nM
[(1R,5S)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl] (2R)-3-oxidanyl-2-phenyl-propanoate;iodide	IC50	2230 nM
SMR000564432	IC50	2240 nM
N-(3-methoxyphenyl)-1-methylpyridin-1-ium-3-carboxamide;iodide	IC50	2330 nM
MLS001030075	IC50	2360 nM
cid_16240614	IC50	2480 nM
(4-hydroxy-4,4-diphenylbut-2-ynyl)-dimethyl-propan-2-ylazanium;bromide	IC50	2550 nM
N-[3-[4-methyl-5-(2-morpholin-4-yl-2-oxidanylidene-ethyl)sulfanyl-1,2,4-triazol-3-yl]phenyl]benzamide	IC50	2620 nM
SMR000425384	IC50	2620 nM
cid_24746774	IC50	2710 nM
cid_9593400	IC50	2740 nM
4-propyl-1,2,3,5,6,7-hexahydrodicyclopenta[1,2-c:1’,2’-g]pyridin-8-imine;hydroiodide	IC50	2760 nM
MLS000766745	IC50	2790 nM
SMR000555824	IC50	2790 nM
SMR000427247	IC50	2800 nM
(6E)-6-[(4-methoxyphenyl)methylidene]-1-methyl-piperazine-2,5-dione	IC50	2810 nM
(6E)-6-[(1-pyridin-1-iumylamino)methylidene]-1-cyclohexa-2,4-dienone;iodide	IC50	2880 nM
[2-(furan-2-ylmethylamino)-2-oxoethyl] 2-(4-bromo-2-methylphenyl)sulfanylacetate	IC50	2940 nM
MLS000097330	IC50	3370 nM
2-[4-(2-naphthalenylsulfonyl)-1-piperazinyl]-N-propan-2-ylpropanamide	IC50	3380 nM
(4S,5R,6R)-1-ethyl-2-(2-methoxyethylamino)-6-methyl-4-(2-phenylethyl)-5,6-dihydro-4H-pyrimidine-5-carboxylic acid methyl ester	IC50	3390 nM
2-chloranyl-N-ethyl-5-(4-ethylpiperazin-1-yl)sulfonyl-N-[2-[(4-methoxyphenyl)amino]-2-oxidanylidene-ethyl]benzamide	IC50	3400 nM
SMR000672087	IC50	3510 nM
MLS000829960	IC50	3560 nM
N-[1-[4-ethyl-5-[2-oxidanylidene-2-[(phenylmethyl)amino]ethyl]sulfanyl-1,2,4-triazol-3-yl]-2-oxidanyl-ethyl]benzamide	IC50	3670 nM
SMR000672072	IC50	3860 nM
MLS000560945	IC50	4150 nM
cid_5989040	IC50	4300 nM
MLS001217275	IC50	4370 nM
SMR000011434	EC50	4380 nM
cid_1051609	IC50	4440 nM
[2-({3-[(2,4-dichlorobenzyl)oxy]-4-methoxybenzylidene}hydrazono)-4-oxo-1,3-thiazolidin-5-yl]acetic acid	IC50	4480 nM
(2-Cyclopropyl-quinazolin-4-ylsulfanyl)-acetic acid ethyl ester	IC50	4510 nM
SMR000465526	IC50	4700 nM
9-chloro-2-keto-8,8-dimethyl-pyrano[2,3-f]chromene-10-carbaldehyde oxime	IC50	4970 nM
(4E)-2,3-dihydroxy-4-[[(2-methylimino-4-thiophen-2-yl-1,3-thiazol-3-yl)amino]methylidene]cyclohexa-2,5-dien-1-one	EC50	5050 nM
(4-methoxy-1,3-benzothiazol-2-yl)-[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]amine	IC50	5160 nM

ChEMBL bioactivities

90 potent at pChembl≥5 of 370 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.88	IC50	1320	nM	CHEMBL1497773
5.88	IC50	1330	nM	CHEMBL1545487
5.78	IC50	1680	nM	CHEMBL1464460
5.73	IC50	1850	nM	CHEMBL1423915
5.73	IC50	1870	nM	CHEMBL592588
5.65	IC50	2220	nM	CHEMBL589711
5.61	IC50	2480	nM	CHEMBL1383779
5.57	IC50	2725	nM	CHEMBL1577127
5.56	IC50	2760	nM	CHEMBL1445700
5.55	IC50	2810	nM	CHEMBL1563641
5.55	IC50	2790	nM	CHEMBL1463019
5.49	IC50	3250	nM	CHEMBL1301276
5.49	IC50	3265	nM	CHEMBL1303289
5.48	IC50	3290	nM	CHEMBL1377588
5.47	Kd	3356	nM	CHEMBL3752910
5.47	ED50	3356	nM	CHEMBL3752910
5.46	IC50	3495	nM	CHEMBL1497097
5.46	IC50	3480	nM	CHEMBL1572009
5.45	IC50	3565	nM	CHEMBL3197066
5.43	IC50	3685	nM	CHEMBL1789987
5.42	IC50	3830	nM	CHEMBL1342158
5.40	IC50	4000	nM	CHEMBL1464460
5.39	IC50	4075	nM	CHEMBL1324692
5.39	IC50	4085	nM	CHEMBL1505531
5.37	IC50	4320	nM	CHEMBL1359526
5.37	IC50	4320	nM	CHEMBL1364684
5.36	IC50	4395	nM	CHEMBL3195960
5.36	IC50	4405	nM	CHEMBL1416798
5.36	IC50	4390	nM	CHEMBL1485592
5.35	IC50	4470	nM	CHEMBL1469272
5.34	IC50	4535	nM	CHEMBL1469858
5.34	IC50	4550	nM	CHEMBL1332525
5.34	IC50	4585	nM	CHEMBL1562954
5.33	IC50	4680	nM	CHEMBL1303289
5.31	IC50	4860	nM	CHEMBL1480280
5.31	IC50	4910	nM	CHEMBL1319469
5.30	IC50	4950	nM	CHEMBL1547939
5.29	IC50	5140	nM	CHEMBL3196705
5.28	IC50	5270	nM	CHEMBL1388052
5.27	IC50	5320	nM	CHEMBL1573412
5.27	IC50	5325	nM	CHEMBL1318253
5.27	IC50	5425	nM	CHEMBL1423236
5.27	IC50	5405	nM	CHEMBL1320897
5.26	IC50	5515	nM	CHEMBL1432423
5.26	IC50	5470	nM	CHEMBL1480992
5.25	IC50	5630	nM	CHEMBL1355123
5.25	IC50	5575	nM	CHEMBL3210843
5.24	IC50	5700	nM	CHEMBL1343383
5.24	IC50	5825	nM	CHEMBL3213476
5.23	IC50	5930	nM	CHEMBL1610821

PubChem BioAssay actives

1 with measured affinity, of 10 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148926: Binding affinity to human PABPC1 incubated for 45 mins by Kinobead based pull down assay	kd	3.3559	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, affects expression, decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
epigallocatechin gallate	increases expression, affects cotreatment	2
bisphenol S	decreases expression, increases expression, affects cotreatment	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Cisplatin	decreases expression, increases response to substance	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
sodium arsenite	affects localization	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
potassium chromate(VI)	affects cotreatment, increases expression	1
nivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-hydroxy-equilenin	increases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
pateamine A	affects localization	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
bromovanin	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 8 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614548	Binding	PUBCHEM_BIOASSAY: uHTS fluorescence polarization assay for the identification of translation initiation inhibitors (PABP). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2012, AID2030, AID435011, AID435018, AI	PubChem BioAssay data set
CHEMBL1738357	Functional	PUBCHEM_BIOASSAY: SAR analysis for the identification of translation initiation inhibitors (PABP). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2012, AID2014, AID2030]	PubChem BioAssay data set

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5C3	SEES3-1V human PABPC1, clone1	Embryonic stem cell	Male
CVCL_A5C4	SEES3-1V human PABPC1, clone2	Embryonic stem cell	Male
CVCL_A5C5	SEES3-1V human PABPC1, clone3	Embryonic stem cell	Male
CVCL_B7IM	BC-PAK1	Cancer cell line	Female
CVCL_D1Y2	Abcam A-549 PABPC1 KO	Cancer cell line	Male
CVCL_D2CA	Abcam HCT 116 PABPC1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00104676	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage II or Stage III Germ Cell Tumors
NCT02375204	PHASE3	ACTIVE_NOT_RECRUITING	Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients with Relapsed or Refractory Germ Cell Tumors
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00002931	PHASE2	COMPLETED	Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Germ Cell Cancer
NCT00301782	PHASE2	COMPLETED	Combination Chemotherapy in Treating Male Patients With Germ Cell Tumors
NCT00432094	PHASE2	COMPLETED	Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors
NCT00453232	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Men With Metastatic Germ Cell Tumors
NCT00453310	PHASE2	COMPLETED	Sunitinib in Treating Patients With Metastatic Germ Cell Tumors That Have Relapsed or Not Responded to Treatment
NCT00470366	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Patients With Previously Untreated Germ Cell Tumors
NCT02300987	PHASE2	COMPLETED	A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders