PCBP2

Summary

PCBP2 (poly(rC) binding protein 2, HGNC:8648) is a protein-coding gene on chromosome 12q13.13, encoding Poly(rC)-binding protein 2 (Q15366). Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. It is a common-essential gene (DepMap: required in 99.2% of cancer cell lines).

The protein encoded by this gene appears to be multifunctional. Along with PCBP-1 and hnRNPK, it is one of the major cellular poly(rC)-binding proteins. The encoded protein contains three K-homologous (KH) domains which may be involved in RNA binding. Together with PCBP-1, this protein also functions as a translational coactivator of poliovirus RNA via a sequence-specific interaction with stem-loop IV of the IRES, promoting poliovirus RNA replication by binding to its 5’-terminal cloverleaf structure. It has also been implicated in translational control of the 15-lipoxygenase mRNA, human papillomavirus type 16 L2 mRNA, and hepatitis A virus RNA. The encoded protein is also suggested to play a part in formation of a sequence-specific alpha-globin mRNP complex which is associated with alpha-globin mRNA stability. This multiexon structural mRNA is thought to be retrotransposed to generate PCBP-1, an intronless gene with functions similar to that of PCBP2. This gene and PCBP-1 have paralogous genes (PCBP3 and PCBP4) which are thought to have arisen as a result of duplication events of entire genes. This gene also has two processed pseudogenes (PCBP2P1 and PCBP2P2). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5094 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 49 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_031989

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8648
Approved symbol	PCBP2
Name	poly(rC) binding protein 2
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	HNRPE2, hnRNP-E2, HNRNPE2
Ensembl gene	ENSG00000197111
Ensembl biotype	protein_coding
OMIM	601210
Entrez	5094

Gene structure

Transcript identifiers

Ensembl transcripts: 66 — 58 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay

ENST00000359282, ENST00000359462, ENST00000437231, ENST00000439930, ENST00000447282, ENST00000455667, ENST00000546463, ENST00000546652, ENST00000547048, ENST00000547859, ENST00000547987, ENST00000548190, ENST00000548933, ENST00000549272, ENST00000549863, ENST00000550192, ENST00000550520, ENST00000550585, ENST00000550733, ENST00000550910, ENST00000551104, ENST00000552296, ENST00000552819, ENST00000552980, ENST00000553064, ENST00000562264, ENST00000868134, ENST00000868135, ENST00000868136, ENST00000868137, ENST00000868138, ENST00000868139, ENST00000868140, ENST00000868141, ENST00000868142, ENST00000868143, ENST00000868144, ENST00000868145, ENST00000868146, ENST00000868147, ENST00000868148, ENST00000868149, ENST00000868150, ENST00000868151, ENST00000868152, ENST00000868153, ENST00000868154, ENST00000868155, ENST00000868156, ENST00000868157, ENST00000868158, ENST00000868159, ENST00000868160, ENST00000868161, ENST00000868162, ENST00000868163, ENST00000868164, ENST00000868165, ENST00000868166, ENST00000923986, ENST00000923987, ENST00000923988, ENST00000946734, ENST00000946735, ENST00000946736, ENST00000946737

RefSeq mRNA: 7 — MANE Select: NM_031989 NM_001098620, NM_001128911, NM_001128912, NM_001128913, NM_001128914, NM_005016, NM_031989

CCDS: CCDS44900, CCDS44901, CCDS44902, CCDS44903, CCDS44904, CCDS55830, CCDS8859

Canonical transcript exons

ENST00000546463 — 15 exons

Exon	Start	End
ENSE00003480577	53455347	53455370
ENSE00003489517	53455461	53455493
ENSE00003493178	53471638	53471807
ENSE00003523658	53465932	53465973
ENSE00003532538	53454726	53454869
ENSE00003577141	53467221	53467293
ENSE00003602867	53455885	53456001
ENSE00003627413	53464760	53464852
ENSE00003645717	53462493	53462567
ENSE00003673222	53459272	53459403
ENSE00003677361	53467805	53467843
ENSE00003691939	53468777	53468832
ENSE00003787788	53461015	53461143
ENSE00003899734	53452102	53452376
ENSE00003902597	53479406	53481162

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 856.4611 / max 31777.5021, expressed in 1828 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125766	843.2439	1828
125780	3.8747	1409
125772	2.4753	1215
125776	1.6751	995
125774	1.3197	715
125773	1.1389	591
125778	1.0963	619
125779	0.6091	310
125784	0.5348	299
125771	0.3186	136

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.69	gold quality
ventricular zone	UBERON:0003053	99.64	gold quality
stromal cell of endometrium	CL:0002255	99.62	gold quality
left testis	UBERON:0004533	99.61	gold quality
cortical plate	UBERON:0005343	99.61	gold quality
right testis	UBERON:0004534	99.60	gold quality
left ovary	UBERON:0002119	99.57	gold quality
right adrenal gland cortex	UBERON:0035827	99.57	gold quality
right lobe of thyroid gland	UBERON:0001119	99.56	gold quality
left lobe of thyroid gland	UBERON:0001120	99.56	gold quality
right adrenal gland	UBERON:0001233	99.55	gold quality
right ovary	UBERON:0002118	99.55	gold quality
metanephros cortex	UBERON:0010533	99.55	gold quality
endocervix	UBERON:0000458	99.54	gold quality
left adrenal gland	UBERON:0001234	99.54	gold quality
right lung	UBERON:0002167	99.54	gold quality
body of pancreas	UBERON:0001150	99.53	gold quality
colonic epithelium	UBERON:0000397	99.52	gold quality
embryo	UBERON:0000922	99.52	gold quality
right uterine tube	UBERON:0001302	99.52	gold quality
skin of leg	UBERON:0001511	99.52	gold quality
left adrenal gland cortex	UBERON:0035825	99.52	gold quality
tibial nerve	UBERON:0001323	99.51	gold quality
body of uterus	UBERON:0009853	99.51	gold quality
body of stomach	UBERON:0001161	99.50	gold quality
skin of abdomen	UBERON:0001416	99.50	gold quality
cerebellar hemisphere	UBERON:0002245	99.50	gold quality
mucosa of stomach	UBERON:0001199	99.49	gold quality
thyroid gland	UBERON:0002046	99.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.48	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	915.40
E-MTAB-10042	yes	10.80
E-CURD-122	yes	5.51
E-CURD-79	no	1228.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNRNPK

miRNA regulators (miRDB)

133 targeting PCBP2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6721-5P	99.93	68.92	2981

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The binding of HuR, CP1, and CP2 to AR mRNA suggests a role for each of these proteins in the post-transcriptional regulation of AR expression in cancer cells. (PMID:12011088)
• specific PCBP2 domains may have distinct roles for differential picornavirus template utilization during viral translation and RNA replication (PMID:12414943)
• deletion of NLS I from alphaCP1 blocks its nuclear accumulation, whereas NLS I and NLS II must both be inactivated to block nuclear accumulation of alphaCP2 (PMID:14612387)
• Data suggest that poly(C)-binding protein 2 KH domain 1 interactions with telomeric DNA and telomerase RNA may be involved in the regulation of telomere/telomerase functions. (PMID:15331611)
• PCBP2 KH1 binds to C-rich strand of human telomeric DNA, indicating that that PCBPs may participate in mechanisms involved in the regulation of telomere/telomerase functions (PMID:16186123)
• 2’,5’-oligoadenylate synthetase activation may occur in prostate cancer cells stimulated by cellular mRNAs for PCBP2. (PMID:17145707)
• Downregulation of HnRNP E2 is associated with oral cancer (PMID:17219427)
• molecular model of the interaction of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA. (PMID:17426136)
• Crystal structures of PCBP2 KH1 domain in complex with a 12-nucleotide DNA corresponding to two repeats of the human C-rich strand telomeric DNA and its RNA equivalent. (PMID:17526645)
• Study shows that through the loss of the KH3 domain, and therefore loss of its ability to function in translation, PCBP2 can mediate the switch from viral translation to RNA replication. (PMID:17581994)
• validated occurrence of an unusual TG 3’ splice site in intron 7 (PMID:17672918)
• The interaction of PCBP2 with RNA target sequences at the 5’ end of the coxsackievirus B3 genome was investigated. (PMID:18086560)
• PCBP2 may be involved in stress-induced remodeling of mRNP complexes and that it may also play a role in the rapid transition of certain silenced mRNAs into a translationally active state. (PMID:18174314)
• Using a novel protein-RNA tethering system, We establish PCBP2 as an essential co-factor in the initiation of poliovirus negative-strand synthesis. (PMID:18252259)
• The authors showed that the PCBP2 linker domain modulates binding to poliovirus stem-loop IV RNA via a mechanism that is not inhibited by the antibody. (PMID:18656221)
• SIN1 and PCBP2 are generally coregulated with large numbers of genes implicated in both cell survival and death and in cellular stress responses, including RNA translation and processing (PMID:18687895)
• analysis of the human poly(C)-binding protein containing the first and second KH domains reveals insights into its regulatory mechanisms (PMID:18701464)
• The data demonstrate interaction of isolated PCBP2 KH1 and KH3 domains to four distinct target sites within the 5’-nontranslated region of the CVB3 genomic RNA. (PMID:18929541)
• reveal a pivotal role for alphaCP1 and alphaCP2 in a p53-independent pathway of p21(WAF) control and cell cycle progression (PMID:19211566)
• Results establish the compositional diversity among P-bodies, and that PCBP2, probably in complex with other mRNP factors, may dynamically recognize such differences and accumulate to specific P-bodies. (PMID:19230839)
• PCBP2-AIP4 axis defines a new signaling cascade for MAVS degradation and ‘fine tuning’ of antiviral innate immunity. (PMID:19881509)
• The authors established that the 5’CL-PCBP complex is required for optimal poliovirus viral RNA translation and identified the KH3 domain of PCBP2 as the functional region. (PMID:19945132)
• Study reports that loss of miR-328 occurs in blast crisis chronic myelogenous leukemia (CML-BC) in a BCR/ABL dose- and kinase-dependent manner through the MAPK-hnRNP E2 pathway. (PMID:20211135)
• study demonstrates the mechanism of the participation of PCBP2 in hepatitis C virus translation and replication (PMID:21632751)
• SRp75 inhibits splicing of tau exon 10 by binding to the CA repeat in the intronic splicing silencer downstream of the exon, and requires hnRNPG to exert its full regulatory effect on tau exon 10. (PMID:21723381)
• Overall, the results presented here suggest that cellular PCBP2 and PCBP1 antagonize vesiculovirus growth by affecting viral gene expression and highlight the importance of these two cellular proteins in restricting virus infections. (PMID:21752917)
• PCBP2 stabilizes the mRNA of STAT1 and STAT2 through binding the 3’Untranslated Region (UTR) of these two molecules. (PMID:22022391)
• PCBP2 specifically and selectively interacts with rabies virus glycoprotein mRNA and this interaction may contribute to the post-transcriptional regulation of glycoprotein expression (PMID:22438951)
• Cytosolic iron may modulate the association between PCBP2 and Dicer, as well as the multimerization of PCBP2 and its ability to bind to miRNA precursors (PMID:22633452)
• PCBP2 is an RNA-binding protein that modulates glioma growth by regulating FHL3 (PMID:23585479)
• PCBP2 controls the 3’ processing of its own transcript. (PMID:23629627)
• PCBP1 and -2 form a complex for iron delivery to ferritin, and all PCBPs may share iron chaperone activity. (PMID:23640898)
• Inhibition of poliovirus-induced cleavage of cellular PCBP2 protein reduces the viral RNA replication. (PMID:24371074)
• PCBP2 and PTB are differentially cleaved by human rhinovirus proteinase in infected cells. (PMID:24418535)
• SIRT6 inhibits glioma cell proliferation and colony formation in vitro and glioma cell growth in vivo in a PCBP2 dependent manner. SIRT6 inhibits PCBP2 expression through deacetylating H3K9ac and SIRT6 acts as a tumor suppressor in glioma. (PMID:24607900)
• PCBP2-depletion induces apoptosis in gastric cancer cells via up-regulating expression of pro-apoptotic proteins and down-regulating anti-apoptotic proteins. miR-34a is a target of PCBP2, and miR-34a is critically essential for the function of PCBP2. (PMID:24796666)
• PCBP1 and PCBP2 may serve as iron chaperones to multiple classes of cytosolic nonheme iron enzymes and may have a particular role in restoring metal cofactors that are spontaneously lost in iron deficient cells. (PMID:24843120)
• STAT3 functions via cellular PCBP2 to regulate B-cell lytic susceptibility by restraining Epstein-Barr Virus lytic activation. (PMID:25717101)
• Protein and mRNA levels of PCBP2 were down-regulated under insulin-resistant conditions. Over-expression of PCBP2 inhibits HIF1alpha and STAT3 pathway. (PMID:26002461)
• PCBP2 knockdown promoted angiotensin II-induced hypertrophy (increase in cell size, protein synthesis and activation of fetal genes) of cardiomyocytes, while PCBP2 overexpression obtained oppose effects. (PMID:26116532)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcbp2	ENSDARG00000099039
mus_musculus	Pcbp2	ENSMUSG00000056851
rattus_norvegicus	AC128212.1	ENSRNOG00000054355
drosophila_melanogaster	ps	FBGN0261552
drosophila_melanogaster	mub	FBGN0262737
drosophila_melanogaster	Imp	FBGN0285926
caenorhabditis_elegans		WBGENE00003978
caenorhabditis_elegans		WBGENE00010908
caenorhabditis_elegans		WBGENE00013347
caenorhabditis_elegans		WBGENE00016489
caenorhabditis_elegans	fubl-4	WBGENE00019692

Paralogs (12): IGF2BP2 (ENSG00000073792), KHSRP (ENSG00000088247), PCBP4 (ENSG00000090097), NOVA2 (ENSG00000104967), FUBP3 (ENSG00000107164), IGF2BP3 (ENSG00000136231), NOVA1 (ENSG00000139910), IGF2BP1 (ENSG00000159217), FUBP1 (ENSG00000162613), HNRNPK (ENSG00000165119), PCBP1 (ENSG00000169564), PCBP3 (ENSG00000183570)

Protein

Protein identifiers

Poly(rC)-binding protein 2 — Q15366 (reviewed: Q15366)

Alternative names: Alpha-CP2, Heterogeneous nuclear ribonucleoprotein E2

All UniProt accessions (12): A0A384N6B9, F8VRH0, F8VTZ0, F8VXH9, F8VZX2, F8W0G4, F8W1G6, Q15366, H3BND9, H3BRU6, H3BSP4, H3BSS4

UniProt curated annotations — full annotation on UniProt →

Function. Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. Major cellular poly(rC)-binding protein. Also binds poly(rU). Acts as a negative regulator of antiviral signaling. Negatively regulates cellular antiviral responses mediated by MAVS signaling. It acts as an adapter between MAVS and the E3 ubiquitin ligase ITCH, therefore triggering MAVS ubiquitination and degradation. Negativeley regulates the cGAS-STING pathway via interaction with CGAS, preventing the formation of liquid-like droplets in which CGAS is activated. Together with PCBP1, required for erythropoiesis, possibly by regulating mRNA splicing. (Microbial infection) In case of infection by poliovirus, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation. Also plays a role in initiation of viral RNA replication in concert with the viral protein 3CD.

Subunit / interactions. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Interacts with IFIH1 and RNF135. Interacts with MAVS (via C-terminus) and ITCH (via WW domains). Interacts with CGAS; preventing the formation of liquid-like droplets in which CGAS is activated.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Detected in all tissues examined.

Post-translational modifications. Phosphorylated. The non-phosphorylated form(s) exhibited the strongest poly(rC)-binding activity. (Microbial infection) Proteolytically cleaved by picornavirus proteinase 3CD.

Domain organisation. The KH domains mediates poly(C) binding.

Isoforms (8)

UniProt ID	Names	Canonical?
Q15366-1	1	yes
Q15366-2	2
Q15366-3	3
Q15366-4	4
Q15366-5	5
Q15366-6	6
Q15366-7	7
Q15366-8	8

RefSeq proteins (7): NP_001092090, NP_001122383, NP_001122384, NP_001122385, NP_001122386, NP_005007, NP_114366* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF00013

UniProt features (39 total): helix 12, strand 10, modified residue 5, splice variant 4, domain 3, cross-link 3, chain 1, site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2P2R	X-RAY DIFFRACTION	1.6
2AXY	X-RAY DIFFRACTION	1.7
2PQU	X-RAY DIFFRACTION	2.12
2PY9	X-RAY DIFFRACTION	2.56
2JZX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15366-F1	67.42	0.05

Functional residue map

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

Catalytic / active sites (1): 253–254 (cleavage, by viral proteinase 3cd)

Post-translational modifications (8): 115, 185, 322, 173, 189, 272, 364, 365

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 374 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_INNATE_IMMUNE_SYSTEM, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, LFA1_Q6, MORF_UBE2I, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, HSIAO_HOUSEKEEPING_GENES, MEF2_02, CAGCTG_AP4_Q5, BOYLAN_MULTIPLE_MYELOMA_D_DN, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (12): regulation of transcription by RNA polymerase II (GO:0006357), mRNA metabolic process (GO:0016071), viral RNA genome replication (GO:0039694), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), innate immune response (GO:0045087), negative regulation of defense response to virus (GO:0050687), defense response to virus (GO:0051607), IRES-dependent viral translational initiation (GO:0075522), chromatin looping (GO:0140588), negative regulation of cGAS/STING signaling pathway (GO:0160049), immune system process (GO:0002376), cGAS/STING signaling pathway (GO:0140896)

GO Molecular Function (10): single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), mRNA binding (GO:0003729), enzyme binding (GO:0019899), ubiquitin protein ligase binding (GO:0031625), lncRNA binding (GO:0106222), promoter-enhancer loop anchoring activity (GO:0140585), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), extracellular exosome (GO:0070062), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
mRNA Splicing	1
Metabolism of RNA	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
SARS-CoV-1-host interactions	1
mRNA 3’-end processing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nucleic acid binding	2
RNA binding	2
binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
RNA metabolic process	1
viral genome replication	1
RNA biosynthetic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
immune response	1
defense response to symbiont	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of defense response to virus	1
defense response to virus	1
defense response	1
response to virus	1
viral process	1
viral translation	1
chromatin organization	1
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	1
cGAS/STING signaling pathway	1
biological_process	1
cytoplasmic pattern recognition receptor signaling pathway	1
DNA binding	1
protein binding	1
ubiquitin-like protein ligase binding	1
chromatin loop anchoring activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
extracellular vesicle	1
protein-containing complex	1

Protein interactions and networks

STRING

3028 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCBP2	SRSF3	P23152	988
PCBP2	CEBPA	P49715	921
PCBP2	PCBP1	Q15365	919
PCBP2	SLC40A1	Q9NP59	867
PCBP2	TIA1	P31483	867
PCBP2	ITCH	Q96J02	864
PCBP2	KCNG1	Q9UIX4	840
PCBP2	HNRNPD	P07029	808
PCBP2	HNRNPC	P07910	749
PCBP2	DICER1	Q9UPY3	745
PCBP2	HNRNPA1	P09651	739
PCBP2	HNRNPDL	O14979	739
PCBP2	EIF4G1	Q04637	738
PCBP2	PABPC1	P11940	732
PCBP2	AGO2	Q9UKV8	714

IntAct

183 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PCBP2	SRSF3	psi-mi:“MI:0915”(physical association)	0.580
SNRPA	PCBP2	psi-mi:“MI:0915”(physical association)	0.560
PCBP2	SNRPA	psi-mi:“MI:0915”(physical association)	0.560
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
SETMAR	HSPA8	psi-mi:“MI:0914”(association)	0.530
PABPC1	PCBP2	psi-mi:“MI:0407”(direct interaction)	0.530
PCBP2	PABPC1	psi-mi:“MI:0915”(physical association)	0.530
	PCBP2	psi-mi:“MI:0915”(physical association)	0.530
	PCBP2	psi-mi:“MI:0407”(direct interaction)	0.530
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
PCBP1	PCBP2	psi-mi:“MI:0915”(physical association)	0.510
	PCBP2	psi-mi:“MI:0914”(association)	0.500
	PCBP2	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (430): PCBP2 (Affinity Capture-MS), PCBP2 (Affinity Capture-MS), SNRPA (Two-hybrid), PCBP2 (Affinity Capture-MS), PCBP2 (Affinity Capture-MS), PCBP2 (Affinity Capture-MS), PCBP2 (Affinity Capture-MS), PCBP2 (Affinity Capture-MS), PCBP2 (Affinity Capture-Western), PCBP2 (Reconstituted Complex), PCBP1 (Affinity Capture-Western), PCBP2 (Affinity Capture-MS), PCBP2 (Co-fractionation), PCBP2 (Co-fractionation), PCBP2 (Co-fractionation)

ESM2 similar proteins: A0A8I6G705, A1L3K1, B5DFF2, B5DFI8, G3MWR8, O19048, O19137, O88508, P06730, P29338, P57721, P57722, P60335, Q12800, Q13888, Q15365, Q15366, Q16763, Q1LZ53, Q1RML1, Q28D01, Q2TBV5, Q4W5Z4, Q5E9A3, Q5FVR7, Q5NVP9, Q5TDH0, Q61990, Q6AYU1, Q6DH13, Q6P1K8, Q6ZRY4, Q7RTP6, Q8C6G8, Q8CCI5, Q8CJ19, Q8IY57, Q8N488, Q8VC52, Q921J4

Diamond homologs: A0A0B4KGY6, A0A1W2P872, O19048, O19049, O73932, O74919, P51513, P57721, P57722, P60335, P61978, P61979, P61980, Q15365, Q15366, Q2PFW9, Q32PX7, Q3T0D0, Q4R4M6, Q5E9A3, Q5R5H8, Q5RB68, Q5SF07, Q5ZIQ3, Q5ZLP8, Q61990, Q80WA4, Q8UVD9, Q91WJ8, Q96AE4, Q96I24, Q9JKN6, Q9LZ82, Q9SZH4, Q9UNW9, Q9Y6M1, O00425, P38151, P57723, P57724

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
NLRX1	“up-regulates activity”	PCBP2	binding
PCBP2	“down-regulates quantity by destabilization”	MAVS	binding
PCBP2	“up-regulates activity”	ITCH	binding
MAPK1	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
MAPK3	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
ERK1/2	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
LPAR	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
Ggamma	“up-regulates quantity by stabilization”	PCBP2	phosphorylation
Gbeta	“up-regulates quantity by stabilization”	PCBP2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 160 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
Dengue Virus Genome Translation and Replication	5	15.1×	2e-03
mRNA 3’-end processing	6	11.2×	2e-03
Processing of Capped Intron-Containing Pre-mRNA	14	10.9×	2e-08
mRNA Polyadenylation	11	9.2×	7e-06
mRNA Splicing	8	8.4×	8e-04
mRNA Splicing - Major Pathway	16	8.3×	3e-08
Metabolism of RNA	13	5.2×	3e-04
Dengue Virus-Host Interactions	11	4.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA stabilization	5	14.1×	4e-03
intrinsic apoptotic signaling pathway	5	13.8×	4e-03
mRNA splicing, via spliceosome	17	12.0×	7e-11
negative regulation of translation	7	10.6×	1e-03
mRNA processing	10	6.1×	1e-03
RNA splicing	8	5.4×	9e-03
DNA damage response	12	4.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2087 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53454700:T:TA	acceptor_gain	1.0000
12:53454712:T:G	acceptor_gain	1.0000
12:53454724:A:AG	acceptor_gain	1.0000
12:53454725:G:GA	acceptor_gain	1.0000
12:53454725:GTTT:G	acceptor_gain	1.0000
12:53454725:GTTTT:G	acceptor_gain	1.0000
12:53454868:AGGT:A	donor_loss	1.0000
12:53454869:GGTA:G	donor_loss	1.0000
12:53454870:G:C	donor_loss	1.0000
12:53454871:T:A	donor_loss	1.0000
12:53455341:TTGCA:T	acceptor_loss	1.0000
12:53455344:CA:C	acceptor_loss	1.0000
12:53455345:A:AG	acceptor_gain	1.0000
12:53455346:G:GG	acceptor_gain	1.0000
12:53455346:G:GT	acceptor_loss	1.0000
12:53455346:GGAA:G	acceptor_gain	1.0000
12:53455455:TTACA:T	acceptor_loss	1.0000
12:53455457:ACAG:A	acceptor_loss	1.0000
12:53455459:A:AG	acceptor_gain	1.0000
12:53455460:G:GA	acceptor_loss	1.0000
12:53455460:G:GG	acceptor_gain	1.0000
12:53455460:GAAA:G	acceptor_gain	1.0000
12:53455494:G:T	donor_loss	1.0000
12:53455495:T:A	donor_loss	1.0000
12:53455879:A:AG	acceptor_gain	1.0000
12:53455880:TCTA:T	acceptor_loss	1.0000
12:53455883:A:AG	acceptor_gain	1.0000
12:53455883:A:AT	acceptor_loss	1.0000
12:53455883:AGAGT:A	acceptor_gain	1.0000
12:53455884:G:GA	acceptor_gain	1.0000

AlphaMissense

2378 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53454850:G:C	R17P	1.000
12:53454853:T:C	L18P	1.000
12:53454856:T:A	L19H	1.000
12:53454856:T:C	L19P	1.000
12:53454859:T:C	M20T	1.000
12:53454864:G:A	G22R	1.000
12:53454864:G:C	G22R	1.000
12:53454865:G:A	G22E	1.000
12:53454865:G:T	G22V	1.000
12:53455347:G:A	E24K	1.000
12:53455350:G:C	V25L	1.000
12:53455350:G:T	V25F	1.000
12:53455351:T:A	V25D	1.000
12:53455353:G:C	G26R	1.000
12:53455353:G:T	G26C	1.000
12:53455354:G:A	G26D	1.000
12:53455354:G:T	G26V	1.000
12:53455360:T:A	I28N	1.000
12:53455360:T:C	I28T	1.000
12:53455360:T:G	I28S	1.000
12:53455363:T:A	I29N	1.000
12:53455363:T:G	I29S	1.000
12:53455365:G:A	G30R	1.000
12:53455365:G:C	G30R	1.000
12:53455366:G:A	G30E	1.000
12:53455366:G:C	G30A	1.000
12:53455366:G:T	G30V	1.000
12:53455464:G:A	G33R	1.000
12:53455464:G:C	G33R	1.000
12:53455465:G:A	G33E	1.000

dbSNP variants (sampled 300 via entrez): RS1000006052 (12:53454645 A>G), RS1000042479 (12:53454954 G>A,C), RS1000180832 (12:53461302 C>G,T), RS1000269022 (12:53460905 T>A,G), RS1000339968 (12:53477895 A>C), RS1000356649 (12:53464295 CTT>C), RS1000445847 (12:53472816 C>T), RS1000630293 (12:53469018 T>A,C), RS1000651450 (12:53450194 A>G), RS1000699840 (12:53469994 C>G), RS1000740700 (12:53463102 A>G), RS1000874784 (12:53471277 T>C,G), RS1000894328 (12:53476937 C>T), RS1000988653 (12:53478791 G>A), RS1001031072 (12:53476817 C>T)

Disease associations

OMIM: gene MIM:601210 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004608_177	Granulocyte percentage of myeloid white cells	5.000000e-23
GCST004609_193	Monocyte percentage of white cells	1.000000e-22
GCST005956_70	Waist-to-hip ratio adjusted for BMI	4.000000e-13
GCST005957_6	Waist-to-hip ratio adjusted for BMI (age <50)	6.000000e-06
GCST005958_9	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-08
GCST005962_20	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295826 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, decreases expression	5
Valproic Acid	affects expression, decreases expression	5
Arsenic Trioxide	affects binding, decreases reaction, decreases expression, increases expression	3
Arsenic	increases abundance, increases expression, affects methylation	2
Benzo(a)pyrene	decreases expression	2
Dronabinol	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression, decreases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	increases expression	1
coumarin	increases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
CD 437	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119037	Binding	Binding affinity to PCBP2 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

202 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,
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
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
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
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
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice