PAIP2

Summary

PAIP2 (poly(A) binding protein interacting protein 2, HGNC:17970) is a protein-coding gene on chromosome 5q31.2, encoding Polyadenylate-binding protein-interacting protein 2 (Q9BPZ3). Acts as a repressor in the regulation of translation initiation of poly(A)-containing mRNAs.

Enables translation repressor activity. Involved in negative regulation of translational initiation. Located in cytoplasm.

Source: NCBI Gene 51247 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_016480

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17970
Approved symbol	PAIP2
Name	poly(A) binding protein interacting protein 2
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	PAIP2A
Ensembl gene	ENSG00000120727
Ensembl biotype	protein_coding
OMIM	605604
Entrez	51247

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 20 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000265192, ENST00000394795, ENST00000507415, ENST00000507755, ENST00000510080, ENST00000510409, ENST00000511381, ENST00000511706, ENST00000881921, ENST00000881922, ENST00000881923, ENST00000917509, ENST00000917510, ENST00000917511, ENST00000917512, ENST00000917513, ENST00000917514, ENST00000917515, ENST00000917516, ENST00000954475, ENST00000954476, ENST00000954477, ENST00000954478

RefSeq mRNA: 2 — MANE Select: NM_016480 NM_001033112, NM_016480

CCDS: CCDS4211

Canonical transcript exons

ENST00000265192 — 4 exons

Exon	Start	End
ENSE00001425481	139341854	139341980
ENSE00001898705	139368733	139369717
ENSE00003513430	139364564	139364743
ENSE00003561860	139363759	139363922

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 99.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.9466 / max 910.9452, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58824	83.8235	1822
58827	0.0722	20
58826	0.0318	5
58825	0.0191	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	99.78	gold quality
left ventricle myocardium	UBERON:0006566	99.77	gold quality
cerebellar vermis	UBERON:0004720	99.44	gold quality
pons	UBERON:0000988	99.36	gold quality
myocardium	UBERON:0002349	99.35	gold quality
kidney epithelium	UBERON:0004819	99.26	gold quality
thymus	UBERON:0002370	99.15	gold quality
deltoid	UBERON:0001476	99.10	gold quality
tibialis anterior	UBERON:0001385	99.08	gold quality
cartilage tissue	UBERON:0002418	99.05	gold quality
postcentral gyrus	UBERON:0002581	99.05	gold quality
upper arm skin	UBERON:0004263	99.02	gold quality
embryo	UBERON:0000922	99.01	gold quality
ganglionic eminence	UBERON:0004023	99.01	gold quality
quadriceps femoris	UBERON:0001377	98.99	gold quality
superior vestibular nucleus	UBERON:0007227	98.95	gold quality
parotid gland	UBERON:0001831	98.94	gold quality
vastus lateralis	UBERON:0001379	98.93	gold quality
superior frontal gyrus	UBERON:0002661	98.89	gold quality
parietal lobe	UBERON:0001872	98.88	gold quality
substantia nigra pars compacta	UBERON:0001965	98.87	gold quality
heart right ventricle	UBERON:0002080	98.82	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.77	gold quality
substantia nigra	UBERON:0002038	98.72	gold quality
monocyte	CL:0000576	98.71	gold quality
prefrontal cortex	UBERON:0000451	98.71	gold quality
ventricular zone	UBERON:0003053	98.71	gold quality
midbrain	UBERON:0001891	98.70	gold quality
hypothalamus	UBERON:0001898	98.69	gold quality
leukocyte	CL:0000738	98.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-17	no	632.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

99 targeting PAIP2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3681-3P	99.88	70.46	2254

Literature-anchored findings (GeneRIF, showing 5)

• Role of PAIP2 in modulation of GLUT5 mRNA stability. (PMID:12820898)
• PAIP2 is a crucial regulator of VEGF mRNA and has a role in regulating angiogenesis (PMID:15175342)
• The turnover of Paip2 in the cell is mediated by EDD and is regulated by PABP. (PMID:16601676)
• Paip2 is a host antiviral restriction factor antagonized by PABP accumulation in HCMV-infected cells (PMID:23964095)
• These results indicated that PAIP1 and PAIP2 participate in translation termination and are important regulators of readthrough at the premature termination codon. (PMID:30992367)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Paip2	ENSMUSG00000037058
rattus_norvegicus	Paip2	ENSRNOG00000019934
drosophila_melanogaster	Paip2	FBGN0038100

Paralogs (1): PAIP2B (ENSG00000124374)

Protein

Protein identifiers

Polyadenylate-binding protein-interacting protein 2 — Q9BPZ3 (reviewed: Q9BPZ3)

All UniProt accessions (3): D6R9Y1, D6RA77, Q9BPZ3

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a repressor in the regulation of translation initiation of poly(A)-containing mRNAs. Its inhibitory activity on translation is mediated via its action on PABPC1. Displaces the interaction of PABPC1 with poly(A) RNA and competes with PAIP1 for binding to PABPC1. Its association with PABPC1 results in disruption of the cytoplasmic poly(A) RNP structure organization.

Subunit / interactions. Interacts with the second and third RRM domains and C-terminus regions of PABPC1 in a 2:1 stoichiometry.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed at highest level in testis, but also abundant in brain, cervix, lung, ovary, placenta, adipose tissue, thymus and thyroid.

Post-translational modifications. Ubiquitinated, leading to its degradation by the proteasome.

Domain organisation. Only the PABPC1-interacting motif-1 (PAM1) interferes with the binding of PABPC1 to poly(A) RNA and translation initiation.

Similarity. Belongs to the PAIP2 family.

RefSeq proteins (2): NP_001028284, NP_057564* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009818	PAM2_motif	Conserved_site
IPR040396	PAIP2-like	Family

Pfam: PF07145

UniProt features (7 total): region of interest 3, sequence conflict 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3KUS	X-RAY DIFFRACTION	1.4
3KUT	X-RAY DIFFRACTION	1.5
1JGN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BPZ3-F1	72.02	0.26

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors

MSigDB gene sets: 205 (showing top): GOBP_MEMORY, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_TRANSLATIONAL_INITIATION, AP2_Q3, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_CELL_CELL_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_TRANSLATIONAL_INITIATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, OCT1_03

GO Biological Process (7): translation (GO:0006412), spermatogenesis (GO:0007283), memory (GO:0007613), negative regulation of translation (GO:0017148), negative regulation of translational initiation (GO:0045947), regulation of long-term synaptic potentiation (GO:1900271), regulation of translation (GO:0006417)

GO Molecular Function (4): mRNA regulatory element binding translation repressor activity (GO:0000900), mRNA binding (GO:0003729), translation repressor activity (GO:0030371), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	2
translation	2
negative regulation of translation	2
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
learning or memory	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
regulation of translational initiation	1
regulation of synaptic plasticity	1
long-term synaptic potentiation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
mRNA binding	1
translation repressor activity	1
RNA binding	1
translation regulator activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAIP2	PABPC1	P11940	977
PAIP2	PAIP1	Q9H074	940
PAIP2	EIF4G1	Q04637	783
PAIP2	ELAVL1	Q15717	772
PAIP2	EIF3J	O75822	768
PAIP2	ANKRD52	Q8NB46	671
PAIP2	RRM2	P31350	560
PAIP2	PABPC4	Q13310	559
PAIP2	PABPC1L	Q4VXU2	554
PAIP2	PABPC5	Q96DU9	541
PAIP2	PABPC3	Q9H361	521
PAIP2	HNRNPL	P14866	466
PAIP2	PABPC4L	P0CB38	460
PAIP2	EIF4E	P06730	454
PAIP2	PABPC1L2A	Q5JQF8	452

IntAct

60 interactions, top by confidence:

A	B	Type	Score
PAIP2	PABPC1	psi-mi:“MI:0915”(physical association)	0.860
PABPC1	PAIP2	psi-mi:“MI:0407”(direct interaction)	0.860
PABPC1	PAIP2	psi-mi:“MI:0915”(physical association)	0.860
PAIP2	PABPC1	psi-mi:“MI:0407”(direct interaction)	0.860
N	PABPC1	psi-mi:“MI:0915”(physical association)	0.700
PAIP2	UBR5	psi-mi:“MI:0915”(physical association)	0.680
PAIP2	UBR5	psi-mi:“MI:0407”(direct interaction)	0.680
UBR5	PAIP2	psi-mi:“MI:0407”(direct interaction)	0.680
UBR5	PAIP2	psi-mi:“MI:0220”(ubiquitination reaction)	0.680
PABPC5	PAIP2	psi-mi:“MI:0915”(physical association)	0.670
DNALI1	PAIP2	psi-mi:“MI:0915”(physical association)	0.560
KLF11	PAIP2	psi-mi:“MI:0915”(physical association)	0.560
PAIP2	NUP58	psi-mi:“MI:0915”(physical association)	0.560
PABPC1	P/V/C	psi-mi:“MI:0915”(physical association)	0.520
PAIP2	NDN	psi-mi:“MI:0915”(physical association)	0.470
PABPC1	P/V/C	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (94): PAIP2 (Affinity Capture-RNA), PAIP2 (Affinity Capture-MS), PAIP2 (Affinity Capture-MS), PAIP2 (Affinity Capture-MS), PAIP2 (Affinity Capture-MS), PAIP2 (Reconstituted Complex), PAIP2 (Reconstituted Complex), PAIP2 (Affinity Capture-MS), PAIP2 (Affinity Capture-MS), PAIP2 (Affinity Capture-MS), PAIP2 (Affinity Capture-RNA), PAIP2 (Affinity Capture-MS), PAIP2 (Affinity Capture-MS), PABPC5 (Two-hybrid), PAIP2 (Proximity Label-MS)

ESM2 similar proteins: A1YEW9, A2D4U8, A2D5N1, A2D671, A2T6K9, A8MQL1, B8AE37, F4HY56, G3V9A7, O23116, O60238, P48785, P79149, Q0DKP4, Q15170, Q15361, Q15390, Q1PEB4, Q2KIJ9, Q3T013, Q3ULM0, Q3ZBJ9, Q5H9J7, Q5PPP3, Q5PR69, Q5RFN3, Q5XVC4, Q67XL4, Q6K678, Q7XRV0, Q86X53, Q8GYL9, Q8GZ92, Q8RY18, Q91W45, Q921P9, Q94F39, Q96GX8, Q99MB2, Q9AV50

Diamond homologs: Q3ZC67, Q5R596, Q5ZJS6, Q6AXZ0, Q91W45, Q9BPZ3, Q9D6V8, Q9ULR5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UBR5	“down-regulates quantity by destabilization”	PAIP2	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

781 predictions. Top by Δscore:

Variant	Effect	Δscore
5:139363757:A:G	acceptor_gain	1.0000
5:139363905:G:GT	donor_gain	1.0000
5:139363918:GACAA:G	donor_gain	1.0000
5:139363920:CAAG:C	donor_loss	1.0000
5:139363923:G:GG	donor_gain	1.0000
5:139363924:T:G	donor_gain	1.0000
5:139364732:G:GT	donor_gain	1.0000
5:139341945:GA:G	donor_gain	0.9900
5:139341979:GG:G	donor_gain	0.9900
5:139341980:GG:G	donor_gain	0.9900
5:139341980:GGT:G	donor_loss	0.9900
5:139341981:GT:G	donor_loss	0.9900
5:139341982:T:G	donor_loss	0.9900
5:139342054:GGGCC:G	donor_gain	0.9900
5:139363756:AAG:A	acceptor_gain	0.9900
5:139363758:G:A	acceptor_gain	0.9900
5:139363758:G:GC	acceptor_loss	0.9900
5:139363758:G:GG	acceptor_gain	0.9900
5:139363758:GGTTA:G	acceptor_gain	0.9900
5:139363919:A:G	donor_gain	0.9900
5:139363919:ACAA:A	donor_gain	0.9900
5:139363921:AA:A	donor_gain	0.9900
5:139363925:TAGTT:T	donor_loss	0.9900
5:139364556:A:AG	acceptor_gain	0.9900
5:139364557:A:G	acceptor_gain	0.9900
5:139364560:CTA:C	acceptor_loss	0.9900
5:139364561:TA:T	acceptor_loss	0.9900
5:139364562:A:AG	acceptor_gain	0.9900
5:139364563:G:GG	acceptor_gain	0.9900
5:139364563:G:T	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000013410 (5:139363668 A>C), RS1000185574 (5:139345869 C>T), RS1000212599 (5:139360361 C>G), RS1000217972 (5:139345616 C>T), RS1000383563 (5:139340283 A>C,T), RS1000409692 (5:139340579 C>A,G), RS1000501105 (5:139364153 A>C), RS1000522816 (5:139347238 C>T), RS1000607282 (5:139357080 C>G), RS1000709632 (5:139353196 T>C), RS1000728620 (5:139352931 C>T), RS1000772632 (5:139351607 A>G), RS1000813100 (5:139359151 T>A), RS1000889839 (5:139344656 A>G), RS1001007084 (5:139346964 C>G)

Disease associations

OMIM: gene MIM:605604 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005951_151	Body mass index	6.000000e-07
GCST010725_68	Malaria	4.000000e-07
GCST010725_7	Malaria	2.000000e-06
GCST90002385_347	High light scatter reticulocyte count	2.000000e-11
GCST90002386_41	High light scatter reticulocyte percentage of red cells	9.000000e-11
GCST90002387_310	Immature fraction of reticulocytes	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	3
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
cupric oxide	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Bile Acids and Salts	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Fructose	affects binding, increases reaction	1
Gasoline	decreases expression, increases abundance, affects cotreatment	1
Glucose	affects binding, increases reaction	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Potassium Dichromate	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3D9	Abcam HEK293T PAIP2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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