RPLP2

Summary

RPLP2 (ribosomal protein lateral stalk subunit P2, HGNC:10377) is a protein-coding gene on chromosome 11p15.5, encoding Large ribosomal subunit protein P2 (P05387). Plays an important role in the elongation step of protein synthesis. It is a common-essential gene (DepMap: required in 99.2% of cancer cell lines).

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal phosphoprotein that is a component of the 60S subunit. The protein, which is a functional equivalent of the E. coli L7/L12 ribosomal protein, belongs to the L12P family of ribosomal proteins. It plays an important role in the elongation step of protein synthesis. Unlike most ribosomal proteins, which are basic, the encoded protein is acidic. Its C-terminal end is nearly identical to the C-terminal ends of the ribosomal phosphoproteins P0 and P1. The P2 protein can interact with P0 and P1 to form a pentameric complex consisting of P1 and P2 dimers, and a P0 monomer. The protein is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

Source: NCBI Gene 6181 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 26 total
• GTEx eGene: eQTL in 31 tissues, sQTL in 23 (q < 0.05)
• Cancer dependency (DepMap): dependent in 99.2% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.97 (loss-of-function intolerant), LOEUF 0.43 (moderately constrained)
• MANE Select transcript: NM_001004
• Interaction hub: 2,588 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10377
Approved symbol	RPLP2
Name	ribosomal protein lateral stalk subunit P2
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	P2, RPP2, MGC71408, LP2
Ensembl gene	ENSG00000177600
Ensembl biotype	protein_coding
OMIM	180530
Entrez	6181

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 32 protein_coding, 7 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000321153

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 4, TSL 3: 2

ENST00000321153, ENST00000524867, ENST00000525722, ENST00000526222, ENST00000527517, ENST00000530398, ENST00000530797, ENST00000532004, ENST00000718237, ENST00000852318, ENST00000852319, ENST00000852320, ENST00000929541, ENST00000929542, ENST00000929543, ENST00000929544, ENST00000929545, ENST00000929546, ENST00000929547, ENST00000929548, ENST00000929549, ENST00000929550, ENST00000929551, ENST00000960563, ENST00000960564, ENST00001053071, ENST00001070432, ENST00001070433, ENST00001070434, ENST00001070438, ENST00001070439, ENST00001070440, ENST00001070442, ENST00001070453, ENST00001070458, ENST00001070462, ENST00001070469, ENST00001095219, ENST00001095220, ENST00001095221, ENST00001095222, ENST00001095223, ENST00001128634, ENST00001144390

RefSeq mRNA: 1 — MANE Select: NM_001004 NM_001004

CCDS: CCDS7717

Canonical transcript exons

ENST00000321153 — 5 exons

Exon	Start	End
ENSE00001296345	810234	810357
ENSE00001318871	809967	810039
ENSE00003535968	812535	812633
ENSE00003564145	811597	811645
ENSE00004034474	812760	812876

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2989.6836 / max 38067.9514, expressed in 1828 samples.

Highest expression (Bgee): nipple, primordial germ cell in gonad, skin of hip, tendon of biceps brachii, superficial temporal artery.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RPLP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 23 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 54 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	6.6e-30	-0.19	11:810009:TCTCCGCCGC:T
Nerve Tibial	eqtl	1.2e-28	-0.18	11:810009:TCTCCGCCGC:T
Artery Tibial	eqtl	9.2e-21	-0.16	11:810009:TCTCCGCCGC:T
Testis	eqtl	9.0e-19	-0.27	11:810009:TCTCCGCCGC:T
Thyroid	eqtl	2.9e-18	-0.17	11:810009:TCTCCGCCGC:T
Lung	eqtl	1.2e-16	-0.17	11:810009:TCTCCGCCGC:T
Artery Aorta	eqtl	4.5e-16	-0.21	11:810009:TCTCCGCCGC:T
Cells Cultured fibroblasts	sqtl	1.7e-14	-0.37	11:810009:TCTCCGCCGC:T
Heart Atrial Appendage	eqtl	1.9e-14	-0.23	11:810009:TCTCCGCCGC:T
Muscle Skeletal	sqtl	1.4e-13	-0.32	11:810009:TCTCCGCCGC:T
Esophagus Muscularis	eqtl	2.2e-13	-0.18	11:810009:TCTCCGCCGC:T
Esophagus Mucosa	eqtl	4.2e-13	+0.16	11:802115:A:G
Whole Blood	sqtl	1.1e-12	-0.28	11:810009:TCTCCGCCGC:T
Adipose Subcutaneous	eqtl	2.0e-12	-0.13	11:810009:TCTCCGCCGC:T
Skin Sun Exposed Lower leg	eqtl	3.6e-12	-0.11	11:810009:TCTCCGCCGC:T
Esophagus Gastroesophageal Junction	eqtl	1.3e-11	-0.20	11:810009:TCTCCGCCGC:T
Colon Sigmoid	eqtl	2.5e-11	-0.22	11:810009:TCTCCGCCGC:T
Artery Tibial	sqtl	1.3e-10	-0.26	11:810009:TCTCCGCCGC:T
Adipose Visceral Omentum	eqtl	1.3e-10	-0.12	11:810009:TCTCCGCCGC:T
Heart Atrial Appendage	sqtl	1.5e-09	-0.40	11:810009:TCTCCGCCGC:T

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
112263	2985.7068	1828
112264	2.3553	1170
112266	1.3162	615
112262	0.3053	98

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	99.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.95	gold quality
skin of hip	UBERON:0001554	99.95	gold quality
tendon of biceps brachii	UBERON:0008188	99.95	gold quality
superficial temporal artery	UBERON:0001614	99.94	gold quality
peritoneum	UBERON:0002358	99.94	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.94	gold quality
lower lobe of lung	UBERON:0008949	99.94	gold quality
omental fat pad	UBERON:0010414	99.94	gold quality
granulocyte	CL:0000094	99.93	gold quality
urethra	UBERON:0000057	99.93	gold quality
pericardium	UBERON:0002407	99.93	gold quality
pylorus	UBERON:0001166	99.92	gold quality
right ovary	UBERON:0002118	99.92	gold quality
left ovary	UBERON:0002119	99.92	gold quality
thymus	UBERON:0002370	99.92	gold quality
upper leg skin	UBERON:0004262	99.92	gold quality
upper arm skin	UBERON:0004263	99.92	gold quality
zone of skin	UBERON:0000014	99.91	gold quality
endocervix	UBERON:0000458	99.91	gold quality
penis	UBERON:0000989	99.91	gold quality
mammalian vulva	UBERON:0000997	99.91	gold quality
left uterine tube	UBERON:0001303	99.91	gold quality
skin of abdomen	UBERON:0001416	99.91	gold quality
skin of leg	UBERON:0001511	99.91	gold quality
spleen	UBERON:0002106	99.91	gold quality
synovial joint	UBERON:0002217	99.91	gold quality
trachea	UBERON:0003126	99.91	gold quality
tendon	UBERON:0000043	99.90	gold quality
ovary	UBERON:0000992	99.90	gold quality
cartilage tissue	UBERON:0002418	99.90	gold quality
mucosa of transverse colon	UBERON:0004991	99.90	gold quality
body of uterus	UBERON:0009853	99.90	gold quality
ectocervix	UBERON:0012249	99.90	gold quality
vagina	UBERON:0000996	99.89	gold quality
cardia of stomach	UBERON:0001162	99.89	gold quality
coronary artery	UBERON:0001621	99.89	gold quality
left coronary artery	UBERON:0001626	99.89	gold quality
right lung	UBERON:0002167	99.89	gold quality
calcaneal tendon	UBERON:0003701	99.89	gold quality
caput epididymis	UBERON:0004358	99.89	gold quality
superior surface of tongue	UBERON:0007371	99.89	gold quality
bone marrow cell	CL:0002092	99.88	gold quality
blood	UBERON:0000178	99.88	gold quality
right lobe of thyroid gland	UBERON:0001119	99.88	gold quality
sigmoid colon	UBERON:0001159	99.88	gold quality
fundus of stomach	UBERON:0001160	99.88	gold quality
mucosa of stomach	UBERON:0001199	99.88	gold quality
tibial nerve	UBERON:0001323	99.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.88	gold quality
left testis	UBERON:0004533	99.88	gold quality
right testis	UBERON:0004534	99.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.88	gold quality
periodontal ligament	UBERON:0008266	99.88	gold quality
upper lobe of lung	UBERON:0008948	99.88	gold quality
metanephros cortex	UBERON:0010533	99.88	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.88	gold quality
pituitary gland	UBERON:0000007	99.87	gold quality
embryo	UBERON:0000922	99.87	gold quality
aorta	UBERON:0000947	99.87	gold quality
seminal vesicle	UBERON:0000998	99.87	gold quality
left lobe of thyroid gland	UBERON:0001120	99.87	gold quality
transverse colon	UBERON:0001157	99.87	gold quality
right adrenal gland	UBERON:0001233	99.87	gold quality
right uterine tube	UBERON:0001302	99.87	gold quality
ascending aorta	UBERON:0001496	99.87	gold quality
thoracic aorta	UBERON:0001515	99.87	gold quality
minor salivary gland	UBERON:0001830	99.87	gold quality
thyroid gland	UBERON:0002046	99.87	gold quality
adenohypophysis	UBERON:0002196	99.87	gold quality
prostate gland	UBERON:0002367	99.87	gold quality
bone marrow	UBERON:0002371	99.87	gold quality
adult organism	UBERON:0007023	99.87	gold quality
upper lobe of left lung	UBERON:0008952	99.87	gold quality
lower esophagus	UBERON:0013473	99.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.87	gold quality
stromal cell of endometrium	CL:0002255	99.86	gold quality
large intestine	UBERON:0000059	99.86	gold quality
colon	UBERON:0001155	99.86	gold quality
body of stomach	UBERON:0001161	99.86	gold quality
left adrenal gland	UBERON:0001234	99.86	gold quality
adrenal cortex	UBERON:0001235	99.86	gold quality
right coronary artery	UBERON:0001625	99.86	gold quality
small intestine	UBERON:0002108	99.86	gold quality
popliteal artery	UBERON:0002250	99.86	gold quality
descending thoracic aorta	UBERON:0002345	99.86	gold quality
mouth mucosa	UBERON:0003729	99.86	gold quality
corpus epididymis	UBERON:0004359	99.86	gold quality
saphenous vein	UBERON:0007318	99.86	gold quality
tibial artery	UBERON:0007610	99.86	gold quality
left adrenal gland cortex	UBERON:0035825	99.86	gold quality
right adrenal gland cortex	UBERON:0035827	99.86	gold quality
renal medulla	UBERON:0000362	99.85	gold quality
myometrium	UBERON:0001296	99.85	gold quality
mammary duct	UBERON:0001765	99.85	gold quality
ganglionic eminence	UBERON:0004023	99.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.85	gold quality
lymph node	UBERON:0000029	99.84	gold quality
oral cavity	UBERON:0000167	99.84	gold quality

Single-cell (SCXA)

Detected in 43 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	11486.83
E-MTAB-10042	yes	5619.02
E-MTAB-7316	yes	4887.25
E-MTAB-6819	yes	1343.37
E-MTAB-4850	yes	880.24
E-CURD-122	yes	98.94
E-MTAB-9221	yes	55.43
E-MTAB-6678	yes	41.05
E-HCAD-31	yes	21.14
E-HCAD-35	yes	18.50
E-GEOD-137537	yes	6.07
E-HCAD-25	yes	4.84
E-MTAB-6653	no	13647.05
E-GEOD-139324	no	12711.01
E-MTAB-10432	no	12683.32

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Vagina	tissue	2308.6	low
Ovary	tissue	2297.9	low
Bone marrow	tissue	2041.3	low
Pancreas	tissue	1967.2	medium
Adipose tissue	tissue	1887.9	not detected
Lymph node	tissue	1800.4	medium
Salivary gland	tissue	1792.2	medium
Skeletal muscle	tissue	1690.7	not detected
Tonsil	tissue	1603.1	medium
Spleen	tissue	1453.4	low
Thymus	tissue	1439.3
Breast	tissue	1369.1	medium
Skin 1	tissue	1328.1	medium
Pituitary gland	tissue	1212.0
Colon	tissue	1193.3	medium
Fallopian tube	tissue	1164.5	medium
Duodenum	tissue	954.2	medium
Appendix	tissue	935.8	medium
Cervix	tissue	906.5	medium
Stomach 1	tissue	903.2	medium
Small intestine	tissue	894.8	medium
Tongue	tissue	873.9
Urinary bladder	tissue	836.8	medium
Rectum	tissue	831.1	medium
Endometrium 1	tissue	827.5	medium
Placenta	tissue	779.4	medium
Seminal vesicle	tissue	729.7	medium
Prostate	tissue	707.9	low
Epididymis	tissue	661.3	medium
Liver	tissue	611.7	medium
Esophagus	tissue	601.2	medium
Smooth muscle	tissue	582.3	not detected
Lung	tissue	580.0	medium
Heart muscle	tissue	578.3	medium
Adrenal gland	tissue	566.9	medium
Gallbladder	tissue	528.9	medium
Parathyroid gland	tissue	510.9	medium
Choroid plexus	tissue	500.3
Nucleus accumbens	tissue	490.1
Caudate putamen	tissue	486.7
Frontal cortex	tissue	453.0
Thyroid gland	tissue	446.0	medium
Hippocampus	tissue	442.1	medium
Locus coeruleus	tissue	423.7
Kidney	tissue	390.1	high
Testis	tissue	282.8	medium
Postcentral gyrus	tissue	253.2
Retina	tissue	167.9
Spinal cord	tissue	77.2
Corpus callosum	tissue	72.3
Pons	tissue	71.0
Substantia nigra	tissue	67.4
Thalamus	tissue	65.6
Superior colliculi	tissue	65.1
Medulla oblongata	tissue	64.3
Midbrain	tissue	63.8
Putamen	tissue	62.2
Hippocampal formation	tissue	60.5
Hypothalamus	tissue	57.5
Septum	tissue	56.4

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (2140.0), Cervical spinal cord, ventral horn (769.1), Temporal white matter (761.8), Lateral funiculus (white matter) (740.5), Cerebellar white matter (701.2).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 0.974, LOEUF 0.427, missense Z -1 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000321153 — one region, missense o/e 1.22. DepMap (CRISPR cell-line fitness): dependent in 99.2% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): OCI-LY-19 (-2.438), KALS-1 (-2.241), OPM-2 (-2.172), KE-37 (-2.148), HSC-2 (-2.14), SK-MM-2 (-2.138), MJ (-2.12), HCC-56 (-2.079), Malme-3M (-2.074), HCC1187 (-2.069), KP-N-SI9s (-2.052), Hs 852.T (-2.043), C2BBe1 (-2.028), Daoy (-2.015), JVM-3 (-2.0).

Literature-anchored findings (GeneRIF, showing 17)

• Ribosomal protein P2 has been identified as a novel substrate of GRK2 in HEK-293 cells where P2 phosphorylation is increased following agonist stimulation of the beta 2-adrenergic receptor under conditions of tyrosine kinase PKC and PKA inhibition. (PMID:12379128)
• the P1 and P2 proteins are not actively transported into the nucleus compartment, remaining predominantly in the cytoplasm (the perinuclear compartment). (PMID:12479870)
• Antisense-mediated depletion may disrupt the proteome of cancer cells. (PMID:14981896)
• Distinct roles for CD39 and P2-purinergic signaling in both tissue remodeling and fibrogenesis with respect to human pancreatic diseases. (PMID:16920697)
• Data indicate that P1/P2 proteins modulate cytoplasmic translation by influencing the interaction between subunits, thereby regulating the rate of cell proliferation. (PMID:18422483)
• These results support the hypothesis that at least some of the changes in the profile of newly synthesized proteins detected in cells deprived of P1 and P2 proteins might be due to an effect on the efficiency of cap-independent translation. (PMID:18675807)
• the eukaryotic stalk protein P2 forms a symmetric homodimer in solution, and is structurally distinct from the bacterial counterpart L12 homodimer. (PMID:20385603)
• P proteins are up-regulated in a considerable number of patients with the most common types of cancer. (PMID:21040949)
• relevance of the observed cross-reactive IgE autoantibodies against P2 proteins in systemic lupus eryth remains to be elucidated (PMID:21410706)
• Data show that ricin A-chain (RTA) interacts directly with recombinant P1-P2 dimer, indicating the importance of P1 and P2 in enabling RTA to bind and depurinate ribosomes. (PMID:22909382)
• Evaluated autoantibodies against native ribosomal P complex and recombinant ribosomal P proteins (anti-Rib-P0, anti-Rib-P1, anti-Rib-P2) for prevalence, diagnostic relevance&clinical associations in a Chinese cohort with systemic lupus erythematosus. (PMID:23400861)
• Results show that the conserved C-terminal segment of P2 from three different eukaryotic species- Human, Plasmodium falciparum and Toxoplasma gondii is intrinsically disordered. (PMID:25412900)
• absence of RPLP0, RPLP1, or RPLP2 resulted in reactive oxygen species (ROS) accumulation and MAPK1/ERK2 signaling pathway activation. (PMID:26176264)
• Collectively, the present results suggest that PhoRpp21 binds the loop between P11 and P12 helices through overall positively charged clusters on the surface of the complex and serves as a scaffold for PhoRpp29 to optimize structural conformation of its N-terminal helix (alpha2) in PhoRpp21, as well as C-terminal residues in PhoRpp29, for RNase P activity. (PMID:27810361)
• A three-gene signature and clinical outcome in pediatric acute myeloid leukemia. (PMID:32862280)
• Ribosomal stalk proteins RPLP1 and RPLP2 promote biogenesis of flaviviral and cellular multi-pass transmembrane proteins. (PMID:32890404)
• Phosphorylation of the conserved C-terminal domain of ribosomal P-proteins impairs the mode of interaction with plant toxins. (PMID:34328639)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	rplp2b	ENSDARG00000011201
mus_musculus	Rplp2	ENSMUSG00000025508
mus_musculus	Rplp2-ps1	ENSMUSG00000118552
rattus_norvegicus	Rplp2l3	ENSRNOG00000031052
rattus_norvegicus	Rplp2l2	ENSRNOG00000038074
rattus_norvegicus	Rplp2	ENSRNOG00000068445
drosophila_melanogaster	RpLP2	FBGN0003274
caenorhabditis_elegans	C37A2.7	WBGENE00016493

Paralogs (2): RPLP0 (ENSG00000089157), RPLP1 (ENSG00000137818)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryctolagus cuniculus	P19943	100.0%	Diamond
Bos taurus	P42899	100.0%	Diamond
Equus caballus	Q6X9Z5	98.3%	Diamond
Arabidopsis thaliana	P51407	96.5%	Diamond
Leishmania donovani	O43940	94.3%	Diamond
Leishmania infantum	Q06383	94.3%	Diamond
Sus scrofa	Q29315	93.2%	Diamond
Schizosaccharomyces pombe 972h-	O14317	91.8%	Diamond
Alternaria alternata	P42037	90.3%	Diamond
Fusarium culmorum	Q8TFM9	90.3%	Diamond
Podospora anserina	Q9C3Z5	89.9%	Diamond
Aspergillus fumigatus Af293	Q9UUZ6	87.4%	Diamond
Rhodotorula glutinis	Q96UQ7	80.2%	Diamond
Cladosporium herbarum	P42039	79.6%	Diamond
Candida albicans	Q9HFQ4	79.3%	Diamond
Branchiostoma floridae	O01725	79.1%	Diamond
Zea mays	O24415	78.6%	Diamond
Triticum aestivum	P05390	78.6%	Diamond
Saccharomyces cerevisiae S288C	P02400	76.8%	Diamond
Trypanosoma brucei brucei	P51408	73.1%	Diamond
Parthenium argentatum	P41099	70.8%	Diamond
Cryptochiton stelleri	O61463	68.2%	Diamond
Artemia salina	P02399	67.6%	Diamond
Babesia bovis	P27055	64.5%	Diamond
Brugia malayi	P90703	64.2%	Diamond
Plasmodium falciparum 3D7	O00806	61.3%	Diamond
Euplotes raikovi	Q9GPU2	59.5%	Diamond
Taenia solium	P50879	57.9%	Diamond
Eimeria tenella	Q967Y9	57.1%	Diamond
Dictyostelium discoideum	P22683	53.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GATD1-DT	ncRNA	171391
CEND1	protein-coding	51286
PIDD1	protein-coding	55367
PNPLA2	protein-coding	57104
SNORA52	snoRNA	619565
SLC25A22	protein-coding	79751
PANO1	protein-coding	101927423
CRACR2B	protein-coding	283229
CD151	protein-coding	977
POLR2L	protein-coding	5441

Protein

Protein identifiers

Large ribosomal subunit protein P2 — P05387 (reviewed: P05387)

Alternative names: 60S acidic ribosomal protein P2, Renal carcinoma antigen NY-REN-44

All UniProt accessions (2): H0YDD8, P05387

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the elongation step of protein synthesis.

Subunit / interactions. Heterodimer with P1 at the lateral ribosomal stalk of the large ribosomal subunit.

Similarity. Belongs to the eukaryotic ribosomal protein P1/P2 family.

RefSeq proteins (1): NP_000995* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027534	Ribosomal_P1/P2	Family
IPR038716	P1/P2_N_sf	Homologous_superfamily
IPR044076	Ribosomal_P2_euk	Family

Pfam: PF00428

UniProt features (23 total): modified residue 9, helix 5, strand 3, turn 2, compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
5DDZ	Crystal structure of the RTA-c10-P2 complex	X-RAY DIFFRACTION	1.5
5GU4	rRNA N-glycosylase RTA	X-RAY DIFFRACTION	1.55
2JDL	Structure of C-terminal region of acidic P2 ribosomal protein complexed with trichosanthin	X-RAY DIFFRACTION	2.2
4V6X	Structure of the human 80S ribosome	ELECTRON MICROSCOPY	5
1S4J	NMR structure of cross-reactive peptides from Homo sapiens	SOLUTION NMR
2LBF	Solution structure of the dimerization domain of human ribosomal protein P1/P2 heterodimer	SOLUTION NMR
2W1O	NMR structure of dimerization domain of human ribosomal protein P2	SOLUTION NMR
4BEH	Solution structure of human ribosomal protein P1.P2 heterodimer	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05387-F1	69.32	0.23

Human Protein Atlas

Protein class: Ribosomal proteins, Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nuclear speckles; mitotic spindle

Antibody reliability (HPA): IH approved · IF approved

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 (9)

Type	Positions
Phosphoserine	86, 102, 105, 17, 19, 79
N-acetylmethionine	1
N6-acetyllysine	21
N6-succinyllysine	21

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 40; 6 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

40 pathways:

ID	Pathway	Evidence
R-HSA-192823	Viral mRNA Translation ⚕	curated
R-HSA-72689	Formation of a pool of free 40S subunits	curated
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit	curated
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression	curated
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol	curated
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	curated
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	curated
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	curated
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-168255	Influenza Infection ⚕	—
R-HSA-168273	Influenza Viral RNA Transcription and Replication ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-422475	Axon guidance	—
R-HSA-72737	Cap-dependent Translation Initiation	—
R-HSA-9711097	Cellular response to starvation	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-1266738	Developmental Biology	—
R-HSA-156842	Eukaryotic Translation Elongation	—
R-HSA-72613	Eukaryotic Translation Initiation	—
R-HSA-72764	Eukaryotic Translation Termination	electronic
R-HSA-1430728	Metabolism	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-71291	Metabolism of amino acids and derivatives	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-9675108	Nervous system development	—
R-HSA-927802	Nonsense-Mediated Decay (NMD)	—
R-HSA-156902	Peptide chain elongation	electronic
R-HSA-9010553	Regulation of expression of SLITs and ROBOs	electronic
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency	electronic
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	electronic
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane	electronic
R-HSA-2408522	Selenoamino acid metabolism	—
R-HSA-2408557	Selenocysteine synthesis	electronic
R-HSA-376176	Signaling by ROBO receptors	—
R-HSA-72766	Translation	—
R-HSA-72312	rRNA processing	—
R-HSA-8868773	rRNA processing in the nucleus and cytosol	—

MSigDB gene sets: 257 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, YAGI_AML_WITH_INV_16_TRANSLOCATION, MORF_UBE2I, MODULE_150, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, MODULE_503, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, MODULE_195, GOBP_MUSCLE_CONTRACTION, MORF_CCNI, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (7): cytoplasmic translation (GO:0002181), cytoplasmic translational elongation (GO:0002182), translation (GO:0006412), striated muscle contraction (GO:0006941), spermatogenesis (GO:0007283), negative regulation of myoblast fusion (GO:1901740), translational elongation (GO:0006414)

GO Molecular Function (2): structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), cytosolic large ribosomal subunit (GO:0022625), extracellular exosome (GO:0070062), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

11 top-level categories:

Category	Pathways
Translation	3
Ribosome-associated quality control	3
Cap-dependent Translation Initiation	2
Nonsense-Mediated Decay (NMD)	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Signaling by ROBO receptors	1
Cellular response to starvation	1

GO top-level categories

27 GO namespaces:

Category	Terms
cellular anatomical structure	3
translation	2
translational elongation	2
macromolecule biosynthetic process	2
cytoplasmic translation	1
peptidyltransferase activity	1
translational initiation	1
translational termination	1
protein metabolic process	1
protein biosynthetic process	1
muscle contraction	1
developmental process involved in reproduction	1
male gamete generation	1
myoblast fusion	1
negative regulation of syncytium formation by plasma membrane fusion	1
regulation of myoblast fusion	1
structural molecule activity	1
ribosome	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
large ribosomal subunit	1
cytosolic ribosome	1
extracellular vesicle	1
intracellular membraneless organelle	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
cytosolic large ribosomal subunit	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
membrane	CC	high-throughput assay
structural constituent of ribosome	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 2,588 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPLP2	RPLP1	P05386	814
RPLP2	RPLP0	P05388	713
RPLP2	RPL21	P46778	592
RPLP2	RPS19	P39019	577
RPLP2	RPS25	P25111	573
RPLP2	RPS21	P35265	569
RPLP2	RPL11	P25121	562
RPLP2	RPL19	P14118	561
RPLP2	RPL18A	Q02543	553
RPLP2	RPL14	P50914	542
RPLP2	RPS18	P25232	522
RPLP2	RPL39	P02404	514
RPLP2	RPSA	P08865	513
RPLP2	RPS28	P25112	507
RPLP2	RPL37	P02403	506
RPLP2	RPL38	P23411	506

IntAct

Human interaction partners of RPLP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

19 partners by confidence:

Partner	Interaction type	MIscore	Records
RPLP1	direct interaction	0.560	2
BEST1	physical association	0.400	1
GPATCH11	physical association	0.400	1
MROH2B	physical association	0.400	1
PKHD1	physical association	0.400	1
SPMIP7	physical association	0.400	1
SUPT20H	physical association	0.400	1
UNC13C	physical association	0.400	1
YWHAZ	physical association	0.400	1
MAPK8	physical association	0.370	1
KDM2A	association	0.350	1
PA2G4	association	0.350	1
PPP1CC	association	0.350	1
IKBKG	physical association	0.000	1
MAP3K1	physical association	0.000	1
MAP3K14	physical association	0.000	1
NFKB2	physical association	0.000	1
PAX8	physical association	0.000	1
RELB	physical association	0.000	1

BioGRID (555 interactions; top human partners by supporting records): RPLP1 (Co-fractionation; 7 records), RPLP0 (Co-fractionation; 6 records), RPL11 (Co-fractionation; 4 records), RPL23 (Co-fractionation; 4 records), RPL4 (Co-fractionation; 4 records), RPL5 (Co-fractionation; 4 records), RPL7A (Co-fractionation; 4 records), RPS6 (Co-fractionation; 4 records), MECP2 (Affinity Capture-MS; 3 records), MYC (Affinity Capture-MS; 3 records), RPL14 (Co-fractionation; 3 records), RPL28 (Co-fractionation; 3 records), RPL30 (Co-fractionation; 3 records), RPL36 (Co-fractionation; 3 records), RPL37A (Co-fractionation; 3 records)

SIGNOR signaling

showing 2 of 3 signaling interactions:

A	Effect	B	Mechanism
GRK2	up-regulates	RPLP2	phosphorylation
RPLP2	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ Nop56p-associated pre-rRNA complex	104	LUC7L2, NCL, RPL27, RPL29, RPL39, RPL7, RPS23, RPS6, MYBBP1A, RPL21, RPL28, RPL5, RPS9, U2AF2, LYAR, RPL13, RPL23, RPL23A, RPL35A, RPL4, RPS24, HNRNPA1, EBNA1BP2, RPLP1, RPS17, U2AF1, DHX9, RPL30, SCYL2, RPL11, RPS11, NOLC1, RPL12, RPL14, RPL17, RPL19, RPL32, RPS13, RPS8, NOP58, RPL36A, RPLP2, RPS2, RPS29, SRP14, TCOF1, TUFM, ACTG2, RBM28, RPL10, RPL37A, RPS12, RPS7, TUBB1, BRIX1, DDX21, GNL3, IGF2BP1, ILF2, RPL10A, RPL15, RPLP0, EEF2, HNRNPU, NOP56, RPL26, RPL3, RPS14, RPS16, RSL1D1, ACTA2, EEF1A1, H1-3, RPL24, RPL6, RPL8, SRPK1, TOP1, FBL, HNRNPM, RPL13A, RPL31, RPL7A, RPS18, H1-10, ILF3, NPM1, RPS15A, TUBA1A, YBX1, H2BC14, PWP1, RPL18A, RPL22, RPL27A, RPS15, RPS3A, SLC25A5, NAP1L1, RPL18, RPL35, RPL36, RPL9, SNU13
Ribosome, cytoplasmic	80	RPS12, RPS27A, RPL12, RPSA, RPL24, RPL27A, RPL37, RPLP0, RPS15, RPS3A, RPL10, RPL15, RPL23A, RPL36A, RPS15A, RPS19, RPL17, RPL6, RPLP1, RPS23, RPS28, RPS6, RPL29, RPL35A, RPS4Y1, RPS7, RPS10, RPL13, RPL28, RPL3, RPL30, RPL36, RPS27, RPS9, RPL14, RPL26, RPS17, RPS2, RPL13A, RPL27, RPL35, RPL38, RPL41, RPS18, RPS26, RPL22, RPL4, RPL5, RPS11, UBA52, RPL18, RPL7A, RPL19, RPL37A, RPL8, RPS14, RPS20, FAU, RPL34, RPL7, RPS21, RPS25, RPS5, RPS13, RPS24, RPS29, RPS8, RPL39, RPL9, RPLP2, RPS3, RPL10A, RPL11, RPL18A, RPL23, RPL31, RPS16, RPS4X, RPL21, RPL32
60S ribosomal subunit, cytoplasmic	47	RPL27, RPL9, RPLP2, RPL17, RPL19, RPL5, RPL12, RPL13, RPL13A, RPL30, RPL35, RPL35A, RPL36, RPL6, RPL18, RPL23A, RPL28, RPL32, RPL37A, RPL38, RPL7, RPL8, RPL10A, RPL21, RPL23, RPL7A, RPLP0, RPL14, RPL27A, RPL29, RPL3, RPL37, RPL39, RPL15, RPL34, RPL36A, RPLP1, RPL10, RPL18A, RPL22, RPL24, RPL31, RPL4, RPL41, UBA52, RPL11, RPL26
TRBP containing complex (DICER, RPL7A, EIF6, MOV10 and subunits of the 60S ribosomal particle)	25	RSL24D1, MOV10, RPL11, RPL14, RPL15, RPL27, RPL28, RPL35A, RPL36, RPL12, RPL13, RPL19, RPL7A, EIF6, RPL18A, RPL21, RPL32, RPL34, RPLP2, DICER1, RPL10A, RPL30, RPL37A, RPL7, RPLP1

Disease & clinical

Genetic variants

Variant evidence for RPLP2: 26 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 206):

Position(s)	Effect	Δscore	Sites
11:810358–810359	donor_loss	1.0000	4
11:811595–811596	acceptor_loss	1.0000	5
11:811646	donor_loss	1.0000
11:812530	acceptor_gain	1.0000
11:812533–812534	acceptor_loss	1.0000	4
11:812634–812635	donor_loss	1.0000	4
11:812757	acceptor_gain	1.0000
11:812758–812759	acceptor_loss	1.0000	4
11:810358	donor_loss	0.9900
11:811589	acceptor_gain	0.9900

AlphaMissense

378 missense substitutions predicted likely pathogenic (of 748 scored), across 100 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F114	8	0.994	1.000
F111	8	0.978	0.995
D108	8	0.975	0.996
D115	8	0.945	0.994
D106	8	0.938	0.993
D22	8	0.869	0.941
M109	7	0.955	0.983
G58	6	0.993	0.999
R2	6	0.974	0.991
L113	6	0.973	0.999
P18	6	0.966	0.995
I26	6	0.948	0.996
G31	6	0.945	0.993
G13	6	0.943	0.997
G14	6	0.941	0.990
V30	6	0.930	0.995
P66	6	0.920	0.984
L27	6	0.883	0.996
D107	6	0.881	0.972
I32	6	0.864	0.981

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	2.05e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	6.16e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	7.34e-05

Disease associations

OMIM: gene MIM:180530 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST90013442_17	Keratoconus	1e-26
GCST006412_42	Intraocular pressure	1e-9

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295698 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.32	Kd	48.25	nM	CHEMBL5653589
7.32	ED50	48.25	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 3 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149279: Binding affinity to human RPLP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0483	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects expression	3
sodium arsenite	affects binding, decreases reaction, decreases expression, increases expression	2
Smoke	decreases expression, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases expression	2
bisphenol F	decreases expression, affects cotreatment	1
TAK-243	affects sumoylation	1
glycidyl methacrylate	increases expression	1
sodium arsenate	decreases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
coumarin	decreases phosphorylation	1
phenanthrene	decreases expression	1
N-benzyloxycarbonylprolylprolinal	increases expression	1
phenethyl isothiocyanate	affects binding	1
CD 437	decreases expression	1
chloropicrin	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	increases expression	1
Atrazine	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4270810	Binding	Binding affinity to 60S acidic ribosomal protein P2 in human Hela cells lysates assessed as protein enrichment by measuring normalized heavy/light ratio at by nano-LC-ESIMS/MS analysis	Determination of Gymnemic Acid I as a Protein Biosynthesis Inhibitor Using Chemical Proteomics. — *J Nat Prod*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RPLP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.