PRCP

Summary

PRCP (prolylcarboxypeptidase, HGNC:9344) is a protein-coding gene on chromosome 11q14, encoding Lysosomal Pro-X carboxypeptidase (P42785). Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin.

This gene encodes a member of the peptidase S28 family of serine exopeptidases. The encoded preproprotein is proteolytically processed to generate the mature lysosomal prolylcarboxypeptidase. This enzyme cleaves C-terminal amino acids linked to proline in peptides such as angiotension II, III and des-Arg9-bradykinin. The cleavage occurs at acidic pH, but the enzyme activity is retained with some substrates at neutral pH. This enzyme has been shown to be an activator of the cell matrix-associated prekallikrein. The importance of angiotension II, one of the substrates of this enzyme, in regulating blood pressure and electrolyte balance suggests that this gene may be related to essential hypertension. A pseudogene of this gene has been identified on chromosome 2. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 5547 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 86 total
• GTEx eGene: eQTL in 30 tissues, sQTL in 10 (q < 0.05)
• ChEMBL bioactivity: 5 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.12 (unconstrained)
• MANE Select transcript: NM_005040
• Notable: 86 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9344
Approved symbol	PRCP
Name	prolylcarboxypeptidase
Location	11q14
Locus type	gene with protein product
Status	Approved
Aliases	PCP, HUMPCP
Ensembl gene	ENSG00000137509
Ensembl biotype	protein_coding
OMIM	176785
Entrez	5547

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 28 protein_coding, 8 retained_intron, 6 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 1 TEC

MANE Select: ENST00000313010

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 4, TSL 4: 4, TSL 5: 5

ENST00000313010, ENST00000393399, ENST00000524642, ENST00000525772, ENST00000526918, ENST00000527444, ENST00000528082, ENST00000529671, ENST00000531128, ENST00000531283, ENST00000531801, ENST00000532709, ENST00000532809, ENST00000533126, ENST00000534264, ENST00000534396, ENST00000534631, ENST00000623464, ENST00000679387, ENST00000679623, ENST00000679809, ENST00000680040, ENST00000680186, ENST00000680341, ENST00000680437, ENST00000680524, ENST00000680566, ENST00000681126, ENST00000681155, ENST00000681322, ENST00000681432, ENST00000681508, ENST00000681592, ENST00000681637, ENST00000681781, ENST00000681826, ENST00000681883, ENST00000913715, ENST00000949391, ENST00000993368, ENST00000993369, ENST00000993370, ENST00000993371, ENST00001031569, ENST00001031570, ENST00001031571, ENST00001141208

RefSeq mRNA: 3 — MANE Select: NM_005040 NM_001319214, NM_005040, NM_199418

CCDS: CCDS41695, CCDS8262, CCDS91553

Canonical transcript exons

ENST00000313010 — 9 exons

Exon	Start	End
ENSE00000927712	82849049	82849218
ENSE00000927714	82850324	82850505
ENSE00002149928	82822936	82825122
ENSE00002150116	82900235	82900430
ENSE00003487282	82838387	82838574
ENSE00003534552	82839261	82839425
ENSE00003554074	82859977	82860117
ENSE00003642450	82853177	82853278
ENSE00003787376	82849914	82850071

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 88.5378 / max 588.2413, expressed in 1823 samples.

Highest expression (Bgee): tendon of biceps brachii, lymph node, monocyte, adrenal gland cortex, mononuclear cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRCP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 40 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	4.7e-28	-0.46	11:82853252:T:G
Pancreas	eqtl	1.8e-24	-0.87	11:82908335:C:T
Muscle Skeletal	eqtl	8.5e-16	-0.61	11:82901653:C:T
Adipose Subcutaneous	eqtl	1.3e-15	-0.63	11:82900186:G:A
Nerve Tibial	eqtl	3.3e-11	-0.40	11:82908335:C:T
Liver	eqtl	1.1e-10	-0.83	11:82901653:C:T
Skin Sun Exposed Lower leg	sqtl	2.3e-09	-0.40	11:82840713:T:C
Testis	sqtl	3.2e-09	+0.62	11:82853252:T:G
Stomach	eqtl	1.1e-08	-0.55	11:82908335:C:T
Artery Tibial	eqtl	2.3e-08	-0.17	11:82818962:C:A
Adipose Subcutaneous	sqtl	5.5e-08	+0.37	11:82842987:A:G
Artery Aorta	eqtl	7.1e-08	-0.19	11:82862229:G:T
Colon Sigmoid	eqtl	8.5e-08	-0.45	11:82900186:G:A
Adipose Visceral Omentum	eqtl	9.6e-08	-0.62	11:82901653:C:T
Skin Sun Exposed Lower leg	eqtl	2.5e-07	-0.41	11:82900186:G:A
Skin Not Sun Exposed Suprapubic	eqtl	2.5e-06	+0.18	11:82887281:G:C
Skin Not Sun Exposed Suprapubic	sqtl	5.1e-06	-0.38	11:82840929:A:G
Esophagus Mucosa	eqtl	6.0e-06	+0.18	11:82927401:CAGA:C
Colon Transverse	eqtl	1.2e-05	-0.36	11:82900186:G:A
Spleen	eqtl	1.9e-04	-0.18	11:82953638:G:A

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
121571	87.6287	1823
121573	0.3473	122
121569	0.1473	61
121574	0.1350	39
121572	0.0943	30
121575	0.0928	41
121570	0.0613	35
121577	0.0166	10
121576	0.0145	4

Top tissues by expression

showing 100 of 302 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.35	gold quality
lymph node	UBERON:0000029	97.46	gold quality
monocyte	CL:0000576	97.29	gold quality
right adrenal gland cortex	UBERON:0035827	97.27	gold quality
mononuclear cell	CL:0000842	97.18	gold quality
right adrenal gland	UBERON:0001233	97.18	gold quality
leukocyte	CL:0000738	97.17	gold quality
gall bladder	UBERON:0002110	97.13	gold quality
periodontal ligament	UBERON:0008266	97.13	gold quality
synovial joint	UBERON:0002217	97.08	gold quality
left adrenal gland	UBERON:0001234	96.91	gold quality
adrenal cortex	UBERON:0001235	96.91	gold quality
urethra	UBERON:0000057	96.89	gold quality
left adrenal gland cortex	UBERON:0035825	96.88	gold quality
adrenal gland	UBERON:0002369	96.87	gold quality
smooth muscle tissue	UBERON:0001135	96.84	gold quality
adrenal tissue	UBERON:0018303	96.82	gold quality
metanephros cortex	UBERON:0010533	96.60	gold quality
decidua	UBERON:0002450	96.57	gold quality
tibia	UBERON:0000979	96.53	gold quality
penis	UBERON:0000989	96.22	gold quality
skin of hip	UBERON:0001554	96.21	gold quality
endocervix	UBERON:0000458	96.19	gold quality
bone marrow cell	CL:0002092	96.16	gold quality
ectocervix	UBERON:0012249	96.14	gold quality
renal medulla	UBERON:0000362	96.11	gold quality
colonic epithelium	UBERON:0000397	96.07	gold quality
right atrium auricular region	UBERON:0006631	96.03	gold quality
upper leg skin	UBERON:0004262	96.01	gold quality
medial globus pallidus	UBERON:0002477	96.00	gold quality
endometrium	UBERON:0001295	95.96	gold quality
vena cava	UBERON:0004087	95.91	gold quality
pericardium	UBERON:0002407	95.83	gold quality
vagina	UBERON:0000996	95.82	gold quality
parietal pleura	UBERON:0002400	95.82	gold quality
stromal cell of endometrium	CL:0002255	95.78	gold quality
peritoneum	UBERON:0002358	95.77	gold quality
omental fat pad	UBERON:0010414	95.77	gold quality
granulocyte	CL:0000094	95.74	gold quality
cranial nerve II	UBERON:0000941	95.72	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.65	gold quality
vermiform appendix	UBERON:0001154	95.63	gold quality
adult mammalian kidney	UBERON:0000082	95.60	gold quality
cortex of kidney	UBERON:0001225	95.59	gold quality
right lung	UBERON:0002167	95.59	gold quality
olfactory bulb	UBERON:0002264	95.56	gold quality
paraflocculus	UBERON:0005351	95.50	gold quality
blood	UBERON:0000178	95.47	gold quality
pleura	UBERON:0000977	95.47	gold quality
left uterine tube	UBERON:0001303	95.45	gold quality
left coronary artery	UBERON:0001626	95.45	gold quality
minor salivary gland	UBERON:0001830	95.44	gold quality
caecum	UBERON:0001153	95.30	gold quality
tonsil	UBERON:0002372	95.28	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.26	gold quality
uterus	UBERON:0000995	95.24	gold quality
esophagus mucosa	UBERON:0002469	95.24	gold quality
coronary artery	UBERON:0001621	95.20	gold quality
islet of Langerhans	UBERON:0000006	95.15	gold quality
saliva-secreting gland	UBERON:0001044	95.13	gold quality
skin of abdomen	UBERON:0001416	95.10	gold quality
adult organism	UBERON:0007023	95.09	gold quality
globus pallidus	UBERON:0001875	95.07	gold quality
mammalian vulva	UBERON:0000997	95.05	gold quality
female reproductive system	UBERON:0000474	95.03	gold quality
right ovary	UBERON:0002118	95.01	gold quality
adipose tissue	UBERON:0001013	94.98	gold quality
superficial temporal artery	UBERON:0001614	94.93	gold quality
connective tissue	UBERON:0002384	94.93	gold quality
urinary bladder	UBERON:0001255	94.92	gold quality
mucosa of urinary bladder	UBERON:0001259	94.92	gold quality
rectum	UBERON:0001052	94.88	gold quality
mouth mucosa	UBERON:0003729	94.86	gold quality
right lobe of thyroid gland	UBERON:0001119	94.83	gold quality
skin of leg	UBERON:0001511	94.82	gold quality
body of uterus	UBERON:0009853	94.78	gold quality
zone of skin	UBERON:0000014	94.72	gold quality
myometrium	UBERON:0001296	94.68	gold quality
left ovary	UBERON:0002119	94.67	gold quality
visceral pleura	UBERON:0002401	94.59	gold quality
thyroid gland	UBERON:0002046	94.56	gold quality
kidney	UBERON:0002113	94.55	gold quality
upper lobe of left lung	UBERON:0008952	94.55	gold quality
descending thoracic aorta	UBERON:0002345	94.52	gold quality
upper lobe of lung	UBERON:0008948	94.51	gold quality
placenta	UBERON:0001987	94.44	gold quality
left lobe of thyroid gland	UBERON:0001120	94.38	gold quality
uterine cervix	UBERON:0000002	94.34	gold quality
bone element	UBERON:0001474	94.34	gold quality
bone marrow	UBERON:0002371	94.34	gold quality
lung	UBERON:0002048	94.33	gold quality
tendon	UBERON:0000043	94.31	gold quality
choroid plexus epithelium	UBERON:0003911	94.30	gold quality
metanephric glomerulus	UBERON:0004736	94.30	gold quality
cardiac atrium	UBERON:0002081	94.26	gold quality
ovary	UBERON:0000992	94.23	gold quality
nipple	UBERON:0002030	94.19	gold quality
nephron tubule	UBERON:0001231	94.13	gold quality
esophagus	UBERON:0001043	94.10	gold quality
mucosa of stomach	UBERON:0001199	94.10	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	2116.53
E-CURD-112	yes	1731.68
E-MTAB-10553	yes	1353.24
E-HCAD-10	yes	1290.84
E-GEOD-124472	yes	1264.52
E-MTAB-8271	yes	797.03
E-GEOD-135922	yes	372.57
E-HCAD-1	yes	30.42
E-MTAB-8410	yes	24.29
E-HCAD-9	yes	19.97
E-MTAB-6701	yes	15.44
E-HCAD-13	yes	12.37
E-MTAB-9067	yes	8.03
E-MTAB-10042	yes	7.90
E-MTAB-9801	yes	7.78

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Placenta	tissue	143.5	low
Liver	tissue	141.9	medium
Kidney	tissue	134.9	high
Urinary bladder	tissue	93.6	low
Cervix	tissue	86.4	not detected
Lymph node	tissue	86.3	medium
Adrenal gland	tissue	82.4	high
Ovary	tissue	81.1	not detected
Salivary gland	tissue	80.6	medium
Tonsil	tissue	79.7	low
Epididymis	tissue	77.0	medium
Smooth muscle	tissue	75.5	low
Parathyroid gland	tissue	73.7	medium
Vagina	tissue	70.5	not detected
Adipose tissue	tissue	70.1	not detected
Choroid plexus	tissue	65.9
Breast	tissue	65.6	medium
Gallbladder	tissue	60.3	not detected
Heart muscle	tissue	59.8	not detected
Thyroid gland	tissue	59.7	medium
Endometrium 1	tissue	58.9	medium
Esophagus	tissue	57.6	not detected
Lung	tissue	54.8	medium
Appendix	tissue	54.6	not detected
Fallopian tube	tissue	53.6	medium
Seminal vesicle	tissue	52.3	medium
Skin 1	tissue	51.1	not detected
Spleen	tissue	50.8	high
Prostate	tissue	49.3	medium
Pituitary gland	tissue	46.5
Colon	tissue	46.2	low
Rectum	tissue	43.8	not detected
Testis	tissue	39.1	medium
Pancreas	tissue	35.8	medium
Bone marrow	tissue	35.8	not detected
Hypothalamus	tissue	32.2
Thymus	tissue	31.5
Spinal cord	tissue	30.9
Substantia nigra	tissue	30.3
Stomach 1	tissue	29.7	low
Corpus callosum	tissue	29.7
Small intestine	tissue	29.3	not detected
Medulla oblongata	tissue	28.9
Periaqueductal gray	tissue	28.1
Septum	tissue	27.8
Duodenum	tissue	26.9	not detected
Hippocampal formation	tissue	26.8
Tongue	tissue	26.5
Pons	tissue	26.1
Hippocampus	tissue	26.0	medium
Midbrain	tissue	24.4
Thalamus	tissue	22.9
Ventral forebrain	tissue	22.9
Locus coeruleus	tissue	22.6
Putamen	tissue	22.1
Entorhinal cortex	tissue	21.5
Amygdala	tissue	21.1
Cerebral cortex	tissue	20.8	medium
Motor cortex	tissue	20.8
Prefrontal cortex	tissue	20.5

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (70.5), Cervical spinal cord, ventral horn (54.7), Cervical spinal cord, central gray (51.0), Dorsal funiculus (white matter) (47.1), Posterior thalamic nucleus (46.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PRCP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 124 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502

Functional genomics

gnomAD constraint: pLI 2.24e-12, LOEUF 1.12, missense Z -0.281 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000313010 — one region, missense o/e 1.03.

Literature-anchored findings (GeneRIF, showing 21)

• PRCP appears to be a HUVEC-associated prekallikrein activator. (PMID:11830581)
• Identification of prolylcarboxypeptidase as the cell matrix-associated prekallikrein activator. (PMID:12123826)
• recombinant protein, identical to enzyme from human umbilical vein endothelial cells, is a prekallikrein activator. (PMID:14996700)
• Prolylcarboxypepdiase E112D (rs2298668)D allele alone and jointly with chronic hypertension were associated with a significantly increased risk of preeclampsia (PMID:16681991)
• role in regulation cardiovascular tone; proinflammatory agent (PMID:18396440)
• These investigations showed that the C-terminal region of the rPRCP(40) contributes to PRCP’s catalytic function, and provided additional experimental evidence for this suggestion. (PMID:18656443)
• Data suggest that the E112D polymorphism in the PRCP gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril treatment in hypertensive patients. (PMID:20079160)
• Purified PrCP yielded crystals belonging to space group R32, with unit-cell parameters a = b = 181.14, c = 240.13 A, that diffracted to better than 2.8 A resolution. (PMID:20516604)
• A single peptide, with the sequence YPRPIHPA, as a novel substrate for PRCP in human cerebrospinal fluid. (PMID:20517885)
• A structure-based alignment with the previously undescribed structure of DPP7 illuminates the mechanism of orthogonal substrate specificity of PRCP and DPP7. (PMID:20540760)
• PRCP as a resistance factor for 4OHTAM resistance in estrogen receptor-positive breast cancer cells. (PMID:21087932)
• analysis of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors (PMID:22079761)
• The present results indicated PRCP rs7104980 can be considered as a marker for EH and Hap3 GAGCACTAACA (PRCP) and Hap16 TTTA (CMA1) might be associated with essential hypertension in Chinese Han population. (PMID:22679278)
• PRCP regulates cell growth, angiogenesis, and the response to vascular injury (PMID:23744584)
• PRCP1 interacts with plasma kallikrein (PK) at multiple sites for PK activation. (PMID:25324000)
• The decrease in PRCP levels in the first 24 h after stroke onset is associated with stroke severity and an unfavourable short-term stroke outcome (PMID:25370794)
• For the first time, PRCP is identified as an apelin-cleaving enzyme. (PMID:27449720)
• Using multiple -omics approach, study validated key molecules, such as CAP1, SHC1 and PRCP, that might play a significant role in IgA nephropathy pathogenesis. (PMID:28831120)
• Fast oxidation of alpha-melanocyte-stimulating hormone and derived peptides under laboratory conditions causes irreproducible results-Insights from studies of prolylcarboxypeptidase in human cell types. (PMID:31837203)
• Genetic association study of prolylcarboxypeptidase polymorphisms with susceptibility to essential hypertension in the Yi minority of China: A case-control study based on an isolated population. (PMID:32448049)
• Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China. (PMID:33319614)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prcp	ENSDARG00000037883
mus_musculus	Prcp	ENSMUSG00000061119
rattus_norvegicus	Prcp	ENSRNOG00000010630
drosophila_melanogaster	CG2493	FBGN0032864
caenorhabditis_elegans		WBGENE00022801

Paralogs (2): PRSS16 (ENSG00000112812), DPP7 (ENSG00000176978)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919711) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body length	1
decreased body weight	1
microphthalmia	1
abnormal eye morphology	1
abnormal response/metabolism to endogenous compounds	1
decreased susceptibility to diet-induced obesity	1
decreased body mass index	1
decreased total fat pad weight	1
decreased gonadal fat pad weight	1
decreased femoral fat pad weight	1
decreased mesenteric fat pad weight	1
decreased retroperitoneal fat pad weight	1
decreased food intake	1

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
Pongo abelii	Q5RBU7	99.2%	Diamond
Bos taurus	Q2TA14	78.3%	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
LINC02734	ncRNA	105369413
DDIAS	protein-coding	220042
FAM181B	protein-coding	220382
SNORA70E	snoRNA	100379250
RAB30	protein-coding	27314
RAB30-DT	ncRNA	100506233
LINC02951	ncRNA	123466204

Protein

Protein identifiers

Lysosomal Pro-X carboxypeptidase — P42785 (reviewed: P42785)

Alternative names: Angiotensinase C, Lysosomal carboxypeptidase C, Proline carboxypeptidase, Prolylcarboxypeptidase

All UniProt accessions (12): P42785, A0A7P0TB23, A0A7P0Z451, B3KR26, B7Z7Q6, E9PKN6, E9PL49, E9PL85, E9PLY4, E9PNF7, E9PNJ1, E9PQB5

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin. This cleavage occurs at acidic pH, but enzymatic activity is retained with some substrates at neutral pH.

Subunit / interactions. Homodimer.

Subcellular location. Lysosome.

Tissue specificity. Highest levels in placenta, lung and liver. Also present in heart, brain, pancreas and kidney.

Similarity. Belongs to the peptidase S28 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P42785-1	1	yes
P42785-2	2

RefSeq proteins (3): NP_001306143, NP_005031, NP_955450 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008758	Peptidase_S28	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR042269	Ser_carbopepase_S28_SKS	Homologous_superfamily

Pfam: PF05577

Enzyme classification (BRENDA)

• EC 3.4.16.2 — lysosomal Pro-Xaa carboxypeptidase (BRENDA: 8 organisms, 43 substrates, 60 inhibitors, 20 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALA-PRO-4-NITROANILIDE	1.5–3.1	3
ANGIOTENSIN II	0.34–1	2
MYOGLOBIN	0.1–0.13	2
N-BENZYLOXYCARBONYL-PRO-PHE	0.77–1.3	2
PREKALLIKREIN	—	2
ANGIOTENSIN III	2	1
GLY-PRO-4-NITROANILIDE	4	1
L-ALA-L-PRO 4-NITROANILIDE	0.157	1
N-BENZYLOXYCARBONYL-GLY-L-PRO 4-NITROANILIDE	0.147	1
N-BENZYLOXYCARBONYL-L-ALA-L-ALA-L-PRO 4-NITROANI	0.34	1
N-BENZYLOXYCARBONYL-L-ALA-L-PRO 4-NITROANILIDE	0.095	1
N-BENZYLOXYCARBONYL-L-PRO 4-NITROANILIDE	0.17	1
N-BENZYLOXYCARBONYL-L-PRO-L-ALA	4.7	1
N-BENZYLOXYCARBONYL-L-PRO-LEU	0.26	1

UniProt features (56 total): helix 18, strand 12, glycosylation site 6, disulfide bond 4, sequence conflict 3, turn 3, active site 3, sequence variant 2, signal peptide 1, propeptide 1, splice variant 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
3N2Z	The Structure of Human Prolylcarboxypeptidase at 2.80 Angstroms Resolution	X-RAY DIFFRACTION	2.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42785-F1	90.99	0.87

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH approved · IF supported

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 (3)

Position	Role
179	charge relay system
430	charge relay system
455	charge relay system

Disulfide bonds (4)

Type	Positions
Disulfide bond	215–372, 233–310, 264–343, 364–394

Glycosylation sites (6)

Type	Positions
N-linked (glcnac…) asparagine	336, 345, 415, 47, 101, 317

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-9970672	FXIIa activates plasma kallikrein-kinin system	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-140837		—
R-HSA-140877		—

MSigDB gene sets: 342 (showing top): GOBP_PROTEIN_ACTIVATION_CASCADE, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_REGULATION_OF_BLOOD_PRESSURE, CCAWYNNGAAR_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (5): angiotensin maturation (GO:0002003), negative regulation of systemic arterial blood pressure (GO:0003085), regulation of blood vessel endothelial cell migration (GO:0043535), angiogenesis involved in wound healing (GO:0060055), proteolysis (GO:0006508)

GO Molecular Function (8): metallocarboxypeptidase activity (GO:0004181), serine-type carboxypeptidase activity (GO:0004185), dipeptidyl-peptidase activity (GO:0008239), carboxypeptidase activity (GO:0004180), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), serine-type exopeptidase activity (GO:0070008)

GO Cellular Component (7): plasma membrane (GO:0005886), azurophil granule membrane (GO:0035577), basal part of cell (GO:0045178), extracellular exosome (GO:0070062), ficolin-1-rich granule membrane (GO:0101003), extracellular region (GO:0005576), lysosome (GO:0005764)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Innate Immune System	2
Immune System	1

GO top-level categories

28 GO namespaces:

Category	Terms
exopeptidase activity	3
carboxypeptidase activity	2
secretory granule membrane	2
cellular anatomical structure	2
regulation of angiotensin levels in blood	1
peptide hormone processing	1
regulation of systemic arterial blood pressure	1
negative regulation of blood pressure	1
regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
angiogenesis	1
wound healing	1
protein metabolic process	1
metalloexopeptidase activity	1
serine-type exopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
serine-type peptidase activity	1
membrane	1
cell periphery	1
lysosomal membrane	1
azurophil granule	1
extracellular vesicle	1
tertiary granule	1
ficolin-1-rich granule	1
lytic vacuole	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular exosome	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 860 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRCP	PREP	P48147	885
PRCP	KNG1	P01042	730
PRCP	MME	P08473	661
PRCP	DPP4	P27487	656
PRCP	THOP1	P52888	640
PRCP	REN	P00797	624
PRCP	GBE1	Q04446	616
PRCP	KLKB1	P03952	611
PRCP	FAM181B	A6NEQ2	573
PRCP	AGT	P01019	570
PRCP	LRPAP1	P30533	512
PRCP	NLN	Q9BYT8	511
PRCP	ACE2	Q9BYF1	511
PRCP	MMEL1	Q495T6	510
PRCP	CPE	P16870	506

IntAct

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

3 partners by confidence:

Partner	Interaction type	MIscore	Records
GPR37L1	protein cleavage	0.560	2
AGT	protein cleavage	0.440	1
VDR	physical association	0.370	1

BioGRID (71 interactions; top human partners by supporting records): FBXO6 (Affinity Capture-MS; 5 records), FAM19A4 (Affinity Capture-MS; 2 records), ABCE1 (Affinity Capture-MS), BCOR (Affinity Capture-MS), CUL3 (Affinity Capture-MS), DDX39A (Affinity Capture-RNA), FAM133A (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), HEXB (Affinity Capture-MS), HIBCH (Co-fractionation), HNRNPH2 (Affinity Capture-MS), IGF2R (Affinity Capture-MS), ISOC1 (Co-fractionation), KCMF1 (Affinity Capture-MS), LDHA (Co-fractionation)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PRCP	“down-regulates activity”	POMC

Disease & clinical

Genetic variants

Variant evidence for PRCP: 86 ClinVar records (0 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	1
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 1,170):

Position(s)	Effect	Δscore	Sites
11:82825123–82825124	acceptor_loss	1.0000	4
11:82825129	acceptor_gain	1.0000
11:82838575–82838576	acceptor_loss	1.0000	6
11:82849912–82849913	donor_loss	1.0000	3
11:82850322–82850323	donor_loss	1.0000	5
11:82850506–82850507	acceptor_loss	1.0000	5
11:82853175–82853176	donor_loss	1.0000	5
11:82853279–82853280	acceptor_loss	1.0000	3
11:82860118–82860119	acceptor_loss	1.0000	6
11:82825123–82825124	acceptor_loss	0.9900	2

AlphaMissense

943 missense substitutions predicted likely pathogenic (of 3,254 scored), across 240 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
D153	8	0.974	0.989
D430	8	0.969	0.981
D458	8	0.941	0.969
D466	8	0.933	0.962
F119	8	0.926	0.990
H122	8	0.922	0.964
F424	8	0.920	0.985
H455	8	0.917	0.980
H456	8	0.881	0.943
C310	7	0.983	0.990
C394	7	0.968	0.985
C233	7	0.961	0.980
F380	7	0.959	0.984
C364	7	0.958	0.974
F68	7	0.939	0.991
F226	7	0.937	0.983
R189	7	0.934	0.988
F99	7	0.931	0.980
E121	7	0.922	0.980
C264	7	0.917	0.946

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.28e-05

Disease associations

OMIM: gene MIM:176785 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST006585_1042	Blood protein levels	2e-9
GCST002826_5	Urate levels (BMI interaction)	1e-6
GCST003209_13	Colorectal or endometrial cancer	2e-6
GCST009391_1386	Metabolite levels	7e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0004230	endometrial neoplasm
EFO:0010412	triacylglycerol 50:5 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2335 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 42,720 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL73234	CARBETAPENTANE	4	7,334
CHEMBL61946	CARAMIPHEN	2	3,903
CHEMBL284237	DIZOCILPINE	2	5,082
CHEMBL275528	PHENCYCLIDINE	2	25,785
CHEMBL279676	TENOCYCLIDINE	2	616

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs2229437	Efficacy	3	benazepril	Hypertension

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2229437	PRCP	3	3.50	1	benazepril

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2229437	benazepril	Efficacy	Genotypes GG + GT are associated with decreased response to benazepril in people with Hypertension as compared to genotype TT.	PMID:20079160

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S28: Lysosomal Pro-Xaa carboxypeptidase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 35 [PMID: 24157366]	Inhibition	10.1	pIC50

Binding affinities (BindingDB)

400 measured of 425 human assays (432 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl 3-[4-[3-(4-fluorophenyl)-1-pyrimidin-2-ylpyrazol-5-yl]piperidin-1-yl]-2-phenylpropanoate	IC50	0.035 nM	US-9365539: Prolylcarboxypeptidase inhibitors
2-[3-(4-chlorophenyl)-5-[1-(2-phenylethyl)piperidin-4-yl]pyrazol-1-yl]pyrimidine	IC50	0.051 nM	US-9365539: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(2-fluoro-4-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	0.079 nM	US-8669252: Prolylcarboxypeptidase inhibitors
CHEMBL1950440	IC50	0.17 nM
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-fluorophenyl)-(2-fluoro-4-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	0.18 nM	US-8669252: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-pyridin-4-ylmethyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	0.18 nM	US-8669252: Prolylcarboxypeptidase inhibitors
CHEMBL2022787	IC50	0.2 nM
CHEMBL2022793	IC50	0.2 nM
CHEMBL2023210	IC50	0.2 nM
CHEMBL1938522	IC50	0.3 nM
CHEMBL2023202	IC50	0.3 nM
2-[4-[3-(4-chlorophenyl)-1-pyrimidin-2-ylpyrazol-5-yl]piperidin-1-yl]-1-phenylethanol	IC50	0.31 nM	US-9365539: Prolylcarboxypeptidase inhibitors
CHEMBL1950444	IC50	0.37 nM
CHEMBL2022794	IC50	0.4 nM
CHEMBL2031595	IC50	0.4 nM
1-(4-chloro-2-pyridinyl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	IC50	0.44 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
5-(4-chloro-2-pyridinyl)-1’-[2-[4-(trifluoromethoxy)phenyl]propan-2-yl]spiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	IC50	0.49 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
CHEMBL2023207	IC50	0.5 nM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	IC50	0.5 nM	US-8569299: Prolylcarboxypeptidase inhibitors
3-[4-[3-(4-fluorophenyl)-1-pyrimidin-2-ylpyrazol-5-yl]piperidin-1-yl]-2-phenylpropanoic acid	IC50	0.51 nM	US-9365539: Prolylcarboxypeptidase inhibitors
CHEMBL1938510	IC50	0.6 nM
CHEMBL3085780	IC50	0.6 nM
(1R,2R,4R)-N-[bis(4-fluorophenyl)methyl]-2-(4-bromophenyl)-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	0.66 nM	US-8669252: Prolylcarboxypeptidase inhibitors
2-[2-(4-chlorophenyl)-5-[1-(2-phenylethyl)piperidin-4-yl]-1H-imidazol-4-yl]pyrimidine	IC50	0.7 nM	US-9006268: Prolylcarboxypeptidase inhibitors
CHEMBL2022786	IC50	0.7 nM
CHEMBL1951474	IC50	0.73 nM
CHEMBL1950439	IC50	0.74 nM
2-(4-fluorophenyl)-5-[1-(2-phenylethyl)piperidin-4-yl]-4-pyrimidin-2-yl-1,3-oxazole	IC50	0.78 nM	US-9006268: Prolylcarboxypeptidase inhibitors
CHEMBL1951478	IC50	0.78 nM
[4-[2-(3,4-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	IC50	0.8 nM	US-8569299: Prolylcarboxypeptidase inhibitors
CHEMBL2031596	IC50	0.8 nM
CHEMBL1938502	IC50	0.9 nM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-3-methylphenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]methanone	IC50	0.9 nM	US-8569299: Prolylcarboxypeptidase inhibitors
CHEMBL2031590	IC50	0.9 nM
CHEMBL2031588	IC50	0.9 nM
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(5-fluoro-2-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	0.95 nM	US-8669252: Prolylcarboxypeptidase inhibitors
2-Amino-N-{(2S,3S)-3-(biphenyl-4-yl)-1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-1-oxobutan-2-yl}-2-methylpropanamide	IC50	1 nM
CHEMBL1950443	IC50	1 nM
CHEMBL1951470	IC50	1 nM
CHEMBL2022785	IC50	1 nM
CHEMBL2022789	IC50	1 nM
CHEMBL2023211	IC50	1 nM
(S)-1-(2-(5,6-dichloro-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-(4-(1-methyl-5-(pyridin-4-yl)-1H-pyrazol-3-yl)piperidin-1-yl)propan-1-one	IC50	1.1 nM
CHEMBL2031580	IC50	1.1 nM
CHEMBL1938523	IC50	1.2 nM
1-(4-chloro-1-oxidopyridin-1-ium-2-yl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	IC50	1.2 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
CHEMBL3086029	IC50	1.2 nM
1-[4-[3-(4-fluorophenyl)-1-pyrimidin-2-ylpyrazol-5-yl]piperidin-1-yl]-2-[2-(trifluoromethyl)phenyl]ethanone	IC50	1.28 nM	US-9365539: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-N-[(4-fluorophenyl)-pyridin-4-ylmethyl]-4-morpholin-4-yl-2-phenylcyclohexane-1-carboxamide	IC50	1.4 nM	US-8669252: Prolylcarboxypeptidase inhibitors
CHEMBL1938519	IC50	1.4 nM

ChEMBL bioactivities

418 potent at pChembl≥5 of 450 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.46	IC50	0.035	nM	CHEMBL3910523
10.29	IC50	0.051	nM	CHEMBL3919329
10.10	IC50	0.079	nM	CHEMBL3086040
9.80	IC50	0.16	nM	CHEMBL3086040
9.77	IC50	0.17	nM	CHEMBL1950440
9.74	IC50	0.18	nM	CHEMBL3086037
9.74	IC50	0.18	nM	CHEMBL3652599
9.70	IC50	0.2	nM	CHEMBL2022787
9.70	IC50	0.2	nM	CHEMBL2022793
9.70	IC50	0.2	nM	CHEMBL2023210
9.52	IC50	0.3	nM	CHEMBL2023202
9.52	IC50	0.3	nM	CHEMBL1938522
9.51	IC50	0.31	nM	CHEMBL3901469
9.43	IC50	0.37	nM	CHEMBL1950444
9.40	IC50	0.4	nM	CHEMBL2022794
9.40	IC50	0.4	nM	CHEMBL2031595
9.36	IC50	0.44	nM	CHEMBL1951465
9.31	IC50	0.49	nM	CHEMBL1951476
9.30	IC50	0.5	nM	CHEMBL2023207
9.30	IC50	0.5	nM	CHEMBL2023209
9.29	IC50	0.51	nM	CHEMBL3932961
9.22	IC50	0.6	nM	CHEMBL3085780
9.22	IC50	0.6	nM	CHEMBL1938510
9.18	IC50	0.66	nM	CHEMBL3086036
9.18	IC50	0.66	nM	CHEMBL1951465
9.15	IC50	0.7	nM	CHEMBL2022786
9.15	IC50	0.7	nM	CHEMBL3677679
9.14	IC50	0.73	nM	CHEMBL1951474
9.13	IC50	0.74	nM	CHEMBL1950439
9.11	IC50	0.78	nM	CHEMBL3677678
9.11	IC50	0.78	nM	CHEMBL1951478
9.10	IC50	0.8	nM	CHEMBL2031596
9.10	IC50	0.8	nM	CHEMBL3655577
9.05	IC50	0.9	nM	CHEMBL2024198
9.05	IC50	0.9	nM	CHEMBL2031590
9.05	IC50	0.9	nM	CHEMBL2031588
9.05	IC50	0.9	nM	CHEMBL1938502
9.02	IC50	0.95	nM	CHEMBL3086041
9.00	IC50	1	nM	CHEMBL2022785
9.00	IC50	1	nM	CHEMBL2022789
9.00	IC50	1	nM	CHEMBL2023211
9.00	IC50	1	nM	CHEMBL1259194
9.00	IC50	1	nM	CHEMBL1950443
9.00	IC50	1	nM	CHEMBL1951470
8.96	IC50	1.1	nM	CHEMBL2031580
8.96	IC50	1.1	nM	CHEMBL1684306
8.92	IC50	1.2	nM	CHEMBL3086029
8.92	IC50	1.2	nM	CHEMBL1938523
8.92	IC50	1.2	nM	CHEMBL1951468
8.89	IC50	1.3	nM	CHEMBL1951468

PubChem BioAssay actives

362 with measured affinity, of 453 total; 50 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
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(2-fluoro-4-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0001	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3-chloro-4-fluorophenyl)pyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0002	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(1S)-1-(5,6-dichloro-1H-benzimidazol-2-yl)ethyl]-3-[4-(2,2,2-trifluoroethoxy)phenyl]butanamide	647767: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate for 30 mins by continuous fluorimetric assay	ic50	0.0002	uM
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-pyridin-4-ylmethyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0002	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3,4-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0002	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3-chloro-4-methylphenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0002	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(2,5-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0003	uM
N-[(4-chlorophenyl)-pyridin-4-ylmethyl]-3-(4-phenylpiperidin-1-yl)propanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0003	uM
1-(4-chloro-2-pyridinyl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0004	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(1S)-1-(5,6-dichloro-1H-benzimidazol-2-yl)ethyl]-3-(4-phenylphenyl)butanamide	647767: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate for 30 mins by continuous fluorimetric assay	ic50	0.0004	uM
[4-[2-(3-chloro-4-fluorophenyl)pyrazol-3-yl]piperidin-1-yl]-[(1S,2S,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0004	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(2,4-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0004	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0005	uM
5-(4-chloro-2-pyridinyl)-1’-[2-[4-(trifluoromethoxy)phenyl]propan-2-yl]spiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0005	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-2-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0005	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(4-chlorophenyl)-pyridin-4-ylmethyl]-3-(4-phenylphenyl)butanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0006	uM
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-fluorophenyl)-pyridin-4-ylmethyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0006	uM
(1R,2R,4R)-N-[bis(4-fluorophenyl)methyl]-2-(4-bromophenyl)-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0007	uM
(2S,3S)-N-[(1S)-1-(5,6-dichloro-1H-benzimidazol-2-yl)ethyl]-2-[(2-hydroxy-2-methylpropanoyl)amino]-3-[4-(2,2,2-trifluoroethoxy)phenyl]butanamide	647767: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate for 30 mins by continuous fluorimetric assay	ic50	0.0007	uM
1-(3,5-dichlorophenyl)-1’-[1-(5-fluoro-2-pyridinyl)ethyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0007	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-2-methylphenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0007	uM
1-(4-chloro-1-oxidopyridin-1-ium-2-yl)-1’-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0008	uM
[4-[2-(3-chloro-4-fluorophenyl)pyrazol-3-yl]piperidin-1-yl]-[(1S,2S,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0008	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(1S)-1-(4-chlorophenyl)ethyl]-3-(4-phenylphenyl)butanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0009	uM
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(5-fluoro-2-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0009	uM
[4-[2-(2,5-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0009	uM
[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0009	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-3-methylphenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0009	uM
2-amino-N-[(2S,3S)-1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-1-oxo-3-(4-phenylphenyl)butan-2-yl]-2-methylpropanamide	517810: Inhibition of human PrCP by FRET	ic50	0.0010	uM
(2S)-2-[(2-amino-2-methylpropyl)amino]-N-[(1S)-1-(5,6-dichloro-1H-benzimidazol-2-yl)ethyl]-3-(4-phenylphenyl)propanamide	647767: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate for 30 mins by continuous fluorimetric assay	ic50	0.0010	uM
1-(4-chloro-2-pyridinyl)-1’-[1-(5-fluoro-2-pyridinyl)ethyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0010	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(5-chloro-2-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0010	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-3-methylphenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0010	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0010	uM
1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-3-[4-(1-methyl-5-pyridin-4-ylpyrazol-3-yl)piperidin-1-yl]propan-1-one	647242: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate after 30 mins by fluorescence analysis	ic50	0.0011	uM
[4-[2-(4-chloro-3-methylphenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0011	uM
1-(4-chloro-1-oxidopyridin-1-ium-2-yl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0012	uM
N-[1-(4-chlorophenyl)-1-pyridin-4-ylethyl]-3-(4-phenylpiperidin-1-yl)propanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0012	uM
[(1R,2R,4R)-2-(4-bromophenyl)-4-morpholin-4-ylcyclohexyl]-(3,3-diphenylazetidin-1-yl)methanone	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0012	uM
N-[1-(4-chlorophenyl)-2,2,2-trifluoroethyl]-3-(4-phenylpiperidin-1-yl)propanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0014	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-3-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0014	uM
N-[(1S)-1-(4-chlorophenyl)-2-methylpropyl]-3-(4-phenylpiperidin-1-yl)propanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0015	uM
5-(3,5-dichlorophenyl)-1’-[4-(trifluoromethoxy)phenyl]sulfonylspiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0016	uM
[4-[2-(2,5-dichlorophenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0016	uM
1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-3-[4-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]propan-1-one	578622: Inhibition of human PrCP	ic50	0.0017	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[1-(4-chlorophenyl)-2,2,2-trifluoroethyl]-3-(4-phenylphenyl)butanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0017	uM
5-(3,5-dichlorophenyl)-1’-[1-(5-fluoro-2-pyridinyl)ethyl]spiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0019	uM
1-(3,5-dichlorophenyl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0019	uM
2-amino-N-[(2S)-1-[(2S)-2-(5-tert-butyl-1H-imidazol-2-yl)pyrrolidin-1-yl]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-2-methylpropanamide	517812: Inhibition of human PrCP by FRET in presence of 1% mouse serum albumin	ic50	0.0020	uM
N-[(2S,3S)-1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-3-[4-(4-fluorophenyl)phenyl]-1-oxobutan-2-yl]-2-hydroxy-2-methylpropanamide	517810: Inhibition of human PrCP by FRET	ic50	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation	3
trichostatin A	affects cotreatment, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
afimoxifene	decreases response to substance	1
sodium arsenite	decreases expression, increases abundance	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression	1
benazepril	affects response to substance	1
arsenic disulfide	decreases expression	1
nutlin 3	increases secretion, affects cotreatment	1
ICG 001	increases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Ozone	increases abundance, increases expression	1

ChEMBL screening assays

46 unique, capped per target: 46 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1110131	Binding	Inhibition of carboxypeptidase P	Inhibitors of prolyl oligopeptidases for the therapy of human diseases: defining diseases and inhibitors. — *J Med Chem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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