CPN2

Summary

CPN2 (carboxypeptidase N subunit 2, HGNC:2313) is a protein-coding gene on chromosome 3q29, encoding Carboxypeptidase N subunit 2 (P22792). The 83 kDa subunit binds and stabilizes the catalytic subunit at 37 degrees Celsius and keeps it in circulation.

Predicted to enable enzyme regulator activity. Predicted to be involved in protein stabilization. Located in blood microparticle and extracellular exosome.

Source: NCBI Gene 1370 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_001080513

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2313
Approved symbol	CPN2
Name	carboxypeptidase N subunit 2
Location	3q29
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178772
Ensembl biotype	protein_coding
OMIM	603104
Entrez	1370

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 17 protein_coding

ENST00000323830, ENST00000429275, ENST00000862543, ENST00000862544, ENST00000862545, ENST00000862546, ENST00000862547, ENST00000862548, ENST00000862549, ENST00000862550, ENST00000862551, ENST00000862552, ENST00000862553, ENST00000862554, ENST00000862555, ENST00000961088, ENST00000961089

RefSeq mRNA: 2 — MANE Select: NM_001080513 NM_001080513, NM_001291988

CCDS: CCDS33920

Canonical transcript exons

ENST00000323830 — 2 exons

Exon	Start	End
ENSE00001226519	194339768	194342705
ENSE00001226528	194351242	194351328

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 97.08.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.5068 / max 955.8376, expressed in 58 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46199	2.5068	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.08	gold quality
liver	UBERON:0002107	95.05	gold quality
adult mammalian kidney	UBERON:0000082	77.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.42	gold quality
adrenal tissue	UBERON:0018303	73.47	gold quality
nephron tubule	UBERON:0001231	72.63	silver quality
kidney epithelium	UBERON:0004819	71.19	silver quality
kidney	UBERON:0002113	70.71	gold quality
diaphragm	UBERON:0001103	70.52	gold quality
right adrenal gland	UBERON:0001233	70.52	gold quality
right adrenal gland cortex	UBERON:0035827	69.68	gold quality
orbitofrontal cortex	UBERON:0004167	69.21	gold quality
renal glomerulus	UBERON:0000074	68.24	silver quality
metanephric glomerulus	UBERON:0004736	68.23	silver quality
left adrenal gland	UBERON:0001234	66.89	gold quality
olfactory bulb	UBERON:0002264	65.51	gold quality
type B pancreatic cell	CL:0000169	65.41	gold quality
left adrenal gland cortex	UBERON:0035825	65.38	gold quality
adrenal gland	UBERON:0002369	64.92	gold quality
adrenal cortex	UBERON:0001235	64.47	gold quality
metanephros	UBERON:0000081	64.23	gold quality
gingival epithelium	UBERON:0001949	64.07	gold quality
epithelial cell of pancreas	CL:0000083	62.26	gold quality
cardiac muscle of right atrium	UBERON:0003379	61.53	gold quality
gingiva	UBERON:0001828	60.85	gold quality
lower lobe of lung	UBERON:0008949	60.13	silver quality
tibia	UBERON:0000979	59.77	silver quality
apex of heart	UBERON:0002098	59.69	gold quality
cortex of kidney	UBERON:0001225	59.59	gold quality
oocyte	CL:0000023	58.69	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting CPN2, 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-4533	100.00	69.48	2758
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-609	99.82	64.26	505
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-548AS-3P	99.12	69.12	2294

Literature-anchored findings (GeneRIF, showing 1)

• Real-time PCR and western blotting show the following CPN2 expression: minimal in MDA-MB-468 cells but obvious in MDA-MB-231 and MCF7 cells. MDA-MB-231 breast cancer cell lines were selected for the control group and CPN2 was knocked out for the experimental group. (PMID:26860443)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cpn2	ENSMUSG00000023176
rattus_norvegicus	Cpn2	ENSRNOG00000024384
drosophila_melanogaster	Con	FBGN0005775
drosophila_melanogaster	kek3	FBGN0028370
drosophila_melanogaster	CG18095	FBGN0028872
drosophila_melanogaster	CG7509	FBGN0035575
caenorhabditis_elegans	lron-9	WBGENE00011971
caenorhabditis_elegans		WBGENE00020649
caenorhabditis_elegans		WBGENE00022789

Paralogs (22): CHADL (ENSG00000100399), LGI1 (ENSG00000108231), LGR6 (ENSG00000133067), CHAD (ENSG00000136457), LRIG3 (ENSG00000139263), LGR5 (ENSG00000139292), LRIG1 (ENSG00000144749), LRRTM2 (ENSG00000146006), LRIT1 (ENSG00000148602), LGI2 (ENSG00000153012), LGI4 (ENSG00000153902), LRRC52 (ENSG00000162763), ELFN2 (ENSG00000166897), LGI3 (ENSG00000168481), LRG1 (ENSG00000171236), LRIT3 (ENSG00000183423), LRRC26 (ENSG00000184709), LRIG2 (ENSG00000198799), LGR4 (ENSG00000205213), ELFN1 (ENSG00000225968), LRRC24 (ENSG00000254402), TRIL (ENSG00000255690)

Protein

Protein identifiers

Carboxypeptidase N subunit 2 — P22792 (reviewed: P22792)

Alternative names: Carboxypeptidase N 83 kDa chain, Carboxypeptidase N large subunit, Carboxypeptidase N polypeptide 2, Carboxypeptidase N regulatory subunit

All UniProt accessions (1): P22792

UniProt curated annotations — full annotation on UniProt →

Function. The 83 kDa subunit binds and stabilizes the catalytic subunit at 37 degrees Celsius and keeps it in circulation. Under some circumstances it may be an allosteric modifier of the catalytic subunit.

Subunit / interactions. Tetramer of two catalytic chains and two glycosylated inactive chains.

Subcellular location. Secreted.

Post-translational modifications. Whether or not any Cys residues participate in intrachain bonds is unknown, but they do not form interchain disulfide bonds with the 50 kDa catalytic subunit.

RefSeq proteins (2): NP_001073982, NP_001278917 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF13855

UniProt features (29 total): repeat 12, glycosylation site 8, sequence variant 3, domain 2, sequence conflict 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22792-F1	85.71	0.70

Functional residue map

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

Glycosylation sites (8): 74, 111, 119, 228, 266, 348, 359, 518

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977606	Regulation of Complement cascade

MSigDB gene sets: 82 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_GSTM1, GNF2_HPN, GOBP_PROTEIN_STABILIZATION, GNF2_LCAT, HSIAO_LIVER_SPECIFIC_GENES, GOBP_REGULATION_OF_PROTEIN_STABILITY, GNF2_HPX, MODULE_88, MODULE_544, GRADE_COLON_AND_RECTAL_CANCER_DN, GOCC_BLOOD_MICROPARTICLE, MODULE_55, MANALO_HYPOXIA_DN, MODULE_23

GO Biological Process (1): protein stabilization (GO:0050821)

GO Molecular Function (3): enzyme regulator activity (GO:0030234), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), blood microparticle (GO:0072562)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Complement cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of protein stability	1
catalytic activity	1
molecular function regulator activity	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
extracellular region	1

Protein interactions and networks

STRING

860 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPN2	CPN1	P15169	933
CPN2	CPB1	P15086	718
CPN2	PGLYRP2	Q96PD5	381
CPN2	LGALS3BP	Q08380	370
CPN2	AFM	P43652	359
CPN2	LURAP1	Q96LR2	348
CPN2	ZNF578	Q96N58	348
CPN2	MINPP1	Q9UNW1	348
CPN2	C2	P06681	347
CPN2	C6	P13671	322
CPN2	HRG	P04196	315
CPN2	FAM234B	A2RU67	310
CPN2	RCN3	Q96D15	308
CPN2	RNF181	Q9P0P0	302
CPN2	CFB	P00751	300

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): CPN2 (Affinity Capture-MS), CPN2 (Synthetic Lethality), CPN2 (Affinity Capture-MS), CPN2 (Affinity Capture-MS)

ESM2 similar proteins: A2VDH3, A6H793, B0BNK7, D2HFT7, D4ABX8, E9Q7T7, O75325, P22792, P40197, Q13641, Q149C3, Q1RMS4, Q2EEY0, Q2I0M4, Q3UVD5, Q3UY51, Q4KLL3, Q4R8Y9, Q50LG9, Q5I2M7, Q5I2M8, Q5PQV5, Q5VT99, Q6NUI6, Q6P3Y9, Q6PEZ8, Q6PJG9, Q6UY18, Q6ZSA7, Q7M6Z0, Q7TQ62, Q7Z5L7, Q80WD0, Q80WD1, Q80XU8, Q86UN2, Q86UN3, Q8BHA1, Q8BLY3, Q8K0S5

Diamond homologs: B1H134, B1H234, D3ZTV3, F1NUK7, O02678, O43155, O46378, O46379, O46390, O46403, P21809, P21810, P22792, P28653, P47853, P50608, P51887, P58682, P79119, Q3MHH9, Q5R6T0, Q6P3Y9, Q6PEZ8, Q6RKD8, Q70AK3, Q8BGT1, Q8BLU0, Q8C031, Q99MQ4, Q9DBB9, Q9HCJ2, Q9NZU0, Q9NZU1, Q9R1B9, Q9TTB4, P50609, A6H793, A6NJW4, G5EG78, O35367

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

406 predictions. Top by Δscore:

Variant	Effect	Δscore
3:194349567:A:AC	donor_gain	1.0000
3:194349568:C:CC	donor_gain	1.0000
3:194349568:CTTGA:C	donor_gain	0.9900
3:194349570:TG:T	donor_gain	0.9900
3:194349578:T:A	donor_gain	0.9900
3:194349582:T:TA	donor_gain	0.9900
3:194351280:T:TA	donor_gain	0.9900
3:194342713:C:CT	acceptor_gain	0.9800
3:194342714:G:T	acceptor_gain	0.9800
3:194351236:GCCTA:G	donor_loss	0.9800
3:194351237:CCTA:C	donor_loss	0.9800
3:194351239:TACC:T	donor_loss	0.9800
3:194351240:ACCGT:A	donor_loss	0.9800
3:194351240:A:AC	donor_gain	0.9700
3:194351241:C:CC	donor_gain	0.9700
3:194349636:CTT:C	acceptor_gain	0.9600
3:194349639:C:CC	acceptor_gain	0.9500
3:194342703:CTT:C	acceptor_gain	0.9300
3:194347401:TGC:T	donor_gain	0.9300
3:194342706:C:CC	acceptor_gain	0.9100
3:194349637:TT:T	acceptor_gain	0.9100
3:194351200:C:A	donor_gain	0.9000
3:194349562:GGCTT:G	donor_loss	0.8900
3:194349563:GCTT:G	donor_loss	0.8900
3:194349564:CTTAC:C	donor_loss	0.8900
3:194349565:TTAC:T	donor_loss	0.8900
3:194349566:T:G	donor_loss	0.8900
3:194349561:GGGCT:G	donor_loss	0.8800
3:194349635:GCTTC:G	acceptor_loss	0.8800
3:194349638:TCTG:T	acceptor_loss	0.8800

AlphaMissense

3538 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:194341514:A:G	W397R	0.986
3:194341514:A:T	W397R	0.986
3:194341507:C:G	C399S	0.983
3:194341508:A:T	C399S	0.983
3:194341512:C:A	W397C	0.982
3:194341512:C:G	W397C	0.982
3:194341432:C:G	C424S	0.981
3:194341433:A:T	C424S	0.981
3:194341590:G:C	N371K	0.977
3:194341590:G:T	N371K	0.977
3:194341518:G:C	N395K	0.973
3:194341518:G:T	N395K	0.973
3:194341432:C:T	C424Y	0.972
3:194341431:G:C	C424W	0.971
3:194341508:A:G	C399R	0.969
3:194341520:T:C	N395D	0.969
3:194341507:C:A	C399F	0.965
3:194341507:C:T	C399Y	0.965
3:194341506:G:C	C399W	0.961
3:194341662:G:C	N347K	0.961
3:194341662:G:T	N347K	0.961
3:194342248:A:G	L152P	0.959
3:194341663:T:A	N347I	0.958
3:194341744:A:T	L320H	0.957
3:194342599:C:G	C35S	0.956
3:194342600:A:T	C35S	0.956
3:194341513:C:G	W397S	0.954
3:194341592:T:C	N371D	0.954
3:194341600:A:T	L368H	0.954
3:194342398:A:G	L102P	0.954

dbSNP variants (sampled 300 via entrez): RS1000115445 (3:194344686 C>A,G,T), RS1000199710 (3:194346119 A>T), RS1000402367 (3:194344415 G>A,C), RS1000475195 (3:194351847 A>G), RS1000653432 (3:194348385 G>T), RS1000826294 (3:194352069 G>A), RS1001214185 (3:194353177 G>A), RS1001496406 (3:194341531 G>T), RS1001589454 (3:194352172 G>A,T), RS1002103635 (3:194348884 T>C), RS1002110365 (3:194347259 C>T), RS1002235038 (3:194341715 C>T), RS1002559302 (3:194348707 A>G), RS1002575093 (3:194343089 A>C,G,T), RS1003671215 (3:194343787 A>G)

Disease associations

OMIM: gene MIM:603104 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011742_26	Triglyceride levels in HIV infection	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M14: Carboxypeptidase A

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	3
Cyclosporine	decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Zinc	affects binding, decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
dicrotophos	increases expression	1
decabromobiphenyl ether	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tetrabromobisphenol A	decreases expression	1
paricalcitol	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Estradiol	affects binding, increases expression	1
Formaldehyde	decreases expression	1
Mercury	affects expression	1
Phosphorus	decreases expression, affects cotreatment	1
Quercetin	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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