CPO

Summary

CPO (carboxypeptidase O, HGNC:21011) is a protein-coding gene on chromosome 2q33.3, encoding Carboxypeptidase O (Q8IVL8). Carboxypeptidase which preferentially cleaves C-terminal acidic residues from peptides and proteins.

This gene is a member of the metallocarboxypeptidase gene family.

Source: NCBI Gene 130749 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_173077

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21011
Approved symbol	CPO
Name	carboxypeptidase O
Location	2q33.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144410
Ensembl biotype	protein_coding
OMIM	609563
Entrez	130749

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000272852

RefSeq mRNA: 1 — MANE Select: NM_173077 NM_173077

CCDS: CCDS2372

Canonical transcript exons

ENST00000272852 — 9 exons

Exon	Start	End
ENSE00000964989	206955463	206955564
ENSE00000964990	206958301	206958405
ENSE00000964991	206959631	206959741
ENSE00000964992	206960852	206960942
ENSE00000964993	206962412	206962614
ENSE00000964994	206969174	206969474
ENSE00001004727	206968263	206968347
ENSE00001187604	206949617	206949713
ENSE00001463439	206939518	206939667

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 87.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0222 / max 30.2191, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24841	0.0470	3
24842	0.0222	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
small intestine Peyer’s patch	UBERON:0003454	87.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.88	gold quality
small intestine	UBERON:0002108	81.54	gold quality
adrenal tissue	UBERON:0018303	67.25	gold quality
metanephros cortex	UBERON:0010533	66.55	gold quality
right adrenal gland cortex	UBERON:0035827	66.38	gold quality
popliteal artery	UBERON:0002250	65.97	gold quality
tibial artery	UBERON:0007610	65.97	gold quality
right adrenal gland	UBERON:0001233	65.75	gold quality
right coronary artery	UBERON:0001625	65.74	gold quality
lower esophagus muscularis layer	UBERON:0035833	65.32	gold quality
lower esophagus	UBERON:0013473	65.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.13	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	65.02	gold quality
aorta	UBERON:0000947	64.63	gold quality
tibial nerve	UBERON:0001323	64.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	64.40	gold quality
left adrenal gland	UBERON:0001234	64.25	gold quality
nucleus accumbens	UBERON:0001882	64.24	gold quality
left adrenal gland cortex	UBERON:0035825	64.15	gold quality
right frontal lobe	UBERON:0002810	63.94	gold quality
thoracic aorta	UBERON:0001515	63.18	gold quality
ascending aorta	UBERON:0001496	63.14	gold quality
adenohypophysis	UBERON:0002196	63.05	gold quality
descending thoracic aorta	UBERON:0002345	63.00	gold quality
left lobe of thyroid gland	UBERON:0001120	62.96	gold quality
adrenal cortex	UBERON:0001235	62.92	gold quality
right lobe of thyroid gland	UBERON:0001119	62.83	gold quality
islet of Langerhans	UBERON:0000006	62.52	gold quality
gastrocnemius	UBERON:0001388	62.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.10

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• CPO cleaves acidic amino acids from dietary proteins and peptides, thus complementing the actions of well known digestive carboxypeptidases CPA and CPB. (PMID:21921028)
• hCPO can also trim C-t extensions of proteins, such as epidermal growth factor, suggesting a role in the maturation and degradation of growth factors and bioactive peptides. (PMID:29636417)

Cross-species orthologs

22 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpo	ENSDARG00000077688
drosophila_melanogaster	CG3097	FBGN0029804
drosophila_melanogaster	CG3108	FBGN0029807
drosophila_melanogaster	CG18585	FBGN0031929
drosophila_melanogaster	CG7025	FBGN0031930
drosophila_melanogaster	CG4017	FBGN0032143
drosophila_melanogaster	CG17633	FBGN0032144
drosophila_melanogaster	CG2915	FBGN0033241
drosophila_melanogaster	CG12374	FBGN0033774
drosophila_melanogaster	CG14820	FBGN0035718
drosophila_melanogaster	CG8563	FBGN0035777
drosophila_melanogaster	CG8562	FBGN0035779
drosophila_melanogaster	CG18417	FBGN0035780
drosophila_melanogaster	CG8560	FBGN0035781
drosophila_melanogaster	CG8539	FBGN0035791
drosophila_melanogaster	CG4408	FBGN0039073
drosophila_melanogaster	CG32379	FBGN0052379
drosophila_melanogaster	CG42264	FBGN0259149
caenorhabditis_elegans		WBGENE00004747
caenorhabditis_elegans	T06A4.1	WBGENE00020281
caenorhabditis_elegans	Y47G6A.19	WBGENE00021645
caenorhabditis_elegans		WBGENE00021984

Paralogs (8): CPB2 (ENSG00000080618), CPA1 (ENSG00000091704), CPA4 (ENSG00000128510), CPB1 (ENSG00000153002), CPA2 (ENSG00000158516), CPA5 (ENSG00000158525), CPA3 (ENSG00000163751), CPA6 (ENSG00000165078)

Protein

Protein identifiers

Carboxypeptidase O — Q8IVL8 (reviewed: Q8IVL8)

All UniProt accessions (1): Q8IVL8

UniProt curated annotations — full annotation on UniProt →

Function. Carboxypeptidase which preferentially cleaves C-terminal acidic residues from peptides and proteins. Can also cleave C-terminal hydrophobic amino acids, with a preference for small residues over large residues.

Subcellular location. Apical cell membrane.

Tissue specificity. Detected in enterocytes of the ileum.

Post-translational modifications. N-glycosylated.

Activity regulation. Strongly inhibited by potato carboxypeptidase inhibitor, and the chelating agents EDTA and 1,10-phenanthroline. Also inhibited by compounds with multiple carboxylic acid groups such as citrate and succinate, and to a lesser exent the amino acids aspartate and glutamate. Not significantly inhibited by benzylsuccinic acid.

Similarity. Belongs to the peptidase M14 family.

RefSeq proteins (1): NP_775100* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR033850	Carboxypeptidase_O	Domain
IPR057246	CARBOXYPEPT_ZN_1	Binding_site

Pfam: PF00246

UniProt features (42 total): helix 12, strand 11, glycosylation site 4, sequence variant 3, turn 3, binding site 3, signal peptide 1, chain 1, propeptide 1, domain 1, active site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5MRV	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVL8-F1	88.28	0.81

Functional residue map

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

Catalytic / active sites (1): 310 (proton donor/acceptor)

Ligand- & substrate-binding residues (3): 108; 111; 236

Post-translational modifications (1): 352

Glycosylation sites (4): 174, 187, 251, 132

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOMF_METALLOPEPTIDASE_ACTIVITY, GOCC_APICAL_PLASMA_MEMBRANE, GOCC_APICAL_PART_OF_CELL, GOCC_SIDE_OF_MEMBRANE, GOBP_PROTEOLYSIS, GOCC_PLASMA_MEMBRANE_REGION, GOMF_CARBOXYPEPTIDASE_ACTIVITY, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_METALLOCARBOXYPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, NFAT_Q6, GOMF_EXOPEPTIDASE_ACTIVITY, TGATTTRY_GFI1_01, FOURATI_BLOOD_TWINRIX_AGE_25_83YO_RESPONDERS_VS_POOR_RESPONDERS_0DY_UP

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (7): metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270), carboxypeptidase activity (GO:0004180), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), side of membrane (GO:0098552), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
membrane	2
cellular anatomical structure	2
protein metabolic process	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPO	FASTKD2	Q9NYY8	534
CPO	TINAG	Q9UJW2	472
CPO	DBF4B	Q8NFT6	419
CPO	SMCP	P49901	412
CPO	SLC7A9	P82251	409
CPO	RNF175	Q8N4F7	401
CPO	EXD3	Q8N9H8	372
CPO	CPS1	P31327	368
CPO	CDH16	O75309	361
CPO	LCNL1	Q6ZST4	355
CPO	AGBL3	Q8NEM8	350
CPO	SLC6A19	Q695T7	344
CPO	IGSF23	A1L1A6	343
CPO	CBLN2	Q8IUK8	315
CPO	XPO7	Q9UIA9	313

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1S4F020, A6XGK3, B6V865, B8JLQ9, B8XGR3, C5FH26, C5FVN6, D4AS12, D4B5N0, D4D675, D4DL57, O02350, O17754, O97397, P00730, P00731, P00732, P09954, P09955, P15085, P15086, P15088, P15089, P16406, P19222, P19223, P21961, P37892, P38836, P42787, P48052, P54969, P55261, Q0II73, Q29NC4, Q2KIG3, Q2KJ83, Q3T905, Q4R7R2, Q504N0

Diamond homologs: A0A1S4F020, A6XGK3, B6H233, B6Q972, B6V865, B8JLQ9, B8XGR3, C5FH26, C5FVN6, D4AS12, D4DL57, O02350, P00730, P00731, P00732, P04069, P09954, P09955, P15085, P15086, P18143, P19222, P19223, P29068, P38836, P42788, P48052, P55261, Q0C9B4, Q0II73, Q29NC4, Q3T905, Q504N0, Q5U901, Q7TPZ8, Q8IVL8, Q8N4T0, Q9VL86, A1CSU3, A1DGH9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1107 predictions. Top by Δscore:

Variant	Effect	Δscore
2:206958299:A:AG	acceptor_gain	1.0000
2:206958300:G:GG	acceptor_gain	1.0000
2:206958300:GATC:G	acceptor_gain	1.0000
2:206958300:GATCA:G	acceptor_gain	1.0000
2:206958403:G:GT	donor_gain	1.0000
2:206958403:GAA:G	donor_gain	1.0000
2:206958405:AGTA:A	donor_loss	1.0000
2:206958406:G:GG	donor_gain	1.0000
2:206958406:GTA:G	donor_loss	1.0000
2:206958407:T:A	donor_loss	1.0000
2:206959621:A:AG	acceptor_gain	1.0000
2:206959622:A:G	acceptor_gain	1.0000
2:206959623:A:G	acceptor_gain	1.0000
2:206959624:T:G	acceptor_gain	1.0000
2:206959626:TCCA:T	acceptor_loss	1.0000
2:206959627:CCAG:C	acceptor_loss	1.0000
2:206959628:CAG:C	acceptor_loss	1.0000
2:206959629:A:AG	acceptor_gain	1.0000
2:206959630:G:GA	acceptor_gain	1.0000
2:206959630:GA:G	acceptor_gain	1.0000
2:206959630:GAT:G	acceptor_gain	1.0000
2:206959630:GATT:G	acceptor_gain	1.0000
2:206959630:GATTC:G	acceptor_gain	1.0000
2:206959737:CAACT:C	donor_gain	1.0000
2:206959738:AACT:A	donor_gain	1.0000
2:206959738:AACTG:A	donor_loss	1.0000
2:206959739:ACT:A	donor_gain	1.0000
2:206959739:ACTG:A	donor_loss	1.0000
2:206959740:CT:C	donor_gain	1.0000
2:206959740:CTG:C	donor_loss	1.0000

AlphaMissense

2450 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:206969266:T:C	F319L	0.996
2:206969268:T:A	F319L	0.996
2:206969268:T:G	F319L	0.996
2:206959711:C:A	N151K	0.995
2:206959711:C:G	N151K	0.995
2:206960919:G:C	R184P	0.995
2:206960924:T:C	F186L	0.995
2:206960926:C:A	F186L	0.995
2:206960926:C:G	F186L	0.995
2:206960917:T:A	N183K	0.992
2:206960917:T:G	N183K	0.992
2:206960923:T:A	N185K	0.992
2:206960923:T:G	N185K	0.992
2:206962447:T:C	F204L	0.992
2:206962449:C:A	F204L	0.992
2:206962449:C:G	F204L	0.992
2:206969185:G:T	G292W	0.992
2:206958365:A:T	E111V	0.991
2:206958387:C:G	C118W	0.991
2:206960868:A:T	K167I	0.989
2:206969186:G:A	G292E	0.989
2:206958369:G:C	W112C	0.988
2:206958369:G:T	W112C	0.988
2:206960863:G:C	W165C	0.988
2:206960863:G:T	W165C	0.988
2:206958337:T:A	W102R	0.987
2:206958337:T:C	W102R	0.987
2:206958367:T:A	W112R	0.987
2:206958367:T:C	W112R	0.987
2:206960910:A:G	D181G	0.987

dbSNP variants (sampled 300 via entrez): RS1000025355 (2:206969945 G>A,C), RS1000230162 (2:206951678 C>T), RS1000608547 (2:206958070 A>C), RS1000654063 (2:206945659 A>G), RS1000843928 (2:206944223 T>C), RS1000971441 (2:206958133 G>A), RS1000993078 (2:206950328 A>G), RS1001057146 (2:206954056 C>A,T), RS1001175017 (2:206957389 A>G), RS1001285196 (2:206950919 C>A), RS1001358509 (2:206944556 A>T), RS1001393834 (2:206957172 T>G), RS1001532149 (2:206969817 G>T), RS1001705718 (2:206939313 T>C), RS1001867504 (2:206968400 G>A)

Disease associations

OMIM: gene MIM:609563 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Silicon Dioxide	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1

Clinical trials (associated diseases)

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