AGBL3

Summary

AGBL3 (AGBL carboxypeptidase 3, HGNC:27981) is a protein-coding gene on chromosome 7q33, encoding Cytosolic carboxypeptidase 3 (Q8NEM8). Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins.

Enables metallocarboxypeptidase activity. Involved in protein side chain deglutamylation. Predicted to be located in cytosol. Predicted to be active in centriole and cytoplasm.

Source: NCBI Gene 340351 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 140 total — 3 pathogenic
• MANE Select transcript: NM_178563

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27981
Approved symbol	AGBL3
Name	AGBL carboxypeptidase 3
Location	7q33
Locus type	gene with protein product
Status	Approved
Aliases	MGC32955, CCP3
Ensembl gene	ENSG00000146856
Ensembl biotype	protein_coding
OMIM	617346
Entrez	340351

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000275763, ENST00000435976, ENST00000436302, ENST00000455283, ENST00000470839, ENST00000476700, ENST00000494702

RefSeq mRNA: 9 — MANE Select: NM_178563 NM_001345850, NM_001345851, NM_001367812, NM_001367813, NM_001367815, NM_001367816, NM_001367817, NM_001367818, NM_178563

CCDS: CCDS47718

Canonical transcript exons

ENST00000436302 — 17 exons

Exon	Start	End
ENSE00001199502	135032844	135032982
ENSE00001232043	135017052	135017159
ENSE00001662034	135034149	135034928
ENSE00001691812	135045799	135045911
ENSE00001705554	134986508	134986701
ENSE00001719821	135044025	135044151
ENSE00001727910	135115380	135115611
ENSE00001794315	135037418	135037580
ENSE00001804468	135045474	135045574
ENSE00002104953	135134841	135135778
ENSE00003473508	134987875	134987996
ENSE00003508019	135076397	135076468
ENSE00003537042	135080203	135080260
ENSE00003574086	135081719	135081790
ENSE00003601376	134989250	134989310
ENSE00003617215	134993493	134993678
ENSE00003679069	135059169	135059235

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 88.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.3915 / max 55.9979, expressed in 1392 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81341	4.3915	1392

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	88.54	silver quality
calcaneal tendon	UBERON:0003701	86.06	gold quality
left ovary	UBERON:0002119	85.57	gold quality
right uterine tube	UBERON:0001302	84.63	gold quality
right ovary	UBERON:0002118	84.00	gold quality
mucosa of stomach	UBERON:0001199	83.87	gold quality
metanephros cortex	UBERON:0010533	83.38	gold quality
body of uterus	UBERON:0009853	83.18	gold quality
right coronary artery	UBERON:0001625	82.16	gold quality
body of pancreas	UBERON:0001150	81.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.02	gold quality
adenohypophysis	UBERON:0002196	80.77	gold quality
tibial nerve	UBERON:0001323	80.19	gold quality
endocervix	UBERON:0000458	80.11	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.08	gold quality
popliteal artery	UBERON:0002250	79.85	gold quality
tibial artery	UBERON:0007610	79.83	gold quality
cerebellar hemisphere	UBERON:0002245	79.80	gold quality
right lung	UBERON:0002167	79.66	gold quality
left coronary artery	UBERON:0001626	79.65	gold quality
descending thoracic aorta	UBERON:0002345	79.58	gold quality
ascending aorta	UBERON:0001496	79.54	gold quality
left testis	UBERON:0004533	79.51	gold quality
cerebellar cortex	UBERON:0002129	79.45	gold quality
aorta	UBERON:0000947	79.43	gold quality
right testis	UBERON:0004534	79.37	gold quality
thoracic aorta	UBERON:0001515	79.36	gold quality
ovary	UBERON:0000992	79.29	gold quality
left uterine tube	UBERON:0001303	79.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting AGBL3, 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-188-3P	100.00	68.76	1240
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
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-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-5093	99.67	69.26	2291

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Agbl3	ENSMUSG00000038836
rattus_norvegicus	Agbl3	ENSRNOG00000010397

Paralogs (5): AGBL5 (ENSG00000084693), AGTPBP1 (ENSG00000135049), AGBL2 (ENSG00000165923), AGBL4 (ENSG00000186094), AGBL1 (ENSG00000273540)

Protein

Protein identifiers

Cytosolic carboxypeptidase 3 — Q8NEM8 (reviewed: Q8NEM8)

Alternative names: ATP/GTP-binding protein-like 3, Protein deglutamylase CCP3

All UniProt accessions (3): Q8NEM8, F8W6Y5, F8W7R4

UniProt curated annotations — full annotation on UniProt →

Function. Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of tubulin protein. Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate. Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of non-tubulin proteins such as MYLK. May catalyze the hydrolysis of aspartate from the carboxy-terminus of target proteins. Does not show detyrosinase or deglycylase activities from the carboxy-terminus of target proteins. Metallocarboxypeptidase that mediates tubulin deglutamylation.

Subcellular location. Cytoplasm. Cytosol.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M14 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NEM8-1	1	yes
Q8NEM8-2	2
Q8NEM8-3	3
Q8NEM8-4	4

RefSeq proteins (3): NP_001332779, NP_001332780, NP_848658* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR040626	Pepdidase_M14_N	Domain
IPR050821	Cytosolic_carboxypeptidase	Family

Pfam: PF00246, PF18027

Catalyzed reactions (Rhea), 1 shown:

• (L-glutamyl)(n+1)-gamma-L-glutamyl-L-glutamyl-[protein] + H2O = (L-glutamyl)(n)-gamma-L-glutamyl-L-glutamyl-[protein] + L-glutamate (RHEA:60004)

UniProt features (20 total): splice variant 5, sequence variant 3, binding site 3, sequence conflict 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEM8-F1	64.26	0.42

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): 534 (proton donor/acceptor)

Ligand- & substrate-binding residues (3): 364; 367; 460

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 82 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GOCC_MICROTUBULE_ORGANIZING_CENTER, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, AAAGACA_MIR511, GOBP_PEPTIDYL_GLUTAMIC_ACID_MODIFICATION, GOCC_CENTRIOLE, GOBP_PROTEOLYSIS, GOMF_CARBOXYPEPTIDASE_ACTIVITY, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_METALLOCARBOXYPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_CYTOSKELETAL_PROTEIN_BINDING, GOMF_EXOPEPTIDASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A

GO Biological Process (2): proteolysis (GO:0006508), protein side chain deglutamylation (GO:0035610)

GO Molecular Function (8): metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270), tubulin binding (GO:0015631), carboxypeptidase activity (GO:0004180), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), centriole (GO:0005814), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein metabolic process	1
protein deglutamylation	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
cytoskeletal protein binding	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
microtubule organizing center	1
intracellular membraneless organelle	1
cytoplasm	1
cytoskeleton	1

Protein interactions and networks

STRING

402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGBL3	C3	P01024	855
AGBL3	CD46	P15529	711
AGBL3	CD55	P08174	692
AGBL3	CXADR	P78310	650
AGBL3	CD59	P13987	592
AGBL3	PRTN3	P15637	580
AGBL3	C4A	P01028	569
AGBL3	C4A	P01028	547
AGBL3	CCPG1	Q9ULG6	509
AGBL3	SVOPL	Q8N434	485
AGBL3	ZC3H12C	Q9C0D7	482
AGBL3	RHOBTB3	O94955	460
AGBL3	AGBL2	Q5U5Z8	452
AGBL3	FLG	P20930	447
AGBL3	FLG2	Q5D862	447

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
AGBL3	CLIC3	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): AGBL3 (Affinity Capture-MS), AGBL3 (Affinity Capture-MS), AGBL3 (Affinity Capture-MS), AGBL3 (Affinity Capture-RNA), CLIC3 (Affinity Capture-MS), C17orf97 (Affinity Capture-MS), AGBL3 (Affinity Capture-MS), AGBL3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GXY4, A0A1L8I2C5, A1A5R7, A6PWY4, A9X1C6, B1ANS9, B2KIQ4, D3Z3I0, E9Q7R9, F1QHZ6, O13286, O74845, O94411, P26309, P43254, P51956, P93471, Q09786, Q4V837, Q5R6T6, Q5TKR9, Q5XHI9, Q5ZKI7, Q6DTM3, Q6GM71, Q6GPU3, Q6VZ17, Q7Z2W4, Q80Z32, Q86VD1, Q86Y33, Q8BZ21, Q8CDP0, Q8K3E5, Q8L4H0, Q8N157, Q8N4N8, Q8NA75, Q8NDM7, Q8NEM8

Diamond homologs: A0A096LPI5, A6NIU2, A6NJG6, F2Z398, P0DTE4, P51957, Q09FC8, Q5H9K5, Q5T7P6, Q68CZ1, Q6B4Z3, Q6UX73, Q86U02, Q8IV13, Q8N7M2, Q8N9N2, Q8NDZ0, Q8NEM8, Q8TDM0, Q92918, Q96J02, Q96MD7, Q9BUA6, Q9NXG0, A6H8T7, A9JRL3, B2GV17, D2GXM8, E1B9D8, E1C3P4, O76373, Q09296, Q09LZ8, Q09M02, Q09M05, Q0P4M4, Q4R632, Q4U2V3, Q5U5Z8, Q5VU57

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	112
Likely benign	6
Benign	7

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1527395	GRCh37/hg19 7q32.1-34(chr7:127295698-139524358)	Pathogenic
395363	GRCh37/hg19 7q32.3-34(chr7:131642114-139107211)x1	Pathogenic
563417	GRCh37/hg19 7q33(chr7:133230189-137972605)x1	Pathogenic

SpliceAI

3286 predictions. Top by Δscore:

Variant	Effect	Δscore
7:134987994:TCGGT:T	donor_loss	1.0000
7:134987997:G:GG	donor_gain	1.0000
7:134987998:T:A	donor_loss	1.0000
7:135017046:TTCCA:T	acceptor_loss	1.0000
7:135017048:CCA:C	acceptor_loss	1.0000
7:135017049:CAGAT:C	acceptor_loss	1.0000
7:135017050:A:AC	acceptor_loss	1.0000
7:135017050:A:AG	acceptor_gain	1.0000
7:135017050:AGATT:A	acceptor_gain	1.0000
7:135017051:G:GG	acceptor_gain	1.0000
7:135017051:GA:G	acceptor_gain	1.0000
7:135017051:GAT:G	acceptor_gain	1.0000
7:135017051:GATT:G	acceptor_gain	1.0000
7:135017051:GATTG:G	acceptor_gain	1.0000
7:135017129:G:GT	donor_gain	1.0000
7:135017156:GATG:G	donor_gain	1.0000
7:135032981:GT:G	donor_gain	1.0000
7:135044023:A:AG	acceptor_gain	1.0000
7:135044024:G:GG	acceptor_gain	1.0000
7:135044150:GG:G	donor_gain	1.0000
7:135044151:GG:G	donor_gain	1.0000
7:134986709:GAA:G	donor_gain	0.9900
7:134987874:GAAA:G	acceptor_gain	0.9900
7:134987874:GAAAT:G	acceptor_gain	0.9900
7:134987887:A:AG	acceptor_gain	0.9900
7:134987888:G:GA	acceptor_gain	0.9900
7:134987888:GCCT:G	acceptor_gain	0.9900
7:134987906:A:G	acceptor_gain	0.9900
7:134988460:T:TG	donor_gain	0.9900
7:134988461:A:AA	donor_gain	0.9900

AlphaMissense

6125 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002142 (7:135061961 C>G,T), RS1000021723 (7:135131448 GA>G), RS1000055145 (7:134984911 C>T), RS1000059457 (7:135007287 C>T), RS1000075846 (7:135074707 A>G), RS1000079245 (7:135037151 C>T), RS1000111070 (7:135047678 A>G), RS1000159161 (7:135047521 C>T), RS1000160436 (7:135104120 C>A,G), RS1000164600 (7:135058761 T>A,C), RS1000165672 (7:135011100 A>C), RS1000174164 (7:135007718 A>G), RS1000195969 (7:135044156 G>C), RS1000206857 (7:135104834 C>T), RS1000260499 (7:135104508 G>A)

Disease associations

OMIM: gene MIM:617346 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002590_1	Vascular brain injury	6.000000e-06
GCST002590_10	Vascular brain injury	9.000000e-06
GCST006479_148	Diverticular disease	6.000000e-08
GCST010241_296	Apolipoprotein A1 levels	9.000000e-09
GCST010242_62	HDL cholesterol levels	4.000000e-09
GCST90002394_311	Monocyte percentage of white cells	3.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006800	vascular brain injury measurement
EFO:0009959	diverticular disease
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Formaldehyde	increases expression	1
Nickel	decreases expression	1
Niclosamide	decreases expression	1
Vincristine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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