MATCAP1

Summary

MATCAP1 (microtubule associated tyrosine carboxypeptidase 1, HGNC:34408) is a protein-coding gene on chromosome 16q22.1, encoding Microtubule-associated tyrosine carboxypeptidase 1 (Q68EN5). Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function.

Enables tubulin-tyrosine carboxypeptidase. Predicted to be involved in brain development. Is active in microtubule.

Source: NCBI Gene 653319 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_001040715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34408
Approved symbol	MATCAP1
Name	microtubule associated tyrosine carboxypeptidase 1
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	LOC653319, TMCP1
Ensembl gene	ENSG00000196123
Ensembl biotype	protein_coding
OMIM	619978
Entrez	653319

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000290881, ENST00000561621, ENST00000561679, ENST00000562514, ENST00000563831, ENST00000563902, ENST00000563918, ENST00000564423, ENST00000564835, ENST00000568165, ENST00000568563, ENST00000570009, ENST00000886314, ENST00000886315, ENST00000944219, ENST00000944220

RefSeq mRNA: 8 — MANE Select: NM_001040715 NM_001040715, NM_001369680, NM_001369681, NM_001369682, NM_001369684, NM_001369685, NM_001369686, NM_001369687

CCDS: CCDS42177, CCDS92174

Canonical transcript exons

ENST00000563902 — 7 exons

Exon	Start	End
ENSE00001674068	67180041	67180666
ENSE00002600108	67175599	67176975
ENSE00002625662	67183262	67183963
ENSE00003473008	67179815	67179958
ENSE00003577066	67178199	67178504
ENSE00003648148	67179430	67179562
ENSE00003702588	67178010	67178107

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 98.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6843 / max 868.3864, expressed in 1789 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157747	19.2620	1774
157745	2.9066	1211
157744	1.0242	403
157743	0.4315	96
157746	0.0599	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.60	gold quality
cerebellar hemisphere	UBERON:0002245	98.45	gold quality
cerebellar cortex	UBERON:0002129	98.40	gold quality
cerebellum	UBERON:0002037	97.84	gold quality
cortical plate	UBERON:0005343	97.18	gold quality
adenohypophysis	UBERON:0002196	97.05	gold quality
right ovary	UBERON:0002118	96.40	gold quality
left ovary	UBERON:0002119	96.26	gold quality
pituitary gland	UBERON:0000007	96.25	gold quality
right adrenal gland	UBERON:0001233	95.35	gold quality
right uterine tube	UBERON:0001302	95.34	gold quality
right adrenal gland cortex	UBERON:0035827	95.29	gold quality
left uterine tube	UBERON:0001303	95.17	gold quality
left adrenal gland cortex	UBERON:0035825	94.83	gold quality
embryo	UBERON:0000922	94.49	gold quality
ganglionic eminence	UBERON:0004023	94.49	gold quality
right frontal lobe	UBERON:0002810	94.43	gold quality
left adrenal gland	UBERON:0001234	94.27	gold quality
right lobe of thyroid gland	UBERON:0001119	94.17	gold quality
adrenal cortex	UBERON:0001235	93.52	gold quality
left lobe of thyroid gland	UBERON:0001120	93.39	gold quality
right testis	UBERON:0004534	93.33	gold quality
left testis	UBERON:0004533	92.77	gold quality
anterior cingulate cortex	UBERON:0009835	92.75	gold quality
endocervix	UBERON:0000458	92.64	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.57	gold quality
body of uterus	UBERON:0009853	92.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.24	gold quality
mucosa of stomach	UBERON:0001199	92.21	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting MATCAP1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kiaa0895l	ENSDARG00000059529
mus_musculus	Matcap1	ENSMUSG00000014837
rattus_norvegicus	Matcap1	ENSRNOG00000015625

Paralogs (1): MATCAP2 (ENSG00000164542)

Protein

Protein identifiers

Microtubule-associated tyrosine carboxypeptidase 1 — Q68EN5 (reviewed: Q68EN5)

Alternative names: Microtubule-associated tyrosine carboxypeptidase

All UniProt accessions (2): Q68EN5, I3L230

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function. Also able to remove the C-terminal phenylalanine residue of alpha-tubulin TUBA8. Recognizes adjacent tubulin dimers along the same protofilament.

Subcellular location. Cytoplasm. Cytoskeleton.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. Metalloprotease with an atypical HExxxH zinc-binding motif instead of HExxH, which interrupts the active site-containing helix without affecting the integrity of the catalytic site arrangement. The N-terminal disordered region enhances its anchoring on microtubules, while dampening processivity on the polymerized substrate.

Similarity. Belongs to the peptidase MATCAP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q68EN5-1	1	yes
Q68EN5-2	2
Q68EN5-3	3

RefSeq proteins (8): NP_001035805, NP_001356609, NP_001356610, NP_001356611, NP_001356613, NP_001356614, NP_001356615, NP_001356616 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012548	MATCAP	Family

Pfam: PF08014

Catalyzed reactions (Rhea), 2 shown:

• C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-L-tyrosyl-[tubulin] + H2O = C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-[tubulin] + L-tyrosine (RHEA:57444)
• C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-L-phenylalanyl-[tubulin] + H2O = C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-[tubulin] + L-phenylalanine (RHEA:72663)

UniProt features (50 total): helix 23, mutagenesis site 7, turn 6, strand 4, binding site 3, splice variant 3, region of interest 2, chain 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7Z5G	X-RAY DIFFRACTION	2.11
7Z5H	X-RAY DIFFRACTION	2.5
7Z6S	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68EN5-F1	77.94	0.65

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): 281 (nucleophile)

Ligand- & substrate-binding residues (3): 280; 285; 316

Mutagenesis-validated functional residues (7):

Position	Phenotype
219	reduced binding to microtubules.
223	reduced binding to microtubules.
227	reduced binding to microtubules.
280	abolished tyrosine carboxypeptidase activity.
281	abolished tyrosine carboxypeptidase activity.
285	abolished tyrosine carboxypeptidase activity.
316	abolished tyrosine carboxypeptidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 67 (showing top): chr16q22, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_HEAD_DEVELOPMENT, GOBP_PROTEOLYSIS, GOMF_CARBOXYPEPTIDASE_ACTIVITY, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_METALLOCARBOXYPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_EXOPEPTIDASE_ACTIVITY, KAMMINGA_SENESCENCE, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, GOCC_SUPRAMOLECULAR_POLYMER, ASH1L_TARGET_GENES

GO Biological Process (2): proteolysis (GO:0006508), brain development (GO:0007420)

GO Molecular Function (7): metallocarboxypeptidase activity (GO:0004181), tubulin-tyrosine carboxypeptidase activity (GO:0106423), carboxypeptidase activity (GO:0004180), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (3): microtubule (GO:0005874), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
central nervous system development	1
animal organ development	1
head development	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
metallocarboxypeptidase activity	1
exopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

182 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MATCAP1	ESPNL	Q6ZVH7	560
MATCAP1	EXOC3L1	Q86VI1	479
MATCAP1	PITHD1	Q9GZP4	474
MATCAP1	B3GNT9	Q6UX72	473
MATCAP1	Q8WV35	Q8WV35	447
MATCAP1	GABPB1	Q06547	439
MATCAP1	TMEM208	Q9BTX3	435
MATCAP1	FBXL8	Q96CD0	417
MATCAP1	ATG16L2	Q8NAA4	404
MATCAP1	NEMP1	O14524	397
MATCAP1	ATG4D	Q86TL0	369
MATCAP1	RIMS2	Q9UQ26	353
MATCAP1	CCDC85B	Q15834	328
MATCAP1	ASAP3	Q8TDY4	320
MATCAP1	DEPDC1B	Q8WUY9	311

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MATCAP1	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.560
MATCAP1	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): KIAA0895L (Affinity Capture-RNA), ZBTB8B (Two-hybrid), KIAA0895L (Positive Genetic), KIAA0895L (Affinity Capture-MS), KIAA0895L (Co-fractionation), KIAA0895L (Co-fractionation), KIAA0895L (Co-fractionation), KIAA0895L (Co-fractionation), KIAA0895L (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GU71, A6QPI4, B2RV13, D4A6L0, E1BBQ2, F1LQY6, G3UW36, O08856, P15382, P53801, P55199, P56182, Q08CB3, Q0VF94, Q148E1, Q17RQ9, Q2KJ58, Q32Q90, Q4R5F9, Q4V8A6, Q4VA36, Q5I0I4, Q5NVI6, Q5R8Q2, Q5T6X4, Q5T848, Q5XII8, Q68EN5, Q6P767, Q8C419, Q8CHT6, Q8R143, Q8R1T1, Q8TBN0, Q8VDV3, Q8WUX9, Q90YH8, Q91WM6, Q91ZP9, Q96IL0

Diamond homologs: Q4V7A9, Q68EN5, Q7TQE7, Q810A5, Q8NCT3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1916 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67176971:GACAC:G	acceptor_gain	1.0000
16:67176972:ACAC:A	acceptor_gain	1.0000
16:67176973:CAC:C	acceptor_gain	1.0000
16:67176973:CACC:C	acceptor_gain	1.0000
16:67176974:AC:A	acceptor_gain	1.0000
16:67176975:CC:C	acceptor_gain	1.0000
16:67176975:CCT:C	acceptor_loss	1.0000
16:67176976:C:CC	acceptor_gain	1.0000
16:67176976:CT:C	acceptor_loss	1.0000
16:67178007:CA:C	donor_loss	1.0000
16:67178008:ACCT:A	donor_loss	1.0000
16:67178013:G:A	donor_gain	1.0000
16:67178103:ACAAC:A	acceptor_gain	1.0000
16:67178104:CAAC:C	acceptor_gain	1.0000
16:67178104:CAACC:C	acceptor_gain	1.0000
16:67178105:AAC:A	acceptor_gain	1.0000
16:67178106:AC:A	acceptor_gain	1.0000
16:67178107:CC:C	acceptor_gain	1.0000
16:67178108:C:CC	acceptor_gain	1.0000
16:67178195:ACACC:A	donor_loss	1.0000
16:67178247:C:CA	donor_gain	1.0000
16:67178843:C:A	donor_gain	1.0000
16:67178855:T:TA	donor_gain	1.0000
16:67179420:ACAC:A	donor_gain	1.0000
16:67179421:CACC:C	donor_gain	1.0000
16:67179463:A:AC	donor_gain	1.0000
16:67179464:C:CC	donor_gain	1.0000
16:67176977:T:A	acceptor_loss	0.9900
16:67176979:C:CT	acceptor_gain	0.9900
16:67176980:A:T	acceptor_gain	0.9900

AlphaMissense

3027 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67178014:C:A	G416V	1.000
16:67178075:C:G	G396R	1.000
16:67178094:C:A	K389N	1.000
16:67178094:C:G	K389N	1.000
16:67178383:G:C	S323R	1.000
16:67178383:G:T	S323R	1.000
16:67178385:T:G	S323R	1.000
16:67178392:G:C	S320R	1.000
16:67178392:G:T	S320R	1.000
16:67178394:T:G	S320R	1.000
16:67178403:C:G	G317R	1.000
16:67178405:T:A	E316V	1.000
16:67178463:A:G	W297R	1.000
16:67178463:A:T	W297R	1.000
16:67178497:G:C	H285Q	1.000
16:67178497:G:T	H285Q	1.000
16:67178499:G:C	H285D	1.000
16:67179435:T:A	E281V	1.000
16:67179435:T:G	E281A	1.000
16:67179437:A:C	H280Q	1.000
16:67179437:A:T	H280Q	1.000
16:67179439:G:C	H280D	1.000
16:67179444:A:G	L278P	1.000
16:67179451:C:G	G276R	1.000
16:67176853:G:C	N458K	0.999
16:67176853:G:T	N458K	0.999
16:67176907:G:C	F440L	0.999
16:67176907:G:T	F440L	0.999
16:67176908:A:G	F440S	0.999
16:67176909:A:G	F440L	0.999

dbSNP variants (sampled 300 via entrez): RS1000937270 (16:67175576 TG>T), RS1001482651 (16:67175229 G>A), RS1001641499 (16:67175138 G>A,T), RS1001789917 (16:67184220 A>C,G), RS1003578493 (16:67183667 G>A), RS1004037192 (16:67183410 G>A), RS1004372242 (16:67179146 G>C), RS1005617547 (16:67184136 C>T), RS1005635614 (16:67177808 C>T), RS1005653728 (16:67183958 A>C,G,T), RS1005754673 (16:67183968 T>C), RS1005926909 (16:67176600 A>G,T), RS1005942408 (16:67175543 G>A), RS1005943104 (16:67182934 G>C), RS1006038436 (16:67183693 A>G)

Disease associations

OMIM: gene MIM:619978 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004602_278	Mean corpuscular volume	2.000000e-16
GCST006979_627	Heel bone mineral density	1.000000e-27

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	2
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Methapyrilene	decreases methylation	1
Quercetin	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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