METAP1D

Summary

METAP1D (methionyl aminopeptidase type 1D, mitochondrial, HGNC:32583) is a protein-coding gene on chromosome 2q31.1, encoding Methionine aminopeptidase 1D, mitochondrial (Q6UB28). Removes the N-terminal methionine from nascent proteins.

The N-terminal methionine excision pathway is an essential process in which the N-terminal methionine is removed from many proteins, thus facilitating subsequent protein modification. In mitochondria, enzymes that catalyze this reaction are celled methionine aminopeptidases (MetAps, or MAPs; EC 3.4.11.18) (Serero et al., 2003 [PubMed 14532271]).

Source: NCBI Gene 254042 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 80 total
• Druggable target: yes
• MANE Select transcript: NM_199227

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32583
Approved symbol	METAP1D
Name	methionyl aminopeptidase type 1D, mitochondrial
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	MAP1D, Metap1l
Ensembl gene	ENSG00000172878
Ensembl biotype	protein_coding
OMIM	610267
Entrez	254042

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000315796, ENST00000392582, ENST00000468537, ENST00000488581, ENST00000491440, ENST00000493035, ENST00000493742, ENST00000903316, ENST00000903317, ENST00000903318, ENST00000903319, ENST00000913778, ENST00000913779, ENST00000913780, ENST00000966147

RefSeq mRNA: 3 — MANE Select: NM_199227 NM_001322278, NM_001322279, NM_199227

CCDS: CCDS2246

Canonical transcript exons

ENST00000315796 — 10 exons

Exon	Start	End
ENSE00001192870	172080128	172080206
ENSE00001353602	172080328	172082430
ENSE00001851820	171999953	172000009
ENSE00003492116	172061498	172061655
ENSE00003512356	172066264	172066306
ENSE00003527906	172063711	172063860
ENSE00003556413	172065604	172065752
ENSE00003564793	172077797	172077894
ENSE00003650868	172070907	172071070
ENSE00003684007	172079215	172079262

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 92.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0001 / max 55.3051, expressed in 1629 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23683	6.0001	1629

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	92.71	gold quality
tendon of biceps brachii	UBERON:0008188	88.89	gold quality
left ovary	UBERON:0002119	87.50	gold quality
right ovary	UBERON:0002118	86.75	gold quality
right uterine tube	UBERON:0001302	86.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.98	gold quality
ovary	UBERON:0000992	85.45	gold quality
body of pancreas	UBERON:0001150	85.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.14	gold quality
gastrocnemius	UBERON:0001388	83.45	gold quality
muscle of leg	UBERON:0001383	83.00	gold quality
fallopian tube	UBERON:0003889	82.68	gold quality
tibial nerve	UBERON:0001323	82.48	gold quality
right coronary artery	UBERON:0001625	81.94	gold quality
rectum	UBERON:0001052	81.86	gold quality
tendon	UBERON:0000043	81.55	gold quality
right adrenal gland	UBERON:0001233	81.26	gold quality
tibia	UBERON:0000979	80.99	gold quality
left coronary artery	UBERON:0001626	80.87	gold quality
body of uterus	UBERON:0009853	80.75	gold quality
right adrenal gland cortex	UBERON:0035827	80.67	gold quality
colonic epithelium	UBERON:0000397	80.66	gold quality
ventricular zone	UBERON:0003053	80.29	gold quality
right lobe of liver	UBERON:0001114	80.17	gold quality
pancreas	UBERON:0001264	79.84	gold quality
left uterine tube	UBERON:0001303	79.77	gold quality
left adrenal gland	UBERON:0001234	79.71	gold quality
left adrenal gland cortex	UBERON:0035825	79.61	gold quality
smooth muscle tissue	UBERON:0001135	79.57	gold quality
coronary artery	UBERON:0001621	79.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting METAP1D, 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-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-5001-5P	99.05	66.76	1972

Literature-anchored findings (GeneRIF, showing 2)

• MAP1D is a potentially oncogenic, novel member of the MAP gene family that may play an important role in colon tumorigenesis (PMID:16568094)
• Structural insights into N-terminal methionine cleavage by the human mitochondrial methionine aminopeptidase, MetAP1D. (PMID:38102161)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	metap1d	ENSDARG00000019715
mus_musculus	Metap1d	ENSMUSG00000041921
rattus_norvegicus	Metap1d	ENSRNOG00000061587
drosophila_melanogaster	CG5188	FBGN0032247
caenorhabditis_elegans	app-1	WBGENE00000155
caenorhabditis_elegans		WBGENE00021555

Paralogs (7): XPNPEP1 (ENSG00000108039), METAP2 (ENSG00000111142), XPNPEP2 (ENSG00000122121), PEPD (ENSG00000124299), METAP1 (ENSG00000164024), PA2G4 (ENSG00000170515), XPNPEP3 (ENSG00000196236)

Protein

Protein identifiers

Methionine aminopeptidase 1D, mitochondrial — Q6UB28 (reviewed: Q6UB28)

Alternative names: Methionyl aminopeptidase type 1D, mitochondrial, Peptidase M 1D

All UniProt accessions (1): Q6UB28

UniProt curated annotations — full annotation on UniProt →

Function. Removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed. May play a role in colon tumorigenesis.

Subcellular location. Mitochondrion.

Tissue specificity. Overexpressed in colon cancer cell lines and colon tumors as compared to normal tissues (at protein level).

Cofactor. Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site.

Similarity. Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily.

RefSeq proteins (3): NP_001309207, NP_001309208, NP_954697* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000994	Pept_M24	Domain
IPR001714	Pept_M24_MAP	Family
IPR002467	Pept_M24A_MAP1	Family
IPR036005	Creatinase/aminopeptidase-like	Homologous_superfamily

Pfam: PF00557

Enzyme classification (BRENDA):

• EC 3.4.11.18 — methionyl aminopeptidase (BRENDA: 45 organisms, 219 substrates, 968 inhibitors, 153 Km, 147 kcat entries)

Substrate kinetics (BRENDA)

39 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MET-GLY-MET-MET	0.058–18.3	20
L-MET-7-AMIDO-4-METHYLCOUMARIN	0.0309–0.5467	16
MET-ALA-SER	0.018–4.54	11
L-MET-GLY-L-MET-L-MET	0.6–3.2	10
L-MET 4-NITROANILIDE	0.154–2.77	9
L-MET-PSI[C(O)S]GLY-L-PHE	0.35–16	8
MET-4-METHYLCOUMARYL-7-AMIDE	0.111–0.168	8
MET-PRO-4-NITROANILIDE	0.06–3.26	7
L-ALANINE-4-METHYLCOUMARIN-7-AMIDE	0.125–0.284	6
L-LEU-7-AMIDO-4-METHYLCOUMARIN	0.0345–0.9795	6
L-METHIONINE 4-NITROANILIDE	0.0002–0.543	4
L-METHIONINE-4-METHYLCOUMARIN-7-AMIDE	0.011–0.17	4
MET-7-AMIDO-4-METHYLCOUMARIN	0.12–6.27	4
L-MET-L-ALA-L-SER	3–15	3
MET-ALA-ALA	1.5–5.2	3

UniProt features (12 total): binding site 9, transit peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8KHM	X-RAY DIFFRACTION	1.39
8KHO	X-RAY DIFFRACTION	1.45
8KHN	X-RAY DIFFRACTION	1.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UB28-F1	87.98	0.83

Functional residue map

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

Ligand- & substrate-binding residues (9): 315; 161; 178; 189; 189; 252; 259; 284; 315

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, USF_C, MYCMAX_01, USF_01, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, USF_02, NFE2_01, YGCGYRCGC_UNKNOWN, PAX6_01, GOBP_PROTEOLYSIS, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_AMINOPEPTIDASE_ACTIVITY, MAX_01, GOMF_EXOPEPTIDASE_ACTIVITY

GO Biological Process (2): proteolysis (GO:0006508), post-translational protein modification (GO:0043687)

GO Molecular Function (8): aminopeptidase activity (GO:0004177), initiator methionyl aminopeptidase activity (GO:0004239), metalloexopeptidase activity (GO:0008235), metal ion binding (GO:0046872), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
exopeptidase activity	2
aminopeptidase activity	2
protein metabolic process	1
protein modification process	1
metallopeptidase activity	1
cation binding	1
metalloexopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1784 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
METAP1D	MAP1B	P46821	769
METAP1D	PDF	Q9HBH1	659
METAP1D	GFM2	Q969S9	521
METAP1D	PMPCB	O75439	505
METAP1D	PTCD3	Q96EY7	495
METAP1D	METAP2	P50579	467
METAP1D	XPNPEP3	Q9NQH7	462
METAP1D	IMMP1L	Q96LU5	441
METAP1D	RIMS3	Q9UJD0	436
METAP1D	MTFMT	Q96DP5	411
METAP1D	PMPCA	Q10713	409
METAP1D	CDCA7	Q9BWT1	391
METAP1D	MRTFA	Q969V6	353
METAP1D	GSR	P00390	352
METAP1D	SAMM50	Q9Y512	352

IntAct

19 interactions, top by confidence:

A	B	Type	Score
LRRC56	HSPA8	psi-mi:“MI:0914”(association)	0.530
NDUFC2	NDUFS4	psi-mi:“MI:0914”(association)	0.530
XAGE3	WIZ	psi-mi:“MI:0914”(association)	0.530
METAP1D	PRICKLE4	psi-mi:“MI:0915”(physical association)	0.500
METAP1D	SIRT3	psi-mi:“MI:0915”(physical association)	0.400
METAP1D	CRAT	psi-mi:“MI:0915”(physical association)	0.400
Gspt1	MRPL27	psi-mi:“MI:0914”(association)	0.350
PAK5	SUPT5H	psi-mi:“MI:0914”(association)	0.350
XAGE3	PSMG1	psi-mi:“MI:0914”(association)	0.350
CPEB1	APBA3	psi-mi:“MI:0914”(association)	0.350
PRICKLE4	USO1	psi-mi:“MI:0914”(association)	0.350
SLC51B	CTNND1	psi-mi:“MI:0914”(association)	0.350
XPR1	GOLIM4	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): METAP1D (Affinity Capture-MS), METAP1D (Affinity Capture-MS), METAP1D (Affinity Capture-MS), METAP1D (Affinity Capture-MS), METAP1D (Affinity Capture-MS), SIRT3 (Affinity Capture-MS), METAP1D (Affinity Capture-MS), METAP1D (Synthetic Lethality), METAP1D (Affinity Capture-RNA), PRICKLE4 (Affinity Capture-MS), METAP1D (Affinity Capture-MS), METAP1D (Affinity Capture-MS), METAP1D (Affinity Capture-MS), METAP1D (Affinity Capture-MS), METAP1D (Affinity Capture-MS)

ESM2 similar proteins: A1CH02, A1CXT5, A2QHX0, A4RDI6, A6QLA4, A6ZKL2, A8QBZ2, B3LNM2, B5VDQ0, B6HTQ4, B6Q1N3, B8LUH2, B8NA06, C4JF09, C5DE35, C7GSF3, C8Z3V4, C9SB49, D1ZEN1, D8PR70, E3QW41, E5R4J3, O08663, O59730, O60085, P38062, P38174, P50579, P53582, Q01662, Q0CL94, Q0UTI9, Q2GSJ7, Q3ZC89, Q4QRK0, Q4VBS4, Q54WU3, Q56Y85, Q5I0A0, Q5RBF3

Diamond homologs: A6QLA4, B6YTG0, O34484, O51132, O59730, O66489, O83814, O84859, P0A078, P0A079, P0A080, P0A1X6, P0A1X7, P0A5J3, P0AE18, P0AE19, P0AE20, P0AE21, P19994, P33111, P41392, P44421, P50614, P53579, P53580, P53581, P53582, P56102, P57324, P69000, P99121, P9WK18, P9WK19, P9WK20, P9WK21, Q01662, Q4QRK0, Q4VBS4, Q54VU7, Q54WU3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2321 predictions. Top by Δscore:

Variant	Effect	Δscore
2:172000007:GAG:G	donor_gain	1.0000
2:172061496:A:AG	acceptor_gain	1.0000
2:172061497:G:GG	acceptor_gain	1.0000
2:172061647:GTTCC:G	donor_gain	1.0000
2:172061648:TTCCT:T	donor_gain	1.0000
2:172061651:CTAAG:C	donor_loss	1.0000
2:172061652:TAAG:T	donor_loss	1.0000
2:172061653:AAG:A	donor_loss	1.0000
2:172061654:AGGTA:A	donor_loss	1.0000
2:172061656:G:GA	donor_loss	1.0000
2:172061657:T:A	donor_loss	1.0000
2:172063848:G:GT	donor_gain	1.0000
2:172063848:G:T	donor_gain	1.0000
2:172065689:G:GT	donor_gain	1.0000
2:172066256:C:CA	acceptor_gain	1.0000
2:172066256:C:G	acceptor_gain	1.0000
2:172066262:A:AG	acceptor_gain	1.0000
2:172066263:G:GA	acceptor_gain	1.0000
2:172066307:G:GG	donor_gain	1.0000
2:172000007:GAGGT:G	donor_loss	0.9900
2:172000008:AGG:A	donor_loss	0.9900
2:172061497:GGTT:G	acceptor_gain	0.9900
2:172063709:A:G	acceptor_gain	0.9900
2:172063775:T:G	donor_gain	0.9900
2:172063811:C:T	donor_gain	0.9900
2:172063893:A:AG	donor_gain	0.9900
2:172063899:G:T	donor_gain	0.9900
2:172065683:GC:G	donor_gain	0.9900
2:172066255:AC:A	acceptor_gain	0.9900
2:172066261:TAGTC:T	acceptor_loss	0.9900

AlphaMissense

2213 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:172065694:T:C	F147L	0.994
2:172065696:T:A	F147L	0.994
2:172065696:T:G	F147L	0.994
2:172070937:T:C	S191P	0.994
2:172079254:T:C	F281S	0.994
2:172065722:A:T	N156I	0.993
2:172070932:A:T	D189V	0.992
2:172070938:C:T	S191F	0.992
2:172079260:T:A	I283K	0.992
2:172065711:T:G	C152W	0.991
2:172070933:C:A	D189E	0.991
2:172070933:C:G	D189E	0.991
2:172071015:G:C	A217P	0.991
2:172066300:T:A	D178E	0.990
2:172066300:T:G	D178E	0.990
2:172080338:T:C	F314L	0.990
2:172080340:C:A	F314L	0.990
2:172080340:C:G	F314L	0.990
2:172079253:T:C	F281L	0.989
2:172079255:C:A	F281L	0.989
2:172079255:C:G	F281L	0.989
2:172063815:T:G	C101W	0.988
2:172065723:C:A	N156K	0.988
2:172065723:C:G	N156K	0.988
2:172065746:C:A	P164H	0.988
2:172070932:A:C	D189A	0.988
2:172079260:T:G	I283R	0.988
2:172080129:G:C	E284D	0.988
2:172080129:G:T	E284D	0.988
2:172080343:G:C	E315D	0.988

dbSNP variants (sampled 300 via entrez): RS1000002340 (2:172081311 C>T), RS1000082801 (2:172007222 T>C), RS1000095234 (2:172036621 T>G), RS1000131599 (2:172014403 T>C), RS1000150237 (2:172021184 A>C), RS1000184418 (2:172004282 T>G), RS1000201424 (2:172039139 A>T), RS1000227900 (2:172081142 T>C), RS1000264898 (2:172007513 G>C), RS1000284741 (2:172010185 G>A), RS1000361795 (2:172024598 A>C,G), RS1000397748 (2:172001477 G>A), RS1000404785 (2:172068137 A>G), RS1000431106 (2:172064479 G>C), RS1000457671 (2:172053971 T>C)

Disease associations

OMIM: gene MIM:610267 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001937_49	Breast cancer	1.000000e-08
GCST003997_44	Myopia	3.000000e-15
GCST006268_501	Reaction time	4.000000e-08
GCST006291_115	Spherical equivalent or myopia (age of diagnosis)	3.000000e-16
GCST009764_17	Body mass index	1.000000e-07
GCST010002_404	Refractive error	2.000000e-39
GCST010988_193	Adult body size	6.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008393	reaction time measurement
EFO:0004847	age at onset
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3831223 (PROTEIN FAMILY)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M24: Methionyl aminopeptidase

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	3
Acetaminophen	decreases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Manganese	decreases expression, increases abundance	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4334276	ADMET	Stability in pH 2 HCl assessed as aminopeptidase (unknown origin)-mediated compound hydrolysis by measuring parent compound remaining at 200 uM up to 6 hrs by RP-HPLC analysis	Astratides: Insulin-Modulating, Insecticidal, and Antifungal Cysteine-Rich Peptides from Astragalus membranaceus. — J Nat Prod

Clinical trials (associated diseases)

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