AMZ2

Summary

AMZ2 (archaelysin family metallopeptidase 2, HGNC:28041) is a protein-coding gene on chromosome 17q24.2, encoding Archaemetzincin-2 (Q86W34). Probable zinc metalloprotease.

The protein encoded by this gene is a zinc metalloprotease that displays some activity against angiotensin-3. The encoded protein is inhibited by the aminopeptidase inhibitor amastatin, as well as by the general inhibitors o-phenanthroline and batimastat. Defects in this gene may be associated with lung tumorigenesis.

Source: NCBI Gene 51321 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 85 total — 1 pathogenic
• MANE Select transcript: NM_016627

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28041
Approved symbol	AMZ2
Name	archaelysin family metallopeptidase 2
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196704
Ensembl biotype	protein_coding
OMIM	615169
Entrez	51321

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 21 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000359783, ENST00000359904, ENST00000392720, ENST00000577273, ENST00000577866, ENST00000577985, ENST00000578175, ENST00000579724, ENST00000580548, ENST00000580753, ENST00000580837, ENST00000581779, ENST00000582430, ENST00000584350, ENST00000584494, ENST00000584836, ENST00000584837, ENST00000585050, ENST00000612294, ENST00000674770, ENST00000871321, ENST00000871322, ENST00000871323, ENST00000940109, ENST00000951990, ENST00000951991, ENST00000951992

RefSeq mRNA: 23 — MANE Select: NM_016627 NM_001033569, NM_001033570, NM_001033571, NM_001033572, NM_001033574, NM_001289054, NM_001289056, NM_001346471, NM_001346472, NM_001346473, NM_001346474, NM_001346475, NM_001346476, NM_001346477, NM_001346478, NM_001346479, NM_001346480, NM_001346481, NM_001346482, NM_001346483, NM_001346484, NM_001346485, NM_016627

CCDS: CCDS11674, CCDS32714

Canonical transcript exons

ENST00000359904 — 7 exons

Exon	Start	End
ENSE00002709793	68248043	68248705
ENSE00003460596	68256814	68257155
ENSE00003593678	68255700	68255876
ENSE00003625697	68254404	68254567
ENSE00003632386	68250794	68250967
ENSE00003756916	68250188	68250470
ENSE00003786515	68251050	68251178

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.9505 / max 270.9342, expressed in 1818 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162392	36.1106	1815
162381	5.3518	1419
162390	0.6786	357
162380	0.5256	310
162391	0.2180	100
162389	0.0467	13
162394	0.0192	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.30	gold quality
left testis	UBERON:0004533	99.06	gold quality
right testis	UBERON:0004534	99.02	gold quality
male germ cell	CL:0000015	98.97	gold quality
caudate nucleus	UBERON:0001873	98.07	gold quality
putamen	UBERON:0001874	98.05	gold quality
testis	UBERON:0000473	97.94	gold quality
nucleus accumbens	UBERON:0001882	97.70	gold quality
right frontal lobe	UBERON:0002810	97.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.64	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.56	gold quality
lateral globus pallidus	UBERON:0002476	97.54	gold quality
amygdala	UBERON:0001876	97.40	gold quality
secondary oocyte	CL:0000655	97.39	gold quality
anterior cingulate cortex	UBERON:0009835	97.37	gold quality
cingulate cortex	UBERON:0003027	97.34	gold quality
adenohypophysis	UBERON:0002196	97.28	gold quality
prefrontal cortex	UBERON:0000451	97.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.25	gold quality
ventricular zone	UBERON:0003053	97.19	gold quality
pituitary gland	UBERON:0000007	97.14	gold quality
cerebellar hemisphere	UBERON:0002245	97.13	gold quality
cerebellar cortex	UBERON:0002129	97.11	gold quality
spinal cord	UBERON:0002240	97.08	gold quality
adult organism	UBERON:0007023	97.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.03	gold quality
frontal cortex	UBERON:0001870	96.98	gold quality
neocortex	UBERON:0001950	96.94	gold quality
telencephalon	UBERON:0001893	96.92	gold quality
forebrain	UBERON:0001890	96.87	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	1912.35
E-HCAD-35	yes	73.33
E-ANND-3	yes	7.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting AMZ2, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-483-3P	97.77	64.95	731

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	AMZ2	ENSDARG00000089248
mus_musculus	Amz2	ENSMUSG00000020610
rattus_norvegicus	Amz2	ENSRNOG00000000246

Paralogs (1): AMZ1 (ENSG00000174945)

Protein

Protein identifiers

Archaemetzincin-2 — Q86W34 (reviewed: Q86W34)

Alternative names: Archeobacterial metalloproteinase-like protein 2

All UniProt accessions (9): Q86W34, J3KRD0, J3KRS2, J3KS38, J3KSH1, J3KTM1, J3QL25, J3QLK6, J3QQR3

UniProt curated annotations — full annotation on UniProt →

Function. Probable zinc metalloprotease.

Tissue specificity. Down-regulated in testis from patients with maturation arrest (MA) or Sertoli cell-only syndrome (SCOS).

Cofactor. Binds 2 Zn(2+) ions per subunit. One is catalytic, whereas the other seems to have a structural role.

Similarity. Belongs to the peptidase M54 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86W34-4	1	yes
Q86W34-5	2

RefSeq proteins (23): NP_001028741, NP_001028742, NP_001028743, NP_001028744, NP_001028746, NP_001275983, NP_001275985, NP_001333400, NP_001333401, NP_001333402, NP_001333403, NP_001333404, NP_001333405, NP_001333406, NP_001333407, NP_001333408, NP_001333409, NP_001333410, NP_001333411, NP_001333412, NP_001333413, NP_001333414, NP_057711* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012962	Pept_M54_archaemetzincn	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR052009	Archaemetzincin	Family

Pfam: PF07998

UniProt features (25 total): sequence conflict 13, binding site 7, sequence variant 2, chain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W34-F1	90.55	0.75

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): 255 (proton acceptor)

Ligand- & substrate-binding residues (7): 254; 258; 264; 265; 270; 289; 292

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_255, MODULE_317, ONKEN_UVEAL_MELANOMA_UP, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, NUYTTEN_EZH2_TARGETS_DN, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MODULE_69, GOBP_PROTEOLYSIS, SCGGAAGY_ELK1_02, GOMF_PEPTIDASE_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, DAVICIONI_MOLECULAR_ARMS_VS_ERMS_UP, PURBEY_TARGETS_OF_CTBP1_AND_SATB1_DN

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

GO Molecular Function (4): metallopeptidase activity (GO:0008237), metal ion binding (GO:0046872), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (1): cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
peptidase activity	1
cation binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1

Protein interactions and networks

STRING

672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMZ2	SMIM17	P0DL12	527
AMZ2	FAM234B	A2RU67	447
AMZ2	LRRIQ3	A6PVS8	447
AMZ2	TMEM214	Q6NUQ4	433
AMZ2	SPRYD7	Q5W111	424
AMZ2	ZACN	Q401N2	406
AMZ2	HSDL1	Q3SXM5	391
AMZ2	TMEM266	Q2M3C6	387
AMZ2	ARSG	Q96EG1	384
AMZ2	ABITRAM	Q9NX38	376
AMZ2	SUPT3H	O75486	373
AMZ2	PNMA8A	Q86V59	368
AMZ2	SLC41A3	Q96GZ6	365
AMZ2	CMIP	Q8IY22	360
AMZ2	CALHM3	Q86XJ0	359

IntAct

25 interactions, top by confidence:

A	B	Type	Score
LRRC46	TFPT	psi-mi:“MI:0914”(association)	0.640
KCNV2	HSPA8	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530
CCL14	DNLZ	psi-mi:“MI:0914”(association)	0.530
PAK5	OBSL1	psi-mi:“MI:0914”(association)	0.530
Mad2l1bp	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
NDE1	AMZ2	psi-mi:“MI:0914”(association)	0.350
ZNFX1	DRC1	psi-mi:“MI:0914”(association)	0.350
Setdb1	INPP5B	psi-mi:“MI:0914”(association)	0.350
INSL5	LAMA5	psi-mi:“MI:0914”(association)	0.350
PAK5	SUPT5H	psi-mi:“MI:0914”(association)	0.350
IL17RC	C2CD2L	psi-mi:“MI:0914”(association)	0.350
DENR	ATG13	psi-mi:“MI:0914”(association)	0.350
CCL4	PEX14	psi-mi:“MI:0914”(association)	0.350
CCL14	PDIA5	psi-mi:“MI:0914”(association)	0.350
S	COPE	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
CCL3L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
CCL4L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
PCCB	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
LARS2	CREB1	psi-mi:“MI:0914”(association)	0.350
LRRC46	GTPBP6	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS)

ESM2 similar proteins: A0JMU5, A1A4L5, A1CBC9, A1DE13, A2QX45, A2RAF3, A3KPA3, A6H8I2, A7UL74, A8E5V7, C5IAW9, D6WMX4, E0W1I1, F8VPZ3, I3J7Q8, O22977, O44997, P53355, P54789, Q008S8, Q02723, Q0CW42, Q0P564, Q17QK9, Q1DKI1, Q2TBM9, Q2U6C4, Q38898, Q3MHC1, Q3TL26, Q3U213, Q4U3Y2, Q4WVE3, Q5R4A6, Q5R6Y2, Q5SNQ7, Q5U2T7, Q6DCB7, Q6NRS1, Q7T2Z5

Diamond homologs: B0R889, C3MQ90, C3MVY2, C3N5V8, C3NEH4, C3NH77, C4KHI7, O29917, O59484, Q18KE9, Q3ITQ5, Q400C7, Q400C8, Q4JB73, Q4R684, Q57729, Q5JGD6, Q5R4A6, Q5V0J7, Q74M83, Q86W34, Q8TXW1, Q8TZW5, Q8ZW37, Q9HMC3, Q9UX78, Q9V1Q1, Q9YFV3, Q400C9, Q400G9, Q8BVF9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
chemokine-mediated signaling pathway	5	47.7×	2e-05
antimicrobial humoral immune response mediated by antimicrobial peptide	5	23.8×	3e-04
positive regulation of cell migration	6	10.9×	1e-03
inflammatory response	6	6.7×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	63
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
149337	GRCh38/hg38 17q24.2(chr17:67584224-68639875)x1	Pathogenic

SpliceAI

1258 predictions. Top by Δscore:

Variant	Effect	Δscore
17:68247720:G:GT	donor_gain	1.0000
17:68254399:TGTA:T	acceptor_loss	1.0000
17:68254400:GTAG:G	acceptor_loss	1.0000
17:68254401:TAGGT:T	acceptor_loss	1.0000
17:68254402:A:G	acceptor_loss	1.0000
17:68254403:GGT:G	acceptor_gain	1.0000
17:68254563:GTAAG:G	donor_gain	1.0000
17:68254566:AGGTA:A	donor_loss	1.0000
17:68254568:GTAA:G	donor_loss	1.0000
17:68255695:TGCA:T	acceptor_loss	1.0000
17:68255696:GCAG:G	acceptor_loss	1.0000
17:68255697:CAG:C	acceptor_loss	1.0000
17:68255698:A:AG	acceptor_gain	1.0000
17:68255698:AG:A	acceptor_loss	1.0000
17:68255699:G:GA	acceptor_gain	1.0000
17:68255699:GA:G	acceptor_gain	1.0000
17:68255699:GACT:G	acceptor_gain	1.0000
17:68255699:GACTT:G	acceptor_gain	1.0000
17:68255875:AAGTA:A	donor_loss	1.0000
17:68255876:AGTA:A	donor_loss	1.0000
17:68255877:G:GG	donor_gain	1.0000
17:68255877:G:T	donor_loss	1.0000
17:68255878:TAA:T	donor_loss	1.0000
17:68256809:TCCA:T	acceptor_loss	1.0000
17:68256810:CCAG:C	acceptor_loss	1.0000
17:68256812:A:AG	acceptor_gain	1.0000
17:68256812:A:G	acceptor_loss	1.0000
17:68256813:G:GA	acceptor_gain	1.0000
17:68256813:GGC:G	acceptor_gain	1.0000
17:68247808:G:GT	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001304402 (17:68210094 G>C), RS1004865159 (17:68209832 G>C,T), RS1005478392 (17:68209586 G>A,C), RS1009456099 (17:68209561 T>C), RS1014125632 (17:68209864 A>G), RS1015896344 (17:68209589 T>G), RS1020001435 (17:68213332 C>A), RS1024191849 (17:68210060 G>A), RS1024556805 (17:68209867 C>T), RS1032750962 (17:68210112 G>A), RS1036409979 (17:68213157 T>A), RS1036765993 (17:68210018 T>A), RS1040483528 (17:68209576 T>C), RS1040935620 (17:68209805 G>A,C), RS1049138759 (17:68209820 C>T)

Disease associations

OMIM: gene MIM:615169 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006922_1	Regular attendance at a religious group	2.000000e-06
GCST006923_7	Loneliness	6.000000e-09
GCST006924_5	Loneliness (MTAG)	1.000000e-09
GCST010796_912	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement
EFO:0007865	loneliness measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases expression	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
azoxystrobin	increases expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Ethyl Methanesulfonate	increases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Rotenone	increases expression	1
Thiram	decreases expression	1
Tungsten Compounds	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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