MBLAC2

Summary

MBLAC2 (metallo-beta-lactamase domain containing 2, HGNC:33711) is a protein-coding gene on chromosome 5q14.3, encoding Acyl-coenzyme A thioesterase MBLAC2 (Q68D91). Acyl-CoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH.

Enables beta-lactamase activity and long-chain fatty acyl-CoA hydrolase activity. Predicted to be involved in fatty acid metabolic process. Located in endoplasmic reticulum membrane and plasma membrane.

Source: NCBI Gene 153364 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_203406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33711
Approved symbol	MBLAC2
Name	metallo-beta-lactamase domain containing 2
Location	5q14.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686P15118, MGC46734
Ensembl gene	ENSG00000176055
Ensembl biotype	protein_coding
OMIM	620907
Entrez	153364

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000316610, ENST00000514906

RefSeq mRNA: 1 — MANE Select: NM_203406 NM_203406

CCDS: CCDS4067

Canonical transcript exons

ENST00000316610 — 2 exons

Exon	Start	End
ENSE00002309740	90458209	90461552
ENSE00003543437	90473839	90474771

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 86.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7083 / max 145.9400, expressed in 1708 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62526	3.5845	1444
62522	2.3434	1280
62527	1.7232	830
62524	1.1421	698
62525	0.6095	345
62523	0.3057	133

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	86.59	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.78	gold quality
epithelial cell of pancreas	CL:0000083	84.37	silver quality
middle temporal gyrus	UBERON:0002771	83.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.51	gold quality
upper arm skin	UBERON:0004263	81.74	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.21	gold quality
skin of hip	UBERON:0001554	81.10	gold quality
Brodmann (1909) area 46	UBERON:0006483	81.07	gold quality
left ventricle myocardium	UBERON:0006566	80.57	gold quality
primary visual cortex	UBERON:0002436	79.99	gold quality
upper leg skin	UBERON:0004262	79.38	gold quality
esophagus squamous epithelium	UBERON:0006920	79.36	gold quality
tibia	UBERON:0000979	79.18	gold quality
gingival epithelium	UBERON:0001949	78.54	gold quality
palpebral conjunctiva	UBERON:0001812	78.09	gold quality
germinal epithelium of ovary	UBERON:0001304	77.75	gold quality
prefrontal cortex	UBERON:0000451	77.64	gold quality
cortical plate	UBERON:0005343	77.55	gold quality
gingiva	UBERON:0001828	76.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.20	gold quality
secondary oocyte	CL:0000655	75.62	gold quality
entorhinal cortex	UBERON:0002728	75.59	gold quality
calcaneal tendon	UBERON:0003701	75.44	gold quality
pigmented layer of retina	UBERON:0001782	75.40	gold quality
cerebral cortex	UBERON:0000956	75.06	gold quality
cerebellar cortex	UBERON:0002129	74.89	gold quality
cerebellar hemisphere	UBERON:0002245	74.80	gold quality
neocortex	UBERON:0001950	74.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

234 targeting MBLAC2, 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-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-656-3P	100.00	72.15	2788
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-3646	100.00	73.56	5283
HSA-MIR-6740-5P	100.00	65.64	932

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mblac2	ENSDARG00000059689
mus_musculus	Mblac2	ENSMUSG00000051098
rattus_norvegicus	Mblac2	ENSRNOG00000016252
drosophila_melanogaster	tzn	FBGN0037024
caenorhabditis_elegans		WBGENE00012459

Paralogs (4): HAGH (ENSG00000063854), HAGHL (ENSG00000103253), ETHE1 (ENSG00000105755), PNKD (ENSG00000127838)

Protein

Protein identifiers

Acyl-coenzyme A thioesterase MBLAC2 — Q68D91 (reviewed: Q68D91)

Alternative names: Beta-lactamase MBLAC2, Metallo-beta-lactamase domain-containing protein 2, Palmitoyl-coenzyme A thioesterase MBLAC2

All UniProt accessions (1): Q68D91

UniProt curated annotations — full annotation on UniProt →

Function. Acyl-CoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. Has an acyl-CoA thioesterase activity towards the long chain fatty acyl-CoA thioester palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA). Displays a substrate preference for fatty acyl-CoAs with chain-lengths C12-C18. Possesses beta-lactamase activity, catalyzing the hydrolysis of penicillin G and nitrocefin. Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem).

Subcellular location. Endoplasmic reticulum membrane. Cell membrane.

Post-translational modifications. Palmitoylated on Cys-254 by ZDHHC20.

Activity regulation. Beta-lactamase activity is inhibited by sulbactam.

Cofactor. Binds 2 Zn(2+) ions per subunit.

Similarity. Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q68D91-1	1	yes
Q68D91-2	2

RefSeq proteins (1): NP_981951* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001279	Metallo-B-lactamas	Domain
IPR036866	RibonucZ/Hydroxyglut_hydro	Homologous_superfamily
IPR050855	NDM-1-like	Family

Pfam: PF00753

Catalyzed reactions (Rhea), 5 shown:

• hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+) (RHEA:16645)
• a beta-lactam + H2O = a substituted beta-amino acid (RHEA:20401)
• dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+) (RHEA:30135)
• octadecanoyl-CoA + H2O = octadecanoate + CoA + H(+) (RHEA:30139)
• tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+) (RHEA:40119)

UniProt features (22 total): binding site 8, mutagenesis site 7, initiator methionine 1, chain 1, modified residue 1, lipid moiety-binding region 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68D91-F1	94.46	0.87

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 (8): 83; 85; 87; 88; 170; 189; 189; 231

Post-translational modifications (2): 2, 254

Mutagenesis-validated functional residues (7):

Position	Phenotype
87	loss of enzyme activity.
88	loss of enzyme activity.
89	no effect on enzyme activity.
93	no effect on enzyme activity.
176	no effect on zdhh20-catalyzed palmitoylation.
212	no effect on zdhh20-catalyzed palmitoylation.
254	loss of zdhh20-catalyzed palmitoylation. shows only a slight reduction in the vmax and a small increase in the km toward

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 167 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, TATTATA_MIR374, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, CATTTCA_MIR203, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, CCAGGTT_MIR490, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, CUI_TCF21_TARGETS_2_DN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_FATTY_ACID_METABOLIC_PROCESS

GO Biological Process (2): fatty acid metabolic process (GO:0006631), lipid metabolic process (GO:0006629)

GO Molecular Function (5): beta-lactamase activity (GO:0008800), metal ion binding (GO:0046872), long-chain fatty acyl-CoA hydrolase activity (GO:0052816), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): mitochondrion (GO:0005739), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular membrane-bounded organelle	2
lipid metabolic process	1
monocarboxylic acid metabolic process	1
primary metabolic process	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides	1
cation binding	1
fatty acyl-CoA hydrolase activity	1
binding	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
extracellular vesicle	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1290 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBLAC2	MBLAC1	A4D2B0	664
MBLAC2	LYSMD3	Q7Z3D4	608
MBLAC2	KIAA2013	Q8IYS2	591
MBLAC2	RMDN3	Q96TC7	554
MBLAC2	HAGHL	Q6PII5	507
MBLAC2	LRRC39	Q96DD0	499
MBLAC2	DCLRE1A	Q6PJP8	492
MBLAC2	ESYT2	A0FGR8	490
MBLAC2	ARL15	Q9NXU5	483
MBLAC2	POLR3G	O15318	478
MBLAC2	DCLRE1B	Q9H816	478
MBLAC2	OSBPL8	Q9BZF1	461
MBLAC2	LYRM9	A8MSI8	450
MBLAC2	PIGBOS1	A0A0B4J2F0	440
MBLAC2	TMEM256	Q8N2U0	430

IntAct

75 interactions, top by confidence:

A	B	Type	Score
ADCY9	NEMP1	psi-mi:“MI:0914”(association)	0.640
BZW2	ENDOD1	psi-mi:“MI:0914”(association)	0.640
PBX3	MBLAC2	psi-mi:“MI:0915”(physical association)	0.560
MBLAC2	PBX3	psi-mi:“MI:0915”(physical association)	0.560
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
CACNG5	ZNF316	psi-mi:“MI:0914”(association)	0.530
FAM131B	AURKA	psi-mi:“MI:0914”(association)	0.530
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
CD226	MEN1	psi-mi:“MI:0914”(association)	0.530
RNF19B	PIK3R2	psi-mi:“MI:0914”(association)	0.530
IGSF8	CLGN	psi-mi:“MI:0914”(association)	0.530
OPCML	CANX	psi-mi:“MI:0914”(association)	0.530
SLC9A6	IFNGR1	psi-mi:“MI:0914”(association)	0.530
CD53	FAM171A2	psi-mi:“MI:0914”(association)	0.530
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
VAMP4	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
GRPR	GPR89A	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	MAP2K7	psi-mi:“MI:0914”(association)	0.350
MINDY2	SLC27A2	psi-mi:“MI:0914”(association)	0.350
BSPRY	DEAF1	psi-mi:“MI:0914”(association)	0.350
SELE	SBF1	psi-mi:“MI:0914”(association)	0.350
CDHR5	LGALS1	psi-mi:“MI:0914”(association)	0.350
OPCML	HLA-A	psi-mi:“MI:0914”(association)	0.350
IGSF8	CD9	psi-mi:“MI:0914”(association)	0.350
MBLAC2	STAT3	psi-mi:“MI:0914”(association)	0.350
CMBL	H2BC11	psi-mi:“MI:0914”(association)	0.350

BioGRID (109): MBLAC2 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS), SLC9A6 (Affinity Capture-MS), TMEM230 (Affinity Capture-MS), FLRT3 (Affinity Capture-MS), EPHA7 (Affinity Capture-MS), BCS1L (Affinity Capture-MS), ATP11C (Affinity Capture-MS)

ESM2 similar proteins: A0PKS1, A0R2V9, A0R4H4, A0R635, A1KMV6, A1R8P8, A1S203, A1SF33, A1TE33, A4T9A9, A5CU73, A5PJT0, A5U6X0, B0RD37, B2HT62, B3Q953, C1A2D8, O86779, P0AES0, P0AES1, P0AEX5, P0AEX6, P12033, P19650, P20092, P38035, P54581, P64718, P71838, P9WH20, P9WH21, P9WKU0, P9WKU1, P9WN08, P9WN09, P9WP64, P9WP65, Q13E42, Q1D9X8, Q2J338

Diamond homologs: A5PJT0, Q0AM20, Q5F336, Q68D91, Q6ML19, Q8BL86, P75849, Q57544, Q49649

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

217 predictions. Top by Δscore:

Variant	Effect	Δscore
5:90473837:ACCAT:A	donor_gain	1.0000
5:90473838:CCATC:C	donor_gain	1.0000
5:90473841:T:A	donor_gain	0.9900
5:90461393:AT:A	donor_gain	0.9800
5:90461549:TCCC:T	acceptor_gain	0.9800
5:90461549:TCCCC:T	acceptor_loss	0.9800
5:90461550:CCC:C	acceptor_gain	0.9800
5:90461550:CCCC:C	acceptor_gain	0.9800
5:90461551:CC:C	acceptor_gain	0.9800
5:90461551:CCC:C	acceptor_gain	0.9800
5:90461551:CCCT:C	acceptor_loss	0.9800
5:90461552:CC:C	acceptor_gain	0.9800
5:90461552:CCTA:C	acceptor_loss	0.9800
5:90461553:C:CC	acceptor_gain	0.9800
5:90461553:C:CG	acceptor_loss	0.9800
5:90461554:T:A	acceptor_loss	0.9800
5:90461394:T:C	donor_gain	0.9600
5:90473834:ATTAC:A	donor_loss	0.9500
5:90473836:TA:T	donor_loss	0.9500
5:90473837:ACCA:A	donor_loss	0.9500
5:90473838:C:A	donor_loss	0.9500
5:90473917:C:CT	donor_gain	0.9500
5:90473287:T:C	donor_gain	0.9400
5:90473802:C:A	donor_gain	0.9400
5:90473918:C:CT	donor_gain	0.9400
5:90473916:A:AC	donor_gain	0.9300
5:90461555:A:C	acceptor_loss	0.9100
5:90473838:CCAT:C	donor_gain	0.9100
5:90473868:G:GA	donor_gain	0.8900
5:90473839:C:G	donor_loss	0.8800

AlphaMissense

1811 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:90461441:T:A	D189V	0.999
5:90461446:A:C	S187R	0.999
5:90461446:A:T	S187R	0.999
5:90461448:T:G	S187R	0.999
5:90461314:G:C	H231Q	0.998
5:90461314:G:T	H231Q	0.998
5:90461316:G:C	H231D	0.998
5:90461440:G:C	D189E	0.998
5:90461440:G:T	D189E	0.998
5:90461441:T:C	D189G	0.998
5:90461441:T:G	D189A	0.998
5:90461477:A:G	L177S	0.998
5:90461481:A:G	C176R	0.998
5:90461495:G:A	S171F	0.998
5:90461516:A:T	V164D	0.998
5:90474031:G:C	H88D	0.998
5:90474033:T:A	D87V	0.998
5:90474159:T:A	D45V	0.998
5:90474231:T:A	E21V	0.998
5:90461319:C:A	G230W	0.997
5:90461442:C:G	D189H	0.997
5:90461444:C:A	G188V	0.997
5:90461444:C:T	G188E	0.997
5:90461450:A:G	F186S	0.997
5:90461453:A:G	L185P	0.997
5:90461479:G:C	C176W	0.997
5:90461485:A:C	S174R	0.997
5:90461485:A:T	S174R	0.997
5:90461487:T:G	S174R	0.997
5:90461496:A:G	S171P	0.997

dbSNP variants (sampled 300 via entrez): RS1000426804 (5:90458538 C>T), RS1000473994 (5:90459673 T>C), RS1000833591 (5:90467091 C>G), RS1000865865 (5:90473441 G>A,C), RS1000882163 (5:90473685 G>A,C), RS1000994281 (5:90473924 G>A), RS1001035267 (5:90467010 G>A,C), RS1001213052 (5:90458487 T>C), RS1001341621 (5:90473676 G>A,T), RS1001600690 (5:90458034 T>C), RS1001811140 (5:90466666 A>AT), RS1001839506 (5:90473295 G>A,T), RS1002180542 (5:90473024 C>T), RS1002731018 (5:90472785 G>A,T), RS1002845445 (5:90469917 G>A,C)

Disease associations

OMIM: gene MIM:620907 | 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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
avobenzone	decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
bisphenol S	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaldehyde	decreases expression	1
Glyphosate	decreases expression	1
Air Pollutants	decreases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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