MAT2B

Summary

MAT2B (methionine adenosyltransferase 2 non-catalytic beta subunit, HGNC:6905) is a protein-coding gene on chromosome 5q34, encoding Methionine adenosyltransferase 2 subunit beta (Q9NZL9). Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP.

The protein encoded by this gene belongs to the methionine adenosyltransferase (MAT) family. MAT catalyzes the biosynthesis of S-adenosylmethionine from methionine and ATP. This protein is the regulatory beta subunit of MAT. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 27430 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 54 total
• GTEx eGene: eQTL in 23 tissues, sQTL in 5 (q < 0.05)
• Constraint (gnomAD): pLI 0.34 (intermediate), LOEUF 0.67 (unconstrained)
• MANE Select transcript: NM_013283
• Interaction hub: 2,054 STRING partners (top 7% of genes corpus-wide)
• Notable: 54 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6905
Approved symbol	MAT2B
Name	methionine adenosyltransferase 2 non-catalytic beta subunit
Location	5q34
Locus type	gene with protein product
Status	Approved
Aliases	MATIIbeta, SDR23E1
Ensembl gene	ENSG00000038274
Ensembl biotype	protein_coding
OMIM	605527
Entrez	27430

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 24 protein_coding, 11 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000321757

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 2, TSL 4: 1, TSL 5: 1

ENST00000321757, ENST00000280969, ENST00000421814, ENST00000518095, ENST00000519719, ENST00000520449, ENST00000523606, ENST00000694938, ENST00000694939, ENST00000694940, ENST00000694941, ENST00000694942, ENST00000694943, ENST00000694944, ENST00000694945, ENST00000694946, ENST00000694947, ENST00000694952, ENST00000694953, ENST00000694954, ENST00000694955, ENST00000695023, ENST00000695024, ENST00000695025, ENST00000695026, ENST00000695027, ENST00000695028, ENST00000695029, ENST00000695030, ENST00000695031, ENST00000695032, ENST00000695033, ENST00000695034, ENST00000891311, ENST00000911813, ENST00001046140, ENST00001046141, ENST00001046142, ENST00001046143, ENST00001134888

RefSeq mRNA: 2 — MANE Select: NM_013283 NM_013283, NM_182796

CCDS: CCDS4364, CCDS4365

Canonical transcript exons

ENST00000321757 — 7 exons

Exon	Start	End
ENSE00001132174	163513555	163513669
ENSE00001223544	163512002	163512196
ENSE00001923790	163505619	163505749
ENSE00002137078	163517561	163517674
ENSE00003570632	163518193	163519354
ENSE00003585966	163516518	163516711
ENSE00003690485	163513842	163513994

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.1985 / max 435.9345, expressed in 1817 samples.

Highest expression (Bgee): secondary oocyte, germinal epithelium of ovary, ventricular zone, mucosa of sigmoid colon, corpus epididymis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MAT2B is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	1.8e-94	-1.38	5:163513993:A:G
Muscle Skeletal	eqtl	9.7e-50	+0.69	5:163519304:TAAAAC:T
Heart Left Ventricle	eqtl	6.9e-10	+0.30	5:163519304:TAAAAC:T
Thyroid	eqtl	5.8e-08	-0.14	5:163515833:A:G
Testis	eqtl	7.7e-07	+0.16	5:163509458:A:G
Heart Atrial Appendage	eqtl	1.0e-06	+0.26	5:163519304:TAAAAC:T
Lung	eqtl	2.5e-06	+0.17	5:163509458:A:G
Liver	eqtl	4.6e-06	+0.28	5:163509458:A:G
Esophagus Muscularis	eqtl	7.2e-05	+0.11	5:163509458:A:G
Cells Cultured fibroblasts	eqtl	8.4e-05	-0.23	5:163519304:TAAAAC:T
Breast Mammary Tissue	eqtl	1.5e-03	-0.13	5:163515833:A:G
Colon Sigmoid	eqtl	2.7e-03	+0.23	5:163519304:TAAAAC:T
Muscle Skeletal	sqtl	2.7e-03	+0.21	5:163797986:C:T
Lung	sqtl	3.4e-03	-0.96	5:163381702:A:AGTAGG
Spleen	eqtl	3.7e-03	-0.14	5:163539763:A:C
Colon Transverse	eqtl	4.7e-03	+0.08	5:163517703:A:G
Small Intestine Terminal Ileum	eqtl	5.0e-03	+0.23	5:163509458:A:G
Esophagus Gastroesophageal Junction	eqtl	5.6e-03	+0.12	5:163509458:A:G
Adipose Subcutaneous	eqtl	6.9e-03	-0.16	5:163519304:TAAAAC:T
Adipose Visceral Omentum	eqtl	9.7e-03	-0.08	5:163515833:A:G

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
59978	41.8960	1815
59976	6.7811	1426
59975	2.7719	1036
59974	1.1975	685
59980	0.2363	82
59979	0.2048	78
59973	0.1109	43

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.34	gold quality
germinal epithelium of ovary	UBERON:0001304	98.44	gold quality
ventricular zone	UBERON:0003053	98.29	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.20	gold quality
corpus epididymis	UBERON:0004359	98.16	gold quality
palpebral conjunctiva	UBERON:0001812	98.12	gold quality
oocyte	CL:0000023	98.04	gold quality
caput epididymis	UBERON:0004358	98.02	gold quality
colonic mucosa	UBERON:0000317	97.89	gold quality
trabecular bone tissue	UBERON:0002483	97.70	gold quality
leukocyte	CL:0000738	97.55	gold quality
mononuclear cell	CL:0000842	97.53	gold quality
heart right ventricle	UBERON:0002080	97.50	gold quality
monocyte	CL:0000576	97.49	gold quality
ileal mucosa	UBERON:0000331	97.47	gold quality
cartilage tissue	UBERON:0002418	97.42	gold quality
adult organism	UBERON:0007023	97.42	gold quality
upper leg skin	UBERON:0004262	97.39	gold quality
lymph node	UBERON:0000029	97.37	gold quality
eye	UBERON:0000970	97.36	gold quality
nephron tubule	UBERON:0001231	97.36	gold quality
skin of hip	UBERON:0001554	97.31	gold quality
jejunal mucosa	UBERON:0000399	97.28	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.24	gold quality
myocardium	UBERON:0002349	97.09	gold quality
duodenum	UBERON:0002114	96.99	gold quality
rectum	UBERON:0001052	96.97	gold quality
esophagus squamous epithelium	UBERON:0006920	96.97	gold quality
left ventricle myocardium	UBERON:0006566	96.94	gold quality
cauda epididymis	UBERON:0004360	96.86	gold quality
bronchial epithelial cell	CL:0002328	96.84	gold quality
parietal pleura	UBERON:0002400	96.79	gold quality
metanephric glomerulus	UBERON:0004736	96.77	gold quality
epithelium of bronchus	UBERON:0002031	96.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.70	gold quality
tibia	UBERON:0000979	96.68	gold quality
biceps brachii	UBERON:0001507	96.67	gold quality
vermiform appendix	UBERON:0001154	96.66	gold quality
kidney epithelium	UBERON:0004819	96.65	gold quality
bronchus	UBERON:0002185	96.60	gold quality
pleura	UBERON:0000977	96.53	gold quality
epithelium of nasopharynx	UBERON:0001951	96.52	gold quality
nasopharynx	UBERON:0001728	96.50	gold quality
thymus	UBERON:0002370	96.48	gold quality
ganglionic eminence	UBERON:0004023	96.40	gold quality
diaphragm	UBERON:0001103	96.38	gold quality
caecum	UBERON:0001153	96.37	gold quality
seminal vesicle	UBERON:0000998	96.36	gold quality
stromal cell of endometrium	CL:0002255	96.34	gold quality
epithelium of esophagus	UBERON:0001976	96.31	gold quality
renal glomerulus	UBERON:0000074	96.29	gold quality
superficial temporal artery	UBERON:0001614	96.25	gold quality
pons	UBERON:0000988	96.23	gold quality
granulocyte	CL:0000094	96.21	gold quality
cerebellar vermis	UBERON:0004720	96.21	gold quality
embryo	UBERON:0000922	96.15	gold quality
visceral pleura	UBERON:0002401	96.08	gold quality
jejunum	UBERON:0002115	96.07	gold quality
tongue squamous epithelium	UBERON:0006919	96.07	gold quality
lower lobe of lung	UBERON:0008949	96.04	gold quality
blood	UBERON:0000178	96.01	gold quality
nasal cavity mucosa	UBERON:0001826	95.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.90	gold quality
adult mammalian kidney	UBERON:0000082	95.83	gold quality
kidney	UBERON:0002113	95.82	gold quality
metanephros	UBERON:0000081	95.80	gold quality
postcentral gyrus	UBERON:0002581	95.79	gold quality
deltoid	UBERON:0001476	95.78	gold quality
spleen	UBERON:0002106	95.70	gold quality
tibialis anterior	UBERON:0001385	95.67	gold quality
renal medulla	UBERON:0000362	95.62	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.62	gold quality
endometrium	UBERON:0001295	95.55	gold quality
cortex of kidney	UBERON:0001225	95.51	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.46	gold quality
nasal cavity epithelium	UBERON:0005384	95.45	gold quality
oral cavity	UBERON:0000167	95.41	gold quality
quadriceps femoris	UBERON:0001377	95.41	gold quality
vastus lateralis	UBERON:0001379	95.41	gold quality
superior frontal gyrus	UBERON:0002661	95.41	gold quality
gall bladder	UBERON:0002110	95.37	gold quality
prefrontal cortex	UBERON:0000451	95.36	gold quality
parotid gland	UBERON:0001831	95.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.25	gold quality
mucosa of urinary bladder	UBERON:0001259	95.21	gold quality
calcaneal tendon	UBERON:0003701	95.18	gold quality
tonsil	UBERON:0002372	95.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.17	gold quality
bone marrow	UBERON:0002371	95.16	gold quality
mammary duct	UBERON:0001765	95.15	gold quality
ovary	UBERON:0000992	95.10	gold quality
smooth muscle tissue	UBERON:0001135	95.09	gold quality
bone marrow cell	CL:0002092	95.07	gold quality
muscle tissue	UBERON:0002385	95.05	gold quality
orbitofrontal cortex	UBERON:0004167	95.00	gold quality
parietal lobe	UBERON:0001872	94.96	gold quality
skeletal muscle tissue	UBERON:0001134	94.94	gold quality
urinary bladder	UBERON:0001255	94.94	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.89	gold quality
adrenal tissue	UBERON:0018303	94.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	568.03
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	182.5
Caudate putamen	tissue	121.0
Kidney	tissue	99.9	medium
Lymph node	tissue	94.7	not detected
Tonsil	tissue	87.1	medium
Cerebral cortex	tissue	84.9	medium
Somatosensory cortex	tissue	84.9
Thymus	tissue	83.8
Occipital cortex	tissue	80.6
Spleen	tissue	80.0	low
Duodenum	tissue	79.9	medium
Liver	tissue	79.4	low
Small intestine	tissue	79.4	medium
Pons	tissue	77.3
Thyroid gland	tissue	76.4	low
Ovary	tissue	75.0	medium
Motor cortex	tissue	72.7
Thalamus	tissue	71.3
Hippocampal formation	tissue	71.2
Entorhinal cortex	tissue	71.2
Heart muscle	tissue	70.7	not detected
Retrosplenial and cingulate cortex	tissue	69.4
Prefrontal cortex	tissue	66.5
Substantia nigra	tissue	66.5
Parathyroid gland	tissue	65.8	medium
Hypothalamus	tissue	65.6
Superior colliculi	tissue	65.6
Putamen	tissue	65.5
Midbrain	tissue	64.9
Temporal cortex	tissue	64.9
Septum	tissue	64.5
Rectum	tissue	62.9	medium
Fallopian tube	tissue	62.8	medium
Retrosplenial cortex	tissue	62.0
Medulla oblongata	tissue	61.7
Periaqueductal gray	tissue	61.0
Appendix	tissue	60.3	medium
Tongue	tissue	59.8
Spinal cord	tissue	59.7
Salivary gland	tissue	59.1	not detected
Skeletal muscle	tissue	59.1	not detected
Colon	tissue	58.4	medium
Epididymis	tissue	58.3	medium
Ventral forebrain	tissue	57.5
Urinary bladder	tissue	57.4	medium
Insular cortex	tissue	56.1
Stomach 1	tissue	54.9	medium
Basal ganglia	tissue	53.2	low
Amygdala	tissue	52.6
Lung	tissue	52.5	medium
Adrenal gland	tissue	51.4	medium
Cerebellum	tissue	50.9	low
Seminal vesicle	tissue	50.4	medium
Corpus callosum	tissue	49.0
Breast	tissue	47.3	low
Choroid plexus	tissue	46.3
Placenta	tissue	45.9	medium
Retina	tissue	45.2
Cervix	tissue	44.3	low
Prostate	tissue	43.7	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal hippocampus (66.9), Subiculum (61.2), Ventral hippocampus (59.9), Dorsal spinal cord (59.7), Ventral spinal cord (55.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

miRNA regulators (miRDB)

Targeting MAT2B by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 104 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
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-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
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-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836

Functional genomics

gnomAD constraint: pLI 0.343, LOEUF 0.671, missense Z 1.28 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000321757 — one region, missense o/e 0.83.

Literature-anchored findings (GeneRIF, showing 19)

• Lower expression of both MAT2A and MAT2beta and interfere with leptin signaling in liver cancer cells. (PMID:18041713)
• Splicing variants of MAT2beta are up-regulated in hepatocellular carcinoma and regulated tumor cell growth and death. (PMID:18045590)
• a switch in MAT expression in liver cancer was accompanied by increasing expression of MAT2B (PMID:18698677)
• differences in malignant cell survival, effected by MAT-IIbeta ablation, suggest that it may be possible to use this approach to disadvantage leukemic cell survival in vivo with little to no harm to normal cells. (PMID:18753136)
• Data show MAT2beta variants reside mostly in the nucleus and regulate HuR subcellular content to affect cell proliferation. (PMID:20421296)
• Coexpression of MAT2A and MAT2B in COS-1 cells resulted in significantly increased MAT enzyme activity. (PMID:21813468)
• MAT2B and GIT1 form a scaffold, which recruits and activates MEK and ERK to promote growth and tumorigenesis. (PMID:23325601)
• The structure of MAT2B reveals a short-chain dehydrogenase/reductase (SDR) core with specificity for the NADP/H cofactor, and harbors the SDR catalytic triad. (PMID:23425511)
• resveratrol induces HuR, SIRT1, and MAT2B expression; the last may represent a compensatory response against apoptosis and growth inhibition. (PMID:23814050)
• Mutagenesis of MATalpha2 and MATbeta phospho-sites destabilized them and prevented hepatic stellate cell trans-differentiation. (PMID:25294683)
• Interaction between MAT2B and GIT1 serves as a scaffold and facilitates signaling in multiple steps of the Ras/Raf/MEK/ERK pathway (PMID:25794709)
• Results show that MAT2B expression is frequently upregulated in malignant melanoma tissues. MAT2B downregulation delays tumor growth in vivo, and suppressed cell growth, colony formation ability and induced apoptosis in vitro indicating that MAT2B is critical for melanoma cell proliferation and tumorigenicity. (PMID:27573889)
• This study showed that variant upstream of MAT2B whose association is prominent in back, hip, knee, and neck pain-provides preliminary evidence of shared contributing mechanisms at the genetic-molecular level. (PMID:29240606)
• the protein-protein interacting surface formed in MATa2:MATbeta complexes is explored to demonstrate that several quinolone-based compounds modulate the activity of MATa2 and its mutants, providing a rational for chemical design/intervention responsive to the level of S-Adenosylmethionine in the cellular environment (PMID:30776190)
• MAT2B was markedly increased in osteosarcoma (OS) specimens compared with the normal bone tissues, and it was additionally abundantly expressed in OS cell lines. Inhibition of MAT2B expression caused a marked decrease in proliferation and significant increase in apoptosis. Results demonstrated that MAT2B functions as a tumor oncogene in OS in vivo and in vitro via regulation of EGFR and PCNA. (PMID:30942439)
• Results found that MAT2B was overexpressed in hepatocellular carcinoma (HCC) tissues and correlated with poor prognosis for HCC patients. Its silencing could suppress liver cancer cell migration and invasion through the inhibition of EGFR signaling, which suggested that MAT2B might serve as a new prognostic marker for HCC. (PMID:31493275)
• lncMat2B regulated by severe hypoxia induces cisplatin resistance by increasing DNA damage repair and tumor-initiating population in breast cancer cells. (PMID:32710610)
• Human Mat2A Uses an Ordered Kinetic Mechanism and Is Stabilized but Not Regulated by Mat2B. (PMID:34780697)
• CircMAT2B facilitates the progression of head and neck squamous cell carcinoma via sponging miR-491-5p to trigger ASCT2-mediated glutaminolysis. (PMID:36219356)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mat2b	ENSDARG00000012932
mus_musculus	Mat2b	ENSMUSG00000042032
rattus_norvegicus	Mat2b	ENSRNOG00000003177

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R4E0	100.0%	Diamond
Bos taurus	Q29RI9	96.1%	Diamond
Xenopus laevis	Q4QQZ4	93.1%	Diamond
Xenopus tropicalis	Q566L8	93.1%	Diamond
Mycolicibacterium smegmatis MC2 155	A0QTF8	62.7%	Diamond
Burkholderia thailandensis E264	Q2SYI1	45.2%	Diamond
Aggregatibacter actinomycetemcomitans	O66251	41.1%	Diamond
Sinorhizobium fredii NGR234	P55463	41.1%	Diamond
Haloferax volcanii DS2	D4GU71	39.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
NUDCD2	protein-coding	134492
HMMR	protein-coding	3161
CCNG1	protein-coding	900
HMMR-AS1	ncRNA	101927813

Protein

Protein identifiers

Methionine adenosyltransferase 2 subunit beta — Q9NZL9 (reviewed: Q9NZL9)

Alternative names: Methionine adenosyltransferase II beta, Putative dTDP-4-keto-6-deoxy-D-glucose 4-reductase

All UniProt accessions (12): A0A140VJP2, A0A8Q3SIE5, A0A8Q3WK74, A0A8Q3WK80, A0A8Q3WK84, A0A8Q3WK93, A0A8Q3WKR9, A0A8Q3WLC0, A0A8Q3WLP1, E5RJR3, Q9NZL9, H7C0X7

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine. Can bind NADP (in vitro).

Subunit / interactions. Heterotrimer; composed of a catalytic MAT2A homodimer that binds one regulatory MAT2B chain. Heterohexamer; composed of a central, catalytic MAT2A homotetramer flanked on either side by a regulatory MAT2B chain. NADP binding increases the affinity for MAT2A.

Tissue specificity. Widely expressed.

Pathway. Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis; S-adenosyl-L-methionine from L-methionine: step 1/1.

Miscellaneous. Its expression in hepatoma cell lines may lead to increase DNA synthesis and thereby participate in cell proliferation.

Similarity. Belongs to the dTDP-4-dehydrorhamnose reductase family. MAT2B subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9NZL9-1	1	yes
Q9NZL9-2	2
Q9NZL9-3	3
Q9NZL9-4	4
Q9NZL9-5	5

RefSeq proteins (2): NP_037415, NP_877725 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005913	RmlD	Family
IPR029903	RmlD-like-bd	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF04321

Enzyme classification (BRENDA)

• EC 2.5.1.6 — methionine adenosyltransferase (BRENDA: 64 organisms, 105 substrates, 289 inhibitors, 269 Km, 118 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-METHIONINE	0.0023–3.3	118
ATP	0.002–6.54	93
TRIPOLYPHOSPHATE	0.0013–0.026	12
METHIONINE	0.0083–1.12	9
S-ADENOSYL-L-METHIONINE	0.32–0.45	6
S-(6-AZIDOHEX-2-YNYL)-L-HOMOCYSTEINE	0.92–1.518	4
L-ETHIONINE	0.0056–0.74	3
S-(-)-METHIONINOL	0.39–2.4	3
CTP	0.4	2
GTP	0.62	2
MG2+	0.006–0.007	2
UTP	2.2	2
D-METHIONINE	3.5	1
ITP	1.4	1
L-METHIONINE METHYL ESTHER	2.6	1

UniProt features (56 total): helix 16, strand 14, splice variant 7, binding site 7, turn 5, sequence conflict 2, initiator methionine 1, chain 1, modified residue 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

9 structures by resolution:

PDB	Title	Method	Resolution (Å)
2YDY	Crystal structure of human S-adenosylmethionine synthetase 2, beta subunit in …	X-RAY DIFFRACTION	2.25
4NDN	Structural insights of MAT enzymes: MATa2b complexed with SAM and PPNP	X-RAY DIFFRACTION	2.34
4KTT	Structural insights of MAT enzymes: MATa2b complexed with SAM	X-RAY DIFFRACTION	2.59
9QPO	CryoEM structure of human MATa2 in complex with MATBv2 at 2.6 A resolution	ELECTRON MICROSCOPY	2.6
9QPP	CryoEM structure of human MATa2 in complex with MAT2B isoform v1 at 2.6 A resolution	ELECTRON MICROSCOPY	2.6
2YDX	Crystal structure of human S-adenosylmethionine synthetase 2, beta subunit	X-RAY DIFFRACTION	2.8
30GD	CryoEM structure of human MATa2 in complex with MAT2B isoform v1 at 2.6 A resolution	ELECTRON MICROSCOPY	2.9
30GH	CryoEM structure of human MATa2 in complex with MAT2B isoform v1 at 2.6 A resolution	ELECTRON MICROSCOPY	3.1
4KTV	Structural insights of MAT enzymes: MATa2b complexed with adenosine and pyrophosphate	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZL9-F1	93.82	0.83

Human Protein Atlas

Protein class: Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH uncertain · IF approved

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 (7)

Position	Role
37–40	NADP(+)
60–62	NADP(+)
71–72	NADP(+)
93	NADP(+)
97	NADP(+)
159	NADP(+)
185	NADP(+)

Post-translational modifications (1)

Type	Positions
Phosphothreonine	309

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-156581	Methylation	curated
R-HSA-5689880	Ub-specific processing proteases	curated
R-HSA-211859	Biological oxidations	—
R-HSA-5688426	Deubiquitination	—
R-HSA-1430728	Metabolism	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-156580	Phase II - Conjugation of compounds	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 182 (showing top): LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, TAATAAT_MIR126, REACTOME_BIOLOGICAL_OXIDATIONS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_DN, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_DN, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_S_ADENOSYLMETHIONINE_METABOLIC_PROCESS, GOBP_ONE_CARBON_METABOLIC_PROCESS, KOKKINAKIS_METHIONINE_DEPRIVATION_48HR_UP, ACTTTAT_MIR1425P, DANG_BOUND_BY_MYC, GOCC_TRANSFERASE_COMPLEX, MARSON_BOUND_BY_FOXP3_STIMULATED

GO Biological Process (2): S-adenosylmethionine biosynthetic process (GO:0006556), one-carbon metabolic process (GO:0006730)

GO Molecular Function (4): enzyme binding (GO:0019899), enzyme regulator activity (GO:0030234), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), methionine adenosyltransferase complex (GO:0048269), extracellular exosome (GO:0070062)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Phase II - Conjugation of compounds	1
Deubiquitination	1
Biological oxidations	1
Metabolism	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

13 GO namespaces:

Category	Terms
catalytic activity	2
sulfur compound biosynthetic process	1
S-adenosylmethionine metabolic process	1
small molecule metabolic process	1
protein binding	1
molecular function regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
intracellular protein-containing complex	1
transferase complex	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
S-adenosylmethionine biosynthetic process	BP	direct assay
extracellular exosome	CC	high-throughput assay
methionine adenosyltransferase complex	CC	direct assay
nucleus	CC	direct assay
enzyme binding	MF	physical interaction
enzyme regulator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,054 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAT2B	MAT2A	P31153	984
MAT2B	MAT1A	Q00266	723
MAT2B	BHMT	Q93088	602
MAT2B	GNMT	Q14749	599
MAT2B	AHCY	P23526	519
MAT2B	MTR	Q99707	515
MAT2B	AHCYL1	O43865	502
MAT2B	SARDH	Q9UL12	449
MAT2B	MTRR	Q9UBK8	446
MAT2B	BHMT2	Q9H2M3	431
MAT2B	SHMT1	P34896	422
MAT2B	PDRG1	Q9NUG6	410
MAT2B	MTHFR	P42898	409
MAT2B	GIMD1	P0DJR0	404
MAT2B	MTAP	Q13126	404

IntAct

Human interaction partners of MAT2B in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
KPNA3	physical association	0.720	6
MAT2A	physical association	0.680	5
KPNA4	physical association	0.560	3
PLA2G6	physical association	0.560	3
RABEP1	physical association	0.560	3
TEPSIN	physical association	0.560	3
TRIM27	physical association	0.560	3
HRH1	physical association	0.370	1
FN1	association	0.350	1
TOR1B	association	0.350	1

BioGRID (140 interactions; top human partners by supporting records): MAT2A (Two-hybrid; 12 records), MAT1A (Affinity Capture-MS; 3 records), BAG3 (Affinity Capture-MS; 2 records), G6PD (Co-fractionation; 2 records), KPNA3 (Two-hybrid; 2 records), STMN1 (Cross-Linking-MS (XL-MS); 2 records), AHCY (Co-fractionation), AIMP1 (Co-fractionation), AP1B1 (Co-fractionation), AP2A1 (Co-fractionation), AP2M1 (Co-fractionation), APP (Reconstituted Complex), ARHGAP21 (Affinity Capture-MS), ARHGAP25 (Affinity Capture-MS), ATG7 (Co-fractionation)

SIGNOR signaling

showing 3 of 4 signaling interactions:

A	Effect	B	Mechanism
MAT2B	up-regulates	Proliferation
MAT2B	down-regulates	Apoptosis
MAT2B	“up-regulates activity”	GIT1	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Methionine adenosyltransferase alpha1 beta-v1	2	MAT1A, MAT2B
GIT1-MAT2B complex	2	GIT1, MAT2B

Disease & clinical

Genetic variants

Variant evidence for MAT2B: 54 ClinVar records (0 pathogenic / likely pathogenic); 16 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 437):

Position(s)	Effect	Δscore	Sites
5:163513837	acceptor_gain	1.0000
5:163513840–163513841	acceptor_loss	1.0000	4
5:163513995–163513996	donor_loss	1.0000	4
5:163516507	acceptor_gain	1.0000
5:163516516–163516517	acceptor_loss	1.0000	3
5:163516712–163516713	donor_loss	1.0000	6
5:163517559–163517560	acceptor_loss	1.0000	5
5:163517675–163517676	donor_loss	1.0000	5
5:163518190–163518191	acceptor_gain	1.0000	2
5:163518191–163518192	acceptor_loss	1.0000	5

AlphaMissense

992 missense substitutions predicted likely pathogenic (of 2,205 scored), across 243 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M261	9	0.867	0.997
D137	8	0.984	0.996
F140	8	0.978	0.999
D226	8	0.978	0.993
D214	8	0.969	0.993
N113	8	0.963	0.997
F311	8	0.961	0.992
H92	8	0.958	0.994
S135	8	0.946	0.999
D100	8	0.935	0.985
F48	8	0.930	0.994
H249	8	0.919	0.995
F269	8	0.897	0.982
H275	8	0.825	0.940
R181	7	0.988	0.999
E167	7	0.986	0.996
W250	7	0.982	0.998
W53	7	0.979	0.997
R219	7	0.979	0.996
K163	7	0.978	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.18e-12
Rectum Adenocarcinoma (TCGA)	favorable	4.59e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000638

Disease associations

OMIM: gene MIM:605527 | disease phenotypes:

GWAS associations

16 associations:

Study	Trait	p-value
GCST007254_2	Broad depression or major depressive disorder (self-reported)	8e-16
GCST007576_283	Chronotype	6e-10
GCST006618_1	Uterine fibroid size (maximum dimension)	2e-9
GCST007326_31	Number of sexual partners	2e-9
GCST90000047_135	Age at first sexual intercourse	7e-9
GCST007325_193	General risk tolerance (MTAG)	1e-8
GCST001178_11	Plasma omega-3 polyunsaturated fatty acid level (eicosapentaenoic acid)	8e-8
GCST002689_1	Very long-chain saturated fatty acid levels (fatty acid 24:0)	9e-7
GCST001599_1	Aging	1e-6
GCST002337_33	Amyotrophic lateral sclerosis (sporadic)	2e-6
GCST002396_23	Smoking initiation	2e-6
GCST004136_8	Methadone dose in opioid dependence	4e-6
GCST003963_2	Possible neuropathic pain in post total joint replacement surgery for osteoarthritis	5e-6
GCST005183_6	Common carotid intima-media thickness	5e-6
GCST002688_5	Very long-chain saturated fatty acid levels (fatty acid 22:0)	6e-6
GCST008829_8	Neuritic plaque	6e-6

EFO canonical traits (from GWAS)

11 canonical traits:

EFO ID	Trait name
EFO:0007760	eicosapentaenoic acid measurement
EFO:0022597	aging
EFO:0005670	smoking initiation
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0005762	neuropathic pain
EFO:0007907	methadone dose measurement
EFO:0009410	uterine fibroid measurement
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0006798	neuritic plaque measurement
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067225 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.28	Kd	52.64	nM	CHEMBL5653589
7.04	ED50	90.29	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148723: Binding affinity to human MAT2B incubated for 45 mins by Kinobead based pull down assay	kd	0.0526	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	increases stability, decreases reaction, increases expression, affects binding, affects cotreatment (+1 more)	2
Air Pollutants	increases oxidation, affects expression, affects cotreatment, increases abundance	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
dicrotophos	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
uranyl acetate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	increases abundance, increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651765	Binding	Binding affinity to human MAT2B incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3AU	Abcam HEK293T MAT2B KO	Transformed cell line	Female
CVCL_SX30	HAP1 MAT2B (-) 1	Cancer cell line	Male
CVCL_SX31	HAP1 MAT2B (-) 2	Cancer cell line	Male
CVCL_SX32	HAP1 MAT2B (-) 3	Cancer cell line	Male
CVCL_SX33	HAP1 MAT2B (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MAT2B across ~30M SureChEMBL compounds — explore on Sugi Predict.