MYL12B

gene
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Also known as MRLC2

Summary

MYL12B (myosin light chain 12B, HGNC:29827) is a protein-coding gene on chromosome 18p11.31, encoding Myosin regulatory light chain 12B (O14950). Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation.

The activity of nonmuscle myosin II (see MYH9; MIM 160775) is regulated by phosphorylation of a regulatory light chain, such as MRLC2. This phosphorylation results in higher MgATPase activity and the assembly of myosin II filaments (Iwasaki et al., 2001 [PubMed 11942626]).

Source: NCBI Gene 103910 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 10 total
  • Druggable target: yes
  • MANE Select transcript: NM_033546

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:29827
Approved symbolMYL12B
Namemyosin light chain 12B
Location18p11.31
Locus typegene with protein product
StatusApproved
AliasesMRLC2
Ensembl geneENSG00000118680
Ensembl biotypeprotein_coding
OMIM609211
Entrez103910

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000237500, ENST00000400175, ENST00000581193, ENST00000584539, ENST00000648965, ENST00000874764, ENST00000874765, ENST00000874766, ENST00000918456, ENST00000918457, ENST00000965090

RefSeq mRNA: 3 — MANE Select: NM_033546 NM_001144944, NM_001144945, NM_033546

CCDS: CCDS11831

Canonical transcript exons

ENST00000237500 — 4 exons

ExonStartEnd
ENSE0000080018432728843273082
ENSE0000120779832621333262237
ENSE0000174912232772533277414
ENSE0000390083332777653278461

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 329.0447 / max 3722.8457, expressed in 1827 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter IDTPM avgSamples expressed
169156164.42001825
169155163.85911825
1691580.2073108
1691540.198979
1691590.145580
1691600.125645
1691570.088337

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
gingival epitheliumUBERON:000194999.69gold quality
pancreatic ductal cellCL:000207999.66gold quality
colonic mucosaUBERON:000031799.65gold quality
gingivaUBERON:000182899.64gold quality
mucosa of sigmoid colonUBERON:000499399.61gold quality
metanephros cortexUBERON:001053399.61gold quality
esophagus squamous epitheliumUBERON:000692099.59gold quality
right lungUBERON:000216799.57gold quality
jejunal mucosaUBERON:000039999.55gold quality
renal medullaUBERON:000036299.53gold quality
mucosa of transverse colonUBERON:000499199.52gold quality
squamous epitheliumUBERON:000691499.51gold quality
epithelium of esophagusUBERON:000197699.49gold quality
islet of LangerhansUBERON:000000699.48gold quality
mammalian vulvaUBERON:000099799.48gold quality
right adrenal glandUBERON:000123399.48gold quality
amniotic fluidUBERON:000017399.47gold quality
left adrenal glandUBERON:000123499.47gold quality
mammary ductUBERON:000176599.47gold quality
rectumUBERON:000105299.46gold quality
left lobe of thyroid glandUBERON:000112099.46gold quality
adrenal cortexUBERON:000123599.46gold quality
right adrenal gland cortexUBERON:003582799.46gold quality
palpebral conjunctivaUBERON:000181299.45gold quality
placentaUBERON:000198799.45gold quality
nasal cavity epitheliumUBERON:000538499.45gold quality
upper lobe of left lungUBERON:000895299.45gold quality
left adrenal gland cortexUBERON:003582599.45gold quality
right lobe of thyroid glandUBERON:000111999.43gold quality
upper lobe of lungUBERON:000894899.43gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 12.

ExperimentMarker?Max mean expression
E-MTAB-5061yes2020.50
E-CURD-122yes45.12
E-HCAD-11yes39.96
E-MTAB-6701yes36.95
E-GEOD-81547yes24.50
E-HCAD-1yes16.90
E-HCAD-9yes15.16
E-MTAB-8410yes15.09
E-MTAB-10042yes8.40
E-ENAD-27yes6.37
E-GEOD-130148yes6.03
E-MTAB-8495no3070.66
E-GEOD-81383no1781.44
E-CURD-46no10.98
E-MTAB-9388no6.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting MYL12B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-190A-3P100.0080.355520
HSA-MIR-302E99.9670.742669
HSA-MIR-23C99.9573.923192
HSA-MIR-23A-3P99.9574.243163
HSA-MIR-23B-3P99.9574.243163
HSA-MIR-314399.9371.963104
HSA-MIR-145-5P99.9271.131836
HSA-MIR-5195-3P99.9270.921877
HSA-MIR-153-5P99.8973.866317
HSA-MIR-990299.8969.152250
HSA-MIR-444799.8567.812900
HSA-MIR-3180-5P99.8269.122422
HSA-MIR-378G99.7164.901106
HSA-MIR-425199.4069.193363
HSA-MIR-612899.3367.831581
HSA-MIR-499A-3P99.1869.201392
HSA-MIR-499B-3P99.1869.271391
HSA-MIR-62298.9966.481050
HSA-MIR-548AO-5P98.5569.571362
HSA-MIR-548AX98.5569.581362
HSA-MIR-6804-5P98.3965.771084
HSA-MIR-6730-5P98.0368.121299
HSA-MIR-392097.7569.021168
HSA-MIR-495-5P97.6268.28682
HSA-MIR-937-5P97.4368.39667
HSA-MIR-6729-3P96.9166.79703
HSA-MIR-570296.6868.21958
HSA-MIR-808196.4267.75738
HSA-MIR-5586-5P96.2968.02685

Literature-anchored findings (GeneRIF, showing 5)

  • These results suggest that EGCG inhibits the cell growth by reducing the MRLC phosphorylation and this effect is mediated by the 67LR. (PMID:15946647)
  • Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
  • The study data show that manipulation of the activation sites (Thr18/Ser19) significantly alters myosin II function in a number of these assays while manipulation of the putative inhibitory sites (Ser1/Ser2/Thr9) does not. (PMID:22136066)
  • These results suggest that 2P-MRLC has a role different from that of 1P-MRLC at the midzone, and is not a subunit of myosin II. (PMID:22166199)
  • phosphorylated MRLC temporally controls its own accumulation, but not that of actin, in cultured mammalian cells. (PMID:22374324)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriomyl12.2ENSDARG00000025326
mus_musculusMyl12bENSMUSG00000034868
rattus_norvegicusMyl12bENSRNOG00000091388
caenorhabditis_elegansWBGENE00003369
caenorhabditis_elegansWBGENE00003370

Paralogs (7): MYL9 (ENSG00000101335), MYL12A (ENSG00000101608), MYL10 (ENSG00000106436), MYL7 (ENSG00000106631), MYL2 (ENSG00000111245), MYL11 (ENSG00000180209), MYL5 (ENSG00000215375)

Protein

Protein identifiers

Myosin regulatory light chain 12BO14950 (reviewed: O14950)

Alternative names: MLC-2A, Myosin regulatory light chain 2-B, smooth muscle isoform, Myosin regulatory light chain 20 kDa, Myosin regulatory light chain MRLC2, SHUJUN-1

All UniProt accessions (1): O14950

UniProt curated annotations — full annotation on UniProt →

Function. Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation. Phosphorylation triggers actin polymerization in vascular smooth muscle. Implicated in cytokinesis, receptor capping, and cell locomotion.

Subunit / interactions. Myosin is a hexamer of 2 heavy chains and 4 light chains: interacts with myosin heavy chain MYO19.

Tissue specificity. Ubiquitously expressed in various hematopoietic cells.

Post-translational modifications. Phosphorylation increases the actin-activated myosin ATPase activity and thereby regulates the contractile activity. It is required to generate the driving force in the migration of the cells but not necessary for localization of myosin-2 at the leading edge. Phosphorylation is reduced following epigallocatechin-3-O-gallate treatment.

Miscellaneous. This chain binds calcium.

RefSeq proteins (3): NP_001138416, NP_001138417, NP_291024* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR002048EF_hand_domDomain
IPR011992EF-hand-dom_pairHomologous_superfamily
IPR015070EF_hand_DJBPDomain
IPR018247EF_Hand_1_Ca_BSBinding_site
IPR050403Myosin_RLCFamily

Pfam: PF08976, PF13499

UniProt features (19 total): sequence conflict 4, binding site 4, domain 3, modified residue 2, mutagenesis site 2, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O14950-F183.780.60

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 (4): 42; 44; 46; 53

Post-translational modifications (2): 19, 20

Mutagenesis-validated functional residues (2):

PositionPhenotype
19–20shows a decrease in the number of actin filament bundles.
19–20shows a larger number of actin filament bundles.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

IDPathway
R-HSA-3928663EPHA-mediated growth cone collapse
R-HSA-416572Sema4D induced cell migration and growth-cone collapse
R-HSA-445355Smooth Muscle Contraction
R-HSA-5625740RHO GTPases activate PKNs
R-HSA-5625900RHO GTPases activate CIT
R-HSA-5627117RHO GTPases Activate ROCKs
R-HSA-5627123RHO GTPases activate PAKs
R-HSA-1266738Developmental Biology
R-HSA-162582Signal Transduction
R-HSA-194315Signaling by Rho GTPases
R-HSA-195258RHO GTPase Effectors
R-HSA-2682334EPH-Ephrin signaling
R-HSA-373755Semaphorin interactions
R-HSA-397014Muscle contraction
R-HSA-400685Sema4D in semaphorin signaling
R-HSA-422475Axon guidance
R-HSA-9675108Nervous system development
R-HSA-9716542Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 200 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, MODULE_151, MORI_IMMATURE_B_LYMPHOCYTE_UP, KEGG_TIGHT_JUNCTION, RIZKI_TUMOR_INVASIVENESS_3D_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, REACTOME_SMOOTH_MUSCLE_CONTRACTION, LAIHO_COLORECTAL_CANCER_SERRATED_UP, MODULE_114, GOBP_REGULATION_OF_CELL_SHAPE, GOCC_I_BAND, GOCC_APICAL_PART_OF_CELL, GOCC_ACTIN_FILAMENT_BUNDLE

GO Biological Process (1): regulation of cell shape (GO:0008360)

GO Molecular Function (4): calcium ion binding (GO:0005509), myosin heavy chain binding (GO:0032036), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): stress fiber (GO:0001725), cytoplasm (GO:0005737), cytosol (GO:0005829), brush border (GO:0005903), cell cortex (GO:0005938), myosin II complex (GO:0016460), myofibril (GO:0030016), Z disc (GO:0030018), extracellular exosome (GO:0070062), myosin complex (GO:0016459), protein-containing complex (GO:0032991), apical part of cell (GO:0045177)

Reactome top-level categories

Rollup of top-11 pathways:

CategoryPathways
RHO GTPase Effectors4
Axon guidance2
EPH-Ephrin signaling1
Sema4D in semaphorin signaling1
Muscle contraction1
Signaling by Rho GTPases, Miro GTPases and RHOBTB31
Signaling by Rho GTPases1
Semaphorin interactions1
Nervous system development1
Developmental Biology1
Signal Transduction1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
cytoplasm2
regulation of cell morphogenesis1
regulation of biological quality1
metal ion binding1
myosin binding1
binding1
cation binding1
actomyosin1
contractile actin filament bundle1
intracellular anatomical structure1
microvillus1
apical part of cell1
cluster of actin-based cell projections1
cell periphery1
myosin complex1
contractile muscle fiber1
I band1
extracellular vesicle1
actin cytoskeleton1
protein-containing complex1
cellular_component1

Protein interactions and networks

STRING

2724 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MYL12BCNPY2Q9Y2B0827
MYL12BMYH9P35579809
MYL12BMYOD1P15172774
MYL12BPPP1R12AO14974756
MYL12BMYLIPQ8WY64684
MYL12BRHOAP06749671
MYL12BMYLK3Q32MK0657
MYL12BPPP1R14AQ96A00639
MYL12BMYL6P16475595
MYL12BROCK1Q13464568
MYL12BMYH7P12883567
MYL12BPPP1R12CQ9BZL4536
MYL12BROCK2O75116530
MYL12BXPR1Q9UBH6497
MYL12BMYBPC2Q14324495

IntAct

98 interactions, top by confidence:

ABTypeScore
CFTRESYT2psi-mi:“MI:0914”(association)0.710
MYH9MYL12Bpsi-mi:“MI:0914”(association)0.640
MYL12BNSMFpsi-mi:“MI:0915”(physical association)0.560
MYL12BMYH11psi-mi:“MI:0915”(physical association)0.560
ACTBMYL12Bpsi-mi:“MI:0915”(physical association)0.540
MYL12BACTBpsi-mi:“MI:0914”(association)0.540
ACTBMYL12Bpsi-mi:“MI:0403”(colocalization)0.540
MYO19MYL12Bpsi-mi:“MI:0914”(association)0.530
VCAM1PSMD11psi-mi:“MI:0914”(association)0.530
UBE3BMYL12Bpsi-mi:“MI:0915”(physical association)0.500
CFTRPLEKHG3psi-mi:“MI:0914”(association)0.480
MYL12Bpsi-mi:“MI:0914”(association)0.460
MYL12BDAPK3psi-mi:“MI:0217”(phosphorylation reaction)0.440
MYL12BACTA2psi-mi:“MI:0403”(colocalization)0.430
GNAT3psi-mi:“MI:0915”(physical association)0.400
MYL12BHSPB1psi-mi:“MI:0915”(physical association)0.370
FOXD3MYL12Bpsi-mi:“MI:0914”(association)0.350
FOXP1MYL12Bpsi-mi:“MI:0914”(association)0.350
Prkaa1MYL12Bpsi-mi:“MI:0914”(association)0.350
Prkab1MYL12Bpsi-mi:“MI:0914”(association)0.350
PLEKHA7PLEKHG3psi-mi:“MI:0914”(association)0.350
OCRLMYO1Cpsi-mi:“MI:0914”(association)0.350

BioGRID (173): MYL12B (Affinity Capture-MS), MYL12B (Two-hybrid), MYL12B (Affinity Capture-MS), MYL12B (Affinity Capture-MS), MYL12B (Affinity Capture-MS), MYL12B (Affinity Capture-MS), MYL12B (Affinity Capture-MS), PA2G4 (Affinity Capture-MS), TRAP1 (Affinity Capture-MS), SND1 (Affinity Capture-MS), CPSF6 (Affinity Capture-MS), UBE2N (Affinity Capture-MS), MYL12B (Affinity Capture-MS), MYL12B (Affinity Capture-MS), MYL12B (Affinity Capture-MS)

ESM2 similar proteins: A0A125YHX7, A0A125YZN2, A4IF97, J9W034, O14950, O23184, O74435, O82659, P02612, P08733, P13832, P15845, P18666, P19105, P24032, P24844, P29269, P40423, P41208, P41209, P41210, P41691, P48593, P53441, Q09510, Q0IQB6, Q0IUU4, Q12798, Q24956, Q27177, Q27178, Q27179, Q2TBN3, Q32LE3, Q338P8, Q39584, Q3SEK0, Q3SEK2, Q3THE2, Q40642

Diamond homologs: A2WN93, A2WNH1, A2Y609, A3E3H0, A3E4D8, A3E4F9, A4IF97, A4UHC0, A8CEP3, A8I1Q0, B7SNI3, F1SSF9, O14950, O93409, O94739, P02597, P02598, P02608, P02609, P02610, P02611, P02612, P02613, P04112, P04113, P04353, P04464, P04466, P05419, P05944, P05963, P07461, P08051, P08052, P08733, P0DH95, P0DH96, P10916, P11120, P13543

SIGNOR signaling

10 interactions.

AEffectBMechanism
ILK“up-regulates activity”MYL12Bphosphorylation
MAP3K12up-regulatesMYL12Bphosphorylation
DAPK3up-regulatesMYL12Bphosphorylation
ROCK2“up-regulates activity”MYL12Bphosphorylation
PAK1“up-regulates activity”MYL12Bphosphorylation
ROCK1up-regulatesMYL12Bphosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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.

Reactome pathways:

PathwayPartnersFoldFDR
Oncogenic MAPK signaling520.0×1e-03
Signaling by BRAF and RAF1 fusions616.5×9e-04
Activation of STAT3 by cadherin engagement513.2×5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance5
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

564 predictions. Top by Δscore:

VariantEffectΔscore
18:3262139:G:GTdonor_gain1.0000
18:3272877:A:AGacceptor_gain1.0000
18:3272878:A:Gacceptor_gain1.0000
18:3272879:TCCAG:Tacceptor_loss1.0000
18:3272882:A:ACacceptor_loss1.0000
18:3272882:A:AGacceptor_gain1.0000
18:3272883:G:GGacceptor_gain1.0000
18:3272883:GA:Gacceptor_gain1.0000
18:3272883:GAA:Gacceptor_gain1.0000
18:3272883:GAAT:Gacceptor_gain1.0000
18:3272883:GAATT:Gacceptor_gain1.0000
18:3273052:G:Tdonor_gain1.0000
18:3273052:GAAGA:Gdonor_gain1.0000
18:3273053:A:Tdonor_gain1.0000
18:3273065:A:Gdonor_gain1.0000
18:3277244:T:Gacceptor_gain1.0000
18:3277249:ACAG:Aacceptor_gain1.0000
18:3277250:C:Gacceptor_gain1.0000
18:3277250:CA:Cacceptor_loss1.0000
18:3277251:A:AGacceptor_gain1.0000
18:3277251:A:ATacceptor_loss1.0000
18:3277251:AG:Aacceptor_gain1.0000
18:3277251:AGG:Aacceptor_gain1.0000
18:3277252:G:GCacceptor_gain1.0000
18:3277252:GG:Gacceptor_gain1.0000
18:3277252:GGG:Gacceptor_gain1.0000
18:3277252:GGGA:Gacceptor_gain1.0000
18:3277252:GGGAA:Gacceptor_gain1.0000
18:3277410:AACAG:Adonor_gain1.0000
18:3277411:ACAG:Adonor_gain1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000145143 (18:3275045 C>T), RS1000271933 (18:3263728 TCTTC>T), RS1000451010 (18:3269261 G>T), RS1000699477 (18:3273798 G>A,T), RS1000737064 (18:3269472 A>G), RS1000897054 (18:3274828 T>C), RS1001017278 (18:3267263 T>G), RS1001191559 (18:3270527 C>G), RS1001219292 (18:3262263 G>C), RS1001319257 (18:3270800 A>T), RS1001343964 (18:3268155 A>G), RS1001471215 (18:3267471 A>G), RS1001795086 (18:3268466 A>T), RS1002133871 (18:3264471 A>G), RS1002233309 (18:3260787 C>T)

Disease associations

OMIM: gene MIM:609211 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST002408_15Response to methotrexate in juvenile idiopathic arthritis5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295652 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
bisphenol Aaffects expression, decreases expression, increases expression4
Valproic Acidincreases expression, decreases methylation3
sodium arsenitedecreases expression, increases expression2
Estradiolaffects cotreatment, decreases expression2
Phenylmercuric Acetateincreases expression, affects cotreatment2
Dronabinoldecreases expression, increases expression2
Tobacco Smoke Pollutionaffects expression, increases expression2
aristolochic acid Idecreases expression1
moringinaffects cotreatment, increases expression1
dicrotophosdecreases expression1
2,4,6-tribromophenoldecreases expression1
triphenyl phosphateaffects expression1
decabromobiphenyl etherdecreases expression1
tetrabromobisphenol Adecreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
ICG 001increases expression1
2,2’,4,4’-tetrabromodiphenyl etherdecreases expression1
dorsomorphinaffects cotreatment, increases expression1
pentabrominated diphenyl ether 100decreases expression1
hexabrominated diphenyl ether 153decreases expression1
bisphenol AFincreases expression1
Resveratrolaffects cotreatment, decreases expression1
Acetaminophendecreases expression1
Cannabidiolaffects cotreatment, increases expression1
Dichlorodiphenyl Dichloroethyleneincreases expression1
Bucladesineaffects cotreatment, decreases expression1
Diethylhexyl Phthalateincreases expression1
Diurondecreases expression1
Doxorubicinincreases expression1
Methotrexateincreases expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4118949BindingBinding affinity to MYL12B in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assayStudies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): juvenile idiopathic arthritis