MARCKSL1

Summary

MARCKSL1 (MARCKS like 1, HGNC:7142) is a protein-coding gene on chromosome 1p35.1, encoding MARCKS-related protein (P49006). Controls cell movement by regulating actin cytoskeleton homeostasis and filopodium and lamellipodium formation.

This gene encodes a member of the myristoylated alanine-rich C-kinase substrate (MARCKS) family. Members of this family play a role in cytoskeletal regulation, protein kinase C signaling and calmodulin signaling. The encoded protein affects the formation of adherens junction. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are located on the long arm of chromosomes 6 and 10.

Source: NCBI Gene 65108 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_023009

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7142
Approved symbol	MARCKSL1
Name	MARCKS like 1
Location	1p35.1
Locus type	gene with protein product
Status	Approved
Aliases	F52, MacMARCKS, MLP1
Ensembl gene	ENSG00000175130
Ensembl biotype	protein_coding
OMIM	602940
Entrez	65108

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000329421, ENST00000853128, ENST00000932579

RefSeq mRNA: 1 — MANE Select: NM_023009 NM_023009

CCDS: CCDS361

Canonical transcript exons

ENST00000329421 — 2 exons

Exon	Start	End
ENSE00001306260	32335947	32336233
ENSE00001460793	32333839	32335097

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 176.0840 / max 2689.5218, expressed in 1805 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11537	176.0840	1805

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	99.82	gold quality
cortical plate	UBERON:0005343	99.78	gold quality
ganglionic eminence	UBERON:0004023	99.72	gold quality
spinal cord	UBERON:0002240	99.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.67	gold quality
superior vestibular nucleus	UBERON:0007227	99.64	gold quality
embryo	UBERON:0000922	99.63	gold quality
middle frontal gyrus	UBERON:0002702	99.61	gold quality
pons	UBERON:0000988	99.60	gold quality
medulla oblongata	UBERON:0001896	99.60	gold quality
subthalamic nucleus	UBERON:0001906	99.60	gold quality
ventricular zone	UBERON:0003053	99.57	gold quality
ventral tegmental area	UBERON:0002691	99.54	gold quality
olfactory bulb	UBERON:0002264	99.48	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.46	gold quality
inferior olivary complex	UBERON:0002127	99.35	gold quality
midbrain	UBERON:0001891	99.30	gold quality
substantia nigra	UBERON:0002038	99.26	gold quality
amygdala	UBERON:0001876	99.16	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.16	gold quality
lateral globus pallidus	UBERON:0002476	99.15	gold quality
hypothalamus	UBERON:0001898	99.08	gold quality
globus pallidus	UBERON:0001875	99.05	gold quality
right ovary	UBERON:0002118	99.03	gold quality
medial globus pallidus	UBERON:0002477	98.97	gold quality
corpus epididymis	UBERON:0004359	98.89	gold quality
paraflocculus	UBERON:0005351	98.85	gold quality
left ovary	UBERON:0002119	98.75	gold quality
putamen	UBERON:0001874	98.72	gold quality
substantia nigra pars compacta	UBERON:0001965	98.72	gold quality

Single-cell (SCXA)

Detected in 36 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	2701.99
E-MTAB-8207	yes	2495.06
E-MTAB-6701	yes	2463.29
E-MTAB-7407	yes	2367.20
E-GEOD-139324	yes	1653.01
E-HCAD-10	yes	1376.22
E-CURD-46	yes	1327.56
E-MTAB-6653	yes	1303.96
E-GEOD-125970	yes	1003.37
E-GEOD-180759	yes	721.77
E-CURD-114	yes	563.58
E-MTAB-10553	yes	59.22
E-HCAD-6	yes	53.07
E-GEOD-134144	yes	52.59
E-MTAB-8410	yes	44.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

139 targeting MARCKSL1, 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-340-5P	100.00	72.50	4437
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631
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-450B-5P	99.92	71.48	3175

Literature-anchored findings (GeneRIF, showing 11)

• Gene knockdown in prostate cancer cells or in neurons reveals a critical role for MARCKSL1 in migration that is dependent on the phosphorylation state. (PMID:22751924)
• Patients with high expression of PPH3 and high MARCKSL1 protein had a lower survival rate versus patients with low MARCKSL1 and high PPH3 expression. (PMID:22772381)
• MARCKSL1 suppresses LOXL2-induced oncogenesis. (PMID:24863880)
• MARCKSL1 showed potent anti-angiogenic activity and reduced the levels of VEGF and HIF-1alpha expression. MARCKSL1 decreased VEGFinduced phosphorylation of the PI3K/Akt signaling pathway components. (PMID:26555156)
• Validation study of MARCKSL1 as a prognostic factor in lymph node-negative breast cancer patients. (PMID:30856208)
• Direct Reprogramming of Human Neurons Identifies MARCKSL1 as a Pathogenic Mediator of Valproic Acid-Induced Teratogenicity. (PMID:31155484)
• METTL14-Mediated miR-30c-1-3p Maturation Represses the Progression of Lung Cancer via Regulation of MARCKSL1 Expression. (PMID:34586620)
• MARCKSL1-2 reverses docetaxel-resistance of lung adenocarcinoma cells by recruiting SUZ12 to suppress HDAC1 and elevate miR-200b. (PMID:35864549)
• MARCKSL1 interacted with F-actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia. (PMID:35894387)
• IncRNA TYMSOS Promotes Epithelial-Mesenchymal Transition and Metastasis in Thyroid Carcinoma through Regulating MARCKSL1 and Activating the PI3K/Akt Signaling Pathway. (PMID:36374807)
• Circulating extracellular vesicle-derived MARCKSL1 is a potential diagnostic non-invasive biomarker in metastatic colorectal cancer patients. (PMID:37340044)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Marcksl1	ENSMUSG00000047945
rattus_norvegicus	Marcksl1	ENSRNOG00000009113
rattus_norvegicus	LOC103689966	ENSRNOG00000066033

Paralogs (1): MARCKS (ENSG00000277443)

Protein

Protein identifiers

MARCKS-related protein — P49006 (reviewed: P49006)

Alternative names: MARCKS-like protein 1, Macrophage myristoylated alanine-rich C kinase substrate

All UniProt accessions (1): P49006

UniProt curated annotations — full annotation on UniProt →

Function. Controls cell movement by regulating actin cytoskeleton homeostasis and filopodium and lamellipodium formation. When unphosphorylated, induces cell migration. When phosphorylated by MAPK8, induces actin bundles formation and stabilization, thereby reducing actin plasticity, hence restricting cell movement, including neuronal migration. May be involved in coupling the protein kinase C and calmodulin signal transduction systems.

Subunit / interactions. Binds to filamentous actin (F-actin), but not to monomeric G-actin, independently of its phosphorylation status.

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane.

Post-translational modifications. Phosphorylated. Phosphorylation at Ser-120 and Thr-178 is non-redundantly catalyzed by MAPK8 in vivo. Phosphorylation at Thr-148 is preferentially catalyzed by MAPK8 in vivo, but this modification can also be catalyzed by other kinases in the absence of MAPK8. May be phosphorylated by protein kinase C, which disrupts the interaction with calmodulin.

Similarity. Belongs to the MARCKS family.

RefSeq proteins (1): NP_075385* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002101	MARCKS	Family

Pfam: PF02063

UniProt features (30 total): modified residue 19, compositionally biased region 5, region of interest 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49006-F1	55.65	0.00

Functional residue map

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

Post-translational modifications (20): 22, 36, 41, 48, 71, 85, 93, 101, 104, 119, 120, 135, 148, 151, 162, 165, 178, 187, 2, 14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 411 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, AHRARNT_01, FREAC2_01, SP3_Q3, AREB6_03, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, TGACCTY_ERR1_Q2, FOXO4_01, AP2_Q3, GGGTGGRR_PAX4_03

GO Biological Process (4): actin filament organization (GO:0007015), central nervous system development (GO:0007417), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284)

GO Molecular Function (4): calmodulin binding (GO:0005516), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
actin cytoskeleton organization	1
supramolecular fiber organization	1
nervous system development	1
system development	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
protein binding	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
binding	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MARCKSL1	CALML6	Q8TD86	962
MARCKSL1	CALML3	P27482	962
MARCKSL1	CALML4	Q96GE6	962
MARCKSL1	CALML5	Q9NZT1	962
MARCKSL1	CALM1	P02593	940
MARCKSL1	LCK	P06239	585
MARCKSL1	NXF1	Q9UBU9	584
MARCKSL1	NAB2	Q15742	545
MARCKSL1	ABCC3	O15438	542
MARCKSL1	BASP1	P80723	538
MARCKSL1	GAP43	P17677	532
MARCKSL1	GP2	P55259	489
MARCKSL1	NUP35	Q8NFH5	488
MARCKSL1	ADD3	Q9UEY8	463
MARCKSL1	ADD1	P35611	451

IntAct

69 interactions, top by confidence:

A	B	Type	Score
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LOXL2	MARCKSL1	psi-mi:“MI:0915”(physical association)	0.580
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
MARCKSL1	NMT2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
	AP3D1	psi-mi:“MI:0914”(association)	0.460
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
PAX6	EPB41L2	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
SPHK1	TAF4	psi-mi:“MI:0914”(association)	0.350
SPHK1	MYO1C	psi-mi:“MI:0914”(association)	0.350
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
MAPT	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (200): BRCA1 (Two-hybrid), MARCKSL1 (Affinity Capture-MS), MARCKSL1 (Affinity Capture-MS), MARCKSL1 (Proximity Label-MS), MARCKSL1 (Proximity Label-MS), MARCKSL1 (Affinity Capture-MS), SNX21 (Affinity Capture-MS), RBP4 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), RMI1 (Affinity Capture-MS), BCCIP (Affinity Capture-MS), NMT1 (Affinity Capture-MS), SMEK1 (Affinity Capture-MS), TOP3A (Affinity Capture-MS), SCRN2 (Affinity Capture-MS)

ESM2 similar proteins: P02313, P02314, P02316, P05114, P05204, P06836, P06837, P07936, P09602, P12274, P12624, P16527, P17677, P17691, P23614, P26645, P27123, P28667, P29966, P30009, P35001, P35566, P43393, P49006, P49321, P55860, P80272, P80723, P80724, Q02952, Q05175, Q0VBZ9, Q1RM09, Q2T9P4, Q39967, Q3ZBV4, Q5IS67, Q5NVP7, Q5R4H5, Q5RAA0

Diamond homologs: P12624, P16527, P26645, P29966, P30009, P49006, P28667, P35566, Q0VBZ9, Q6PD99, Q9EPH2, Q6NWH2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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:

Pathway	Partners	Fold	FDR
VEGFR2 mediated cell proliferation	5	50.1×	4e-06
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	45.5×	6e-06
Downstream signal transduction	6	40.1×	1e-06
Signaling by FGFR1 in disease	5	25.7×	5e-05
Signaling by SCF-KIT	5	21.8×	9e-05
Signaling by VEGF	5	19.3×	1e-04
Signaling by BRAF and RAF1 fusions	6	17.9×	4e-05
VEGFA-VEGFR2 Pathway	6	14.7×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

264 predictions. Top by Δscore:

Variant	Effect	Δscore
1:32335943:CCAC:C	donor_loss	1.0000
1:32335945:A:T	donor_loss	1.0000
1:32335946:C:A	donor_loss	1.0000
1:32335093:TTCTC:T	acceptor_gain	0.9900
1:32335095:CTC:C	acceptor_gain	0.9900
1:32335098:C:CC	acceptor_gain	0.9900
1:32335099:T:G	acceptor_loss	0.9900
1:32335942:CCCA:C	donor_gain	0.9900
1:32335096:TC:T	acceptor_gain	0.9800
1:32335097:CC:C	acceptor_gain	0.9800
1:32335945:A:AC	donor_gain	0.9800
1:32335946:C:CC	donor_gain	0.9800
1:32335946:CCTGG:C	donor_gain	0.9800
1:32335941:AC:A	donor_gain	0.9600
1:32335942:CC:C	donor_gain	0.9600
1:32335101:C:CT	acceptor_gain	0.9400
1:32335575:C:CT	donor_gain	0.9400
1:32335576:C:CT	donor_gain	0.9300
1:32335106:C:CT	acceptor_gain	0.9200
1:32335253:C:A	donor_gain	0.9200
1:32335364:T:TA	donor_gain	0.9100
1:32335107:A:T	acceptor_gain	0.9000
1:32335550:C:CA	donor_gain	0.9000
1:32335102:A:T	acceptor_gain	0.8800
1:32335252:T:TA	donor_gain	0.8800
1:32335196:TGC:T	donor_gain	0.8700
1:32335359:T:A	donor_gain	0.8700
1:32335943:CCACC:C	donor_gain	0.8700
1:32335094:TCTC:T	acceptor_gain	0.8600
1:32335095:CTCC:C	acceptor_gain	0.8600

AlphaMissense

1265 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:32334900:C:A	K95N	0.999
1:32334900:C:G	K95N	0.999
1:32334902:T:C	K95E	0.999
1:32334904:A:G	F94S	0.998
1:32334910:A:G	F92S	0.998
1:32334886:A:G	L100S	0.997
1:32334890:T:C	K99E	0.997
1:32334867:C:A	K106N	0.996
1:32334867:C:G	K106N	0.996
1:32334871:A:G	F105S	0.996
1:32334909:G:C	F92L	0.996
1:32334909:G:T	F92L	0.996
1:32334910:A:C	F92C	0.996
1:32334911:A:G	F92L	0.996
1:32334899:T:C	K96E	0.995
1:32334904:A:C	F94C	0.994
1:32334869:T:C	K106E	0.993
1:32334871:A:C	F105C	0.993
1:32334914:T:C	K91E	0.993
1:32334915:C:A	K90N	0.993
1:32334915:C:G	K90N	0.993
1:32334864:T:A	R107S	0.992
1:32334864:T:G	R107S	0.992
1:32335092:A:C	N31K	0.992
1:32335092:A:T	N31K	0.992
1:32334901:T:G	K95T	0.991
1:32334901:T:A	K95M	0.990
1:32335090:C:T	G32D	0.989
1:32334891:G:C	F98L	0.988
1:32334891:G:T	F98L	0.988

dbSNP variants (sampled 300 via entrez): RS1000340570 (1:32334347 C>T), RS1000801599 (1:32335335 A>C), RS1001028949 (1:32336374 G>A,C,T), RS1001346509 (1:32335746 C>G), RS1001500748 (1:32336237 C>A,G,T), RS1003868053 (1:32336210 C>A,T), RS1003907231 (1:32333950 A>G), RS1004342845 (1:32335938 C>G,T), RS1004657859 (1:32337898 G>C), RS1004736171 (1:32338074 C>T), RS1005611106 (1:32337187 C>G), RS1005951843 (1:32337483 C>A,T), RS1006659598 (1:32335329 G>A), RS1006882370 (1:32337361 C>G), RS1007226119 (1:32336190 C>A,T)

Disease associations

OMIM: gene MIM:602940 | 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, affects expression, decreases expression, increases expression	5
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
Cyclosporine	decreases expression	3
bisphenol F	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tunicamycin	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
glycidyl methacrylate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1

Clinical trials (associated diseases)

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