MEMO1

Summary

MEMO1 (mediator of cell motility 1, HGNC:14014) is a protein-coding gene on chromosome 2p22.3, encoding Protein MEMO1 (Q9Y316). May control cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton. It is a selective cancer dependency (DepMap: 28.6% of cell lines).

Involved in regulation of microtubule-based process. Located in cytosol and nucleus.

Source: NCBI Gene 51072 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 28.6% of screened cell lines
• MANE Select transcript: NM_001301833

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14014
Approved symbol	MEMO1
Name	mediator of cell motility 1
Location	2p22.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-27, MEMO
Ensembl gene	ENSG00000162959
Ensembl biotype	protein_coding
OMIM	611786
Entrez	51072

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000295065, ENST00000379383, ENST00000404530, ENST00000407893, ENST00000413686, ENST00000422936, ENST00000426310, ENST00000437854, ENST00000490459, ENST00000908848, ENST00000908849, ENST00000908850, ENST00000908851, ENST00000908852, ENST00000908853, ENST00000924200, ENST00000924201, ENST00000924202, ENST00000924203, ENST00000951230

RefSeq mRNA: 13 — MANE Select: NM_001301833 NM_001137602, NM_001301833, NM_001301852, NM_001371912, NM_001371913, NM_001371914, NM_001371916, NM_001371917, NM_001371918, NM_001371920, NM_001371921, NM_001385196, NM_015955

CCDS: CCDS1776, CCDS46255

Canonical transcript exons

ENST00000404530 — 10 exons

Exon	Start	End
ENSE00001552021	32010942	32011008
ENSE00001557439	31867823	31868492
ENSE00003502784	31869848	31869952
ENSE00003512411	31883386	31883462
ENSE00003695685	31920798	31920910
ENSE00003699602	31891992	31892134
ENSE00003699776	31917926	31918037
ENSE00003700565	31943302	31943383
ENSE00003701172	31932067	31932135
ENSE00003797752	32010187	32010264

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 96.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9090 / max 50.4187, expressed in 1726 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27700	2.4004	1239
27699	1.9792	1168
27701	1.0463	659
27698	0.3487	161
202149	0.1344	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.70	gold quality
right testis	UBERON:0004534	96.49	gold quality
testis	UBERON:0000473	95.75	gold quality
gastrocnemius	UBERON:0001388	95.46	gold quality
muscle of leg	UBERON:0001383	95.18	gold quality
monocyte	CL:0000576	94.92	gold quality
leukocyte	CL:0000738	94.71	gold quality
corpus callosum	UBERON:0002336	93.84	gold quality
cortical plate	UBERON:0005343	93.67	gold quality
ventricular zone	UBERON:0003053	93.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.16	gold quality
lymph node	UBERON:0000029	92.80	gold quality
esophagus mucosa	UBERON:0002469	92.79	gold quality
heart left ventricle	UBERON:0002084	92.41	gold quality
granulocyte	CL:0000094	92.38	gold quality
embryo	UBERON:0000922	92.25	gold quality
ganglionic eminence	UBERON:0004023	92.25	gold quality
right adrenal gland cortex	UBERON:0035827	91.87	gold quality
right adrenal gland	UBERON:0001233	91.69	gold quality
lower esophagus mucosa	UBERON:0035834	91.62	gold quality
islet of Langerhans	UBERON:0000006	91.58	gold quality
heart	UBERON:0000948	91.52	gold quality
left adrenal gland	UBERON:0001234	91.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.40	gold quality
vermiform appendix	UBERON:0001154	91.33	gold quality
left adrenal gland cortex	UBERON:0035825	91.25	gold quality
esophagus	UBERON:0001043	91.17	gold quality
apex of heart	UBERON:0002098	91.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.89	gold quality
spinal cord	UBERON:0002240	90.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	168.30
E-ANND-3	yes	5.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, ESR1

miRNA regulators (miRDB)

79 targeting MEMO1, 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-548AW	99.99	72.57	3559
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-454-3P	99.91	74.01	1925
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
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-153-5P	99.89	73.86	6317
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-8067	99.86	69.59	2260
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 15)

• data suggest that Memo controls cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton [Memo] (PMID:15156151)
• 2.1A crystal structure and homology to class III nonheme iron-dependent dioxygenases (PMID:18045866)
• Memo-RhoA-mDia1 signaling coordinates the organization of the lamellipodial actin network, adhesion site formation, and microtubule outgrowth within the cell leading edge to sustain cell motility. (PMID:18955552)
• Memo was detected in complexes with cofilin, ErbB2 and PLCgamma1. (PMID:19223396)
• MEMO1 is involved in breast carcinogenesis via regulating insulin-like growth factor-I receptor-dependent signaling events. (PMID:22824790)
• Mediator of ERBB2-driven cell motility (MEMO) promotes extranuclear estrogen receptor signaling involving the growth factor receptors IGF1R and ERBB2. (PMID:23861392)
• Biochemical assays revealed that Memo is a copper-dependent redox enzyme that promoted a more oxidized intracellular milieu and stimulated the production of reactive oxygen species (ROS) in cellular structures involved in migration. (PMID:24917593)
• Study identify Memo as an important key mediator between the heregulin and estrogen signaling pathways, which affects both breast cancer cell migration and proliferation. (PMID:27472465)
• HRG/HER2/HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer (PMID:27941874)
• Memo1 is a mediator of radial glial cell scaffold tiling, necessary to generate and organize neurons into functional ensembles in the developing cerebral cortex. (PMID:31277925)
• Finding MEMO-Emerging Evidence for MEMO1’s Function in Development and Disease. (PMID:33172038)
• miR-219a-1 inhibits colon cancer cells proliferation and invasion by targeting MEMO1. (PMID:33218285)
• Memo1 binds reduced copper ions, interacts with copper chaperone Atox1, and protects against copper-mediated redox activity in vitro. (PMID:36067318)
• WD repeat protein 54-mediator of ErbB2-driven cell motility 1 axis promotes bladder cancer tumorigenesis and metastasis and impairs chemosensitivity. (PMID:36627049)
• MEMO1 binds iron and modulates iron homeostasis in cancer cells. (PMID:38640016)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	memo1	ENSDARG00000010823
mus_musculus	Memo1	ENSMUSG00000058704
rattus_norvegicus	Memo1	ENSRNOG00000006340
drosophila_melanogaster	CG8031	FBGN0038110
caenorhabditis_elegans		WBGENE00016500

Protein

Protein identifiers

Protein MEMO1 — Q9Y316 (reviewed: Q9Y316)

Alternative names: C21orf19-like protein, Hepatitis C virus NS5A-transactivated protein 7, Mediator of ErbB2-driven cell motility 1

All UniProt accessions (3): B5MCI6, C9JSD7, Q9Y316

UniProt curated annotations — full annotation on UniProt →

Function. May control cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton. Mediator of ERBB2 signaling. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Is required for breast carcinoma cell migration.

Subunit / interactions. Interacts with ERBB2 phosphorylated on ‘Tyr-1248’.

Similarity. Belongs to the MEMO1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y316-1	1	yes
Q9Y316-2	2
Q9Y316-3	3

RefSeq proteins (13): NP_001131074, NP_001288762, NP_001288781, NP_001358841, NP_001358842, NP_001358843, NP_001358845, NP_001358846, NP_001358847, NP_001358849, NP_001358850, NP_001372125, NP_057039 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002737	MEMO1_fam	Family

Pfam: PF01875

UniProt features (39 total): helix 13, strand 12, mutagenesis site 6, sequence conflict 2, turn 2, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7M8H	X-RAY DIFFRACTION	1.75
3BCZ	X-RAY DIFFRACTION	2.1
7KQ8	X-RAY DIFFRACTION	2.15
7L5C	X-RAY DIFFRACTION	2.55
3BD0	X-RAY DIFFRACTION	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y316-F1	97.60	0.98

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 (1): 210

Mutagenesis-validated functional residues (6):

Position	Phenotype
16	abolishes interaction with erbb2.
49	abolishes interaction with erbb2.
54	diminishes interaction with erbb2.
81	abolishes interaction with erbb2.
192	abolishes interaction with erbb2.
244	abolishes interaction with erbb2.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6785631	ERBB2 Regulates Cell Motility
R-HSA-1227986	Signaling by ERBB2
R-HSA-162582	Signal Transduction
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 181 (showing top): AHRARNT_01, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, SP3_Q3, ONKEN_UVEAL_MELANOMA_UP, TGACATY_UNKNOWN, GGCAGTG_MIR3243P, DODD_NASOPHARYNGEAL_CARCINOMA_UP, VANTVEER_BREAST_CANCER_ESR1_DN, LIU_VMYB_TARGETS_UP, TTTGCAC_MIR19A_MIR19B, BLALOCK_ALZHEIMERS_DISEASE_DN, YKACATTT_UNKNOWN, P53_02, GCM_MAX, TTTGCAG_MIR518A2

GO Biological Process (1): regulation of microtubule-based process (GO:0032886)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by ERBB2	1
Signaling by Receptor Tyrosine Kinases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
microtubule-based process	1
regulation of cellular process	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEMO1	CAMSAP2	Q08AD1	520
MEMO1	CAMSAP3	Q9P1Y5	490
MEMO1	ERBB2	P04626	473
MEMO1	SHC1	P29353	455
MEMO1	MACO1	Q8N5G2	446
MEMO1	YPEL5	P62699	388
MEMO1	PRDM16	Q9HAZ2	374
MEMO1	SLC30A6	Q6NXT4	360
MEMO1	MCC	P23508	346
MEMO1	DPY30	Q9C005	342
MEMO1	INKA1	Q96EL1	341
MEMO1	ARHGAP11A	Q6P4F7	337
MEMO1	TPD52L3	Q96J77	334
MEMO1	NWD2	Q9ULI1	333
MEMO1	AKNA	Q7Z591	326

IntAct

85 interactions, top by confidence:

A	B	Type	Score
COPRS	PRMT5	psi-mi:“MI:0914”(association)	0.770
LNX1	MEMO1	psi-mi:“MI:0915”(physical association)	0.720
TACC1	MEMO1	psi-mi:“MI:0915”(physical association)	0.670
MEMO1	TACC1	psi-mi:“MI:0915”(physical association)	0.670
MEMO1	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
MEMO1	TCF4	psi-mi:“MI:0915”(physical association)	0.560
MEMO1	REL	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	MEMO1	psi-mi:“MI:0915”(physical association)	0.560
RBM45	MEMO1	psi-mi:“MI:0915”(physical association)	0.560
MEMO1	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	MEMO1	psi-mi:“MI:0915”(physical association)	0.560
TCF4	MEMO1	psi-mi:“MI:0915”(physical association)	0.560
REL	MEMO1	psi-mi:“MI:0915”(physical association)	0.560
MEMO1	RBM45	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	MEMO1	psi-mi:“MI:0915”(physical association)	0.560
MEMO1	CT55	psi-mi:“MI:0915”(physical association)	0.560
RFX6	MEMO1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (80): MEMO1 (Two-hybrid), MEMO1 (Two-hybrid), MEMO1 (Two-hybrid), MEMO1 (Two-hybrid), MEMO1 (Two-hybrid), LZTS2 (Two-hybrid), LNX1 (Two-hybrid), RBM45 (Two-hybrid), UBE3D (Affinity Capture-MS), UPF1 (Affinity Capture-MS), ANKFY1 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), DNAAF2 (Affinity Capture-MS), HMBOX1 (Affinity Capture-MS), WDR54 (Affinity Capture-MS)

ESM2 similar proteins: A3MS51, A4FWD2, A4FWR5, A4YIM6, A5IKY3, A5UN65, A6LX30, A6UQ31, A6VGK5, A6VGX3, A8AB69, A8M9U2, A9A2Y3, A9A9S6, A9AA46, B1LA64, B7IGB4, B8D6F2, C3MJQ3, C3MZ11, C3N060, C3N8S4, C3NMP4, C4KJ99, D9TQ02, O26151, O27974, O67039, P61400, P61652, P95994, Q0TQH4, Q12TI1, Q18BQ3, Q46CL1, Q4JCG3, Q4R6D9, Q57846, Q803S3, Q891E7

Diamond homologs: A9A2Y3, P47085, Q10212, Q22915, Q2HJH7, Q4QQR9, Q4R6D9, Q54NZ1, Q6DJ03, Q6GNT9, Q803S3, Q91VH6, Q9HLJ1, Q9Y316, A1RTJ4, A3MS51, A4FWD2, A4WH12, A4YIM6, A5IKY3, A5UN65, A6UQ31, A6VGX3, A8AB69, A8M9U2, A9A9S6, B1LA64, B6YST0, B8D6F2, B9K748, C3MJQ3, C3MZ11, C3N060, C3N8S4, C3NMP4, C4KJ99, C5A7L6, O26151, O27974, O59292

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2473 predictions. Top by Δscore:

Variant	Effect	Δscore
2:31869839:GATAC:G	donor_loss	1.0000
2:31869840:ATACT:A	donor_loss	1.0000
2:31869841:TACT:T	donor_loss	1.0000
2:31869842:AC:A	donor_loss	1.0000
2:31869843:CTC:C	donor_loss	1.0000
2:31869844:T:TA	donor_loss	1.0000
2:31869845:CACAT:C	donor_loss	1.0000
2:31869846:A:AC	donor_gain	1.0000
2:31869847:C:CC	donor_gain	1.0000
2:31883477:CATG:C	acceptor_gain	1.0000
2:31891985:AACTT:A	donor_loss	1.0000
2:31891986:ACTT:A	donor_loss	1.0000
2:31891987:CTTAC:C	donor_loss	1.0000
2:31891988:TTAC:T	donor_loss	1.0000
2:31891989:TA:T	donor_loss	1.0000
2:31891990:A:AC	donor_gain	1.0000
2:31891990:A:C	donor_loss	1.0000
2:31891990:AC:A	donor_gain	1.0000
2:31891990:ACC:A	donor_gain	1.0000
2:31891991:C:CA	donor_loss	1.0000
2:31891991:C:CC	donor_gain	1.0000
2:31891991:CC:C	donor_gain	1.0000
2:31891991:CCC:C	donor_gain	1.0000
2:31892050:A:AC	donor_gain	1.0000
2:31892051:C:CC	donor_gain	1.0000
2:31892130:TATGG:T	acceptor_gain	1.0000
2:31892132:TGG:T	acceptor_gain	1.0000
2:31892133:GG:G	acceptor_gain	1.0000
2:31892135:C:CC	acceptor_gain	1.0000
2:31892136:T:C	acceptor_gain	1.0000

AlphaMissense

1963 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:31869876:C:A	G245V	1.000
2:31869876:C:T	G245E	1.000
2:31869879:C:T	C244Y	1.000
2:31869882:A:T	I243K	1.000
2:31883393:T:A	D217V	1.000
2:31883394:C:G	D217H	1.000
2:31883452:G:C	F197L	1.000
2:31883452:G:T	F197L	1.000
2:31883454:A:G	F197L	1.000
2:31891996:A:C	H192Q	1.000
2:31891996:A:T	H192Q	1.000
2:31891998:G:C	H192D	1.000
2:31891999:G:C	C191W	1.000
2:31892000:C:T	C191Y	1.000
2:31892005:A:C	D189E	1.000
2:31892005:A:T	D189E	1.000
2:31892006:T:A	D189V	1.000
2:31892006:T:C	D189G	1.000
2:31892009:G:A	S188F	1.000
2:31917970:G:C	H131Q	1.000
2:31917970:G:T	H131Q	1.000
2:31920880:A:C	H81Q	1.000
2:31920880:A:T	H81Q	1.000
2:31920882:G:C	H81D	1.000
2:32010200:C:A	W16C	1.000
2:32010200:C:G	W16C	1.000
2:32010202:A:G	W16R	1.000
2:32010202:A:T	W16R	1.000
2:31868380:C:T	G292E	0.999
2:31868390:A:G	Y289H	0.999

dbSNP variants (sampled 300 via entrez): RS1000001764 (2:31914666 A>G), RS1000029831 (2:31984441 C>T), RS1000057671 (2:31921174 A>G), RS1000081051 (2:31960874 C>A), RS1000088226 (2:31929843 C>A), RS1000098827 (2:31906173 T>C), RS1000112793 (2:31998497 C>T), RS1000120492 (2:31946477 T>C), RS1000121451 (2:31996580 T>C), RS1000127639 (2:32001788 G>A), RS1000159778 (2:31969014 A>G), RS1000169929 (2:31875142 A>G), RS1000178836 (2:32006627 G>A), RS1000192584 (2:31929307 T>C), RS1000209855 (2:31966345 T>C)

Disease associations

OMIM: gene MIM:611786 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006661_237	Male-pattern baldness	7.000000e-26
GCST011011_61	Youthful appearance (self-reported)	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, affects expression	1
Ozone	affects expression, increases abundance	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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