MAPRE1

Summary

MAPRE1 (microtubule associated protein RP/EB family member 1, HGNC:6890) is a protein-coding gene on chromosome 20q11.21, encoding Microtubule-associated protein RP/EB family member 1 (Q15691). Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. It is a selective cancer dependency (DepMap: 24.6% of cell lines).

The protein encoded by this gene was first identified by its binding to the APC protein which is often mutated in familial and sporadic forms of colorectal cancer. This protein localizes to microtubules, especially the growing ends, in interphase cells. During mitosis, the protein is associated with the centrosomes and spindle microtubules. The protein also associates with components of the dynactin complex and the intermediate chain of cytoplasmic dynein. Because of these associations, it is thought that this protein is involved in the regulation of microtubule structures and chromosome stability. This gene is a member of the RP/EB family.

Source: NCBI Gene 22919 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 22 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 24.6% of screened cell lines
• MANE Select transcript: NM_012325

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6890
Approved symbol	MAPRE1
Name	microtubule associated protein RP/EB family member 1
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	EB1
Ensembl gene	ENSG00000101367
Ensembl biotype	protein_coding
OMIM	603108
Entrez	22919

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 37 protein_coding

ENST00000375571, ENST00000908452, ENST00000908453, ENST00000908454, ENST00000908455, ENST00000908456, ENST00000908457, ENST00000908458, ENST00000908459, ENST00000908460, ENST00000908461, ENST00000908462, ENST00000912275, ENST00000912276, ENST00000912277, ENST00000912278, ENST00000912279, ENST00000912280, ENST00000912281, ENST00000912282, ENST00000912283, ENST00000912284, ENST00000912285, ENST00000912286, ENST00000912287, ENST00000912288, ENST00000912289, ENST00000912290, ENST00000912291, ENST00000912292, ENST00000912293, ENST00000912294, ENST00000912295, ENST00000912296, ENST00000941960, ENST00000941961, ENST00000941962

RefSeq mRNA: 1 — MANE Select: NM_012325 NM_012325

CCDS: CCDS13208

Canonical transcript exons

ENST00000375571 — 7 exons

Exon	Start	End
ENSE00000661239	32833717	32833862
ENSE00000661240	32836634	32836841
ENSE00000661241	32839735	32839856
ENSE00000661242	32846618	32846770
ENSE00001467571	32825925	32826048
ENSE00001467575	32819954	32820028
ENSE00001950425	32848672	32850405

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.0805 / max 1307.4279, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184065	56.3617	1822
184063	7.3316	1692
184064	2.3873	1358

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.77	gold quality
ganglionic eminence	UBERON:0004023	98.57	gold quality
ventricular zone	UBERON:0003053	98.24	gold quality
islet of Langerhans	UBERON:0000006	98.14	gold quality
embryo	UBERON:0000922	97.75	gold quality
cartilage tissue	UBERON:0002418	97.75	gold quality
mononuclear cell	CL:0000842	97.48	gold quality
monocyte	CL:0000576	97.47	gold quality
cortical plate	UBERON:0005343	97.40	gold quality
leukocyte	CL:0000738	97.39	gold quality
oocyte	CL:0000023	97.29	gold quality
bone marrow	UBERON:0002371	97.29	gold quality
cauda epididymis	UBERON:0004360	97.22	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.99	gold quality
esophagus squamous epithelium	UBERON:0006920	96.98	gold quality
epithelial cell of pancreas	CL:0000083	96.97	gold quality
smooth muscle tissue	UBERON:0001135	96.96	gold quality
pancreatic ductal cell	CL:0002079	96.90	gold quality
vermiform appendix	UBERON:0001154	96.71	gold quality
squamous epithelium	UBERON:0006914	96.69	gold quality
visceral pleura	UBERON:0002401	96.66	gold quality
pleura	UBERON:0000977	96.63	gold quality
hair follicle	UBERON:0002073	96.62	gold quality
parietal pleura	UBERON:0002400	96.60	gold quality
corpus epididymis	UBERON:0004359	96.54	gold quality
saphenous vein	UBERON:0007318	96.45	gold quality
epithelium of esophagus	UBERON:0001976	96.43	gold quality
caecum	UBERON:0001153	96.32	gold quality
colonic mucosa	UBERON:0000317	96.20	gold quality
mucosa of urinary bladder	UBERON:0001259	96.17	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, KAT5, NFKB2, USF2, ZHX2

miRNA regulators (miRDB)

205 targeting MAPRE1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 24.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• EB1 employs the hydrophobic interaction to bind to microtubules (PMID:12857735)
• neither APC nor p150glued binding domain is necessary for EB1 or EBF3 to induce microtubule bundling (PMID:14514668)
• APC and EB1 together give rise to similar defects in mitotic spindles and chromosome alignment without arresting cells in mitosis. (PMID:16030254)
• MCAK is held in an inactive conformation when associated with EB1 (PMID:17968321)
• Aurora-B is an EB1-interacting protein; EB1 stimulates Aurora-B activity through antagonizing its dephosphorylation/inactivation by PP2A (PMID:18477699)
• Proteomic profiling revealed the molecular signature behind the progression of hepatocellular carcinoma (HCC), and the prognostic value of EB1 in HCC. (PMID:18937283)
• EB1 specifically recognizes the distinct lattice structure at the growing microtubule end; EB1 is both necessary and sufficient to mediate plus-end tracking by CLIP-170. (PMID:19126680)
• Protein depletion and rescue experiments showed that EB1 and EB3, but not EB2, promote persistent microtubule growth by suppressing catastrophes. (PMID:19255245)
• heterodimer formation between EB1 and EB3, but not between EB2 and the other two EBs, occurs both in vitro and in cells as revealed by live cell imaging (PMID:20008324)
• Targeting of KIF17 to plus ends of growing microtubules requires kinesin motor activity and interaction with EB1. (PMID:20696710)
• decreased MAPRE1 expression coincided with increased miR-10b expression, suggesting that miR-10b targets MAPRE1 transcription (PMID:21562367)
• Kif18B is a new MT dynamics regulatory protein that interacts with EB1 to control astral MT length (PMID:21737685)
• Insights into EB1 structure and the role of its C-terminal domain for discriminating microtubule tips from the lattice (PMID:21737692)
• Data indicated that EB1 and EB3 interact with proteins implicated in MT minus-end anchoring or vesicular trafficking to the cilia base, suggesting that EB1 and EB3 promote ciliogenesis by facilitating such trafficking. (PMID:21768326)
• Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 precede a diagnosis of colorectal cancer in women (PMID:22277732)
• Multisite phosphorylation disrupts arginine-glutamate salt bridge networks required for binding of cytoplasmic linker-associated protein 2 (CLASP2) to end-binding protein 1 (EB1). (PMID:22467876)
• We further demonstrate that this binding was prevented when the C-terminal tyrosine of EB1 was absent in the peptidic probes. (PMID:22543185)
• EB1 is a potential biomarker and therapeutic target in colorectal cancer. (PMID:22735596)
• STIM1 dissociates from EB1 in mitosis. (PMID:22748319)
• End binding protein 1 directly interacted with AIM2 and ASC in vitro and in vivo. (PMID:22869553)
• the Amer2-EB1-APC complex regulates cell migration by altering microtubule stability. (PMID:22898821)
• Data indicate that EB1 is a substrate of P300/CBP-associated factor (PCAF) and K220 was identified as a responsible site. (PMID:23001180)
• the intramolecular interaction site of EB1 overlaps the MT binding sites, indicating that the MT binding sites are masked by interaction with the C-terminal domain. (PMID:23128140)
• These observations indicate that EB1 and ch-TOG regulate microtubule organisation differently via distinct regions in the plus ends of microtubules. (PMID:23251535)
• TIP150-EB1 interaction governs kinetochore microtubule plus-end plasticity and establish that the temporal control of the TIP150-EB1 interaction by PCAF acetylation ensures chromosome stability in mitosis. (PMID:23595990)
• phosphorylation of STIM1 at Ser575, Ser608 and Ser621 regulates the interaction with EB1. (PMID:23687376)
• regulation of EB1 dimerization might play a role in controlling EB1 function (PMID:23864329)
• EB proteins appear to play an active role inthe subsequent association of STIM1 to APC at the ER-PM junction. (PMID:23871111)
• Depletion of end-binding protein 1 (EB1) promotes apoptosis of human non-small-cell lung cancer cells via reactive oxygen species and Bax-mediated mitochondrial dysfunction. (PMID:23900080)
• EB1 and EB3 proteins are obligatory dimers. (PMID:24040250)
• EB1-kinesin complex actively steered growing microtubules in an in vitro model (PMID:24462004)
• Aptamers binding to human EB1 and EB3, which have sequence requirements similar to but distinct from each other and from Drosophila EB1, were identified. (PMID:24478452)
• Dysregulation of EB1 is an important early event in colon carcinogenesis (PMID:24492008)
• The CYLD-EB1 interaction was confirmed both in cells and in vitro, and these 2 proteins colocalized at the plus ends of microtubules. The association of CYLD with EB1 was significantly increased upon the stimulation of cell migration. (PMID:24552808)
• EB1 enables the spindle microtubules to regulate the phosphorylation of kinetochores through recruitment of the Aurora B kinase. (PMID:24616220)
• Study finds that frictional forces increase nonlinearly with microtubule-associated proteins (MAP) velocity across microtubules and depend on filament polarity, with NuMA’s friction being lower when moving toward minus ends, EB1’s lower toward plus ends, and PRC1’s exhibiting no directional preference. (PMID:24725408)
• We showed for the first time that EB1 associates with microtubules in a phosphorylation-dependent manner, under control of reactive oxygen species (PMID:24930764)
• Studies show that IQGAP1 functions as a hub linking HGF-induced signaling to microtubules and actin remodeling via EB1-IQGAP1-cortactin interactions. (PMID:25022754)
• The functions of EB1 in the regulation of microtubule dynamics and recruitment of other +TIPs, as well as the dimerization of EB1, undergo exquisite control by phosphorylation. (PMID:25048701)
• We find that the presence of EB1 can stiffen microtubules in a manner that depends on the hydrolysis state of the tubulin-bound nucleotide (PMID:25160006)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	mapre1b	ENSDARG00000002659
danio_rerio	mapre1a	ENSDARG00000042927
mus_musculus	Mapre1	ENSMUSG00000027479
rattus_norvegicus	Mapre1	ENSRNOG00000011798
caenorhabditis_elegans		WBGENE00007062
caenorhabditis_elegans		WBGENE00012156
caenorhabditis_elegans		WBGENE00013344

Paralogs (2): MAPRE3 (ENSG00000084764), MAPRE2 (ENSG00000166974)

Protein

Protein identifiers

Microtubule-associated protein RP/EB family member 1 — Q15691 (reviewed: Q15691)

Alternative names: APC-binding protein EB1, End-binding protein 1

All UniProt accessions (1): Q15691

UniProt curated annotations — full annotation on UniProt →

Function. Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Recruits other +TIP proteins to microtubules by binding to a conserved Ser-X-Leu-Pro (SXLP) motif in their polypeptide chains. Promotes cytoplasmic microtubule nucleation and elongation. Involved in mitotic spindle positioning by stabilizing microtubules and promoting dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation. Assists chromosome alignment in metaphase by recruiting the SKA complex to the spindle and stabilizing its interactions with microtubule bundles (K-fibers). Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules. Acts as a regulator of autophagosome transport via interaction with CAMSAP2. Functions downstream of Rho GTPases and DIAPH1 in stable microtubule formation. May play a role in cell migration.

Subunit / interactions. Homodimer. Heterodimer with MAPRE3. Interacts with DCTN1, DCTN2, TERF1 and dynein intermediate chain. Interaction with DIAPH1 and DIAPH2. Interacts (via C-terminal residues 206-211) with APC (via C-terminal residues 2674-2843); the interaction inhibits association with and bundling of F-actin. Interacts with CLASP2, DST, KIF2C and STIM1; probably required for their targeting to the growing microtubule plus ends. Interacts with MTUS2; interaction is direct and probably targets MTUS2 to microtubules. Interacts (via C-terminus) with SKA1 (via SXIP motif); the interaction is direct and stabilizes the kinetochore-microtubule attachment of the SKA1 complex. Interacts with APC2. Interacts with CLASP1. Interacts with CDK5RAP2. Interacts with MACF1. Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2. Interacts with KCNAB2. Interacts (via C-terminus) with CLIP1. Interacts with SLAIN2 and SLAIN1. Interacts with KIF18B; this interaction is required for efficient accumulation of KIF18B at microtubule plus ends. Interacts with MISP. Interacts with KNSTRN. Interacts with NCKAP5L. Interacts with CAMSAP2. Interacts with PDE4DIP isoform 13/MMG8/SMYLE; this interaction is required for its recruitment to the Golgi apparatus. Forms a pericentrosomal complex with AKAP9, CDK5RAP2 and PDE4DIP isoform 13/MMG8/SMYLE; within this complex, MAPRE1 binding to CDK5RAP2 may be mediated by PDE4DIP. Interacts with AKNA. Interacts with GAS2L1, GAS2L2, and GAS2L3. Interacts with RARRES1 and AGBL2.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Golgi apparatus. Spindle. Spindle pole.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Acetylation at Lys-220 by KAT2B/PCAF promotes dynamic kinetochore-microtubule interactions in early mitosis. Crotonylated by KAT5 during mitosis, promoting astral microtubule plasticity and dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation, thereby ensuring accurate spindle positioning in mitosis. Decrotonylated by HDAC3.

Domain organisation. Composed of two functionally independent domains. The N-terminal domain forms a hydrophobic cleft involved in microtubule binding and the C-terminal is involved in the formation of mutually exclusive complexes with APC and DCTN1.

Similarity. Belongs to the MAPRE family.

RefSeq proteins (1): NP_036457* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR004953	EB1_C	Domain
IPR027328	MAPRE	Family
IPR036133	EB1_C_sf	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily

Pfam: PF00307, PF03271

UniProt features (35 total): helix 11, region of interest 7, modified residue 6, mutagenesis site 4, domain 2, turn 2, initiator methionine 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2QJZ	X-RAY DIFFRACTION	1.25
2R8U	X-RAY DIFFRACTION	1.35
1PA7	X-RAY DIFFRACTION	1.45
1WU9	X-RAY DIFFRACTION	1.54
5JVM	X-RAY DIFFRACTION	1.57
1VKA	X-RAY DIFFRACTION	1.6
5JX1	X-RAY DIFFRACTION	1.67
1TXQ	X-RAY DIFFRACTION	1.8
1YIB	X-RAY DIFFRACTION	1.8
6YF5	X-RAY DIFFRACTION	1.83
2HKQ	X-RAY DIFFRACTION	1.86
2HL5	X-RAY DIFFRACTION	1.93
5JVU	X-RAY DIFFRACTION	1.95
1YIG	X-RAY DIFFRACTION	2
5JV3	X-RAY DIFFRACTION	2.01
2HL3	X-RAY DIFFRACTION	2.03
3MTU	X-RAY DIFFRACTION	2.1
5JVP	X-RAY DIFFRACTION	2.1
5JVR	X-RAY DIFFRACTION	2.1
6PF2	X-RAY DIFFRACTION	2.17
3MUD	X-RAY DIFFRACTION	2.2
6PFP	X-RAY DIFFRACTION	2.2
5JVS	X-RAY DIFFRACTION	2.25
3TQ7	X-RAY DIFFRACTION	2.3
1UEG	X-RAY DIFFRACTION	2.4
3GJO	X-RAY DIFFRACTION	2.5
4XA3	X-RAY DIFFRACTION	2.55
9CO5	X-RAY DIFFRACTION	2.77
6YSH	X-RAY DIFFRACTION	2.83
5WLQ	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15691-F1	81.65	0.58

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 (6): 2, 66, 124, 155, 165, 220

Mutagenesis-validated functional residues (4):

Position	Phenotype
59–60	no effect.
66	abolished crotonylation by kat5.
89	loss of binding to microtubules.
220	abolished acetylation by kat2b/pcaf, impairing kinetochore-microtubule interactions during mitosis.

Function

Pathways and Gene Ontology

Reactome pathways

31 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-8852276	The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints

MSigDB gene sets: 377 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, MORF_DNMT1, MODULE_52, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, PAX4_01, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497

GO Biological Process (16): establishment of mitotic spindle orientation (GO:0000132), microtubule bundle formation (GO:0001578), intracellular protein localization (GO:0008104), cell migration (GO:0016477), regulation of microtubule polymerization or depolymerization (GO:0031110), negative regulation of microtubule polymerization (GO:0031115), positive regulation of microtubule polymerization (GO:0031116), protein localization to microtubule (GO:0035372), microtubule polymerization (GO:0046785), spindle assembly (GO:0051225), cell division (GO:0051301), attachment of mitotic spindle microtubules to kinetochore (GO:0051315), protein localization to centrosome (GO:0071539), protein localization to mitotic spindle (GO:1902480), protein localization to astral microtubule (GO:1902888), non-motile cilium assembly (GO:1905515)

GO Molecular Function (7): RNA binding (GO:0003723), identical protein binding (GO:0042802), cadherin binding (GO:0045296), microtubule plus-end binding (GO:0051010), protein serine/threonine kinase binding (GO:0120283), protein binding (GO:0005515), microtubule binding (GO:0008017)

GO Cellular Component (21): Golgi apparatus (GO:0005794), centrosome (GO:0005813), microtubule organizing center (GO:0005815), cytosol (GO:0005829), microtubule (GO:0005874), cytoplasmic microtubule (GO:0005881), focal adhesion (GO:0005925), cortical microtubule cytoskeleton (GO:0030981), cell projection membrane (GO:0031253), microtubule plus-end (GO:0035371), ciliary basal body (GO:0036064), spindle midzone (GO:0051233), mitotic spindle pole (GO:0097431), mitotic spindle astral microtubule end (GO:1905721), mitotic spindle microtubule (GO:1990498), spindle pole (GO:0000922), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Mitotic Prometaphase	3
G2/M Transition	3
Centrosome maturation	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Assembly of the 9+0 primary cilium	1
RHO GTPase Effectors	1
M Phase	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
microtubule cytoskeleton	4
cytoplasm	3
microtubule polymerization or depolymerization	2
regulation of microtubule polymerization	2
microtubule polymerization	2
protein localization to microtubule cytoskeleton	2
microtubule organizing center	2
microtubule end	2
spindle	2
mitotic spindle	2
intracellular membraneless organelle	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
microtubule cytoskeleton organization	1
macromolecule localization	1
cell motility	1
regulation of microtubule cytoskeleton organization	1
negative regulation of microtubule polymerization or depolymerization	1
negative regulation of protein polymerization	1
negative regulation of supramolecular fiber organization	1
positive regulation of microtubule polymerization or depolymerization	1
positive regulation of protein polymerization	1
positive regulation of supramolecular fiber organization	1
microtubule nucleation	1
protein polymerization	1
supramolecular fiber organization	1
spindle organization	1
chromosome segregation	1
membraneless organelle assembly	1
cellular process	1
mitotic metaphase chromosome alignment	1
attachment of spindle microtubules to kinetochore	1
mitotic cell cycle process	1
protein localization to microtubule organizing center	1
protein localization to spindle microtubule	1
protein localization to cytoplasmic microtubule	1
cilium assembly	1
nucleic acid binding	1

Protein interactions and networks

STRING

3245 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAPRE1	CLIP1	P30622	885
MAPRE1	DCTN1	Q14203	882
MAPRE1	SPEF1	Q9Y4P9	809
MAPRE1	KIF2C	Q99661	784
MAPRE1	AURKB	Q96GD4	762
MAPRE1	KHK	P50053	713
MAPRE1	APC	P25054	692
MAPRE1	CLASP2	O75122	686
MAPRE1	MACF1	Q9UPN3	680
MAPRE1	IQGAP1	P46940	678
MAPRE1	BUB1	O43683	662
MAPRE1	KIF17	Q9P2E2	643
MAPRE1	RCC2	Q9P258	621
MAPRE1	AIM2	O14862	610
MAPRE1	APC2	O95996	580
MAPRE1	STIM1	Q13586	580

IntAct

278 interactions, top by confidence:

A	B	Type	Score
MAPRE3	MAPRE1	psi-mi:“MI:0915”(physical association)	0.960
MAPRE1	MAPRE3	psi-mi:“MI:0915”(physical association)	0.960
MAPRE1	MAPRE3	psi-mi:“MI:2364”(proximity)	0.960
MAPRE2	MAPRE1	psi-mi:“MI:0915”(physical association)	0.930
DCTN1	MAPRE1	psi-mi:“MI:0407”(direct interaction)	0.900
MAPRE1	DCTN1	psi-mi:“MI:0407”(direct interaction)	0.900
MAPRE1	KIF2C	psi-mi:“MI:0915”(physical association)	0.890
TROAP	MAPRE1	psi-mi:“MI:0915”(physical association)	0.850
MAPRE1	TROAP	psi-mi:“MI:0915”(physical association)	0.850
MAPRE1	CLASP2	psi-mi:“MI:0914”(association)	0.850
MAPRE1	CLASP2	psi-mi:“MI:0915”(physical association)	0.850

BioGRID (804): MAPRE1 (Two-hybrid), MAPRE1 (Two-hybrid), MAPRE1 (Two-hybrid), MAPRE1 (Two-hybrid), MAPRE1 (Two-hybrid), MAPRE1 (Two-hybrid), MAPRE1 (Two-hybrid), MAPRE1 (Two-hybrid), MAPRE3 (Two-hybrid), SPDYE2 (Two-hybrid), MAPRE1 (Affinity Capture-Western), CYLD (Affinity Capture-Western), CYLD (Reconstituted Complex), MAPRE1 (Phenotypic Enhancement), CYLD (Two-hybrid)

ESM2 similar proteins: A1A4P5, A1DGS2, A2R7Z2, B0BN18, O04350, O35685, O70591, O75347, O76031, P48427, P48428, P50502, P50503, P80584, Q07866, Q08851, Q08DB5, Q0VCY1, Q13190, Q15691, Q17QG2, Q3ZBD9, Q4SPU8, Q5D016, Q5R581, Q5R601, Q5R7N3, Q5R7Z5, Q5RF31, Q5U2U0, Q5ZLC7, Q5ZLF0, Q61166, Q63525, Q66HR2, Q66T82, Q68FJ8, Q6P848, Q6V291, Q8K1E0

Diamond homologs: E2RU10, P40013, Q15555, Q15691, Q3B8Q0, Q3SZP2, Q3ZBD9, Q5R4I6, Q5R7Z5, Q5XIT1, Q5ZKK1, Q5ZLC7, Q61166, Q66HR2, Q66T82, Q6P848, Q6PER3, Q6V291, Q7XJ60, Q7ZXP1, Q8R001, Q8WQ86, Q9FGQ6, Q9FJJ5, Q9UPY8, Q10113

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CEP43	up-regulates	MAPRE1	relocalization
CLASP1	“up-regulates activity”	MAPRE1	binding
SRC	“down-regulates activity”	MAPRE1	phosphorylation
CSNK1D	“up-regulates activity”	MAPRE1	phosphorylation
CLASP2	“up-regulates activity”	MAPRE1	binding
MAPRE1	up-regulates	Microtubule_polimerization	binding

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
Loss of Nlp from mitotic centrosomes	6	18.7×	1e-04
Loss of proteins required for interphase microtubule organization from the centrosome	6	18.7×	1e-04
AURKA Activation by TPX2	6	17.9×	1e-04
Recruitment of mitotic centrosome proteins and complexes	6	16.0×	2e-04
Regulation of PLK1 Activity at G2/M Transition	6	14.9×	2e-04
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	6	13.7×	3e-04
Recruitment of NuMA to mitotic centrosomes	6	13.7×	3e-04
Anchoring of the basal body to the plasma membrane	6	13.3×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of microtubule polymerization or depolymerization	6	90.3×	3e-08
mitotic spindle organization	5	19.4×	1e-03
microtubule cytoskeleton organization	6	10.4×	2e-03
cell division	13	8.6×	1e-06
cilium assembly	8	8.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

22 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

1311 predictions. Top by Δscore:

Variant	Effect	Δscore
20:32820025:GCCG:G	donor_gain	1.0000
20:32820029:G:GG	donor_gain	1.0000
20:32820029:GT:G	donor_loss	1.0000
20:32825916:A:AG	acceptor_gain	1.0000
20:32825916:AT:A	acceptor_gain	1.0000
20:32825917:T:G	acceptor_gain	1.0000
20:32825917:T:TA	acceptor_gain	1.0000
20:32825921:TTA:T	acceptor_loss	1.0000
20:32825923:A:AG	acceptor_gain	1.0000
20:32825924:G:GG	acceptor_gain	1.0000
20:32825924:GA:G	acceptor_gain	1.0000
20:32825924:GAA:G	acceptor_gain	1.0000
20:32825924:GAAGA:G	acceptor_gain	1.0000
20:32826047:AGGT:A	donor_loss	1.0000
20:32826049:G:C	donor_loss	1.0000
20:32826049:G:GG	donor_gain	1.0000
20:32826050:T:A	donor_loss	1.0000
20:32833703:C:CA	acceptor_gain	1.0000
20:32833706:T:A	acceptor_gain	1.0000
20:32833713:TCAG:T	acceptor_loss	1.0000
20:32833714:CA:C	acceptor_loss	1.0000
20:32833715:A:AC	acceptor_loss	1.0000
20:32833715:A:AG	acceptor_gain	1.0000
20:32833715:AG:A	acceptor_gain	1.0000
20:32833715:AGG:A	acceptor_gain	1.0000
20:32833715:AGGG:A	acceptor_gain	1.0000
20:32833716:G:GA	acceptor_gain	1.0000
20:32833716:GG:G	acceptor_gain	1.0000
20:32833716:GGG:G	acceptor_gain	1.0000
20:32833716:GGGG:G	acceptor_gain	1.0000

AlphaMissense

1775 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:32825939:C:A	N4K	1.000
20:32825939:C:G	N4K	1.000
20:32825941:T:A	V5E	1.000
20:32825973:A:C	S16R	1.000
20:32825974:G:T	S16I	1.000
20:32825975:T:A	S16R	1.000
20:32825975:T:G	S16R	1.000
20:32825976:C:G	R17G	1.000
20:32825977:G:A	R17Q	1.000
20:32825977:G:T	R17L	1.000
20:32825989:T:C	L21P	1.000
20:32825994:T:A	W23R	1.000
20:32825994:T:C	W23R	1.000
20:32825996:G:C	W23C	1.000
20:32825996:G:T	W23C	1.000
20:32826033:G:A	E36K	1.000
20:32826048:G:A	G41R	1.000
20:32826048:G:C	G41R	1.000
20:32826048:G:T	G41W	1.000
20:32833717:G:A	G41E	1.000
20:32833717:G:T	G41V	1.000
20:32833728:T:C	C45R	1.000
20:32833729:G:A	C45Y	1.000
20:32833730:T:G	C45W	1.000
20:32833747:T:C	L51P	1.000
20:32833749:T:C	F52L	1.000
20:32833750:T:C	F52S	1.000
20:32833751:C:A	F52L	1.000
20:32833751:C:G	F52L	1.000
20:32833797:G:A	E68K	1.000

dbSNP variants (sampled 300 via entrez): RS1000019509 (20:32845517 A>T), RS1000044894 (20:32820344 C>A,T), RS1000047232 (20:32830471 A>G,T), RS1000110468 (20:32825032 A>G), RS1000180499 (20:32842177 C>T), RS1000197115 (20:32827038 G>A), RS1000264313 (20:32848337 T>G), RS1000348947 (20:32832948 A>T), RS1000455868 (20:32839269 G>C), RS1000643588 (20:32831649 C>T), RS1000652409 (20:32826742 C>T), RS1000698441 (20:32848138 C>A,T), RS1000717954 (20:32834758 A>G), RS1000789151 (20:32836302 G>A), RS1000817252 (20:32845391 T>A,G)

Disease associations

OMIM: gene MIM:603108 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST007089_14	Polycystic ovary syndrome	2.000000e-09
GCST009723_68	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2.000000e-09
GCST009724_102	Vertical cup-disc ratio (multi-trait analysis)	4.000000e-13
GCST010135_49	Oily fish consumption	4.000000e-08
GCST010140_39	Pork consumption	4.000000e-08
GCST010703_192	Brain morphology (MOSTest)	8.000000e-11
GCST90002395_594	Mean platelet volume	1.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067322 (SINGLE PROTEIN)

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

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
7.04	Kd	92.21	nM	CHEMBL5653589
7.04	ED50	92.21	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	2148715: Binding affinity to human MAPRE1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0922	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
bisphenol A	decreases methylation, increases expression	2
ochratoxin A	decreases acetylation, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation	2
Cadmium	increases abundance, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
N’-(3-bromo-4-hydroxybenzylidene)-2-(9-oxo-10(9H)-acridinyl)acetohydrazide	affects localization	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ON 01910	affects localization	1
olesoxime	affects localization, decreases localization, decreases reaction	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Benztropine	decreases expression	1
Caffeine	decreases phosphorylation	1
Clozapine	decreases expression, affects cotreatment	1
Cuprizone	decreases expression, affects cotreatment	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Furaldehyde	increases expression, affects cotreatment	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
CHEMBL5651757	Binding	Binding affinity to human MAPRE1 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

Clinical trials (associated diseases)

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