MAPRE1 (Microtubule-associated protein, RP/EB family, member 1)

2004-11-01 Jennifer S Tirnauer Affiliation

Center for Molecular Medicine, University of Connecticut Health Center, 263 Farmington Avenue, E1032, Farmington, CT 06030-3101, USA

Identity

HGNC

MAPRE1

LOCATION

20q11.21

IMAGE

LEGEND

EB1-GFP fluorescence on polymerizing microtubule plus ends in a living PtK1 cell.

LOCUSID

22919

ALIAS

EB1

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

22 Kb genomic locus, 5 introns

Transcription

2540 bp open reading frame

Proteins

Description

268 amino acids; 35 kDa; EB1 was cloned in yeast two-hybrid screen as binding partner for the tumor suppressor APC (Adenomatous Polyposis Coli); EB1 is a microtubule plus end tracking protein (+tip). It contains a calponin homology domain and a leucine zipper

Expression

EB1 is ubiquitously expressed. Protein levels remain similar throughout the cell cycle.

Localisation

EB1 targets to the plus ends of microtubules when they are polymerizing, producing a "comet tail" pattern. (Figure 1). The mechanism is treadmilling, in which new subunits are continually added at the tip. EB1 also shows additional weak binding to the microtubule lattice (along the length of the microtubule). EB1 targets to kinetochores moving anti-poleward. This is suspected to be due to binding to kinetochore microtubule plus ends rather than the kinetochore itself. Through its carboxyl terminus, EB1 localizes to centrosomes and spindle poles.

Function

The primary function identified to date is regulation of microtubule dynamic instability. Microtubules dynamically convert between growth (polymerization) and shrinkage (depolymerization). The transition from growth to shrinkage is called catastrophe, while the conversion from shrinkage to growth is called rescue. Microtubules also pause in their polymerization. EB1 reduces these pauses and reduces the frequency of catastrophes. EB1 increases the frequency of rescues. The net result is more stable, longer microtubules. This effect is predominantly seen during mitosis.

EB1 is important in maintaining the structure of the mitotic spindle. This is thought to be mediated by its effects on spindle microtubule dynamic instability.

EB1 is important in spindle positioning within the cell. This is thought to be due to its effects on astral microtubule dynamic instability. In budding yeast, EB1 also plays a role in positioning the mitotic spindle through the bud neck. In this case, it is through microtubule dynamics as well direct binding to a protein at the bud tip, creating a physical link between the microtubule end and the cell cortex.

EB1 plays a role in linking kinetochores to kinetochore microtubules, which is important for chromosome stability. It is not known whether it regulates kinetochore microtubule dynamics or end-on attachment.

EB1 also has an independent role in anchoring microtubule minus ends to centrosomes

Protein-protein interactions: Adenomatous Polyposis Coli (APC) tumor suppressor, polymerized tubulin (microtubules), p150glued/dynactin, CLIP-170, mDia, Pin2/TRF1, RhoGEF2 (drosophila), shortstop (drosophila)

Homology

MAPRE2, MAPRE3

Mutations

Note

none known

Implicated in

Entity name

Colon cancer

Disease

Truncation of the Adenomatous Polyposis Coli (APC) protein is seen in Familial Adenomatous Polyposis (FAP) as well as most sporadic colon cancers. EB1 binds to the APC C-terminus, so its binding is lost in most truncations. Also lost are other APC binding partners including the transcription factor beta-catenin. The role of APC as a tumor suppressor is thought to be through the beta-catenin pathway. Some evidence in the mouse suggests that this is true.
However, there is increasing evidence that connections between APC and the cytoskeleton are important in cell migration, which could have an important role in colon cancer. One Italian FAP family has been reported in which APC is truncated distal to the beta-catenin binding site but including the EB1 binding site. There is no direct evidence of EB1 mutation in colon cancer, and a single report found no evidence of somatic mutations by reverse transcriptase single-strand conformational polymorphism (SSCP) analysis in 21 sporadic colorectal cancers and seven colorectal adenomas.

Entity name

Meduloblastoma

Disease

A single report showed that EB1 is transcriptionally elevated in pediatric meduloblastoma. There is no direct evidence of EB1 mutation in meduloblastoma.

Breakpoints

Note

none known

Bibliography

Pubmed ID	Last Year	Title	Authors
10773885	2000	Regulation and function of the interaction between the APC tumour suppressor protein and EB1.	Askham JM et al
12388762	2002	Evidence that an interaction between EB1 and p150(Glued) is required for the formation and maintenance of a radial microtubule array anchored at the centrosome.	Askham JM et al
11950877	2002	Dissecting interactions between EB1, microtubules and APC in cortical clusters at the plasma membrane.	Barth AI et al
10226031	1999	The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain.	Berrueta L et al
14514668	2003	Characterization of functional domains of human EB1 family proteins.	Bu W et al
12789661	2003	CLIP-170 interacts with dynactin complex and the APC-binding protein EB1 by different mechanisms.	Goodson HV et al
12857735	2003	Crystal structure of the amino-terminal microtubule-binding domain of end-binding protein 1 (EB1).	Hayashi I et al
9823979	1998	Absence of somatic alterations of the EB1 gene adenomatous polyposis coli-associated protein in human sporadic colorectal cancers.	Jaïs P et al
10188731	1999	EB/RP gene family encodes tubulin binding proteins.	Juwana JP et al
10731146	2000	Molecular linkage underlying microtubule orientation toward cortical sites in yeast.	Korinek WS et al
10731147	2000	Positioning of the mitotic spindle by a cortical-microtubule capture mechanism.	Lee L et al
12686597	2003	The microtubule plus-end proteins EB1 and dynactin have differential effects on microtubule polymerization.	Ligon LA et al
14970257	2004	Adenomatous polyposis coli and EB1 localize in close proximity of the mother centriole and EB1 is a functional component of centrosomes.	Louie RK et al
14614826	2003	A novel localization pattern for an EB1-like protein links microtubule dynamics to endomembrane organization.	Mathur J et al
10899006	2000	The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules.	Mimori-Kiyosue Y et al
10030671	1998	EB1, a protein which interacts with the APC tumour suppressor, is associated with the microtubule cytoskeleton throughout the cell cycle.	Morrison EE et al
9624007	1998	A cytokinesis checkpoint requiring the yeast homologue of an APC-binding protein.	Muhua L et al
11470413	2001	Critical role for the EB1 and APC interaction in the regulation of microtubule polymerization.	Nakamura M et al
9233623	1997	RP1, a new member of the adenomatous polyposis coli-binding EB1-like gene family, is differentially expressed in activated T cells.	Renner C et al
12213835	2002	Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle.	Rogers SL et al
15498490	2004	Drosophila RhoGEF2 associates with microtubule plus ends in an EB1-dependent manner.	Rogers SL et al
9398684	1997	BIM1 encodes a microtubule-binding protein in yeast.	Schwartz K et al
7606712	1995	APC binds to the novel protein EB1.	Su LK et al
11161807	2001	Characterization of human MAPRE genes and their proteins.	Su LK et al
12842007	2003	Shortstop recruits EB1/APC1 and promotes microtubule assembly at the muscle-tendon junction.	Subramanian A et al
12388761	2002	EB1-microtubule interactions in Xenopus egg extracts: role of EB1 in microtubule stabilization and mechanisms of targeting to microtubules.	Tirnauer JS et al
15311282	2004	EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration.	Wen Y et al

Other Information

Locus ID:

NCBI: 22919
MIM: 603108
HGNC: 6890
Ensembl: ENSG00000101367

Variants:

dbSNP: 22919
ClinVar: 22919
TCGA: ENSG00000101367
COSMIC: MAPRE1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000101367	ENST00000375571	Q15691

Expression (GTEx)

100

150

200

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

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

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
19255245	2009	Mammalian end binding proteins control persistent microtubule growth.	149
16030254	2005	APC and EB1 function together in mitosis to regulate spindle dynamics and chromosome alignment.	93
19126680	2009	Microtubule plus-end tracking by CLIP-170 requires EB1.	86
12857735	2003	Crystal structure of the amino-terminal microtubule-binding domain of end-binding protein 1 (EB1).	71
21768326	2011	EB1 and EB3 promote cilia biogenesis by several centrosome-related mechanisms.	49
20696710	2010	KIF17 stabilizes microtubules and contributes to epithelial morphogenesis by acting at MT plus ends with EB1 and APC.	45
22748319	2012	Phosphoregulation of STIM1 leads to exclusion of the endoplasmic reticulum from the mitotic spindle.	45
21737685	2011	Kif18B interacts with EB1 and controls astral microtubule length during mitosis.	43
21562367	2011	Epigenetic regulation of microRNA-10b and targeting of oncogenic MAPRE1 in gastric cancer.	39
22467876	2012	Multisite phosphorylation disrupts arginine-glutamate salt bridge networks required for binding of cytoplasmic linker-associated protein 2 (CLASP2) to end-binding protein 1 (EB1).	39

Citation

Jennifer S Tirnauer

MAPRE1 (Microtubule-associated protein, RP/EB family, member 1)

Atlas Genet Cytogenet Oncol Haematol. 2004-11-01

Online version: http://atlasgeneticsoncology.org/gene/455/mapre1