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Gene Section
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MAP2 (microtubule-associated protein 2)
Ashika Jayanthy, Vijayasaradhi Setaluri
Department of Dermatology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. (AJ, VS)
Published in Atlas Database: August 2011
Online updated version : http://AtlasGeneticsOncology.org/Genes/MAP2ID44216ch2q34.html
DOI: 10.4267/2042/46934
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
base pairs. Alternative splicing of this gene gives rise to
a large variety of transcripts and isoforms.
Other names: DKFZp686I2148, MAP2A, MAP2B,
MAP2C,
HGNC (Hugo): MAP2
Location: 2q34
Note
The protein encoded by this gene plays a role in
dendrite morphogenesis in the vertebrate central
nervous system. This function is accomplished by
regulating microtubule stability and preventing the
depolymerization of microtubules by stiffening them. It
is known to have a number of distinctive isoforms.
Transcription
Four transcription variants have been characterized.
- MAP2 Isoform 5 (NM_001039538.1 -->
NP_001034627.1): The difference in this isoform is
characterized by the 5' UTR which results in the
production of a longer protein when compared to
isoform 2.
- MAP2 Isoform 1 (NM_002374.3 --> NP_002365.3):
This isoform is thought to be the longest encoded and
contains three alternative in-frame exons when
compared to isoform 2. The tubulin binding and MAP2
projection domains are conserved.
- MAP2 Isoform 2 (NM_031845.2 --> NP_114033.2):
This is the shortest transcript.
- MAP2 Isoform 4 (NM_031847.2 --> NP_114035.2):
One alternate in-frame exon compared to isoform 2.
DNA/RNA
Description
The DNA consists of three or four tandem repeats that
code for 31 amino acid long residues.
The gene contains 15 exons and has a size of 310064
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2)
Pseudogene
None.
87
MAP2 (microtubule-associated protein 2)
Variant 5
Jayanthy A, Setaluri V
mRNA
Gene
Exon
Start
End
Length
Start
End
Length
1
1
230
230
1
230
230
2
231
280
50
83546
83595
50
3
281
345
65
155990
156054
65
4
346
422
77
201007
201083
77
5
423
713
291
229096
229386
291
6
714
827
114
254526
254639
114
7
828
905
78
256704
256781
78
8
906
967
62
276231
276292
62
9
968
1138
171
280404
280574
171
10
1139
1286
148
281534
281681
148
11
1287
1627
341
285868
286208
341
12
1628
1720
93
299549
299641
93
13
1721
1802
82*
301633
301744
112*
14
1803
1915
113
305804
305916
113
15
1916
5844
3929
306136
310064
3929
TOTAL LENGTH : 5844*
Variant 1
mRNA
Gene
Exon
Start
End
Length
Start
End
Length
1
1
77
77
155633
155709
77
2
78
142
65
155990
156054
65
3
143
219
77
201007
201083
77
4
220
510
291
229096
229386
291
5
511
624
114
254526
254639
114
6
625
702
78
256704
256781
78
7
703
4428
3726
268579
272304
3726
8
4429
4635
207
272496
272702
207
9
4636
4770
135
272871
273005
135
10
4771
4832
62
276231
276292
62
11
4833
4980
148
281534
281681
148
12
4981
5321
341
285868
286208
341
13
5322
5403
82
301663
301744
82
14
5404
5516
113
305804
305916
113
15
5517
9445
3929
306136
310064
3929
TOTAL LENGTH : 9445
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2)
88
MAP2 (microtubule-associated protein 2)
Variant 4
Jayanthy A, Setaluri V
mRNA
Gene
Exon
Start
End
Length
Start
End
Length
1
1
77
77
155633
155709
77
2
78
142
65
155990
156054
65
3
143
219
77
201007
201083
77
4
220
510
291
229096
229386
291
5
511
624
114
254526
254639
114
6
625
702
78
256704
256781
78
7
703
764
62
276231
276292
62
8
765
912
148
281534
281681
148
9
913
1253
341
285868
286208
341
10
1254
1346
93
299549
299641
93
11
1347
1428
82
301663
301744
82
12
1429
1541
113
305804
305916
113
13
1542
5470
3929
306136
310064
3929
TOTAL LENGTH : 5470
Variant 2
mRNA
Gene
Exon
Star
End
Length
Start
End
Length
1
1
77
77
155633
155709
77
2
78
142
65
155990
156054
65
3
143
219
77
201007
201083
77
4
220
510
291
229096
229386
291
5
511
624
114
254526
254639
114
6
625
702
78
256704
256781
78
7
703
764
62
276231
276292
62
8
765
912
148
281534
281681
148
9
913
1253
341
285868
286208
341
10
1254
1335
82
301663
301744
82
11
1336
1448
113
305804
305916
113
12
1449
5377
3929
306136
310064
3929
TOTAL LENGTH : 5377
*There is a discrepancy between base pair numbers recorded for the transcript and the gene for this exon.
phosphorylation is hypothesized to be catalyzed by
ATM or ATR. In the rat brain, the various isoforms
were characterized at different stages of development isoform MAP2B is found throughout rat brain
development, while MAP2A appears towards the end
of the second week of post-natal life. MAP2C is found
during the early development of the brain, but after
maturation is only found in the neural cells of the
retina, olfactory bulb and the cerebellum.
Protein
Note
MAP2 is an approximately 1827 amino acid long
protein with an estimated molecular weight of 200 kDa,
with the exact molecular weight varying by isoform.
Four isoforms have been characterized, but additional
ones are thought to exist. The protein undergoes posttranslational phosphorylation upon DNA damage. The
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2)
89
MAP2 (microtubule-associated protein 2)
Jayanthy A, Setaluri V
simultaneous knockouts of MAP2 and MAP1B died in
the prenatal stage (Teng et al., 2001). There are several
reports of functional redundancy amongst the MAP
proteins.
Description
MAP2 is a mostly unfolded protein that changes
conformation upon binding to its target molecule. A
domain near its carboxyl terminus enables MAP2
protein to bind to the microtubules. A 31 amino acid
long repeating motif is characteristic of this protein.
However, it is found that this motif is not sufficient by
itself to bind to microtubules. Two contiguous
sequences on either end of this repeating structure on
both the amino and carboxyl ends enable the binding of
this protein to the microtubules. A proline rich domain
on the amino end is thought to be especially crucial in
this process. The protein is known to have three tubulin
binding domains spanning residues 1160-1691; 16921722; 1723-1754. The protein also has a projection
domain which extends from residues 377-1505. All
isoforms have a conserved C-terminal domain which
contain tubulin binding repeats and a conserved Nterminal projection domain. The projection domain
varies in size across isoforms, has a net negative charge
and exerts a long range repulsive force. This gives a
potential mechanism that explains how MAP2 regulates
the spacing between microtubules.
Homology
A microtubule associated protein with similar function
to MAP2 is known to be expressed in the rat (Rattus
norvegicus), chicken (Gallus gallus) and lizard (Anolis
carolinensis) with varying levels of sequence
homology. In the fruit fly, the tau gene seems to
perform a similar function.
Mutations
Note
35 SNPs associated with MAP2 have been identified.
The CAGs, which are a set of trinucleotide sequences
starting at exon 1 of the MAP2 gene on the 5' UTR
region, are conserved in the general population
(Kalcheva et al., 1999).
Implicated in
Melanoma
Expression
Note
It has been found by Soltani et al. that primary
melanomas that express the MAP2 gene have a lower
rate of metastasis later on than primary melanomas that
do not express the MAP2 gene. It has been proposed
that MAP2 expression disrupts microtubule formation
in cancer cells and interferes with cell cycle
progression.
MAP2 plays a major role in dendrite morphogenesis
and is normally expressed in neurons. It has also been
reported to be ectopically expressed in several cancers
including melanoma and breast cancer.
Localisation
MAP2 mRNAs were found in the avian neuronal cell
body cytoplasm; however the protein was found
localized to the dendrites in mammals (Cristofanilli et
al., 2004). The same report shows that avian neuronal
MAP2 mRNA lacks a dendritic targeting element in its
3' UTR. Local expression within dendrites is
hypothesized to be more suited to regulate need based
synthesis. Tubulin, a protein expressed in both axons
and dendrites is known to be expressed in the
cytoplasm of the cell body showing that location
specific expression of proteins is important to the
maintenance of polarity of the neural cells.
Multiple sclerosis lesions
Note
Novel transcript of MAP2 that expresses exon 13 is
shown to be up-regulated in multiple sclerosis lesions
(Shafit-Zagardo et al., 1998). They proposed that this
transcript is involved in remyelination of
oligodendrocytes.
Alzheimer's disease
Note
Abnormal hyperphosphorylation of several tau
proteins, MAP1 and MAP2 have been implicated in
leading to progressive degeneration and loss of
connectivity between neurons.
Function
MAP2 stabilizes microtubule bundling and stiffening
through the interactions of several weak binding sites to
the microtubules on the protein. The strength of
bundling of microtubules is directly correlated to the
strength of the binding to MAP2. This enables the
microtubules to support outgrowth from the cells.
When MAP2 was expressed by transfection in non
neuronal cells, it induced the rearrangement of the
microtubules into long bundles. These bundles enabled
outgrowths from the non neuronal cells.
Experiments done with knockout mice show that the
role of MAP2 in neuronal morphogenesis may be
redundant (Teng et al., 2001). Single knockouts of
MAP2 did not show any severe phenotypes but
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2)
Various diseases
Note
MAP2 expression is altered in response to various
illnesses and thus is used as a marker in the diagnosis
of many specific illnesses and especially as a marker of
neuronal differentiation.
References
Shafit-Zagardo B, Kalcheva N. Making sense of the multiple
MAP-2 transcripts and their role in the neuron. Mol Neurobiol.
1998 Apr;16(2):149-62
90
MAP2 (microtubule-associated protein 2)
Jayanthy A, Setaluri V
Kalcheva N, Lachman HM, Shafit-Zagardo B. Survey for CAG
repeat polymorphisms in the human MAP-2 gene. Psychiatr
Genet. 1999 Mar;9(1):43-6
Dehmelt L, Halpain S. The MAP2/Tau family of microtubuleassociated proteins. Genome Biol. 2005;6(1):204
Soltani MH, Pichardo R, Song Z, Sangha N, Camacho F,
Satyamoorthy K, Sangueza OP, Setaluri V. Microtubuleassociated protein 2, a marker of neuronal differentiation,
induces mitotic defects, inhibits growth of melanoma cells, and
predicts metastatic potential of cutaneous melanoma. Am J
Pathol. 2005 Jun;166(6):1841-50
Shafit-Zagardo B, Kress Y, Zhao ML, Lee SC. A novel
microtubule-associated
protein-2
expressed
in
oligodendrocytes in multiple sclerosis lesions. J Neurochem.
1999 Dec;73(6):2531-7
Teng J, Takei Y, Harada A, Nakata T, Chen J, Hirokawa N.
Synergistic effects of MAP2 and MAP1B knockout in neuronal
migration, dendritic outgrowth, and microtubule organization. J
Cell Biol. 2001 Oct 1;155(1):65-76
Iqbal K, Liu F, Gong CX, Alonso Adel C, Grundke-Iqbal I.
Mechanisms of tau-induced neurodegeneration. Acta
Neuropathol. 2009 Jul;118(1):53-69
Cristofanilli M, Thanos S, Brosius J, Kindler S, Tiedge H.
Neuronal MAP2 mRNA: species-dependent differential
dendritic targeting competence. J Mol Biol. 2004 Aug
20;341(4):927-34
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2)
This article should be referenced as such:
Jayanthy A, Setaluri V. MAP2 (microtubule-associated protein
2). Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2):87-91.
91