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MAP2 (microtubule-associated protein 2)

Written2011-08Ashika Jayanthy, Vijayasaradhi Setaluri
Department of Dermatology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)MAP2A
MAP2B
MAP2C
Other aliasDKFZp686I2148
HGNC (Hugo) MAP2
LocusID (NCBI) 4133
Atlas_Id 44216
Location 2q34  [Link to chromosome band 2q34]
Location_base_pair Starts at 209424047 and ends at 209734110 bp from pter ( according to hg19-Feb_2009)  [Mapping MAP2.png]
Fusion genes
(updated 2016)
EFTUD2 (17q21.31) / MAP2 (2q34)MAP2 (2q34) / ATP1A1 (1p13.1)MAP2 (2q34) / IQCB1 (3q13.33)
MAP2 (2q34) / NAV1 (1q32.1)RANBP2 (2q12.3) / MAP2 (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.

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 base pairs. Alternative splicing of this gene gives rise to a large variety of transcripts and 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.

Variant 5
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

Variant 4
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.

Pseudogene None.

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 post-translational phosphorylation upon DNA damage. The 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.
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; 1692-1722; 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 N-terminal 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.
Expression 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.
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 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.
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

Note
  
Entity Melanoma
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.
  
  
Entity 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.
  
  
Entity 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.
  
  
Entity 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.
  

Bibliography

Neuronal MAP2 mRNA: species-dependent differential dendritic targeting competence.
Cristofanilli M, Thanos S, Brosius J, Kindler S, Tiedge H.
J Mol Biol. 2004 Aug 20;341(4):927-34.
PMID 15328607
 
The MAP2/Tau family of microtubule-associated proteins.
Dehmelt L, Halpain S.
Genome Biol. 2005;6(1):204. Epub 2004 Dec 23.
PMID 15642108
 
Mechanisms of tau-induced neurodegeneration.
Iqbal K, Liu F, Gong CX, Alonso Adel C, Grundke-Iqbal I.
Acta Neuropathol. 2009 Jul;118(1):53-69. Epub 2009 Jan 30. (REVIEW)
PMID 19184068
 
Survey for CAG repeat polymorphisms in the human MAP-2 gene.
Kalcheva N, Lachman HM, Shafit-Zagardo B.
Psychiatr Genet. 1999 Mar;9(1):43-6.
PMID 10335552
 
A novel microtubule-associated protein-2 expressed in oligodendrocytes in multiple sclerosis lesions.
Shafit-Zagardo B, Kress Y, Zhao ML, Lee SC.
J Neurochem. 1999 Dec;73(6):2531-7.
PMID 10582615
 
Microtubule-associated protein 2, a marker of neuronal differentiation, induces mitotic defects, inhibits growth of melanoma cells, and predicts metastatic potential of cutaneous melanoma.
Soltani MH, Pichardo R, Song Z, Sangha N, Camacho F, Satyamoorthy K, Sangueza OP, Setaluri V.
Am J Pathol. 2005 Jun;166(6):1841-50.
PMID 15920168
 
Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization.
Teng J, Takei Y, Harada A, Nakata T, Chen J, Hirokawa N.
J Cell Biol. 2001 Oct 1;155(1):65-76.
PMID 11581286
 

Citation

This paper should be referenced as such :
Jayanthy, A ; Setaluri, V
MAP2 (microtubule-associated protein 2)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(2):87-91.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MAP2ID44216ch2q34.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  Neuro-Endocrine/Endocrine System: Carcinoid tumors
Head and neck: Retinoblastoma


External links

Nomenclature
HGNC (Hugo)MAP2   6839
Cards
AtlasMAP2ID44216ch2q34
Entrez_Gene (NCBI)MAP2  4133  microtubule associated protein 2
AliasesMAP2A; MAP2B; MAP2C
GeneCards (Weizmann)MAP2
Ensembl hg19 (Hinxton)ENSG00000078018 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000078018 [Gene_View]  chr2:209424047-209734110 [Contig_View]  MAP2 [Vega]
ICGC DataPortalENSG00000078018
TCGA cBioPortalMAP2
AceView (NCBI)MAP2
Genatlas (Paris)MAP2
WikiGenes4133
SOURCE (Princeton)MAP2
Genetics Home Reference (NIH)MAP2
Genomic and cartography
GoldenPath hg38 (UCSC)MAP2  -     chr2:209424047-209734110 +  2q34   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MAP2  -     2q34   [Description]    (hg19-Feb_2009)
EnsemblMAP2 - 2q34 [CytoView hg19]  MAP2 - 2q34 [CytoView hg38]
Mapping of homologs : NCBIMAP2 [Mapview hg19]  MAP2 [Mapview hg38]
OMIM157130   
Gene and transcription
Genbank (Entrez)AB209330 AF088065 AK055674 AK056148 AK291446
RefSeq transcript (Entrez)NM_001039538 NM_002374 NM_031845 NM_031846 NM_031847
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MAP2
Cluster EST : UnigeneHs.368281 [ NCBI ]
CGAP (NCI)Hs.368281
Alternative Splicing GalleryENSG00000078018
Gene ExpressionMAP2 [ NCBI-GEO ]   MAP2 [ EBI - ARRAY_EXPRESS ]   MAP2 [ SEEK ]   MAP2 [ MEM ]
Gene Expression Viewer (FireBrowse)MAP2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4133
GTEX Portal (Tissue expression)MAP2
Protein : pattern, domain, 3D structure
UniProt/SwissProtP11137   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP11137  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP11137
Splice isoforms : SwissVarP11137
PhosPhoSitePlusP11137
Domaine pattern : Prosite (Expaxy)TAU_MAP_1 (PS00229)    TAU_MAP_2 (PS51491)   
Domains : Interpro (EBI)MAP2    MAP2_projctn    MAP_tubulin-bd_rpt   
Domain families : Pfam (Sanger)MAP2_projctn (PF08377)    Tubulin-binding (PF00418)   
Domain families : Pfam (NCBI)pfam08377    pfam00418   
Conserved Domain (NCBI)MAP2
DMDM Disease mutations4133
Blocks (Seattle)MAP2
SuperfamilyP11137
Human Protein AtlasENSG00000078018
Peptide AtlasP11137
HPRD01140
IPIIPI00003842   IPI00293579   IPI00472094   IPI00216900   IPI00735732   IPI00788941   IPI00926254   IPI00925605   
Protein Interaction databases
DIP (DOE-UCLA)P11137
IntAct (EBI)P11137
FunCoupENSG00000078018
BioGRIDMAP2
STRING (EMBL)MAP2
ZODIACMAP2
Ontologies - Pathways
QuickGOP11137
Ontology : AmiGOmicrotubule cytoskeleton organization  microtubule bundle formation  dystroglycan binding  structural molecule activity  protein binding  calmodulin binding  nucleolus  cytosol  microtubule  microtubule associated complex  microtubule binding  central nervous system neuron development  dendrite  neuron projection development  neuron projection  dendrite morphogenesis  
Ontology : EGO-EBImicrotubule cytoskeleton organization  microtubule bundle formation  dystroglycan binding  structural molecule activity  protein binding  calmodulin binding  nucleolus  cytosol  microtubule  microtubule associated complex  microtubule binding  central nervous system neuron development  dendrite  neuron projection development  neuron projection  dendrite morphogenesis  
Pathways : BIOCARTAProtein Kinase A at the Centrosome [Genes]   
NDEx NetworkMAP2
Atlas of Cancer Signalling NetworkMAP2
Wikipedia pathwaysMAP2
Orthology - Evolution
OrthoDB4133
GeneTree (enSembl)ENSG00000078018
Phylogenetic Trees/Animal Genes : TreeFamMAP2
HOVERGENP11137
HOGENOMP11137
Homologs : HomoloGeneMAP2
Homology/Alignments : Family Browser (UCSC)MAP2
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMAP2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MAP2
dbVarMAP2
ClinVarMAP2
1000_GenomesMAP2 
Exome Variant ServerMAP2
ExAC (Exome Aggregation Consortium)MAP2 (select the gene name)
Genetic variants : HAPMAP4133
Genomic Variants (DGV)MAP2 [DGVbeta]
DECIPHERMAP2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMAP2 
Mutations
ICGC Data PortalMAP2 
TCGA Data PortalMAP2 
Broad Tumor PortalMAP2
OASIS PortalMAP2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMAP2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMAP2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MAP2
DgiDB (Drug Gene Interaction Database)MAP2
DoCM (Curated mutations)MAP2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MAP2 (select a term)
intoGenMAP2
NCG5 (London)MAP2
Cancer3DMAP2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM157130   
Orphanet
MedgenMAP2
Genetic Testing Registry MAP2
NextProtP11137 [Medical]
TSGene4133
GENETestsMAP2
Target ValidationMAP2
Huge Navigator MAP2 [HugePedia]
snp3D : Map Gene to Disease4133
BioCentury BCIQMAP2
ClinGenMAP2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4133
Chemical/Pharm GKB GenePA30583
Clinical trialMAP2
Miscellaneous
canSAR (ICR)MAP2 (select the gene name)
Probes
Litterature
PubMed103 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMAP2
EVEXMAP2
GoPubMedMAP2
iHOPMAP2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Jun 7 12:07:04 CEST 2017

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