MAP2 (microtubule-associated protein 2)
2011-08-01 Ashika Jayanthy  , Vijayasaradhi Setaluri   AffiliationDepartment of Dermatology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Identity
HGNC
LOCATION
2q34
LOCUSID
ALIAS
MAP-2,MAP2A,MAP2B,MAP2C
FUSION GENES
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.
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.
- 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.
Proteins
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
Entity name
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 name
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 name
Alzheimers 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 name
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15328607 | 2004 | Neuronal MAP2 mRNA: species-dependent differential dendritic targeting competence. | Cristofanilli M et al |
| 15642108 | 2005 | The MAP2/Tau family of microtubule-associated proteins. | Dehmelt L et al |
| 19184068 | 2009 | Mechanisms of tau-induced neurodegeneration. | Iqbal K et al |
| 10335552 | 1999 | Survey for CAG repeat polymorphisms in the human MAP-2 gene. | Kalcheva N et al |
| 10582615 | 1999 | A novel microtubule-associated protein-2 expressed in oligodendrocytes in multiple sclerosis lesions. | Shafit-Zagardo B et al |
| 15920168 | 2005 | 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 et al |
| 11581286 | 2001 | Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization. | Teng J et al |
Other Information
Locus ID:
NCBI: 4133
MIM: 157130
HGNC: 6839
Ensembl: ENSG00000078018
Variants:
dbSNP: 4133
ClinVar: 4133
TCGA: ENSG00000078018
COSMIC: MAP2
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37258650 | 2023 | Effects of three microtubule-associated proteins (MAP2, MAP4, and Tau) on microtubules' physical properties and neurite morphology. | 4 |
| 37286038 | 2023 | MAP2 caps tau fibrils and inhibits aggregation. | 2 |
| 37702880 | 2023 | Differential regulation of MAP2 by phosphorylation events in proline-rich versus C-terminal domains. | 0 |
| 37258650 | 2023 | Effects of three microtubule-associated proteins (MAP2, MAP4, and Tau) on microtubules' physical properties and neurite morphology. | 4 |
| 37286038 | 2023 | MAP2 caps tau fibrils and inhibits aggregation. | 2 |
| 37702880 | 2023 | Differential regulation of MAP2 by phosphorylation events in proline-rich versus C-terminal domains. | 0 |
| 35139773 | 2022 | Methyltransferase-like (METTL)14-mediated N6-methyladenosine modification modulates retinal pigment epithelial (RPE) activity by regulating the methylation of microtubule-associated protein (MAP)2. | 6 |
| 35229233 | 2022 | Predicting Clinical Outcomes 7-10 Years after Severe Traumatic Brain Injury: Exploring the Prognostic Utility of the IMPACT Lab Model and Cerebrospinal Fluid UCH-L1 and MAP-2. | 0 |
| 35987383 | 2022 | Specific phosphorylation of microtubule-associated protein 2c by extracellular signal-regulated kinase reduces interactions at its Pro-rich regions. | 0 |
| 35139773 | 2022 | Methyltransferase-like (METTL)14-mediated N6-methyladenosine modification modulates retinal pigment epithelial (RPE) activity by regulating the methylation of microtubule-associated protein (MAP)2. | 6 |
| 35229233 | 2022 | Predicting Clinical Outcomes 7-10 Years after Severe Traumatic Brain Injury: Exploring the Prognostic Utility of the IMPACT Lab Model and Cerebrospinal Fluid UCH-L1 and MAP-2. | 0 |
| 35987383 | 2022 | Specific phosphorylation of microtubule-associated protein 2c by extracellular signal-regulated kinase reduces interactions at its Pro-rich regions. | 0 |
| 33931805 | 2021 | The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients. | 18 |
| 34285710 | 2021 | Angiotensin II Induces Differentiation of Human Neuroblastoma Cells by Increasing MAP2 and ROS Levels. | 1 |
| 33931805 | 2021 | The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients. | 18 |
Citation
Ashika Jayanthy ; Vijayasaradhi Setaluri
MAP2 (microtubule-associated protein 2)
Atlas Genet Cytogenet Oncol Haematol. 2011-08-01
Online version: http://atlasgeneticsoncology.org/gene/44216/map2-(microtubule-associated-protein-2)
