Microtubule-associated protein 2

MAP2
Identifiers
Aliases	MAP2 , MAP2A, MAP2B, MAP2C, microtubule associated protein 2, MAP-2
External IDs	OMIM: 157130; MGI: 97175; HomoloGene: 1779; GeneCards: MAP2; OMA:MAP2 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) [1] Band 2q34 Start 209,424,058 bp [1] End 209,734,118 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1 C3|1 33.49 cM Start 66,214,432 bp [2] End 66,481,742 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 endothelial cell superior vestibular nucleus entorhinal cortex pons pars compacta parietal lobe postcentral gyrus middle temporal gyrus pars reticulata Top expressed in anterior amygdaloid area ventromedial nucleus nucleus accumbens lateral septal nucleus superior frontal gyrus paraventricular nucleus of hypothalamus olfactory tubercle dorsomedial hypothalamic nucleus olfactory bulb subiculum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function tubulin binding protein binding structural molecule activity dystroglycan binding calmodulin binding microtubule binding tau protein binding Cellular component nucleolus microtubule microtubule associated complex cytoskeleton cytoplasm cytosol dendrite cell projection intracellular anatomical structure postsynaptic density nuclear periphery neuron projection soma dendritic shaft cell body CA3 pyramidal cell dendrite dendrite cytoplasm axon initial segment axon hillock dendritic growth cone main axon dendritic branch basal dendrite primary dendrite distal dendrite apical distal dendrite dendritic filopodium proximal dendrite proximal neuron projection Biological process neuron projection development microtubule cytoskeleton organization microtubule bundle formation dendrite morphogenesis central nervous system neuron development axonogenesis dendrite development establishment of cell polarity regulation of axonogenesis cellular response to organic substance negative regulation of axon extension regulation of microtubule polymerization negative regulation of microtubule polymerization positive regulation of anterograde dense core granule transport regulation of organelle transport along microtubule positive regulation of anterograde synaptic vesicle transport negative regulation of microtubule binding Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4133 17756 Ensembl ENSG00000078018 ENSMUSG00000015222 UniProt P11137 P20357 RefSeq (mRNA) NM_001039538 NM_002374 NM_031845 NM_031846 NM_031847 NM_001363910 NM_001363911 NM_001363913 NM_001039934 NM_008632 NM_001310634 RefSeq (protein) NP_001034627 NP_002365 NP_114033 NP_114035 NP_001350839 NP_001350840 NP_001350842 NP_001362403 NP_001362422 NP_001362423 NP_001362424 NP_001362425 NP_001362426 NP_001362427 NP_001362428 NP_001362429 NP_001362430 NP_001362431 NP_001362432 NP_001362433 NP_001362434 NP_001362435 NP_001362436 NP_001362437 NP_001362438 NP_001362439 NP_001362455 NP_001362456 NP_001362457 NP_001362458 NP_001362459 NP_001362460 NP_001362461 NP_001362462 NP_001362463 NP_001362464 NP_001362465 NP_001362466 NP_001362467 NP_001362468 NP_001362469 NP_001362470 NP_001362471 NP_001362472 NP_001362473 NP_001362474 NP_001362475 NP_001362477 NP_001362480 NP_001362481 NP_001362482 NP_001362483 NP_001362484 NP_001362485 NP_001362486 NP_001362487 NP_001362488 NP_001362512 NP_001035023 NP_001297563 NP_032658 Location (UCSC) Chr 2: 209.42 – 209.73 Mb Chr 1: 66.21 – 66.48 Mb PubMed search [3] [4]
Wikidata
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Microtubule-associated protein 2 is a protein in humans that is encoded by the MAP2 gene. ^{[5] [6]}

Function

This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family were originally isolated since they copurify with tubulin in polymerization experiments: tubulin in cell extracts can be made to polymerize to produce microtubules (MT) under the influence of heat and the addition of GTP, and the MT can then be collected by centrifugation. When this is done a series of microtubule associated proteins are collected along with the MT and can be detected by SDS-PAGE and other methods. Brain extracts are rich in several of these proteins, MAP2 being one of these. The single MAP2 gene produces four major transcripts producing four proteins, MAP2A, MAP2B, MAP2C and MAP2D. MAP2A and MAP2B are very high molecular weight proteins, with apparent molecular weight on SDS-PAGE about 250 kDa, while MAP2C and MAP2D are much lower molecular weight forms with apparent SDS-PAGE size about 70 kDa. ^[7] All forms of MAP2 share a common core sequence which includes MT binding domains, 18 amino acid sequences which are found in other MT associated proteins such as MAP Tau and MAP1B. The MAP2 isoforms are thought to be involved in MT assembly, which is an essential step in neuritogenesis. MAP2 serves to stabilize MT growth by crosslinking MT with intermediate filaments and other MTs. MAP2 isoforms are neuron-specific cytoskeletal proteins enriched in dendrites and perikarya, implicating a role in determining and stabilizing neuronal morphology during neuron development. As a result antibodies to MAP2 are widely used to identify neuronal cells and trace dendritic processes in experimental contexts.

Interactions

MAP2 has been shown to interact with Grb2, ^{[8] [9]} NEFL ^[10] and MYO7A. ^[11] All MAP2 isoforms bind to microtubules.

Neurons were grown in tissue culture and stained with antibody to MAP2 protein in green and antibody to another microtubule associated protein MAP-tau in red using the immunofluorescence technique. MAP2 is found only in dendrites and perikarya, while MAP-tau is found not only in the dendrites and perikarya but also in axons. As a result, axons appear red since they contain only MAP-tau while the dendrites and perikarya appear yellow, since they contain both proteins and the red and green signals superimpose to produce a yellow signal. DNA is shown in blue using the DAPI stain which highlights the nuclei. Image courtesy EnCor Biotechnology Inc.

References

1. GRCh38: Ensembl release 89: ENSG00000078018 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000015222 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Neve RL, Harris P, Kosik KS, Kurnit DM, Donlon TA (May 1987). "Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2". Brain Res. 387 (3): 271–80. doi:10.1016/0169-328x(86)90033-1. PMID   3103857.
6. Kalcheva N, Albala J, O'Guin K, Rubino H, Garner C, Shafit-Zagardo B (December 1995). "Genomic structure of human microtubule-associated protein 2 (MAP-2) and characterization of additional MAP-2 isoforms". Proc Natl Acad Sci U S A. 92 (24): 10894–8. Bibcode:1995PNAS...9210894K. doi: 10.1073/pnas.92.24.10894 . PMC   40537 . PMID   7479905.
7. "Entrez Gene: MAP2 microtubule-associated protein 2".
8. Lim RW, Halpain S (July 2000). "Regulated association of microtubule-associated protein 2 (MAP2) with Src and Grb2: evidence for MAP2 as a scaffolding protein". J. Biol. Chem. 275 (27): 20578–87. doi: 10.1074/jbc.M001887200 . PMID   10781592.
9. Zamora-Leon SP, Lee G, Davies P, Shafit-Zagardo B (October 2001). "Binding of Fyn to MAP-2c through an SH3 binding domain. Regulation of the interaction by ERK2". J. Biol. Chem. 276 (43): 39950–8. doi: 10.1074/jbc.M107807200 . PMID   11546790.
10. Frappier T, Stetzkowski-Marden F, Pradel LA (April 1991). "Interaction domains of neurofilament light chain and brain spectrin". Biochem. J. 275 (Pt 2): 521–7. doi:10.1042/bj2750521. PMC   1150082 . PMID   1902666.
11. Todorov PT, Hardisty RE, Brown SD (March 2001). "Myosin VIIA is specifically associated with calmodulin and microtubule-associated protein-2B (MAP-2B)". Biochem. J. 354 (Pt 2): 267–74. doi:10.1042/0264-6021:3540267. PMC   1221652 . PMID   11171103.

Further reading

• Roses AD, Einstein G, Gilbert J, Goedert M, Han SH, Huang D, Hulette C, Masliah E, Pericak-Vance MA, Saunders AM, Schmechel DE, Strittmatter WJ, Weisgraber KH, Xi PT (1996). "Morphological, biochemical, and genetic support for an apolipoprotein E effect on microtubular metabolism". Ann. N. Y. Acad. Sci. 777 (1): 146–57. Bibcode:1996NYASA.777..146R. doi:10.1111/j.1749-6632.1996.tb34413.x. PMID   8624078. S2CID   9145181.
• Snásel J, Pichová I (1997). "The cleavage of host cell proteins by HIV-1 protease". Folia Biol. (Praha). 42 (5): 227–30. doi:10.1007/BF02818986. PMID   8997639. S2CID   7617882.
• Shafit-Zagardo B, Kalcheva N (1999). "Making sense of the multiple MAP-2 transcripts and their role in the neuron". Mol. Neurobiol. 16 (2): 149–62. doi:10.1007/BF02740642. PMID   9588626. S2CID   2966442.
• Liu Y, Saad RS, Shen SS, Silverman JF (2003). "Diagnostic value of microtubule-associated protein-2 (MAP-2) for neuroendocrine neoplasms". Advances in Anatomic Pathology. 10 (2): 101–6. doi:10.1097/00125480-200303000-00005. PMID   12605092.
• Ainsztein AM, Purich DL (1992). "Cleavage of bovine brain microtubule-associated protein-2 by human immunodeficiency virus proteinase". J. Neurochem. 59 (3): 874–80. doi:10.1111/j.1471-4159.1992.tb08325.x. PMID   1494913. S2CID   40571317.
• Alberts MJ, Kandt RS, Pericak-Vance MA, Bebout J, Speer MC, Siddique TS, Yamaoka L, Hung WY, Gaskell PC, Roses AD (1991). "MspI RFLP for microtubule associated protein-2 (MAP2)". Nucleic Acids Res. 19 (4): 960. doi:10.1093/nar/19.4.960. PMC   333743 . PMID   1708129.
• Wallin M, Deinum J, Goobar L, Danielson UH (1990). "Proteolytic cleavage of microtubule-associated proteins by retroviral proteinases". J. Gen. Virol. 71 (9): 1985–91. doi: 10.1099/0022-1317-71-9-1985 . PMID   2212989.
• Kosik KS, Orecchio LD, Bakalis S, Duffy L, Neve RL (1988). "Partial sequence of MAP2 in the region of a shared epitope with Alzheimer neurofibrillary tangles". J. Neurochem. 51 (2): 587–98. doi:10.1111/j.1471-4159.1988.tb01079.x. PMID   2455776. S2CID   31087371.
• Dammerman M, Yen SH, Shafit-Zagardo B (1990). "Sequence of a human MAP-2 region sharing epitopes with Alzheimer neurofibrillary tangles". J. Neurosci. Res. 24 (4): 487–95. doi:10.1002/jnr.490240405. PMID   2481044. S2CID   25209290.
• Obar RA, Dingus J, Bayley H, Vallee RB (1990). "The RII subunit of cAMP-dependent protein kinase binds to a common amino-terminal domain in microtubule-associated proteins 2A, 2B, and 2C". Neuron. 3 (5): 639–45. doi:10.1016/0896-6273(89)90274-2. PMID   2561973. S2CID   1329548.
• Rubino HM, Dammerman M, Shafit-Zagardo B, Erlichman J (1990). "Localization and characterization of the binding site for the regulatory subunit of type II cAMP-dependent protein kinase on MAP2". Neuron. 3 (5): 631–8. doi:10.1016/0896-6273(89)90273-0. PMID   2701845. S2CID   45499202.
• Herrmann H, Wiche G (1987). "Plectin and IFAP-300K are homologous proteins binding to microtubule-associated proteins 1 and 2 and to the 240-kilodalton subunit of spectrin". J. Biol. Chem. 262 (3): 1320–5. doi: 10.1016/S0021-9258(19)75789-5 . PMID   3027087.
• Garner CC, Tucker RP, Matus A (1989). "Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites". Nature. 336 (6200): 674–7. doi:10.1038/336674a0. PMID   3200318. S2CID   4368119.
• Takahashi M, Tomizawa K, Sato K, Ohtake A, Omori A (1995). "A novel tau-tubulin kinase from bovine brain". FEBS Lett. 372 (1): 59–64. doi: 10.1016/0014-5793(95)00955-9 . PMID   7556643. S2CID   42295269.
• Kindler S, Garner CC (1995). "Four repeat MAP2 isoforms in human and rat brain". Brain Res. Mol. Brain Res. 26 (1–2): 218–24. doi:10.1016/0169-328X(94)90093-0. PMID   7854050.
• Albala JS, Kalcheva N, Shafit-Zagardo B (1994). "Characterization of the transcripts encoding two isoforms of human microtubule-associated protein-2 (MAP-2)". Gene. 136 (1–2): 377–8. doi:10.1016/0378-1119(93)90502-T. PMID   8294038.
• Illenberger S, Drewes G, Trinczek B, Biernat J, Meyer HE, Olmsted JB, Mandelkow EM, Mandelkow E (1996). "Phosphorylation of microtubule-associated proteins MAP2 and MAP4 by the protein kinase p110mark. Phosphorylation sites and regulation of microtubule dynamics". J. Biol. Chem. 271 (18): 10834–43. doi: 10.1074/jbc.271.18.10834 . PMID   8631898.
• Björkblom B, Ostman N, Hongisto V, Komarovski V, Filén JJ, Nyman TA, Kallunki T, Courtney MJ, Coffey ET (2005). "Constitutively active cytoplasmic c-Jun N-terminal kinase 1 is a dominant regulator of dendritic architecture: role of microtubule-associated protein 2 as an effector". J. Neurosci. 25 (27): 6350–61. doi:10.1523/JNEUROSCI.1517-05.2005. PMC   6725281 . PMID   16000625.