Microtubule-associated protein 2

Microtubule-associated protein 2 is a protein that in humans is encoded by the MAP2 gene.[5][6]

MAP2
Identifiers
Aliases	MAP2, MAP2A, MAP2B, MAP2C, microtubule associated protein 2, MAP-2
External IDs	OMIM: 157130 MGI: 97175 HomoloGene: 1779 GeneCards: MAP2
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 66,175,273 bp[2] End 66,442,583 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • tubulin binding • GO:0001948 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 • GO:0097483, GO:0097481 postsynaptic density • nuclear periphery • neuron projection • neuronal cell body • dendritic shaft • cell body • CA3 pyramidal cell dendrite • dendrite cytoplasm • axon initial segment • axon hillock • dendritic growth cone • main axon • dendritic branch • basilar 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 • regulation of cellular protein localization • negative regulation of microtubule binding • negative regulation of microtubule motor activity 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: 66.18 – 66.44 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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 250kDa, while MAP2C and MAP2D are much lower molecular weight forms with apparent SDS-PAGE size about 70kDa[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 MAP tau in red using the immunofluorescence technique. MAP2 is found only in dendrites and perikarya, while tau is found not only in the dendrites and perikarya but also in axons. As a result, axons appear red while the dendrites and perikarya appear yellow, due to superimposition of the red and green signals. 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. 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: 146–57. doi:10.1111/j.1749-6632.1996.tb34413.x. PMID 8624078.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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. 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.
• 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.
• 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.