MAP4 (microtubule-associated protein 4)
2009-06-01 Eva Maria Murga Penas , Judith Dierlamm AffiliationDept Oncology, Hematology, BMT with section Pneumology, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr 52, 20246 Hamburg, Germany
Identity
HGNC
LOCATION
3p21.31
IMAGE
LEGEND
MAP4 gene (3p21). FISH on normal lymphocytes using the BAC clone 395P16 on 3p21 obtained from the RPCI-11 library (Roswell Park Cancer Institute, Buffalo, NY). BAC 395P16 contains sequences derived immediately downstream of the MAP4 gene and is translocated to the partner chromosome in case of a translocation involving MAP4.
LOCUSID
ALIAS
MAP-4,MGC8617
FUSION GENES
DNA/RNA
mRNA splice variants of MAP4. Nucleotide assignation according to GenBank sequence NT_022517 REGION: 47832180..48070769 GPS_000125239 (Homo sapiens chromosome 3 genomic contig, GRCh37 reference primary assembly).
Description
MAP4 is encoded by a single-copy gene spanning a region of ~238 kb of genomic DNA. Five alternative transcripts have been described (West et al., 1991). MAP4 is down-regulated by P53 at the transcriptional level. The repression of MAP4 by P53 is exerted by interaction with the promoter region of MAP4. Overexpression of MAP4 markedly inhibits P53 mediated apoptosis (Murphy et al., 1996; Murphy et al., 1999).
Transcription
Centromere to telomere transcription. The multiple MAP4 isoforms are generated by alternative splicing (see figure above).
Proteins
Schematic representation of the MAP4 protein.
Description
The protein encoded by the MAP4 gene is the major microtubule-associated protein in non-neuronal tissues and belongs to the group of microtubule-associated proteins (MAPs) of the MAP2/Tau family (Bulinski et al., 1980; Chapin et al., 1995). MAP4 contains a projection domain in its extreme N-terminus and a microtubule binding domain (MTB) in its carboxyl-terminal portion. The MTB domain consists of 3 subdomains, a Proline-rich region, a Repeat region consisting of an Assembly-Promoting (AP) sequence of 18-amino acids (Aas) residues, and a Tail region rich in hydophobic and acidic Aas. Three to five repeats of the AP sequence have been described in MAP4 (Aizawa et al., 1990). In vitro experiments with bovine MAP4 have shown that the number of repeat sequences affects the microtubule surface properties (Tokuraku et al., 2003).
Expression
Widespread tissue distribution but absent from neurons (Bulinski and Borisy, 1980; Aizawa et al., 1990; Chapin and Bulinski, 1991; West et al., 1991).
Localisation
Cytoplasmic.
Function
MAP4 binds to, polymerizes, and stabilizes microtubules and is thought to regulate microtubule dynamics during the cell cycle. In eukaryotic cells, the onset of M phase is regulated by the p34cdc2/Cyclin B complex, which controls changes in microtubule dynamic properties at the G2 to M phase transition of the cell cycle The control of the microtubule reorganization at mitosis is supposed to be directly regulated by phosphorylation of MAP4 by the p34cdc2 kinase activity (Ookata et al., 1997).
Homology
about 80% similarity/70% identity among the human, mouse, and bovine Aas sequences (West et al., 1991).
Implicated in
Entity name
Diffuse large B-cell non-Hodgkins lymphoma (DLBCL), centroblastic subtype
Disease
Non-reciprocal der(18)t(3;18)(p21;q21) / MALT1-MAP4 translocation.
Cytogenetics
Rearrangements of the MALT1 gene by the translocations t(11;18)(q21;q21) / API2-MALT1 and t(14;18)(q32;q21) / IGH-MALT1 are the most frequent structural chromosomal abnormalities in MALT lymphomas and lead to an activation of the NF-kB pathway (Dierlamm et al., 1999; Uren et al., 2000; Lucas et al., 2001; Streubel et al., 2003). In both translocations the caspase-like domain of MALT1 is invariabily involved. Unlike the API2-MALT1 and IGH-MALT1 products, the MALT1-MAP4 fusion product does not involve the caspase-like domain, which is essential for activation of NF-kB. The absence of the caspase like domain in the MALT1-MAP4 fusion product distinguishes this novel gene fusion, MALT1-MAP4, from the t(11;18)/API2-MALT1 and the t(14;18)/IGH-MALT1 and points to a new mechanism of deregulation of MALT1 (Murga Penas et al., 2006).
Hybrid gene
The 5MALT1-3MAP4 fusion product is the result of an unbalanced translocation that fuses "in frame" the exon 9 of MALT1 located on 18q21 to exon 9 of MAP4 located on 3p21 (Murga Penas et al., 2006). The MALT1-MAP4 fusion is located on the derivative chromosome 18 and due to a partial deletion of MALT1 sequences telomeric to exon 9 the reciprocal transcript MAP4-MALT1 is absent.
The MALT1-MAP4 chimeric product corresponds to a fusion of the MALT1 gene at nucleotide 1276 (Genebank Accession No. NM_006785) to the MAP4 gene at nucleotide 2469 (Genebank Accession No. NM_002375).
The MALT1-MAP4 chimeric product corresponds to a fusion of the MALT1 gene at nucleotide 1276 (Genebank Accession No. NM_006785) to the MAP4 gene at nucleotide 2469 (Genebank Accession No. NM_002375).
Schematic representation of the localization of the breakpoints in MALT1 and MAP4 and the corresponding fusion product.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 2033072 | 1991 | Functional analyses of the domain structure of microtubule-associated protein-4 (MAP-U). | Aizawa H et al |
| 6780572 | 1980 | Widespread distribution of a 210,000 mol wt microtubule-associated protein in cells and tissues of primates. | Bulinski JC et al |
| 1905296 | 1991 | Non-neuronal 210 x 10(3) Mr microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau. | Chapin SJ et al |
| 7857940 | 1995 | Differential expression of alternatively spliced forms of MAP4: a repertoire of structurally different microtubule-binding domains. | Chapin SJ et al |
| 10339464 | 1999 | The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. | Dierlamm J et al |
| 11262391 | 2001 | Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. | Lucas PC et al |
| 16804917 | 2006 | A novel fusion of the MALT1 gene and the microtubule-associated protein 4 (MAP4) gene occurs in diffuse large B-cell lymphoma. | Murga Penas EM et al |
| 10521394 | 1999 | Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. | Murphy M et al |
| 8956998 | 1996 | Wild-type p53 negatively regulates the expression of a microtubule-associated protein. | Murphy M et al |
| 9398320 | 1997 | MAP4 is the in vivo substrate for CDC2 kinase in HeLa cells: identification of an M-phase specific and a cell cycle-independent phosphorylation site in MAP4. | Ookata K et al |
| 12406890 | 2003 | T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. | Streubel B et al |
| 12773533 | 2003 | The number of repeat sequences in microtubule-associated protein 4 affects the microtubule surface properties. | Tokuraku K et al |
| 11090634 | 2000 | Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. | Uren AG et al |
| 1718985 | 1991 | A model for microtubule-associated protein 4 structure. Domains defined by comparisons of human, mouse, and bovine sequences. | West RR et al |
Other Information
Locus ID:
NCBI: 4134
MIM: 157132
HGNC: 6862
Ensembl: ENSG00000047849
Variants:
dbSNP: 4134
ClinVar: 4134
TCGA: ENSG00000047849
COSMIC: MAP4
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38341398 | 2024 | MAP4 acts as an oncogene and prognostic marker and affects radioresistance by mediating epithelial-mesenchymal transition in lung adenocarcinoma. | 0 |
| 38630589 | 2024 | A p85 isoform switch enhances PI3K activation on endosomes by a MAP4- and PI3P-dependent mechanism. | 0 |
| 38341398 | 2024 | MAP4 acts as an oncogene and prognostic marker and affects radioresistance by mediating epithelial-mesenchymal transition in lung adenocarcinoma. | 0 |
| 38630589 | 2024 | A p85 isoform switch enhances PI3K activation on endosomes by a MAP4- and PI3P-dependent mechanism. | 0 |
| 37258650 | 2023 | Effects of three microtubule-associated proteins (MAP2, MAP4, and Tau) on microtubules' physical properties and neurite morphology. | 4 |
| 37258650 | 2023 | Effects of three microtubule-associated proteins (MAP2, MAP4, and Tau) on microtubules' physical properties and neurite morphology. | 4 |
| 33139939 | 2020 | Phosphatidylinositol-3-OH kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4. | 31 |
| 33139939 | 2020 | Phosphatidylinositol-3-OH kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4. | 31 |
| 30737623 | 2019 | Expression of Syk and MAP4 proteins in ovarian cancer. | 8 |
| 31253867 | 2019 | Human Papillomavirus 16 oncoprotein E7 retards mitotic progression by blocking Mps1-MAP4 signaling cascade. | 2 |
| 30737623 | 2019 | Expression of Syk and MAP4 proteins in ovarian cancer. | 8 |
| 31253867 | 2019 | Human Papillomavirus 16 oncoprotein E7 retards mitotic progression by blocking Mps1-MAP4 signaling cascade. | 2 |
| 29743960 | 2018 | Microtubule-Associated Protein 4 Is a Prognostic Factor and Promotes Tumor Progression in Lung Adenocarcinoma. | 14 |
| 30091292 | 2018 | MAP4 regulates Tctex-1 and promotes the migration of epidermal cells in hypoxia. | 5 |
| 30275105 | 2018 | Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs. | 20 |
Citation
Eva Maria Murga Penas ; Judith Dierlamm
MAP4 (microtubule-associated protein 4)
Atlas Genet Cytogenet Oncol Haematol. 2009-06-01
Online version: http://atlasgeneticsoncology.org/gene/44410/map4
