MAP4 (microtubule-associated protein 4)

2009-06-01 Eva Maria Murga Penas , Judith Dierlamm Affiliation

Dept 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

MAP4

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

4134

ALIAS

MAP-4,MGC8617

FUSION GENES

Show Gene Fusions

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).

Schematic representation of the localization of the breakpoints in MALT1 and MAP4 and the corresponding fusion product.

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

Gene ID	Transcript ID	Uniprot
ENSG00000047849	ENST00000335271	H0Y2V1
ENSG00000047849	ENST00000360240	P27816
ENSG00000047849	ENST00000383736	B5MEG9
ENSG00000047849	ENST00000395734	P27816
ENSG00000047849	ENST00000420772	F8W9U4
ENSG00000047849	ENST00000423088	H7C456
ENSG00000047849	ENST00000426837	E7EVA0
ENSG00000047849	ENST00000429422	H7C4C5
ENSG00000047849	ENST00000434267	P27816
ENSG00000047849	ENST00000439356	P27816
ENSG00000047849	ENST00000468075	A0A0J9YVV8
ENSG00000047849	ENST00000633710	A0A0J9YW37

Expression (GTEx)

100

150

200

250

300

350

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
16093351	2005	Mammalian septins regulate microtubule stability through interaction with the microtubule-binding protein MAP4.	76
21822276	2011	MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis.	54
23572511	2013	Septins 2, 7 and 9 and MAP4 colocalize along the axoneme in the primary cilium and control ciliary length.	48
19834535	2009	Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.	27
12123579	2002	MAP4 counteracts microtubule catastrophe promotion but not tubulin-sequestering activity in intact cells.	19
25746230	2015	P38/MAPK contributes to endothelial barrier dysfunction via MAP4 phosphorylation-dependent microtubule disassembly in inflammation-induced acute lung injury.	19
18613117	2008	Beta-tubulin isotype classes II and V expression patterns in nonsmall cell lung carcinomas.	15
19367581	2010	Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population.	13
22018492	2012	Knockdown of MAP4 and DNAL1 produces a post-fusion and pre-nuclear translocation impairment in HIV-1 replication.	13
24140250	2014	Activation of cyclic AMP/PKA pathway inhibits bladder cancer cell invasion by targeting MAP4-dependent microtubule dynamics.	13

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