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MAP4 (microtubule-associated protein 4)

Written2009-06Eva Maria Murga Penas, Judith Dierlamm
Dept Oncology, Hematology, BMT with section Pneumology, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr 52, 20246 Hamburg, Germany

(Note : for Links provided by Atlas : click)


Other aliasMAP-4
HGNC (Hugo) MAP4
LocusID (NCBI) 4134
Atlas_Id 44410
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 47973079 and ends at 48089279 bp from pter ( according to hg19-Feb_2009)  [Mapping MAP4.png]
  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.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
GUSBP1 (5p14.3) / MAP4 (3p21.31)MALT1 (18q21.32) / MAP4 (3p21.31)MAP4 (3p21.31) / CBFA2T3 (16q24.3)
MAP4 (3p21.31) / CDC25A (3p21.31)MAP4 (3p21.31) / HSPA8 (11q24.1)MAP4 (3p21.31) / KANK4 (1p31.3)
MAP4 (3p21.31) / KLF7 (2q33.3)MAP4 (3p21.31) / LRRC43 (12q24.31)MAP4 (3p21.31) / MALT1 (18q21.32)
MAP4 (3p21.31) / MAP4 (3p21.31)MAP4 (3p21.31) / MON1A (3p21.31)MAP4 (3p21.31) / MYO1B (2q32.3)
MAP4 (3p21.31) / PARP2 (14q11.2)MAP4 (3p21.31) / RHOA (3p21.31)MAP4 (3p21.31) / SMARCC1 (3p21.31)
MAP4 (3p21.31) / SPINK8 (3p21.31)MAP4 (3p21.31) / TNNC2 (20q13.12)NGLY1 (3p24.2) / MAP4 (3p21.31)
NT5C3A (7p14.3) / MAP4 (3p21.31)PLA2G6 (22q13.1) / MAP4 (3p21.31)PMEL (12q13.2) / MAP4 (3p21.31)
PMPCB (7q22.1) / MAP4 (3p21.31)


  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).


  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 Diffuse large B-cell non-Hodgkin's 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/Mutated Gene The 5'MALT1-3'MAP4 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.


Functional analyses of the domain structure of microtubule-associated protein-4 (MAP-U).
Aizawa H, Emori Y, Mori A, Murofushi H, Sakai H, Suzuki K.
J Biol Chem. 1991 May 25;266(15):9841-6.
PMID 2033072
Widespread distribution of a 210,000 mol wt microtubule-associated protein in cells and tissues of primates.
Bulinski JC, Borisy GG.
J Cell Biol. 1980 Dec;87(3 Pt 1):802-8.
PMID 6780572
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, Bulinski JC.
J Cell Sci. 1991 Jan;98 ( Pt 1):27-36.
PMID 1905296
Differential expression of alternatively spliced forms of MAP4: a repertoire of structurally different microtubule-binding domains.
Chapin SJ, Lue CM, Yu MT, Bulinski JC.
Biochemistry. 1995 Feb 21;34(7):2289-301.
PMID 7857940
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, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK, De Wolf-Peeters C, Hagemeijer A, Van den Berghe H, Marynen P.
Blood. 1999 Jun 1;93(11):3601-9.
PMID 10339464
Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway.
Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, Nunez G.
J Biol Chem. 2001 Jun 1;276(22):19012-9. Epub 2001 Mar 21.
PMID 11262391
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, Kawadler H, Siebert R, Frank M, Ye H, Hinz K, Becher C, Hummel M, Barth TF, Bokemeyer C, Stein H, Trumper L, Moller P, Marynen P, Du MQ, Yang X, Hansmann ML, Dierlamm J.
Genes Chromosomes Cancer. 2006 Sep;45(9):863-73.
PMID 16804917
Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a.
Murphy M, Ahn J, Walker KK, Hoffman WH, Evans RM, Levine AJ, George DL.
Genes Dev. 1999 Oct 1;13(19):2490-501.
PMID 10521394
Wild-type p53 negatively regulates the expression of a microtubule-associated protein.
Murphy M, Hinman A, Levine AJ.
Genes Dev. 1996 Dec 1;10(23):2971-80.
PMID 8956998
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, Hisanaga S, Sugita M, Okuyama A, Murofushi H, Kitazawa H, Chari S, Bulinski JC, Kishimoto T.
Biochemistry. 1997 Dec 16;36(50):15873-83.
PMID 9398320
T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma.
Streubel B, Lamprecht A, Dierlamm J, Cerroni L, Stolte M, Ott G, Raderer M, Chott A.
Blood. 2003 Mar 15;101(6):2335-9. Epub 2002 Oct 24.
PMID 12406890
The number of repeat sequences in microtubule-associated protein 4 affects the microtubule surface properties.
Tokuraku K, Matsushima K, Matui T, Nakagawa H, Katsuki M, Majima R, Kotani S.
J Biol Chem. 2003 Aug 8;278(32):29609-18. Epub 2003 May 28.
PMID 12773533
Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma.
Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM.
Mol Cell. 2000 Oct;6(4):961-7.
PMID 11090634
A model for microtubule-associated protein 4 structure. Domains defined by comparisons of human, mouse, and bovine sequences.
West RR, Tenbarge KM, Olmsted JB.
J Biol Chem. 1991 Nov 15;266(32):21886-96.
PMID 1718985


This paper should be referenced as such :
Murga, Penas EM ; Dierlamm, J
MAP4 (microtubule-associated protein 4)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(5):460-463.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(3;18)(p21;q21) MAP4/MALT1
t(3;18)(p21;q21) MALT1/MAP4

External links

HGNC (Hugo)MAP4   6862
Entrez_Gene (NCBI)MAP4  4134  microtubule associated protein 4
GeneCards (Weizmann)MAP4
Ensembl hg19 (Hinxton)ENSG00000047849 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000047849 [Gene_View]  ENSG00000047849 [Sequence]  chr3:47973079-48089279 [Contig_View]  MAP4 [Vega]
ICGC DataPortalENSG00000047849
TCGA cBioPortalMAP4
AceView (NCBI)MAP4
Genatlas (Paris)MAP4
SOURCE (Princeton)MAP4
Genetics Home Reference (NIH)MAP4
Genomic and cartography
GoldenPath hg38 (UCSC)MAP4  -     chr3:47973079-48089279 -  3p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MAP4  -     3p21.31   [Description]    (hg19-Feb_2009)
EnsemblMAP4 - 3p21.31 [CytoView hg19]  MAP4 - 3p21.31 [CytoView hg38]
Mapping of homologs : NCBIMAP4 [Mapview hg19]  MAP4 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AA206810 AA447222 AA904866 AB209377 AF052156
RefSeq transcript (Entrez)NM_001134364 NM_001134365 NM_002375 NM_030884 NM_030885
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MAP4
Cluster EST : UnigeneHs.517949 [ NCBI ]
CGAP (NCI)Hs.517949
Alternative Splicing GalleryENSG00000047849
Gene ExpressionMAP4 [ NCBI-GEO ]   MAP4 [ EBI - ARRAY_EXPRESS ]   MAP4 [ SEEK ]   MAP4 [ MEM ]
Gene Expression Viewer (FireBrowse)MAP4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4134
GTEX Portal (Tissue expression)MAP4
Human Protein AtlasENSG00000047849-MAP4 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP27816   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP27816  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP27816
Splice isoforms : SwissVarP27816
Domaine pattern : Prosite (Expaxy)TAU_MAP_1 (PS00229)    TAU_MAP_2 (PS51491)   
Domains : Interpro (EBI)MAP_tubulin-bd_rpt   
Domain families : Pfam (Sanger)Tubulin-binding (PF00418)   
Domain families : Pfam (NCBI)pfam00418   
Conserved Domain (NCBI)MAP4
DMDM Disease mutations4134
Blocks (Seattle)MAP4
Human Protein Atlas [tissue]ENSG00000047849-MAP4 [tissue]
Peptide AtlasP27816
IPIIPI00396171   IPI00220113   IPI00888475   IPI00910596   IPI00924603   IPI00385147   IPI00333281   IPI01011707   IPI00880007   IPI00743873   IPI00043863   IPI00926984   
Protein Interaction databases
IntAct (EBI)P27816
Ontologies - Pathways
Ontology : AmiGOmicrotubule cytoskeleton organization  microtubule cytoskeleton organization  RNA binding  structural molecule activity  protein binding  cytosol  microtubule  microtubule associated complex  plasma membrane  axoneme  mitotic spindle organization  microtubule binding  postsynaptic density  microtubule cytoskeleton  axon  neuron projection development  neuron projection  microtubule sliding  establishment of spindle orientation  establishment of spindle orientation  cell division  mitotic spindle  negative regulation of non-motile cilium assembly  
Ontology : EGO-EBImicrotubule cytoskeleton organization  microtubule cytoskeleton organization  RNA binding  structural molecule activity  protein binding  cytosol  microtubule  microtubule associated complex  plasma membrane  axoneme  mitotic spindle organization  microtubule binding  postsynaptic density  microtubule cytoskeleton  axon  neuron projection development  neuron projection  microtubule sliding  establishment of spindle orientation  establishment of spindle orientation  cell division  mitotic spindle  negative regulation of non-motile cilium assembly  
NDEx NetworkMAP4
Atlas of Cancer Signalling NetworkMAP4
Wikipedia pathwaysMAP4
Orthology - Evolution
GeneTree (enSembl)ENSG00000047849
Phylogenetic Trees/Animal Genes : TreeFamMAP4
Homologs : HomoloGeneMAP4
Homology/Alignments : Family Browser (UCSC)MAP4
Gene fusions - Rearrangements
Fusion : MitelmanMALT1/MAP4 [18q21.32/3p21.31]  [t(3;18)(p21;q21)]  
Fusion : MitelmanMAP4/CDC25A [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion : MitelmanMAP4/LRRC43 [3p21.31/12q24.31]  [t(3;12)(p21;q24)]  
Fusion : MitelmanMAP4/MON1A [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion : MitelmanMAP4/RHOA [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion : MitelmanMAP4/SPINK8 [3p21.31/3p21.31]  [t(3;3)(p21;p21)]  
Fusion PortalMAP4 3p21.31 CDC25A 3p21.31 OV
Fusion PortalMAP4 3p21.31 LRRC43 12q24.31 OV
Fusion PortalMAP4 3p21.31 MON1A 3p21.31 PRAD
Fusion PortalMAP4 3p21.31 RHOA 3p21.31 BRCA
Fusion PortalMAP4 3p21.31 SPINK8 3p21.31 LUAD
Fusion : TICdbMALT1 [18q21.32]  -  MAP4 [3p21.31]
Fusion : QuiverMAP4
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMAP4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MAP4
Exome Variant ServerMAP4
ExAC (Exome Aggregation Consortium)ENSG00000047849
GNOMAD BrowserENSG00000047849
Varsome BrowserMAP4
Genetic variants : HAPMAP4134
Genomic Variants (DGV)MAP4 [DGVbeta]
DECIPHERMAP4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMAP4 
ICGC Data PortalMAP4 
TCGA Data PortalMAP4 
Broad Tumor PortalMAP4
OASIS PortalMAP4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMAP4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMAP4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MAP4
DgiDB (Drug Gene Interaction Database)MAP4
DoCM (Curated mutations)MAP4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MAP4 (select a term)
NCG5 (London)MAP4
Cancer3DMAP4(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry MAP4
NextProtP27816 [Medical]
Target ValidationMAP4
Huge Navigator MAP4 [HugePedia]
snp3D : Map Gene to Disease4134
BioCentury BCIQMAP4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4134
Chemical/Pharm GKB GenePA30608
Clinical trialMAP4
canSAR (ICR)MAP4 (select the gene name)
PubMed101 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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