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    MAL mal, T cell differentiation protein [ Homo sapiens (human) ]

    Gene ID: 4118, updated on 11-Apr-2024

    Summary

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    Official Symbol
    MALprovided by HGNC
    Official Full Name
    mal, T cell differentiation proteinprovided by HGNC
    Primary source
    HGNC:HGNC:6817
    See related
    Ensembl:ENSG00000172005 MIM:188860; AllianceGenome:HGNC:6817
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MVP17; VIP17
    Summary
    The protein encoded by this gene is a highly hydrophobic integral membrane protein belonging to the MAL family of proteolipids. The protein has been localized to the endoplasmic reticulum of T-cells and is a candidate linker protein in T-cell signal transduction. In addition, this proteolipid is localized in compact myelin of cells in the nervous system and has been implicated in myelin biogenesis and/or function. The protein plays a role in the formation, stabilization and maintenance of glycosphingolipid-enriched membrane microdomains. Down-regulation of this gene has been associated with a variety of human epithelial malignancies. Alternative splicing produces four transcript variants which vary from each other by the presence or absence of alternatively spliced exons 2 and 3. [provided by RefSeq, May 2012]
    Annotation information
    Note: MAL (Gene ID: 4118), TIRAP (Gene ID: 114609), and MKL1 (Gene ID: 57591) share the MAL symbol/alias in common. MAL is a widely used alternative name for TIR domain containing adaptor protein (TIRAP) and megakaryoblastic leukemia (translocation) 1 (MKL1). [23 May 2018]
    Expression
    Biased expression in esophagus (RPKM 937.0) and kidney (RPKM 115.6) See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    2q11.1
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (95025708..95053992)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (95532209..95560493)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (95691453..95719737)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373487 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:95660342-95660890 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:95660891-95661438 Neighboring gene RNA, 7SL, cytoplasmic 575, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16180 Neighboring gene MAL antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:95687830-95688330 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11737 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:95691837-95692560 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:95697485-95698400 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11738 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:95709333-95709988 Neighboring gene uncharacterized LOC124906047 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:95713447-95713986 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16181 Neighboring gene uncharacterized LOC124907857 Neighboring gene uncharacterized LOC105373488 Neighboring gene NANOG hESC enhancer GRCh37_chr2:95753198-95753763 Neighboring gene mitochondrial ribosomal protein S5 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11739

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein. Leitner J, et al. Eur J Immunol, 2021 Apr. PMID 33345332, Free PMC Article
    2. Clostridium perfringens epsilon toxin binds to erythrocyte MAL receptors and triggers phosphatidylserine exposure. Geng Z, et al. J Cell Mol Med, 2020 Jul. PMID 32463157, Free PMC Article
    3. The Cytotoxicity of Epsilon Toxin from Clostridium perfringens on Lymphocytes Is Mediated by MAL Protein Expression. Blanch M, et al. Mol Cell Biol, 2018 Oct 1. PMID 29987189, Free PMC Article
    4. MAL gene overexpression as a marker of high-grade serous ovarian carcinoma stem-like cells that predicts chemoresistance and poor prognosis. Zanotti L, et al. BMC Cancer, 2017 May 25. PMID 28545541, Free PMC Article
    5. Suppression of MAL gene expression in gastric cancer correlates with metastasis and mortality. Kurashige J, et al. Fukuoka Igaku Zasshi, 2013 Oct. PMID 24511665

    See all (66) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2.
      Title: MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2.
    2. MAL protein suppresses the metastasis and invasion of GC cells by interfering with the phosphorylation of STAT3.
      Title: MAL protein suppresses the metastasis and invasion of GC cells by interfering with the phosphorylation of STAT3.
    3. Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein.
      Title: Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein.
    4. Clostridium perfringens epsilon toxin binds to erythrocyte MAL receptors and triggers phosphatidylserine exposure.
      Title: Clostridium perfringens epsilon toxin binds to erythrocyte MAL receptors and triggers phosphatidylserine exposure.
    5. Experiments on lymphocytic cell lines revealed that MAL protein-expressing T cells, but not B cells, are sensitive to Epsilon toxin (Etx) from Clostridium perfringens and reveal that the toxin may be used as a molecular tool to distinguish subpopulations of lymphocytes.
      Title: The Cytotoxicity of Epsilon Toxin from Clostridium perfringens on Lymphocytes Is Mediated by MAL Protein Expression.
    6. In high-grade serous ovarian carcinoma patients, MAL was overexpressed in platinum-resistant compared to platinum-sensitive patients and resulted as an independent prognostic marker of survival.
      Title: MAL gene overexpression as a marker of high-grade serous ovarian carcinoma stem-like cells that predicts chemoresistance and poor prognosis.
    7. MAL and TMEM220 were specifically methylated and were down-regulated in human gastric cancer.
      Title: MAL and TMEM220 are novel DNA methylation markers in human gastric cancer.
    8. This study revealed that Merkel cell polyomavirus -negative Merkel cell carcinomas significantly expressed higher CADM1 and lower MAL than Merkel cell polyomavirus -positive Merkel cell carcinomas
      Title: Lower expression of CADM1 and higher expression of MAL in Merkel cell carcinomas are associated with Merkel cell polyomavirus infection and better prognosis.
    9. CADM1/MAL methylation increases with severity of cervical intraepithelial neoplasia
      Title: CADM1 and MAL methylation status in cervical scrapes is representative of the most severe underlying lesion in women with multiple cervical biopsies.
    10. Hypermethylation of the selected markers (MAL, PRIMA1, PTGDR and SFRP1) can result in reduced gene expression and may contribute to the formation of colorectal cancer.
      Title: DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (39)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef HIV-1 Nef interacts with MAL-dependent pathway to enhance exosome release PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables lipid binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables peptidase activator activity involved in apoptotic process NAS
    Non-traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables structural constituent of myelin sheath IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables structural constituent of myelin sheath IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in apical protein localization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in apoptotic process NAS
    Non-traceable Author Statement
    more info
    		  
    involved_in cell differentiation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in central nervous system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in central nervous system myelination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in membrane raft polarization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in myelination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in myelination NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in myelination TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of extrinsic apoptotic signaling pathway via death domain receptors IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein insertion into plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein localization to paranode region of axon IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Schmidt-Lanterman incisure IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in apical plasma membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in hinge region between urothelial plaques of apical plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane raft IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane raft IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    myelin and lymphocyte protein
    Names
    T-lymphocyte maturation-associated protein

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_002371.4 → NP_002362.1  myelin and lymphocyte protein isoform a

      See identical proteins and their annotated locations for NP_002362.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a) includes both alternatively spliced exons 2 and 3, resulting in the longest isoform (a).
      Source sequence(s)
      BC000458, DT215613, X76678
      Consensus CDS
      CCDS2006.1
      UniProtKB/Swiss-Prot
      P21145, Q6FH77
      Related
      ENSP00000310880.4, ENST00000309988.9
      Conserved Domains (1) summary
      pfam01284
      Location:19 → 145
      MARVEL; Membrane-associating domain

    2. NM_022438.3 → NP_071883.1  myelin and lymphocyte protein isoform b

      See identical proteins and their annotated locations for NP_071883.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (b) includes alternatively spliced exon 2 but is missing exon 3, resulting in isoform b which is shorter than the predominant isoform (a).
      Source sequence(s)
      BC000458, DT215613, X76679
      Consensus CDS
      CCDS2007.1
      UniProtKB/Swiss-Prot
      P21145
      Related
      ENSP00000306568.4, ENST00000353004.7

    3. NM_022439.3 → NP_071884.1  myelin and lymphocyte protein isoform c

      See identical proteins and their annotated locations for NP_071884.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (c) is missing alternatively spliced exon 2 but includes exon 3, resulting in isoform c which is shorter than the predominant isoform (a).
      Source sequence(s)
      BC000458, DT215613, X76680
      Consensus CDS
      CCDS2008.1
      UniProtKB/Swiss-Prot
      P21145
      Related
      ENSP00000304924.3, ENST00000354078.7
      Conserved Domains (1) summary
      cl04571
      Location:31 → 89
      MARVEL; Membrane-associating domain

    4. NM_022440.3 → NP_071885.1  myelin and lymphocyte protein isoform d

      See identical proteins and their annotated locations for NP_071885.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (d) is missing alternatively spliced exons 2 and 3, resulting in the shortest isoform (d).
      Source sequence(s)
      BC000458, DT215613, X76681
      Consensus CDS
      CCDS2009.1
      UniProtKB/Swiss-Prot
      P21145
      Related
      ENSP00000322860.3, ENST00000349807.3

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      95025708..95053992
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      95532209..95560493
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P21145.1 GenPept UniProtKB/Swiss-Prot:P21145

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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