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MZB1 Gene

protein-coding   GIFtS: 45
GCID: GC05M138723

Marginal Zone B And B1 Cell-Specific Protein

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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Marginal Zone B And B1 Cell-Specific Protein1 2     Proapoptotic Caspase Adapter Protein2 3
PACAP2 3 5     MEDA-72 3
Mesenteric Oestrogen-Dependent Adipose Gene- 71 2     pERp12 3
Plasma Cell-Induced ER Protein 11 2     HSPC1902
Proapoptotic Caspase Adaptor Protein1 2     Caspase-2 Binding Protein2
Mesenteric Estrogen-Dependent Adipose 72 3     Marginal Zone B- And B1-Cell-Specific Protein2
Plasma Cell-Induced Resident Endoplasmic Reticulum Protein2 3     MEDA73
Plasma Cell-Induced Resident ER Protein2 3     MGC295065

External Ids:    HGNC: 301251   Entrez Gene: 512372   Ensembl: ENSG000001704767   OMIM: 6094475   UniProtKB: Q8WU393   

Export aliases for MZB1 gene to outside databases

Previous GC identifer: GC05M133912


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for MZB1 Gene:
MZB1 (marginal zone B and B1 cell-specific protein) is a protein-coding gene.

UniProtKB/Swiss-Prot: MZB1_HUMAN, Q8WU39
Function: Associates with immunoglobulin M (IgM) heavy and light chains and promotes IgM assembly and secretion.
May exert its effect by acting as a molecular chaperone or as an oxidoreductase as it displays a low level of
oxidoreductase activity (By similarity). Isoform 2 may be involved in regulation of apoptosis. Helps to diversify
peripheral B-cell functions by regulating Ca(2+) stores, antibody secretion and integrin activation
Function: Acts as a hormone-regulated adipokine/proinflammatory cytokine that is implicated in causing chronic
inflammation, affecting cellular expansion and blunting insulin response in adipocytes. May have a role in the
onset of insulin resistance




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000005.9  NC_018916.2  NT_034772.7  
Regulatory elements:
   Search for regulatory transcription factor binding sites for MZB1
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidMZB1 promoter sequence
   Search Chromatin IP Primers for MZB1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat MZB1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5q31.2   Ensembl cytogenetic band:  5q31.2   HGNC cytogenetic band: 5q31.2

MZB1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MZB1 gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05M138723:  view genomic region     (about GC identifiers)

Start:
138,723,169 bp from pter      End:
138,725,770 bp from pter
Size:
2,602 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: MZB1_HUMAN, Q8WU39 (See protein sequence)
Recommended Name: Marginal zone B- and B1-cell-specific protein precursor  
Size: 189 amino acids; 20694 Da
Subunit: Part of the ER chaperone complex, a multi-protein complex in the endoplasmic reticulum containing a large
number of molecular chaperones which associates with unassembled incompletely folded immunoglobulin heavy chains
(By similarity). Isoform 2 interacts with CASP2 and CASP9. Interacts with HSP90B1 and PDIA3 in a
calcium-dependent manner (By similarity)
Sequence caution: Sequence=AAF36110.1; Type=Erroneous translation; Note=Wrong choice of frame;
Secondary accessions: D2IYS0 Q7Z6N2 Q96RL5 Q9P0T3
Alternative splicing: 5 isoforms:  Q8WU39-1   Q8WU39-2   Q8WU39-3   Q8WU39-4   Q8WU39-5   (Major)

Explore the universe of human proteins at neXtProt for MZB1: NX_Q8WU39

Explore proteomics data for MZB1 at MOPED

Post-translational modifications: 

  • Forms an interchain disulfide bond with IgM monomers (By similarity)1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See MZB1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_057543.2  
    ENSEMBL proteins: 
     ENSP00000423205   ENSP00000415420   ENSP00000425850   ENSP00000303920   ENSP00000424481  
     ENSP00000414565   ENSP00000406529  

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    antibodies-online proteins for MZB1 (11 products) 

     
    antibodies-online peptides for MZB1

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    1 InterPro protein domain:
     IPR021852 DUF3456

    Graphical View of Domain Structure for InterPro Entry Q8WU39

    ProtoNet protein and cluster: Q8WU39

    UniProtKB/Swiss-Prot: MZB1_HUMAN, Q8WU39
    Similarity: Belongs to the MZB1 family


    Find genes that share domains with MZB1           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: MZB1_HUMAN, Q8WU39
    Function: Associates with immunoglobulin M (IgM) heavy and light chains and promotes IgM assembly and secretion.
    May exert its effect by acting as a molecular chaperone or as an oxidoreductase as it displays a low level of
    oxidoreductase activity (By similarity). Isoform 2 may be involved in regulation of apoptosis. Helps to diversify
    peripheral B-cell functions by regulating Ca(2+) stores, antibody secretion and integrin activation
    Function: Acts as a hormone-regulated adipokine/proinflammatory cytokine that is implicated in causing chronic
    inflammation, affecting cellular expansion and blunting insulin response in adipocytes. May have a role in the
    onset of insulin resistance
    Induction: Down-regulated in primary B-cells early after ligand-stimulated activation. Up-regulated in bacterial
    lipopolysaccharides (LPS)-stimulated peritoneal macrophages

         Gene Ontology (GO): 1 molecular function term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding IPI11350957
         
    Find genes that share ontologies with MZB1           About GenesLikeMe


    Animal Models:
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    MZB1_HUMAN, Q8WU39: Isoform 1: Endoplasmic reticulum lumen (By similarity). Secreted
    MZB1_HUMAN, Q8WU39: Isoform 2: Cytoplasm. Note=Diffuse granular localization in the cytoplasm surrounding the
    nucleus

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IEA--
    GO:0005737cytoplasm IDA11350957
    GO:0005788endoplasmic reticulum lumen ISS--
    GO:0034663endoplasmic reticulum chaperone complex ISS--

    Find genes that share ontologies with MZB1           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for MZB1
        PACAP Signaling



        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for MZB1
    Interactions:

        Search GeneGlobe Interaction Network for MZB1

    STRING Interaction Network Preview (showing 5 interactants - click image to see more details)

    Selected Interacting proteins for MZB1 (Q8WU392, 3 ENSP000003039204) via UniProtKB, MINT, STRING, and/or I2D (see all 7)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MAPK6Q166592, 3MINT-8261472 I2D: score=2 
    CASP2P425753, ENSP000003126644I2D: score=1 STRING: ENSP00000312664
    CASP9P552113, ENSP000003302374I2D: score=1 STRING: ENSP00000330237
    PPP2CAP677753I2D: score=1 
    DNAJC10ENSP000002640654STRING: ENSP00000264065
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002642positive regulation of immunoglobulin biosynthetic process ISS--
    GO:0006915apoptotic process IEA--
    GO:0008284positive regulation of cell proliferation IEA--
    GO:0030888regulation of B cell proliferation ISS--
    GO:0033622integrin activation ISS--

    Find genes that share ontologies with MZB1           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for MZB1



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for MZB1 gene: 
    NM_016459.3  

    Unigene Cluster for MZB1:

    Marginal zone B and B1 cell-specific protein
    Hs.409563  [show with all ESTs]
    Unigene Representative Sequence: AK292706
    10 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000503481(uc003lei.3 uc010jfd.3 uc010jfe.3) ENST00000417694(uc003lej.3)
    ENST00000513389 ENST00000302125 ENST00000503120 ENST00000511979 ENST00000503351
    ENST00000509591 ENST00000412103 ENST00000457570
    miRNA
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      QuantiTect SYBR Green Assays in human, mouse, rat MZB1
      QuantiFast Probe-based Assays in human, mouse, rat MZB1

    Additional mRNA sequence: 

    AF151024.1 AK292706.1 BC009931.2 BC021275.2 GQ477350.1 

    9 DOTS entries:

    DT.91748382  DT.306618  DT.120840207  DT.97835513  DT.120840218  DT.95146073  DT.100677647  DT.91748380 
    DT.95146070 

    Selected AceView cDNA sequences (see all 96):

    AF338109 AI203981 AI762046 AA769445 BE676870 BE267663 BE396753 BG059363 
    AA360205 AI203960 AA864299 BP366737 AI920943 BC021275 BC009931 BM918456 
    AW833239 BU599944 BP429239 BI521443 AI825449 BX644740 BX414871 BX421880 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for MZB1 (see all 6)    About this scheme

    ExUns: 1 ^ 2 ^ 3a · 3b · 3c · 3d ^ 4 ^ 5a · 5b · 5c · 5d · 5e
    SP1:        -     -                                                         
    SP2:        -     -     -                                                   
    SP3:        -     -     -     -                                             
    SP4:        -     -     -     -     -                                       
    SP5:                                                                        


    ECgene alternative splicing isoforms for MZB1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    MZB1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTTGCACTAC
    MZB1 Expression
    About this image

    MZB1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    MZB1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.409563

    UniProtKB/Swiss-Prot: MZB1_HUMAN, Q8WU39
    Tissue specificity: Widely expressed with highest levels in adult brain, small intestine and lymphoid tissues such
    as thymus and spleen. Expression is frequently lower in intestinal-type gastric cancer. In obese patients, more
    abundant in omental than in subcutaneous fat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for MZB1 gene from Selected species (see all 7)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Mzb11 , 5 RIKEN cDNA 2010001M09 gene5
    marginal zone B and B1 cell-specific protein 11
    77.59(n)1
    71.19(a)1
      18 (19.19 cM)5
    698161  NM_027222.31  NP_081498.21 
     356472665 
    chicken
    (Gallus gallus)
    Aves LOC1008591891 plasma cell-induced resident endoplasmic reticulum more 59.1(n)
    49.65(a)
      100859189  XM_003642067.2  XP_003642115.1 


    ENSEMBL Gene Tree for MZB1 (if available)
    TreeFam Gene Tree for MZB1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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      --

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for MZB1 (see all 103)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 5 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1180562911,2
    F--138722758(+) AGCTGG/ATGTCA 1 -- ds50011Minor allele frequency- A:0.06EA 120
    rs1407067501,2
    C--138722773(+) CAGAAC/TTGCTT 1 -- ds50010--------
    rs1850275171,2
    --138722876(+) CCGGGC/TGCGGT 1 -- ds50010--------
    rs1883410051,2
    --138723003(+) AAAATC/TAGCCG 1 -- ds50010--------
    rs1925293511,2
    --138723049(+) AGGAGC/GCTGAG 1 -- ds50010--------
    rs1845084681,2
    --138723059(+) GGTGGG/TAGAAT 1 -- ds50010--------
    rs1384803171,2
    C--138723112(+) CTCCA-/TCCA  
            
    GCCTG
    1 -- ds50010--------
    rs1402867351,2
    C--138723113(+) GCACT-/TCCA  
            
    CCAGC
    1 -- ds50010--------
    rs1383750371,2
    C--138723272(+) GGGTT-/TTATTTGA 1 -- cds10--------
    rs1883104031,2
    --138723371(+) GCTTCA/CTGCCC 1 -- ut310--------

    HapMap Linkage Disequilibrium report for MZB1 (138723169 - 138725770 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for MZB1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv482090CNV Gain20164927
    esv28262CNV Gain19812545

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing MZB1
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 609447    OMIM disorders: --


    Find genes that share disorders with MZB1           About GenesLikeMe


    Export disorders for MZB1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for MZB1 gene, integrated from 10 sources (see all 22):
    (articles sorted by number of sources associating them with MZB1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Characterization of a novel proapoptotic caspase-2- and caspase-9- binding protein. (PubMed id 11350957)1, 2, 3, 9 Bonfoco E.... Cooper N.R. (J. Biol. Chem. 2001)
    2. Novel hormone-regulated genes in visceral adipose tissue: cloning and identification of proinflammatory cytokine-like mouse and human MEDA- 7: implications for obesity, insulin resistance and the metabolic syndrome. (PubMed id 21688198)1, 2, 3 Zhang H.... Sairam M.R. (Diabetologia 2011)
    3. MGC29506 gene, frequently down-regulated in intestinal-type gastric cancer, encodes secreted-type protein with conserved cysteine residues. (PubMed id 12792799)1, 2, 9 Katoh M. and Katoh M. (Int. J. Oncol. 2003)
    4. Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor suppressor in hepatocellular carcinoma. (PubMed id 22573353)1, 3 Matsumura S....Inazawa J. (Clin. Cancer Res. 2012)
    5. Mzb1 protein regulates calcium homeostasis, antibody secretion, and integrin activation in innate-like B cells. (PubMed id 21093319)1, 3 Flach H....Grosschedl R. (Immunity 2010)
    6. pERp1 is significantly up-regulated during plasma cell differentiation and contributes to the oxidative folding of immunoglobulin. (PubMed id 19805157)1, 2 Shimizu Y.... Hendershot L.M. (Proc. Natl. Acad. Sci. U.S.A. 2009)
    7. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (Nat. Genet. 2004)
    8. Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. (PubMed id 11042152)1, 2 Zhang Q.-H.... Chen Z. (Genome Res. 2000)
    9. Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis. (PubMed id 12573802)3, 9 Isobe K....Nakai T. (Regul. Pept. 2003)
    10. High expression of MZB1 predicts adverse prognosis in chronic lymphocytic leukemia, follicular lymphoma and diffuse large B-cell lymphoma and is associated with a unique gene expression signature. (PubMed id 23189934)1 Herold T....Bohlander S.K. (amp 2013)

    (in PubMed, OMIM, and NCBI Bookshelf)
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      Query String
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 51237 HGNC: 30125 AceView: PACAP Ensembl:ENSG00000170476 euGenes: HUgn51237
    ECgene: MZB1 H-InvDB: MZB1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for MZB1 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    IP news from LifeMap Sciences, Inc.)
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    Patent Information for MZB1 gene:
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    GeneCards and IP:
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