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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

ENSG00000226260 Gene

protein-coding   GIFtS: 16
GCID: GC06Pl32446          (predicted)

ENSG00000226260


  Search for ENSG00000226260
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
HLA-DRA13
MHC Class II Antigen DRA3

External Ids:    Ensembl: ENSG000002262607   UniProtKB: P019033   

Export aliases for ENSG00000226260 gene to outside databases


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

GeneCards Summary for ENSG00000226260 Gene: 
ENSG00000226260 is a protein-coding gene.

UniProtKB/Swiss-Prot: DRA_HUMAN, P01903
Function: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC)
and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates
peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation
of proteins that access the endocytic route, where they are processed by lysosomal proteases and other
hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation
via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous.
As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also
contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from
endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with
MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as
epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI
tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of
an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry
of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential
degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP
(class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to
the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high
affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell
membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO.
Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the
regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and
efficient peptide loading




(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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
Regulatory elements:
   Search SABiosciences Regulatory transcription factor binding sites for ENSG00000226260
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search SABiosciences Chromatin IP Primers for ENSG00000226260

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ENSG00000226260


Genomic Location:
Chromosome:6   

Ensembl cytogenetic band:  HSCHR6_MHC_MANNp21.32   

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06Pl32446:       (about GC identifiers)

Start:
32,446,282 bp from pter      End:
32,451,493 bp from pter
Size:
5,212 bases      Orientation:
plus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: DRA_HUMAN, P01903 (See protein sequence)
Recommended Name: HLA class II histocompatibility antigen, DR alpha chain precursor  
Size: 254 amino acids; 28607 Da
Subunit: Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. In the endoplasmic
reticulum (ER) it forms a heterononamer; 3 MHC class II molecules bind to a CD74 homotrimer (also known as
invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system; CD74
undergoes sequential degradation by various proteases; leaving a small fragment termed CLIP on each MHC class II
molecule. MHC class II molecule interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP and
facilitate the binding of antigenic peptides
Subcellular location: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane;
Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane
protein. Endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane
protein. Late endosome membrane; Single-pass type I membrane protein. Note=The MHC class II complex transits
through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for
antigen presentation
Sequence caution: Sequence=CAA25076.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
6/58 PDB 3D structures from and Proteopedia for ENSG00000226260 (see all 58):
1A6A (3D)        1AQD (3D)        1BX2 (3D)        1D5M (3D)        1D5X (3D)        1D5Z (3D)    
Secondary accessions: A2BET4 Q30160 Q6IAZ1 Q861I2 Q9TP70

Explore the universe of human proteins at neXtProt for ENSG00000226260: NX_P01903

Explore proteomics data for ENSG00000226260 at MOPED 

Post-translational modifications:

  • UniProtKB: Ubiquitinated by MARCH1 or MARCH8 at Lys-244 leading to down-regulation of MHC class II. When associated with
    ubiquitination of the beta subunit of HLA-DR: HLA-DRB4 'Lys-254', the down-regulation of MHC class II may be
    highly effective
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P01903

  • ENSG00000226260 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    ENSG00000226260 Protein Expression

    ENSEMBL proteins: 
     ENSP00000404533   ENSP00000392789   ENSP00000449251  
    Reactome Protein details: P01903
    Human Recombinant Protein Products for ENSG00000226260: 
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    Browse Sino Biological Recombinant Proteins
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    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp. 

    Gene Ontology (GO): 5/15 cellular component terms (GO ID links to tree view) (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane ----
    GO:0005764lysosome ----
    GO:0005765lysosomal membrane ----
    GO:0005886plasma membrane ----
    GO:0005887integral to plasma membrane ----

    ENSG00000226260 for ontologies           About GeneDecksing



    ENSG00000226260 Antibody Products: 
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    Assay Products for ENSG00000226260: 
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    Browse ELISAs at Cloud-Clone Corp. 
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    5/7 InterPro protein domains (see all 7):
     IPR007110 Ig-like_dom
     IPR001003 MHC_II_a_N
     IPR003006 Ig/MHC_CS
     IPR011162 MHC_I/II-like_Ag-recog
     IPR013783 Ig-like_fold

    Graphical View of Domain Structure for InterPro Entry P01903

    ProtoNet protein and cluster: P01903

    2 Blocks protein domains:
    IPB001003 MHC Class II alpha chain
    IPB003597 Immunoglobulin C-type


    UniProtKB/Swiss-Prot: DRA_HUMAN, P01903
    Similarity: Belongs to the MHC class II family
    Similarity: Contains 1 Ig-like C1-type (immunoglobulin-like) domain


    ENSG00000226260 for domains           About GeneDecksing


    (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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: DRA_HUMAN, P01903
    Function: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC)
    and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates
    peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation
    of proteins that access the endocytic route, where they are processed by lysosomal proteases and other
    hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation
    via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous.
    As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also
    contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from
    endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with
    MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as
    epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI
    tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of
    an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry
    of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential
    degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP
    (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to
    the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high
    affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell
    membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO.
    Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the
    regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and
    efficient peptide loading

         Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding ----
    GO:0032395MHC class II receptor activity ----
         
    ENSG00000226260 for ontologies           About GeneDecksing


    Animal Models:
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    (Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
    About This Section

    Pathways by sourceSee SuperPaths
    Show all pathways


    5/13        Reactome Pathways for ENSG00000226260 (see all 13)
        Interferon gamma signaling
    Costimulation by the CD28 family
    Cytokine Signaling in Immune system
    Adaptive Immune System
    Translocation of ZAP-70 to Immunological synapse



    ENSG00000226260 for pathways           About GeneDecksing

    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for ENSG00000226260

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/67 Interacting proteins for ENSG00000226260 (P019032, 3 ENSP000004045334) via UniProtKB, MINT, STRING, and/or I2D (see all 67)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HLA-DRB1P019122, 3, ENSP000003530994I2D: score=1 I2D: score=1 MINT-24881 I2D: score=2 MINT-24910 I2D: score=1 I2D: score=1 STRING: ENSP00000353099
    ENSG00000206240P019122, 3MINT-24910 I2D: score=1 
    ENSG00000206306P019122, 3MINT-24910 I2D: score=1 
    CD74P042332, 3, ENSP000000095304MINT-72789 I2D: score=2 STRING: ENSP00000009530
    ENSG00000239329P280683, ENSP000003936464I2D: score=2 STRING: ENSP00000393646
    About this table

    Gene Ontology (GO): 5/8 biological process terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002504antigen processing and presentation of peptide or polysaccharide antigen via MHC class II ----
    GO:0006955immune response ----
    GO:0019221cytokine-mediated signaling pathway ----
    GO:0019882antigen processing and presentation ----
    GO:0019886antigen processing and presentation of exogenous peptide antigen via MHC class II ----

    ENSG00000226260 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for ENSG00000226260 (DRA)

    Search CenterWatch for drugs/clinical trials and news about ENSG00000226260 / DRA

    (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,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    12 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000442960(uc011hek.2 uc011hek.2 uc011hek.2) ENST00000482781
    ENST00000415767 ENST00000549531 ENST00000442960(uc011hek.2 uc011hek.2 uc011hek.2)
    ENST00000482781 ENST00000415767 ENST00000549531 ENST00000442960(uc011hek.2 uc011hek.2 uc011hek.2)
    ENST00000482781 ENST00000415767 ENST00000549531
    miRNA
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    GeneLoc Exon Structure


    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section
    See probesets specificity/sensitivity at GeneAnnot
    CGAP TAG: --


    See ENSG00000226260 Protein Expression from SPIRE MOPED and PaxDB    SABiosciences Custom PCR Arrays for ENSG00000226260
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    In Situ
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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)
    About This Section
      --

    ENSEMBL Gene Tree for ENSG00000226260 (if available)
    TreeFam Gene Tree for ENSG00000226260 (if available)

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

    (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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    UniProtKB/Swiss-Prot: DRA_HUMAN, P01903
    Polymorphism: The following alleles of DRA are known: DRA*01:01 and DRA*01:02. The sequence shown is that of
    DRA*01:01
    Polymorphism: Genetic variations in HLA-DRA influence susceptibility to hepatitis B virus (HBV) infection
    [MIM:610424]

    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
      --

    (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)
    About This Section

    PubMed articles for ENSG00000226260 gene, integrated from 9 sources (see all 35):
    (articles sorted by number of sources associating them with ENSG00000226260)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Initial characterization of the human central proteome. (PubMed id 21269460)2 Burkard T.R.... Colinge J. (2011)
    2. Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. (PubMed id 19159218)2 Chen R.... Zou H. (2009)
    3. MHC class II transport at a glance. (PubMed id 19092054)2 Berger A.C. and Roche P.A. (2009)
    4. CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract. (PubMed id 19533806)2 Beswick E.J. and Reyes V.E. (2009)
    5. The HLA-DRalpha chain is modified by polyubiquitination. (PubMed id 19117940)2 Lapaque N....Kelly A.P. (2009)
    6. The structure of HLA-DR52c: comparison to other HLA-DRB3 alleles. (PubMed id 18697946)2 Dai S.... Kappler J.W. (2008)
    7. MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. (PubMed id 18305173)2 De Gassart A....Gatti E. (2008)
    8. MHC class II molecules on the move for successful antigen presentation. (PubMed id 18046453)2 Rocha N. and Neefjes J. (2008)
    9. Autophagy in MHC class II presentation: sampling from within. (PubMed id 17241953)2 Menendez-Benito V. and Neefjes J. (2007)
    10. Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101: models of a directional alloimmune response and autoimmunity. (PubMed id 17583734)2 Parry C.S....Stern L.J. (2007)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Ensembl:ENSG00000226260

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
      --

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ENSG00000226260 gene:
    Search GeneIP for patents involving ENSG00000226260

    GeneCards and IP:
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    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 3 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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    (GIFtS: 73)
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