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KRT85 Gene

protein-coding   GIFtS: 49
GCID: GC12M052753

Keratin 85

(Previous names: keratin, hair, basic, 5)
(Previous symbol: KRTHB5)
  See KRT85-related disease
at  

(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
Keratin 851 2     HB52 5
KRTHB51 2 3 5     Hard Keratin Type II1
Keratin, Hair, Basic, 51 2     Hb-52
Hair Keratin K2.122 3     hHb52
Type II Hair Keratin Hb52 3     Hard Keratin, Type II, 52
Type-II Keratin Kb252 3     Keratin, Type II Cuticular Hb52
K852 3     keratin-852
ECTD42 5     Keratin-853

External Ids:    HGNC: 64621   Entrez Gene: 38912   Ensembl: ENSG000001354437   OMIM: 6027675   UniProtKB: P783863   

Export aliases for KRT85 gene to outside databases

Previous GC identifers: GC12M051041 GC12M049797


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for KRT85 Gene:
The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic
protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are
clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure
similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related
subfamily includes KRTHB2, KRTHB4, and KRTHB5. (provided by RefSeq, Jul 2008)

GeneCards Summary for KRT85 Gene:
KRT85 (keratin 85) is a protein-coding gene. Diseases associated with KRT85 include ectodermal dysplasia 4, hair/nail type. GO annotations related to this gene include structural molecule activity. An important paralog of this gene is KRT74.

Gene Wiki entry for KRT85 Gene


(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_000012.11  NT_029419.13  NC_018923.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the KRT85 gene promoter:
         c-Fos   AP-1   JunB   ATF-2   Fra-1   FosB   LCR-F1   YY1   CRE-BP1   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidKRT85 promoter sequence
   Search Chromatin IP Primers for KRT85

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat KRT85


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

Entrez Gene cytogenetic band: 12q13   Ensembl cytogenetic band:  12q13.13   HGNC cytogenetic band: 12q13.13

KRT85 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
KRT85 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12M052753:  view genomic region     (about GC identifiers)

Start:
52,753,790 bp from pter      End:
52,761,309 bp from pter
Size:
7,520 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., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: KRT85_HUMAN, P78386 (See protein sequence)
Recommended Name: Keratin, type II cuticular Hb5  
Size: 507 amino acids; 55802 Da
Subunit: Heterotetramer of two type I and two type II keratins
Miscellaneous: There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic)
Secondary accessions: Q9NSB1

Explore the universe of human proteins at neXtProt for KRT85: NX_P78386

Explore proteomics data for KRT85 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See KRT85 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_002274.1  
    ENSEMBL proteins: 
     ENSP00000257901   ENSP00000440240  

    KRT85 Human Recombinant Protein Products:

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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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    HGNC Gene Families:
    IFF2: Intermediate filaments type II, keratins (basic)

    3 InterPro protein domains:
     IPR018039 Intermediate_filament_CS
     IPR001664 IF
     IPR003054 Keratin_II

    Graphical View of Domain Structure for InterPro Entry P78386

    ProtoNet protein and cluster: P78386

    2 Blocks protein domains:
    IPB001664 Intermediate filament protein
    IPB003054 Type II keratin signature


    UniProtKB/Swiss-Prot: KRT85_HUMAN, P78386
    Similarity: Belongs to the intermediate filament family


    Find genes that share domains with KRT85           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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         Gene Ontology (GO): 1 molecular function term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005198structural molecule activity IEA--
         
    Find genes that share ontologies with KRT85           About GenesLikeMe


    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for KRT85
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    miRNA
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    miRTarBase miRNAs that target KRT85:
    hsa-mir-30a-5p (MIRT005174)

    Block miRNA regulation of human, mouse, rat KRT85 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate KRT85 (see all 11):
    hsa-miR-203 hsa-miR-642a hsa-miR-875-3p hsa-miR-516b hsa-miR-33a hsa-miR-1912 hsa-miR-587 hsa-miR-494
    SwitchGear 3'UTR luciferase reporter plasmidKRT85 3' UTR sequence
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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 COMPARTMENTS: 

    CompartmentConfidence
    cytosol3
    cytoskeleton2
    mitochondrion2
    nucleus1
    peroxisome1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005615extracellular space IDA--
    GO:0005882intermediate filament ----
    GO:0045095keratin filament IEA--

    Find genes that share ontologies with KRT85           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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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for KRT85
    Interactions:

        Search GeneGlobe Interaction Network for KRT85

    STRING Interaction Network Preview (showing 5 interactants - click image to see 18)

    Selected Interacting proteins for KRT85 (P783863 ENSP000002579014) via UniProtKB, MINT, STRING, and/or I2D (see all 27)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MLST8Q9BVC43, ENSP000003718884I2D: score=3 STRING: ENSP00000371888
    DLG3Q927963, ENSP000003634804I2D: score=2 STRING: ENSP00000363480
    TWF2Q6IBS03, ENSP000003039084I2D: score=2 STRING: ENSP00000303908
    ATG3Q9NT623, ENSP000002832904I2D: score=1 STRING: ENSP00000283290
    CDK12Q9NYV43, ENSP000003988804I2D: score=1 STRING: ENSP00000398880
    About this table

    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0008544epidermis development TAS9084137

    Find genes that share ontologies with KRT85           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 KRT85



    (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 KRT85 gene: 
    NM_002283.3  

    Unigene Cluster for KRT85:

    Keratin 85
    Hs.182507  [show with all ESTs]
    Unigene Representative Sequence: NM_002283
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000257901(uc001sag.3) ENST00000544265 ENST00000552537
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate KRT85 (see all 11):
    hsa-miR-203 hsa-miR-642a hsa-miR-875-3p hsa-miR-516b hsa-miR-33a hsa-miR-1912 hsa-miR-587 hsa-miR-494
    SwitchGear 3'UTR luciferase reporter plasmidKRT85 3' UTR sequence
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      QuantiFast Probe-based Assays in human, mouse, rat KRT85

    Additional mRNA sequence: 

    AK302303.1 X99140.1 

    9 DOTS entries:

    DT.307433  DT.100044835  DT.100669499  DT.101986469  DT.120864869  DT.120873204  DT.91949124  DT.95069074 
    DT.97770268 

    2 AceView cDNA sequences:

    NM_002283 X99140 

    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™, 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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    KRT85 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GCTGCTCCAG
    KRT85 Expression
    About this image

    KRT85 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    KRT85 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.182507

    UniProtKB/Swiss-Prot: KRT85_HUMAN, P78386
    Tissue specificity: Synthesis occurs immediately above a small population of matrix cells at the base of the hair
    bulb and the trichocytes lining the dermal papilla and extends upward through the matrix and ends in the lower
    part of the cortex of the hair shaft

        Custom PCR Arrays for KRT85
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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for KRT85

    (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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      --

    ENSEMBL Gene Tree for KRT85 (if available)
    TreeFam Gene Tree for KRT85 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for KRT85 gene
    KRT742  KRT772  KRT6B2  KRT832  KRT762  KRT32  KRT842  KRT862  
    KRT82  KRT812  KRT712  KRT72  KRT792  KRT722  KRT732  KRT6C2  
    KRT52  KRT6A2  KRT22  KRT752  KRT12  KRT822  KRT42  
    Selected SIMAP similar genes for KRT85 using alignment to 2 protein entries:     KRT85_HUMAN (see all proteins) (see all similar genes):
    KRT121P    KRTHB6    KRT83    KRTHB1    KRT81    KRT86
    KRT7    KRT5    KRT84    KRT8    KRT82    KRTHB2
    KRT3    KRT1    KRT71    KRT72    KRT4    KRT75

    Find genes that share paralogs with KRT85           About GenesLikeMe


    1 Pseudogenes.org Pseudogene for KRT85
    PGOHUM00000239784


    (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 KRT85 (see all 304)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs616300041,2,,4
    C,FEctodermal dysplasia 4, hair/nail type (ECTD4)4 pathogenic152595267(-) CGGACG/ACAGCT 2 /H /R mis13Minor allele frequency- A:0.04NS NA EU 5627
    rs352994381,2
    C--49804013(+) CATGT-/ACACACA 1 -- int10--------
    rs1894710151,2
    --52587624(+) CAAGGG/TGTATG 1 -- ds50010--------
    rs28576781,2
    C,F,A,H--52587653(-) CTGAGA/GCAGCC 1 -- ds500115Minor allele frequency- G:0.27EA NS NA WA CSA 642
    rs1171855111,2
    F--52587659(+) CTCAGA/TGGGTA 1 -- ds50011Minor allele frequency- T:0.05NA 120
    rs26586651,2
    C,F,A,H--52587859(+) GAGTTC/TTGGCT 1 -- ds500117Minor allele frequency- T:0.34EA NS NA WA CSA 1524
    rs1814625651,2
    --52587911(+) AGTGGA/GGAGCT 1 -- ds50010--------
    rs1463835671,2
    --52587989(+) AAGCAG/TCAGAG 1 -- ds50010--------
    rs1861450431,2
    --52587994(+) GCAGAG/TTTTCT 1 -- ds50010--------
    rs1901223641,2
    --52588098(+) CACACA/GCTCTT 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for KRT85 (52753790 - 52761309 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for KRT85 (see all 12):    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv899089CNV Loss21882294
    nsv832411CNV Loss17160897
    dgv29e180CNV Gain20482838
    dgv200n27CNV Gain19166990
    esv29967CNV Gain17803354
    dgv70e55CNV Gain17911159
    nsv818917CNV Gain17921354
    nsv832410CNV Gain17160897
    nsv516938CNV Gain+Loss19592680
    esv27319CNV Gain+Loss19812545

    Human Gene Mutation Database (HGMD): KRT85
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing KRT85
    DNA2.0 Custom Variant and Variant Library Synthesis for KRT85

    (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: 602767   
    OMIM disorders: 602032  
    UniProtKB/Swiss-Prot: KRT85_HUMAN, P78386
  • Ectodermal dysplasia 4, hair/nail type (ECTD4) [MIM:602032]: A form of ectodermal dysplasia, a
    heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair,
    teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical
    features represents a different type of ectodermal dysplasia. ECTD4 is characterized by complete alopecia,
    hypotricosis and nail dystrophy in all digits. There is no evidence of any other abnormality. Inheritance can be
    autosomal dominant or recessive. Note=The disease is caused by mutations affecting the gene represented in this
    entry

  • 1 disease for KRT85:    
    About MalaCards
    ectodermal dysplasia 4, hair/nail type


    Find genes that share disorders with KRT85           About GenesLikeMe

    Genetic Association Database (GAD): KRT85

    Export disorders for KRT85 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 KRT85 gene, integrated from 10 sources (see all 18):
    (articles sorted by number of sources associating them with KRT85)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Sequences and differential expression of three novel human type-II hair keratins. (PubMed id 9084137)1, 2, 3, 9 Rogers M.A....Schweizer J. (Differentiation 1997)
    2. New consensus nomenclature for mammalian keratins. (PubMed id 16831889)1, 3 Schweizer J....Wright M.W. (J. Cell Biol. 2006)
    3. A mutation in the hair matrix and cuticle keratin KRTHB5 gene causes ectodermal dysplasia of hair and nail type. (PubMed id 16525032)1, 2 Naeem M.... Ahmad W. (J. Med. Genet. 2006)
    4. Characterization of a 300 kbp region of human DNA containing the type II hair keratin. (PubMed id 10692104)1, 2 Rogers M.A.... Schweizer J. (J. Invest. Dermatol. 2000)
    5. Identification of 12-lipoxygenase interaction with cellular proteins by yeast two-hybrid screening. (PubMed id 10727209)1, 9 Tang K....Honn K.V. (Biochemistry 2000)
    6. Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels. (PubMed id 21987572)1 Lee K.A....Doedens J.R. (J. Biol. Chem. 2011)
    7. Mutations in the keratin 85 (KRT85/hHb5) gene underlie pure hair and nail ectodermal dysplasia. (PubMed id 19865094)1 Shimomura Y....Christiano A.M. (J. Invest. Dermatol. 2010)
    8. Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation. (PubMed id 20409997)1 Rasool M....Dahl N. (Eur J Dermatol 2010)
    9. Network organization of the human autophagy system. (PubMed id 20562859)1 Behrends C....Harper J.W. (Nature 2010)
    10. Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. (PubMed id 21145461)1 Bennett E.J....Harper J.W. (Cell 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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      Query String
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    OMIM
    NCBI Bookshelf
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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: 3891 HGNC: 6462 AceView: KRTHB5 Ensembl:ENSG00000135443 euGenes: HUgn3891
    ECgene: KRT85 H-InvDB: KRT85

    (According to HUGE)
    About This Section

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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)
    About This Section

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    NameDescription
    PharmGKB entry for KRT85 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for KRT85 gene:
    Search GeneIP for patents involving KRT85

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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