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    KLHL3 kelch like family member 3 [ Homo sapiens (human) ]

    Gene ID: 26249, updated on 11-Apr-2024

    Summary

    Official Symbol
    KLHL3provided by HGNC
    Official Full Name
    kelch like family member 3provided by HGNC
    Primary source
    HGNC:HGNC:6354
    See related
    Ensembl:ENSG00000146021 MIM:605775; AllianceGenome:HGNC:6354
    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
    PHA2D
    Summary
    This gene is ubiquitously expressed and encodes a full-length protein which has an N-terminal BTB domain followed by a BACK domain and six kelch-like repeats in the C-terminus. These kelch-like repeats promote substrate ubiquitination of bound proteins via interaction of the BTB domain with the CUL3 (cullin 3) component of a cullin-RING E3 ubiquitin ligase (CRL) complex. Muatations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]
    Expression
    Broad expression in thyroid (RPKM 5.9), heart (RPKM 4.0) and 23 other tissues See more
    Orthologs
    NEW
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    Try the new Transcript table

    Genomic context

    Location:
    5q31.2
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (137617500..137736089, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (138138636..138261929, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (136953189..137071778, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene RNA, 5S ribosomal pseudogene 193 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:136372100-136372962 Neighboring gene SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:136385493-136386121 Neighboring gene uncharacterized LOC105379192 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr5:136481153-136482352 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:136536474-136537125 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16381 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:136570305-136571504 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:136655443-136655942 Neighboring gene MPRA-validated peak5485 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16382 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23182 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23183 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:136965897-136966647 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16383 Neighboring gene Sharpr-MPRA regulatory region 15161 Neighboring gene MPRA-validated peak5486 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr5:137020129-137020374 Neighboring gene Sharpr-MPRA regulatory region 14679 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:137023227-137023961 Neighboring gene VISTA enhancer hs2181 Neighboring gene microRNA 874 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23184 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr5:137071377-137072045 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:137088711-137089402 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23186 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:137090093-137090784 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23187 Neighboring gene heterogeneous nuclear ribonucleoprotein A0 Neighboring gene neuropeptide Y receptor Y6 (pseudogene)

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ40871, KIAA1129, MGC44594

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables actin binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables cullin family protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables structural molecule activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables ubiquitin-like ligase-substrate adaptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in distal tubule morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in gene expression IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in macroautophagy TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in monoatomic ion homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in monoatomic ion homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in potassium ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein K48-linked ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in protein K48-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein ubiquitination TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in renal sodium ion absorption IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in renal sodium ion absorption IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in renal sodium ion absorption IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of Cul3-RING ubiquitin ligase complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of Cul3-RING ubiquitin ligase complex TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in cytoskeleton IEA
    Inferred from Electronic Annotation
    more info
     
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_032569.1 RefSeqGene

      Range
      5002..123591
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001257194.1NP_001244123.1  kelch-like protein 3 isoform 2

      See identical proteins and their annotated locations for NP_001244123.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks a 5' coding exon and has an alternate 5' exon which results in the use of a downstream in-frame start codon, compared to variant 1. These differences result in a protein (isoform 2; also known as KLHL3b) with a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AB032955, AC106775, AF208070
      Consensus CDS
      CCDS58970.1
      UniProtKB/Swiss-Prot
      Q9UH77
      Related
      ENSP00000422099.1, ENST00000508657.5
      Conserved Domains (4) summary
      PHA03098
      Location:15534
      PHA03098; kelch-like protein; Provisional
      sd00038
      Location:399444
      Kelch; KELCH repeat [structural motif]
      cd18339
      Location:1117
      BTB_POZ_KLHL3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3)
      cd18513
      Location:115244
      BACK_KLHL3; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 3 (KLHL3)
    2. NM_001257195.2NP_001244124.1  kelch-like protein 3 isoform 3

      See identical proteins and their annotated locations for NP_001244124.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks multiple 5' coding exons and has an alternate 5' exon which results in the use of a downstream in-frame start codon, compared to variant 1. These differences result in a protein (isoform 3; also known as KLHL3c) with a shorter N-terminus, compared to isoform 1. This isoform is predicted to lack the protein binding BTB domain that is present in isoform 1.
      Source sequence(s)
      AB032955, AC092318, AC106775, AF208069
      Consensus CDS
      CCDS58969.1
      UniProtKB/Swiss-Prot
      Q9UH77
      Related
      ENSP00000424828.1, ENST00000506491.5
      Conserved Domains (3) summary
      PHA03098
      Location:15484
      PHA03098; kelch-like protein; Provisional
      sd00038
      Location:349394
      Kelch; KELCH repeat [structural motif]
      cd18513
      Location:65194
      BACK_KLHL3; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 3 (KLHL3)
    3. NM_017415.3NP_059111.2  kelch-like protein 3 isoform 1

      See identical proteins and their annotated locations for NP_059111.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1; also known as KLHL3a).
      Source sequence(s)
      AB032955, AC106775, DA083147
      Consensus CDS
      CCDS4192.1
      UniProtKB/Swiss-Prot
      B2RBK7, Q9UH75, Q9UH76, Q9UH77, Q9ULU0, Q9Y6V6
      Related
      ENSP00000312397.4, ENST00000309755.9
      Conserved Domains (4) summary
      PHA03098
      Location:47566
      PHA03098; kelch-like protein; Provisional
      sd00038
      Location:431476
      Kelch; KELCH repeat [structural motif]
      cd18339
      Location:29149
      BTB_POZ_KLHL3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3)
      cd18513
      Location:147276
      BACK_KLHL3; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 3 (KLHL3)

    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_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      137617500..137736089 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      138138636..138261929 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)