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HIKESHI heat shock protein nuclear import factor hikeshi [ Homo sapiens (human) ]

Gene ID: 51501, updated on 4-Jan-2025

Summary

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Official Symbol
HIKESHIprovided by HGNC
Official Full Name
heat shock protein nuclear import factor hikeshiprovided by HGNC
Primary source
HGNC:HGNC:26938
See related
Ensembl:ENSG00000149196 MIM:614908; AllianceGenome:HGNC:26938
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
HLD13; L7RN6; OPI10; HSPC138; HSPC179; C11orf73
Summary
This gene encodes an evolutionarily conserved nuclear transport receptor that mediates heat-shock-induced nuclear import of 70 kDa heat-shock proteins (Hsp70s) through interactions with FG-nucleoporins. The protein mediates transport of the ATP form but not the ADP form of Hsp70 proteins under conditions of heat shock stress. Structural analyses demonstrate that the protein forms an asymmetric homodimer and that the N-terminal domain consists of a jelly-roll/beta-sandwich fold structure that contains hydrophobic pockets involved in FG-nucleoporin recognition. Reduction of RNA expression levels in HeLa cells using small interfering RNAs results in inhibition of heat shock-induced nuclear accumulation of Hsp70s, indicating a role for this gene in regulation of Hsp70 nuclear import during heat shock stress. [provided by RefSeq, Apr 2016]
Expression
Ubiquitous expression in endometrium (RPKM 9.0), placenta (RPKM 7.6) and 25 other tissues See more
Orthologs
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Genomic context

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See HIKESHI in Genome Data Viewer
Location:
11q14.2
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (86302240..86345943)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (86244638..86288455)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (86013282..86056985)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene embryonic ectoderm development Neighboring gene immunoglobin superfamily member 21 pseudogene Neighboring gene Sharpr-MPRA regulatory region 13347 Neighboring gene SET pseudogene 17 Neighboring gene RNA, 7SL, cytoplasmic 225, pseudogene Neighboring gene uncharacterized LOC105369421 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr11:86067691-86068225 Neighboring gene Sharpr-MPRA regulatory region 8024 Neighboring gene coiled-coil domain containing 81 Neighboring gene PTP4A1 pseudogene 6

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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Related articles in PubMed

  1. The interaction between the import carrier Hikeshi and HSP70 is modulated by heat, facilitating the nuclear import of HSP70 under heat stress conditions. Kose S, et al. Genes Cells, 2024 Sep. PMID 38987995
  2. Heat-shock stress activates a novel nuclear import pathway mediated by Hikeshi. Imamoto N, et al. Nucleus, 2012 Sep-Oct. PMID 22895094, Free PMC Article
  3. Crystallization and preliminary X-ray crystallographic study of human Hikeshi, a new nuclear transport receptor for Hsp70. Song J, et al. Acta Crystallogr F Struct Biol Commun, 2014 Dec 1. PMID 25484218, Free PMC Article
  4. Structural Biology and Regulation of Protein Import into the Nucleus. Christie M, et al. J Mol Biol, 2016 May 22. PMID 26523678
  5. Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene. Edvardson S, et al. J Med Genet, 2016 Feb. PMID 26545878

See all (31) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The interaction between the import carrier Hikeshi and HSP70 is modulated by heat, facilitating the nuclear import of HSP70 under heat stress conditions.
    Title: The interaction between the import carrier Hikeshi and HSP70 is modulated by heat, facilitating the nuclear import of HSP70 under heat stress conditions.
  2. Further Delineation of the Clinical and Pathologic Features of HIKESHI-Related Hypomyelinating Leukodystrophy.
    Title: Further Delineation of the Clinical and Pathologic Features of HIKESHI-Related Hypomyelinating Leukodystrophy.
  3. HIKESHI silencing can enhance mild hyperthermia sensitivity in human oral squamous cell carcinoma HSC3 cells.
    Title: HIKESHI silencing can enhance mild hyperthermia sensitivity in human oral squamous cell carcinoma HSC‑3 cells.
  4. Our results suggest that HIKESHI is a marker of cancer progression and that the combination of HIKESHI inhibition and hyperthermia is a therapeutic tool for refractory gastric cancer
    Title: Heat shock-induced HIKESHI protects cell viability via nuclear translocation of heat shock protein 70.
  5. Depletion of Hikeshi renders HeLa cells proteotoxic stress-sensitive through the abrogation of the nuclear function of HSP70s required for HSF1 regulation.
    Title: Hikeshi modulates the proteotoxic stress response in human cells: Implication for the importance of the nuclear function of HSP70s.
  6. A novel homozygous variant in HIKESHI was identified in a patient with hypomyelinating leukoencephalopathy with periventricular cysts and vermian atrophy. Modified interactions inside Hikeshi's hydrophobic pockets induce mutant protein instability.
    Title: Absence of Hikeshi, a nuclear transporter for heat-shock protein HSP70, causes infantile hypomyelinating leukoencephalopathy.
  7. Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene.P.V54L mutation in Hikeshi is associated with absence of nuclear HSP70 during heat shock stress.
    Title: Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene.
  8. The crystal structure of Hikeshi explains how Hikeshi participates in the regulation of nuclear import through the recognition of FG-Nups and which part of Hikeshi affects its binding to Hsp70.
    Title: Structural and functional analysis of Hikeshi, a new nuclear transport receptor of Hsp70s.
  9. identify a nuclear import pathway that operates during heat shock stress and is mediated by an evolutionarily conserved protein, Hikeshi (coded by the C11orf73 gene) binds to FG-Nups and translocates through nuclear pores on its own, showing characteristic features of nuclear transport carriers.
    Title: Hikeshi, a nuclear import carrier for Hsp70s, protects cells from heat shock-induced nuclear damage.
Submit: New GeneRIF Correction

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

Associated conditions

Description Tests
Hypomyelinating leukodystrophy 13
MedGen: C4225170 OMIM: 616881 GeneReviews: Not available
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EBI GWAS Catalog

Description
A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ43020

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables Hsp70 protein binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables Hsp70 protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables Hsp70 protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables nuclear import signal receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables nuclear import signal receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in Golgi organization IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to heat IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in lung development IEA
Inferred from Electronic Annotation
more info
  
involved_in protein import into nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein import into nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein transport IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
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
  
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
located_in nuclear speck IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
protein Hikeshi
Names
Hikeshi, heat shock protein nuclear import factor
lethal, Chr 7, Rinchik 6

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.

Genomic

  1. NG_046865.1 RefSeqGene

    Range
    5030..48733
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001322404.2 → NP_001309333.1  protein Hikeshi isoform 2

    Status: REVIEWED

    Source sequence(s)
    AP001148
    UniProtKB/TrEMBL
    E9PPG8
    Conserved Domains (1) summary
    pfam05603
    Location:1 → 172
    DUF775; Protein of unknown function (DUF775)

  2. NM_001322407.2 → NP_001309336.1  protein Hikeshi isoform 3

    Status: REVIEWED

    Source sequence(s)
    AP001148
    Conserved Domains (1) summary
    pfam05603
    Location:1 → 156
    DUF775; Protein of unknown function (DUF775)

  3. NM_001322409.2 → NP_001309338.1  protein Hikeshi isoform 3

    Status: REVIEWED

    Source sequence(s)
    AP001148
    Conserved Domains (1) summary
    pfam05603
    Location:1 → 156
    DUF775; Protein of unknown function (DUF775)

  4. NM_016401.4 → NP_057485.2  protein Hikeshi isoform 1

    See identical proteins and their annotated locations for NP_057485.2

    Status: REVIEWED

    Source sequence(s)
    AP001148, BC015991
    Consensus CDS
    CCDS8275.1
    UniProtKB/Swiss-Prot
    Q53FT3, Q8WVE8, Q9NVQ2, Q9NZZ1, Q9P022, Q9P0N1
    UniProtKB/TrEMBL
    E9PPG8
    Related
    ENSP00000278483.3, ENST00000278483.8
    Conserved Domains (1) summary
    pfam05603
    Location:1 → 195
    DUF775; Protein of unknown function (DUF775)

RNA

  1. NR_024597.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AP001148, BC015991, BE858273, BP423222

  2. NR_024598.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AA148558, AP001148, BC021621
    Related
    ENST00000531485.5

  3. NR_136324.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AP001148

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    86302240..86345943
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017017915.2 → XP_016873404.1  protein Hikeshi isoform X2

    Conserved Domains (1) summary
    pfam05603
    Location:1 → 156
    DUF775; Protein of unknown function (DUF775)

  2. XM_017017914.3 → XP_016873403.1  protein Hikeshi isoform X1

    UniProtKB/TrEMBL
    E9PPG8
    Related
    ENSP00000432699.1, ENST00000533986.5

  3. XM_047427117.1 → XP_047283073.1  protein Hikeshi isoform X3

    UniProtKB/TrEMBL
    B4DQE3

RNA

  1. XR_001747904.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    86244638..86288455
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054369111.1 → XP_054225086.1  protein Hikeshi isoform X1

    UniProtKB/TrEMBL
    E9PPG8

  2. XM_054369112.1 → XP_054225087.1  protein Hikeshi isoform X3

    UniProtKB/TrEMBL
    B4DQE3

RNA

  1. XR_008488404.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NR_024596.1: Suppressed sequence

    Description
    NR_024596.1: This RefSeq was removed because currently there is insufficient support for the transcript.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q53FT3.2 GenPept UniProtKB/Swiss-Prot:Q53FT3

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