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

Summary

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: mouse all
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Genomic context

Location:: 11q14.2

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (86302240..86345943)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (86244638..86288455)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (86013282..86056985)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.

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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	Compare labs

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW465254 (e-PCR)
- UniSTS:278080

RH46883 (e-PCR)
- UniSTS:54207

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

NG_046865.1 RefSeqGene

Range

5030..48733

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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)
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)
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)
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

NR_024597.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AP001148, BC015991, BE858273, BP423222
NR_024598.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AA148558, AP001148, BC021621

Related

ENST00000531485.5
NR_136324.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AP001148

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

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

86302240..86345943

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017017915.2 → XP_016873404.1 protein Hikeshi isoform X2

Conserved Domains (1) summary

pfam05603
Location:1 → 156

DUF775; Protein of unknown function (DUF775)
XM_017017914.3 → XP_016873403.1 protein Hikeshi isoform X1

UniProtKB/TrEMBL

E9PPG8

Related

ENSP00000432699.1, ENST00000533986.5
XM_047427117.1 → XP_047283073.1 protein Hikeshi isoform X3

UniProtKB/TrEMBL

B4DQE3

RNA

XR_001747904.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

86244638..86288455

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054369111.1 → XP_054225086.1 protein Hikeshi isoform X1

UniProtKB/TrEMBL

E9PPG8
XM_054369112.1 → XP_054225087.1 protein Hikeshi isoform X3

UniProtKB/TrEMBL

B4DQE3

RNA

XR_008488404.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NR_024596.1: Suppressed sequence

Description

NR_024596.1: This RefSeq was removed because currently there is insufficient support for the transcript.