HIKES_HUMAN
ID HIKES_HUMAN Reviewed; 197 AA.
AC Q53FT3; Q8WVE8; Q9NVQ2; Q9NZZ1; Q9P022; Q9P0N1;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Protein Hikeshi {ECO:0000305};
GN Name=HIKESHI {ECO:0000312|HGNC:HGNC:26938}; Synonyms=C11orf73;
GN ORFNames=HSPC138, HSPC179, HSPC248;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney proximal tubule;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-47.
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION,
RP INTERACTION WITH NUP62; NUP153 AND HSP70 PROTEINS, AND INDUCTION.
RX PubMed=22541429; DOI=10.1016/j.cell.2012.02.058;
RA Kose S., Furuta M., Imamoto N.;
RT "Hikeshi, a nuclear import carrier for hsp70s, protects cells from heat
RT shock-induced nuclear damage.";
RL Cell 149:578-589(2012).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8] {ECO:0007744|PDB:3WVZ, ECO:0007744|PDB:3WW0}
RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF HOMODIMER, FUNCTION, MUTAGENESIS
RP OF VAL-18; VAL-24; TYR-55; LYS-77; PHE-97; 132-VAL--VAL-135 AND PHE-141,
RP INTERACTION WITH HSPA8, REGION, AND SUBUNIT.
RX PubMed=25760597; DOI=10.1107/s1399004714026881;
RA Song J., Kose S., Watanabe A., Son S.Y., Choi S., Hong H., Yamashita E.,
RA Park I.Y., Imamoto N., Lee S.J.;
RT "Structural and functional analysis of Hikeshi, a new nuclear transport
RT receptor of Hsp70s.";
RL Acta Crystallogr. D 71:473-483(2015).
RN [9]
RP INVOLVEMENT IN HLD13, AND VARIANT HLD13 LEU-54.
RX PubMed=26545878; DOI=10.1136/jmedgenet-2015-103232;
RA Edvardson S., Kose S., Jalas C., Fattal-Valevski A., Watanabe A., Ogawa Y.,
RA Mamada H., Fedick A.M., Ben-Shachar S., Treff N.R., Shaag A., Bale S.,
RA Gaertner J., Imamoto N., Elpeleg O.;
RT "Leukoencephalopathy and early death associated with an Ashkenazi-Jewish
RT founder mutation in the Hikeshi gene.";
RL J. Med. Genet. 53:132-137(2016).
CC -!- FUNCTION: Acts as a specific nuclear import carrier for HSP70 proteins
CC following heat-shock stress: acts by mediating the nucleoporin-
CC dependent translocation of ATP-bound HSP70 proteins into the nucleus.
CC HSP70 proteins import is required to protect cells from heat shock
CC damages. Does not translocate ADP-bound HSP70 proteins into the
CC nucleus. {ECO:0000269|PubMed:22541429}.
CC -!- SUBUNIT: Forms an asymmetric homodimer; required for binding and
CC nuclear import of HSP70 proteins (PubMed:25760597). Interacts with ATP-
CC bound HSP70 proteins (PubMed:22541429). Interacts with NUP62 and NUP153
CC (via F-X-F-G repeats) (PubMed:22541429). Interacts with HSPA8
CC (PubMed:25760597). {ECO:0000269|PubMed:22541429,
CC ECO:0000269|PubMed:25760597}.
CC -!- INTERACTION:
CC Q53FT3; O94929-2: ABLIM3; NbExp=3; IntAct=EBI-6137602, EBI-11961672;
CC Q53FT3; P32243-2: OTX2; NbExp=3; IntAct=EBI-6137602, EBI-9087860;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9DD02}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:22541429}. Nucleus
CC {ECO:0000269|PubMed:22541429}.
CC -!- INDUCTION: Following heat-shock treatment.
CC {ECO:0000269|PubMed:22541429}.
CC -!- DISEASE: Leukodystrophy, hypomyelinating, 13 (HLD13) [MIM:616881]: An
CC autosomal recessive neurodegenerative disorder with infantile onset,
CC affecting mainly the central white matter. Clinical features include
CC early feeding difficulties, global developmental delay, postnatal
CC progressive microcephaly, truncal hypotonia, spasticity, and variable
CC neurologic deficits, such as visual impairment.
CC {ECO:0000269|PubMed:26545878}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: 'Hikeshi' is a traditional Japanese compound word used
CC for a firefighter, smokejumper, or troubleshooter.
CC {ECO:0000305|PubMed:22541429}.
CC -!- SIMILARITY: Belongs to the OPI10 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF29102.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAF29142.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAF36168.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF151082; AAF36168.1; ALT_FRAME; mRNA.
DR EMBL; AF161487; AAF29102.1; ALT_FRAME; mRNA.
DR EMBL; AF161527; AAF29142.1; ALT_FRAME; mRNA.
DR EMBL; AK001447; BAA91698.1; -; mRNA.
DR EMBL; AK223198; BAD96918.1; -; mRNA.
DR EMBL; BC001677; AAH01677.1; -; mRNA.
DR EMBL; BC006476; AAH06476.1; -; mRNA.
DR EMBL; BC015991; AAH15991.1; -; mRNA.
DR EMBL; BC018080; AAH18080.1; -; mRNA.
DR EMBL; BC021621; AAH21621.1; -; mRNA.
DR CCDS; CCDS8275.1; -.
DR RefSeq; NP_057485.2; NM_016401.3.
DR PDB; 3WVZ; X-ray; 1.88 A; A/B=1-197.
DR PDB; 3WW0; X-ray; 2.50 A; A/B=1-197.
DR PDBsum; 3WVZ; -.
DR PDBsum; 3WW0; -.
DR AlphaFoldDB; Q53FT3; -.
DR SMR; Q53FT3; -.
DR BioGRID; 119574; 16.
DR IntAct; Q53FT3; 14.
DR MINT; Q53FT3; -.
DR STRING; 9606.ENSP00000278483; -.
DR iPTMnet; Q53FT3; -.
DR PhosphoSitePlus; Q53FT3; -.
DR BioMuta; HIKESHI; -.
DR DMDM; 110278911; -.
DR EPD; Q53FT3; -.
DR jPOST; Q53FT3; -.
DR MassIVE; Q53FT3; -.
DR MaxQB; Q53FT3; -.
DR PaxDb; Q53FT3; -.
DR PeptideAtlas; Q53FT3; -.
DR PRIDE; Q53FT3; -.
DR ProteomicsDB; 62468; -.
DR TopDownProteomics; Q53FT3; -.
DR Antibodypedia; 31443; 175 antibodies from 25 providers.
DR DNASU; 51501; -.
DR Ensembl; ENST00000278483.8; ENSP00000278483.3; ENSG00000149196.17.
DR GeneID; 51501; -.
DR KEGG; hsa:51501; -.
DR MANE-Select; ENST00000278483.8; ENSP00000278483.3; NM_016401.4; NP_057485.2.
DR UCSC; uc001pbu.4; human.
DR CTD; 51501; -.
DR DisGeNET; 51501; -.
DR GeneCards; HIKESHI; -.
DR HGNC; HGNC:26938; HIKESHI.
DR HPA; ENSG00000149196; Low tissue specificity.
DR MalaCards; HIKESHI; -.
DR MIM; 614908; gene.
DR MIM; 616881; phenotype.
DR neXtProt; NX_Q53FT3; -.
DR OpenTargets; ENSG00000149196; -.
DR Orphanet; 495844; C11ORF73-related autosomal recessive hypomyelinating leukodystrophy.
DR PharmGKB; PA144596492; -.
DR VEuPathDB; HostDB:ENSG00000149196; -.
DR eggNOG; KOG4067; Eukaryota.
DR GeneTree; ENSGT00390000004056; -.
DR HOGENOM; CLU_084839_2_0_1; -.
DR InParanoid; Q53FT3; -.
DR OMA; RMEQNPN; -.
DR OrthoDB; 1223488at2759; -.
DR PhylomeDB; Q53FT3; -.
DR TreeFam; TF313222; -.
DR PathwayCommons; Q53FT3; -.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR SignaLink; Q53FT3; -.
DR BioGRID-ORCS; 51501; 125 hits in 1034 CRISPR screens.
DR ChiTaRS; HIKESHI; human.
DR GeneWiki; C11orf73; -.
DR GenomeRNAi; 51501; -.
DR Pharos; Q53FT3; Tbio.
DR PRO; PR:Q53FT3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q53FT3; protein.
DR Bgee; ENSG00000149196; Expressed in left ventricle myocardium and 183 other tissues.
DR ExpressionAtlas; Q53FT3; baseline and differential.
DR Genevisible; Q53FT3; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IDA:UniProtKB.
DR GO; GO:0061608; F:nuclear import signal receptor activity; IDA:GO_Central.
DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IDA:UniProtKB.
DR DisProt; DP02719; -.
DR InterPro; IPR008493; DUF775.
DR InterPro; IPR031318; OPI10.
DR PANTHER; PTHR12925; PTHR12925; 1.
DR Pfam; PF05603; DUF775; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Disease variant; Leukodystrophy; Nucleus;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..197
FT /note="Protein Hikeshi"
FT /id="PRO_0000245262"
FT REGION 18..55
FT /note="Required for F-X-F-G repeats-nucleoporins
FT recognition and nuclear import"
FT /evidence="ECO:0000269|PubMed:22541429"
FT REGION 124..134
FT /note="Flexible linker region involved in nuclear import of
FT HSP70 proteins"
FT /evidence="ECO:0000269|PubMed:22541429"
FT VARIANT 47
FT /note="P -> A (in dbSNP:rs11539213)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026968"
FT VARIANT 54
FT /note="V -> L (in HLD13; dbSNP:rs202003795)"
FT /evidence="ECO:0000269|PubMed:26545878"
FT /id="VAR_076411"
FT MUTAGEN 18
FT /note="V->A: Impairs the nuclear migrating activity."
FT /evidence="ECO:0000269|PubMed:25760597"
FT MUTAGEN 24
FT /note="V->A: Reduces the nuclear migrating activity."
FT /evidence="ECO:0000269|PubMed:25760597"
FT MUTAGEN 55
FT /note="Y->A: Reduces the nuclear migrating activity."
FT /evidence="ECO:0000269|PubMed:25760597"
FT MUTAGEN 77
FT /note="K->A: Decreases nuclear import activity of HSPA8.
FT Does not affect the dimer formation. Impairs binding to
FT HSPA8."
FT /evidence="ECO:0000269|PubMed:25760597"
FT MUTAGEN 97
FT /note="F->A: Increases the nuclear migrating activity."
FT /evidence="ECO:0000269|PubMed:25760597"
FT MUTAGEN 132..135
FT /note="Missing: Decreases nuclear import activity of HSPA8.
FT Does not affect the dimer formation. Markedly decreases
FT binding to HSPA8."
FT /evidence="ECO:0000269|PubMed:25760597"
FT MUTAGEN 141
FT /note="F->A: Decreases nuclear import activity of HSPA8.
FT Does not affect the dimer formation. Decreases binding to
FT HSPA8."
FT /evidence="ECO:0000269|PubMed:25760597"
FT CONFLICT 82
FT /note="F -> L (in Ref. 1; AAF29102 and 3; BAD96918)"
FT /evidence="ECO:0000305"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 16..19
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 22..29
FT /evidence="ECO:0007829|PDB:3WVZ"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 108..117
FT /evidence="ECO:0007829|PDB:3WVZ"
FT HELIX 118..121
FT /evidence="ECO:0007829|PDB:3WVZ"
FT HELIX 137..154
FT /evidence="ECO:0007829|PDB:3WVZ"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:3WVZ"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:3WVZ"
FT HELIX 174..188
FT /evidence="ECO:0007829|PDB:3WVZ"
FT TURN 192..195
FT /evidence="ECO:0007829|PDB:3WW0"
SQ SEQUENCE 197 AA; 21628 MW; 4FA524439B630511 CRC64;
MFGCLVAGRL VQTAAQQVAE DKFVFDLPDY ESINHVVVFM LGTIPFPEGM GGSVYFSYPD
SNGMPVWQLL GFVTNGKPSA IFKISGLKSG EGSQHPFGAM NIVRTPSVAQ IGISVELLDS
MAQQTPVGNA AVSSVDSFTQ FTQKMLDNFY NFASSFAVSQ AQMTPSPSEM FIPANVVLKW
YENFQRRLAQ NPLFWKT
