GRCR1_HUMAN
ID GRCR1_HUMAN Reviewed; 290 AA.
AC A8MXD5;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Glutaredoxin domain-containing cysteine-rich protein 1;
GN Name=GRXCR1; Synonyms=DFNB25;
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 GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2]
RP VARIANT DFNB25 CYS-138, VARIANTS LYS-9 AND VAL-91, AND TISSUE SPECIFICITY.
RX PubMed=20137778; DOI=10.1016/j.ajhg.2009.12.017;
RA Schraders M., Lee K., Oostrik J., Huygen P.L., Ali G., Hoefsloot L.H.,
RA Veltman J.A., Cremers F.P., Basit S., Ansar M., Cremers C.W., Kunst H.P.,
RA Ahmad W., Admiraal R.J., Leal S.M., Kremer H.;
RT "Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal-
RT recessive nonsyndromic hearing impairment.";
RL Am. J. Hum. Genet. 86:138-147(2010).
RN [3]
RP VARIANTS DFNB25 LEU-38; SER-64 AND VAL-153, AND VARIANTS GLU-51 AND VAL-91.
RX PubMed=20137774; DOI=10.1016/j.ajhg.2010.01.016;
RA Odeh H., Hunker K.L., Belyantseva I.A., Azaiez H., Avenarius M.R.,
RA Zheng L., Peters L.M., Gagnon L.H., Hagiwara N., Skynner M.J.,
RA Brilliant M.H., Allen N.D., Riazuddin S., Johnson K.R., Raphael Y.,
RA Najmabadi H., Friedman T.B., Bartles J.R., Smith R.J., Kohrman D.C.;
RT "Mutations in Grxcr1 are the basis for inner ear dysfunction in the
RT pirouette mouse.";
RL Am. J. Hum. Genet. 86:148-160(2010).
CC -!- FUNCTION: May play a role in actin filament architecture in developing
CC stereocilia of sensory cells. {ECO:0000250}.
CC -!- INTERACTION:
CC A8MXD5; P13196: ALAS1; NbExp=3; IntAct=EBI-5235612, EBI-3905054;
CC A8MXD5; P40123: CAP2; NbExp=3; IntAct=EBI-5235612, EBI-1051165;
CC A8MXD5; Q0VD86: INCA1; NbExp=3; IntAct=EBI-5235612, EBI-6509505;
CC A8MXD5; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-5235612, EBI-79165;
CC A8MXD5; Q9NQX0: PRDM6; NbExp=3; IntAct=EBI-5235612, EBI-11320284;
CC A8MXD5; O00560: SDCBP; NbExp=3; IntAct=EBI-5235612, EBI-727004;
CC A8MXD5; Q86XE0: SNX32; NbExp=3; IntAct=EBI-5235612, EBI-8099743;
CC A8MXD5; Q8IYF3-3: TEX11; NbExp=3; IntAct=EBI-5235612, EBI-11523345;
CC -!- SUBCELLULAR LOCATION: Cell projection, stereocilium {ECO:0000250}. Cell
CC projection, microvillus {ECO:0000250}. Cell projection, kinocilium
CC {ECO:0000250}. Note=In the inner ear, localized to stereocilia, apical
CC microvilli of sensory cells and kinocilia. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed at low levels in adult lung, brain and
CC duodenum with moderate levels in testis. Highly expressed in fetal
CC cochlea. {ECO:0000269|PubMed:20137778}.
CC -!- DISEASE: Deafness, autosomal recessive, 25 (DFNB25) [MIM:613285]: A
CC form of non-syndromic sensorineural deafness characterized by moderate
CC to severe or profound hearing loss which is progressive in some
CC individuals but not in others. Speech development is impaired in some
CC but not all affected individuals, and vestibular dysfunction is
CC observed in some affected individuals. Sensorineural deafness results
CC from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. {ECO:0000269|PubMed:20137774,
CC ECO:0000269|PubMed:20137778}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the GRXCR1 family. {ECO:0000305}.
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DR EMBL; AC098861; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108035; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS43225.1; -.
DR RefSeq; NP_001073945.1; NM_001080476.2.
DR AlphaFoldDB; A8MXD5; -.
DR BioGRID; 133037; 30.
DR IntAct; A8MXD5; 9.
DR STRING; 9606.ENSP00000382670; -.
DR iPTMnet; A8MXD5; -.
DR PhosphoSitePlus; A8MXD5; -.
DR BioMuta; GRXCR1; -.
DR MassIVE; A8MXD5; -.
DR PaxDb; A8MXD5; -.
DR PRIDE; A8MXD5; -.
DR Antibodypedia; 51684; 50 antibodies from 13 providers.
DR DNASU; 389207; -.
DR Ensembl; ENST00000399770.3; ENSP00000382670.2; ENSG00000215203.3.
DR GeneID; 389207; -.
DR KEGG; hsa:389207; -.
DR MANE-Select; ENST00000399770.3; ENSP00000382670.2; NM_001080476.3; NP_001073945.1.
DR UCSC; uc003gwt.4; human.
DR CTD; 389207; -.
DR DisGeNET; 389207; -.
DR GeneCards; GRXCR1; -.
DR HGNC; HGNC:31673; GRXCR1.
DR HPA; ENSG00000215203; Tissue enriched (seminal).
DR MalaCards; GRXCR1; -.
DR MIM; 613283; gene.
DR MIM; 613285; phenotype.
DR neXtProt; NX_A8MXD5; -.
DR OpenTargets; ENSG00000215203; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA162390253; -.
DR VEuPathDB; HostDB:ENSG00000215203; -.
DR eggNOG; KOG2824; Eukaryota.
DR GeneTree; ENSGT00940000159219; -.
DR HOGENOM; CLU_067117_0_0_1; -.
DR InParanoid; A8MXD5; -.
DR OMA; NGLQRCR; -.
DR OrthoDB; 1046721at2759; -.
DR PhylomeDB; A8MXD5; -.
DR TreeFam; TF315372; -.
DR PathwayCommons; A8MXD5; -.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR Reactome; R-HSA-9662361; Sensory processing of sound by outer hair cells of the cochlea.
DR SignaLink; A8MXD5; -.
DR BioGRID-ORCS; 389207; 3 hits in 1065 CRISPR screens.
DR ChiTaRS; GRXCR1; human.
DR GeneWiki; GRXCR1; -.
DR GenomeRNAi; 389207; -.
DR Pharos; A8MXD5; Tdark.
DR PRO; PR:A8MXD5; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; A8MXD5; protein.
DR Bgee; ENSG00000215203; Expressed in testis and 3 other tissues.
DR GO; GO:0060091; C:kinocilium; ISS:UniProtKB.
DR GO; GO:0005902; C:microvillus; IEA:UniProtKB-SubCell.
DR GO; GO:0032420; C:stereocilium; ISS:UniProtKB.
DR GO; GO:0097573; F:glutathione oxidoreductase activity; IEA:InterPro.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR GO; GO:0060119; P:inner ear receptor cell development; ISS:UniProtKB.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; ISS:UniProtKB.
DR GO; GO:0048563; P:post-embryonic animal organ morphogenesis; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; ISS:UniProtKB.
DR GO; GO:0060118; P:vestibular receptor cell development; ISS:UniProtKB.
DR InterPro; IPR002109; Glutaredoxin.
DR InterPro; IPR042797; GRXCR1.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR46990; PTHR46990; 1.
DR Pfam; PF00462; Glutaredoxin; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51354; GLUTAREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cilium; Deafness; Disease variant; Hearing;
KW Non-syndromic deafness; Reference proteome.
FT CHAIN 1..290
FT /note="Glutaredoxin domain-containing cysteine-rich protein
FT 1"
FT /id="PRO_0000349189"
FT DOMAIN 127..234
FT /note="Glutaredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT VARIANT 9
FT /note="E -> K (in dbSNP:rs78136490)"
FT /evidence="ECO:0000269|PubMed:20137778"
FT /id="VAR_063159"
FT VARIANT 38
FT /note="P -> L (in DFNB25; dbSNP:rs367784906)"
FT /evidence="ECO:0000269|PubMed:20137774"
FT /id="VAR_063160"
FT VARIANT 51
FT /note="G -> E (in dbSNP:rs727505186)"
FT /evidence="ECO:0000269|PubMed:20137774"
FT /id="VAR_063161"
FT VARIANT 64
FT /note="G -> S (in DFNB25; dbSNP:rs370551174)"
FT /evidence="ECO:0000269|PubMed:20137774"
FT /id="VAR_063162"
FT VARIANT 91
FT /note="G -> V (in dbSNP:rs113203706)"
FT /evidence="ECO:0000269|PubMed:20137774,
FT ECO:0000269|PubMed:20137778"
FT /id="VAR_063163"
FT VARIANT 138
FT /note="R -> C (in DFNB25; dbSNP:rs267606856)"
FT /evidence="ECO:0000269|PubMed:20137778"
FT /id="VAR_063164"
FT VARIANT 153
FT /note="F -> V (in DFNB25; dbSNP:rs770874273)"
FT /evidence="ECO:0000269|PubMed:20137774"
FT /id="VAR_063165"
SQ SEQUENCE 290 AA; 32294 MW; 876595DDA9B9194B CRC64;
MLKREMKPES DRPRKVRFRI ASSHSGRVLK EVYEDGQPSG SLDSECASIC GIDGLGDSDG
QQNGHIESEG DENENDQDSL LVLARAASEK GFGTRRVNIL SKNGTVRGVK YKVSAGQALF
NNLTKVLQQP STDLEFDRVV IYTTCLRVVR TTFERCELVR KIFQNHRVKF EEKNIALNGE
YGKELDERCR RVSEAPSLPV VFIDGHYLGG AEKILSMNES GELQDILTKI ERVQHPHECP
SCGGFGFLPC SVCHGSKMSM FRNCFTDSFK ALKCTACNEN GLQRCKNCAG
