RHEX_HUMAN
ID RHEX_HUMAN Reviewed; 172 AA.
AC Q6ZWK4;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Regulator of hemoglobinization and erythroid cell expansion protein {ECO:0000312|HGNC:HGNC:25341};
DE AltName: Full=Regulator of human erythroid cell expansion protein {ECO:0000303|PubMed:25092874};
GN Name=RHEX {ECO:0000312|HGNC:HGNC:25341};
GN Synonyms=C1orf186 {ECO:0000312|HGNC:HGNC:25341};
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=Kidney;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [4]
RP FUNCTION, INTERACTION WITH GRB2; EPOR AND JAK2, PHOSPHORYLATION AT TYR-132
RP AND TYR-141, INDUCTION, TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=25092874; DOI=10.1084/jem.20130624;
RA Verma R., Su S., McCrann D.J., Green J.M., Leu K., Young P.R., Schatz P.J.,
RA Silva J.C., Stokes M.P., Wojchowski D.M.;
RT "RHEX, a novel regulator of human erythroid progenitor cell expansion and
RT erythroblast development.";
RL J. Exp. Med. 211:1715-1722(2014).
CC -!- FUNCTION: Acts as a signaling transduction factor of the EPO-EPOR
CC signaling pathway promoting erythroid cell differentiation
CC (PubMed:25092874). {ECO:0000269|PubMed:25092874}.
CC -!- SUBUNIT: Interacts with EPOR; this interaction occurs in a
CC erythropoietin (EPO)-dependent manner (PubMed:25092874). Interacts with
CC JAK2; this interaction occurs in a erythropoietin (EPO)-dependent
CC manner (PubMed:25092874). Interacts (via tyrosine-phosphorylated form)
CC with GRB2 (PubMed:25092874). {ECO:0000269|PubMed:25092874}.
CC -!- INTERACTION:
CC Q6ZWK4; Q05329: GAD2; NbExp=3; IntAct=EBI-18304046, EBI-9304251;
CC Q6ZWK4; O43681: GET3; NbExp=3; IntAct=EBI-18304046, EBI-2515857;
CC Q6ZWK4; Q96AL5: PBX3; NbExp=3; IntAct=EBI-18304046, EBI-741171;
CC Q6ZWK4; Q8N0V3: RBFA; NbExp=3; IntAct=EBI-18304046, EBI-3232108;
CC Q6ZWK4; Q99961: SH3GL1; NbExp=3; IntAct=EBI-18304046, EBI-697911;
CC Q6ZWK4; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-18304046, EBI-2623095;
CC Q6ZWK4; Q13596: SNX1; NbExp=3; IntAct=EBI-18304046, EBI-2822329;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25092874};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the proerythroblasts (at protein
CC level) (PubMed:25092874). Expressed strongly in the kidney
CC (PubMed:25092874). Expressed weakly in the pancreas, liver and lung
CC (PubMed:25092874). Expressed strongly in erythroid progenitor cells
CC (EPCs) (PubMed:25092874). Expressed weakly in T-cells and neutrophils
CC (PubMed:25092874). {ECO:0000269|PubMed:25092874}.
CC -!- INDUCTION: Up-regulated during erythroid differentiation
CC (PubMed:25092874). {ECO:0000269|PubMed:25092874}.
CC -!- PTM: Phosphorylated. Phosphorylation on Tyr-132 and Tyr-141 occurs in a
CC erythropoietin (EPO)-dependent manner (PubMed:25092874).
CC {ECO:0000269|PubMed:25092874}.
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DR EMBL; AK122631; BAC85497.1; -; mRNA.
DR EMBL; BX571818; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC071785; AAH71785.1; -; mRNA.
DR CCDS; CCDS73014.1; -.
DR RefSeq; NP_001007545.1; NM_001007544.3.
DR RefSeq; XP_005272795.1; XM_005272738.3.
DR AlphaFoldDB; Q6ZWK4; -.
DR BioGRID; 136831; 35.
DR IntAct; Q6ZWK4; 19.
DR STRING; 9606.ENSP00000356093; -.
DR iPTMnet; Q6ZWK4; -.
DR PhosphoSitePlus; Q6ZWK4; -.
DR BioMuta; C1orf186; -.
DR DMDM; 74749716; -.
DR EPD; Q6ZWK4; -.
DR MassIVE; Q6ZWK4; -.
DR PaxDb; Q6ZWK4; -.
DR PeptideAtlas; Q6ZWK4; -.
DR PRIDE; Q6ZWK4; -.
DR ProteomicsDB; 68491; -.
DR Antibodypedia; 72281; 54 antibodies from 10 providers.
DR DNASU; 440712; -.
DR Ensembl; ENST00000331555.10; ENSP00000356093.1; ENSG00000263961.8.
DR Ensembl; ENST00000582070.3; ENSP00000463990.1; ENSG00000263961.8.
DR Ensembl; ENST00000603488.5; ENSP00000474994.1; ENSG00000263961.8.
DR GeneID; 440712; -.
DR KEGG; hsa:440712; -.
DR MANE-Select; ENST00000331555.10; ENSP00000356093.1; NM_001007544.4; NP_001007545.1.
DR UCSC; uc001hdt.3; human.
DR CTD; 440712; -.
DR GeneCards; RHEX; -.
DR HGNC; HGNC:25341; RHEX.
DR HPA; ENSG00000263961; Tissue enhanced (cervix).
DR MIM; 616088; gene.
DR neXtProt; NX_Q6ZWK4; -.
DR OpenTargets; ENSG00000263961; -.
DR PharmGKB; PA142672434; -.
DR VEuPathDB; HostDB:ENSG00000263961; -.
DR eggNOG; ENOG502T2N6; Eukaryota.
DR GeneTree; ENSGT00390000004770; -.
DR InParanoid; Q6ZWK4; -.
DR OMA; HKPNFWT; -.
DR OrthoDB; 1528344at2759; -.
DR PhylomeDB; Q6ZWK4; -.
DR TreeFam; TF353616; -.
DR PathwayCommons; Q6ZWK4; -.
DR SignaLink; Q6ZWK4; -.
DR BioGRID-ORCS; 440712; 5 hits in 1054 CRISPR screens.
DR ChiTaRS; C1orf186; human.
DR GenomeRNAi; 440712; -.
DR Pharos; Q6ZWK4; Tbio.
DR PRO; PR:Q6ZWK4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6ZWK4; protein.
DR Bgee; ENSG00000263961; Expressed in kidney epithelium and 125 other tissues.
DR ExpressionAtlas; Q6ZWK4; baseline and differential.
DR Genevisible; Q6ZWK4; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005128; F:erythropoietin receptor binding; IDA:UniProtKB.
DR GO; GO:0036018; P:cellular response to erythropoietin; IMP:UniProtKB.
DR GO; GO:0043249; P:erythrocyte maturation; IEA:UniProtKB-KW.
DR GO; GO:0038162; P:erythropoietin-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:UniProtKB.
DR InterPro; IPR031517; RHEX-like.
DR PANTHER; PTHR38491; PTHR38491; 1.
DR Pfam; PF15763; DUF4692; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Differentiation; Erythrocyte maturation; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..172
FT /note="Regulator of hemoglobinization and erythroid cell
FT expansion protein"
FT /id="PRO_0000271103"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 52..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 60..92
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 132
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:25092874"
FT MOD_RES 141
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:25092874"
SQ SEQUENCE 172 AA; 19405 MW; 2AE0407D9F05457B CRC64;
MLTEVMEVWH GLVIAVVSLF LQACFLTAIN YLLSRHMAHK SEQILKAASL QVPRPSPGHH
HPPAVKEMKE TQTERDIPMS DSLYRHDSDT PSDSLDSSCS SPPACQATED VDYTQVVFSD
PGELKNDSPL DYENIKEITD YVNVNPERHK PSFWYFVNPA LSEPAEYDQV AM
