ID ERD23_HUMAN Reviewed; 214 AA. AC O43731; A8K7T7; B8ZZ26; O95557; Q4V750; Q4V767; Q53FP4; Q53GK1; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 18-JUN-2025, entry version 199. DE RecName: Full=ER lumen protein-retaining receptor 3; DE AltName: Full=KDEL endoplasmic reticulum protein retention receptor 3; DE Short=KDEL receptor 3; GN Name=KDELR3; Synonyms=ERD23 {ECO:0000303|PubMed:18086916}; 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] (ISOFORMS 1 AND 2). RX PubMed=12529303; DOI=10.1101/gr.695703; RA Collins J.E., Goward M.E., Cole C.G., Smink L.J., Huckle E.J., Knowles S., RA Bye J.M., Beare D.M., Dunham I.; RT "Reevaluating human gene annotation: a second-generation analysis of RT chromosome 22."; RL Genome Res. 13:27-36(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Synovial cell; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-199. RC TISSUE=Kidney, and Stomach; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP GLY-199. RC TISSUE=Cervix; 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 [8] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18086916; DOI=10.1083/jcb.200705180; RA Raykhel I., Alanen H., Salo K., Jurvansuu J., Nguyen V.D., Latva-Ranta M., RA Ruddock L.; RT "A molecular specificity code for the three mammalian KDEL receptors."; RL J. Cell Biol. 179:1193-1204(2007). CC -!- FUNCTION: Receptor for the C-terminal sequence motif K-D-E-L that is CC present on endoplasmic reticulum resident proteins and that mediates CC their recycling from the Golgi back to the endoplasmic reticulum. CC {ECO:0000269|PubMed:18086916}. CC -!- INTERACTION: CC O43731-2; O60636: TSPAN2; NbExp=3; IntAct=EBI-18157502, EBI-3914288; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:18086916}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:Q5ZKX9}. Golgi apparatus membrane CC {ECO:0000269|PubMed:18086916}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:Q5ZKX9}. Cytoplasmic vesicle, COPI-coated CC vesicle membrane {ECO:0000269|PubMed:18086916}; Multi-pass membrane CC protein {ECO:0000250|UniProtKB:Q5ZKX9}. Note=Localized in the Golgi in CC the absence of bound proteins with the sequence motif K-D-E-L. CC Trafficks back to the endoplasmic reticulum together with cargo CC proteins containing the sequence motif K-D-E-L. CC {ECO:0000305|PubMed:18086916}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43731-1; Sequence=Displayed; CC Name=2; CC IsoId=O43731-2; Sequence=VSP_022856; CC -!- DOMAIN: Binds the C-terminal sequence motif K-D-E-L in a hydrophilic CC cavity between the transmembrane domains. This triggers a conformation CC change that exposes a Lys-rich patch on the cytosolic surface of the CC protein (By similarity). This patch mediates recycling from the Golgi CC to the endoplasmic reticulum, probably via COPI vesicles (By CC similarity). {ECO:0000250|UniProtKB:P24390, CC ECO:0000250|UniProtKB:Q5ZKX9}. CC -!- SIMILARITY: Belongs to the ERD2 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL035081; CAA22673.1; -; mRNA. DR EMBL; AL035082; CAA22674.1; -; mRNA. DR EMBL; CR456509; CAG30395.1; -; mRNA. DR EMBL; AK292102; BAF84791.1; -; mRNA. DR EMBL; AK222930; BAD96650.1; -; mRNA. DR EMBL; AK223238; BAD96958.1; -; mRNA. DR EMBL; Z97056; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471095; EAW60237.1; -; Genomic_DNA. DR EMBL; BC001277; AAH01277.1; -; mRNA. DR EMBL; BC096722; AAH96722.1; -; mRNA. DR EMBL; BC098131; AAH98131.1; -; mRNA. DR EMBL; BC098156; AAH98156.1; -; mRNA. DR EMBL; BC098336; AAH98336.1; -; mRNA. DR CCDS; CCDS13972.1; -. [O43731-1] DR CCDS; CCDS46705.1; -. [O43731-2] DR RefSeq; NP_006846.1; NM_006855.4. [O43731-1] DR RefSeq; NP_057839.1; NM_016657.3. [O43731-2] DR AlphaFoldDB; O43731; -. DR SMR; O43731; -. DR BioGRID; 116205; 58. DR FunCoup; O43731; 931. DR IntAct; O43731; 43. DR MINT; O43731; -. DR STRING; 9606.ENSP00000386918; -. DR iPTMnet; O43731; -. DR PhosphoSitePlus; O43731; -. DR BioMuta; KDELR3; -. DR jPOST; O43731; -. DR MassIVE; O43731; -. DR PaxDb; 9606-ENSP00000386918; -. DR PeptideAtlas; O43731; -. DR ProteomicsDB; 49134; -. [O43731-1] DR ProteomicsDB; 49135; -. [O43731-2] DR Pumba; O43731; -. DR Antibodypedia; 26349; 98 antibodies from 23 providers. DR DNASU; 11015; -. DR Ensembl; ENST00000216014.9; ENSP00000216014.4; ENSG00000100196.11. [O43731-1] DR Ensembl; ENST00000409006.3; ENSP00000386918.3; ENSG00000100196.11. [O43731-2] DR GeneID; 11015; -. DR KEGG; hsa:11015; -. DR MANE-Select; ENST00000216014.9; ENSP00000216014.4; NM_006855.4; NP_006846.1. DR UCSC; uc003avu.5; human. [O43731-1] DR AGR; HGNC:6306; -. DR CTD; 11015; -. DR DisGeNET; 11015; -. DR GeneCards; KDELR3; -. DR HGNC; HGNC:6306; KDELR3. DR HPA; ENSG00000100196; Low tissue specificity. DR MIM; 619900; gene. DR neXtProt; NX_O43731; -. DR OpenTargets; ENSG00000100196; -. DR PharmGKB; PA30085; -. DR VEuPathDB; HostDB:ENSG00000100196; -. DR eggNOG; KOG3106; Eukaryota. DR GeneTree; ENSGT00390000004010; -. DR HOGENOM; CLU_057784_0_0_1; -. DR InParanoid; O43731; -. DR OMA; QEVLWAF; -. DR OrthoDB; 7694678at2759; -. DR PAN-GO; O43731; 5 GO annotations based on evolutionary models. DR PhylomeDB; O43731; -. DR TreeFam; TF314792; -. DR PathwayCommons; O43731; -. DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes. DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport. DR Reactome; R-HSA-6811434; COPI-dependent Golgi-to-ER retrograde traffic. DR SignaLink; O43731; -. DR BioGRID-ORCS; 11015; 21 hits in 1152 CRISPR screens. DR ChiTaRS; KDELR3; human. DR GeneWiki; KDELR3; -. DR GenomeRNAi; 11015; -. DR Pharos; O43731; Tbio. DR PRO; PR:O43731; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; O43731; protein. DR Bgee; ENSG00000100196; Expressed in tibia and 168 other cell types or tissues. DR ExpressionAtlas; O43731; baseline and differential. DR GO; GO:0005801; C:cis-Golgi network; IBA:GO_Central. DR GO; GO:0030663; C:COPI-coated vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0030133; C:transport vesicle; TAS:Reactome. DR GO; GO:0046923; F:ER retention sequence binding; IBA:GO_Central. DR GO; GO:0005046; F:KDEL sequence binding; IDA:UniProtKB. DR GO; GO:0006621; P:protein retention in ER lumen; IBA:GO_Central. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IDA:UniProtKB. DR InterPro; IPR000133; ER_ret_rcpt. DR PANTHER; PTHR10585; ER LUMEN PROTEIN RETAINING RECEPTOR; 1. DR Pfam; PF00810; ER_lumen_recept; 1. DR PRINTS; PR00660; ERLUMENR. DR PROSITE; PS00951; ER_LUMEN_RECEPTOR_1; 1. DR PROSITE; PS00952; ER_LUMEN_RECEPTOR_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasmic vesicle; Endoplasmic reticulum; KW ER-Golgi transport; Golgi apparatus; Membrane; Protein transport; KW Proteomics identification; Receptor; Reference proteome; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..214 FT /note="ER lumen protein-retaining receptor 3" FT /id="PRO_0000194158" FT TOPO_DOM 1..4 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 5..24 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT TOPO_DOM 25..32 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 33..52 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT TOPO_DOM 53..58 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 59..79 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT TOPO_DOM 80..92 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 93..110 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT TOPO_DOM 111..116 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 117..135 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT TOPO_DOM 136..149 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 150..168 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT TOPO_DOM 169..178 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 179..199 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT TOPO_DOM 200..214 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 47..48 FT /note="Interaction with the K-D-E-L motif on target FT proteins" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT REGION 159..169 FT /note="Interaction with the K-D-E-L motif on target FT proteins" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT REGION 204..207 FT /note="Important for recycling of cargo proteins with the FT sequence motif K-D-E-L from the Golgi to the endoplasmic FT reticulum" FT /evidence="ECO:0000250|UniProtKB:P24390" FT SITE 5 FT /note="Interaction with the K-D-E-L motif on target FT proteins" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT SITE 117 FT /note="Interaction with the K-D-E-L motif on target FT proteins" FT /evidence="ECO:0000250|UniProtKB:Q5ZKX9" FT SITE 193 FT /note="Important for recycling of cargo proteins with the FT sequence motif K-D-E-L from the Golgi to the endoplasmic FT reticulum" FT /evidence="ECO:0000250|UniProtKB:P24390" FT VAR_SEQ 202..214 FT /note="VLKGKKLSLPMPI -> GRSWDDSNADTGLRSYSSI (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12529303, FT ECO:0000303|PubMed:15489334" FT /id="VSP_022856" FT VARIANT 199 FT /note="V -> G (in dbSNP:rs12004)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4" FT /id="VAR_014506" FT CONFLICT 42 FT /note="L -> P (in Ref. 4; BAD96650)" FT /evidence="ECO:0000305" SQ SEQUENCE 214 AA; 25027 MW; ED5F7D303390B314 CRC64; MNVFRILGDL SHLLAMILLL GKIWRSKCCK GISGKSQILF ALVFTTRYLD LFTNFISIYN TVMKVVFLLC AYVTVYMIYG KFRKTFDSEN DTFRLEFLLV PVIGLSFLEN YSFTLLEILW TFSIYLESVA ILPQLFMISK TGEAETITTH YLFFLGLYRA LYLANWIRRY QTENFYDQIA VVSGVVQTIF YCDFFYLYVT KVLKGKKLSL PMPI //