ID TMED1_HUMAN Reviewed; 227 AA. AC Q13445; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 24-JUL-2024, entry version 169. DE RecName: Full=Transmembrane emp24 domain-containing protein 1; DE AltName: Full=Interleukin-1 receptor-like 1 ligand; DE AltName: Full=Putative T1/ST2 receptor-binding protein; DE AltName: Full=p24 family protein gamma-1; DE Short=Tp24; DE Short=p24gamma1; DE Flags: Precursor; GN Name=TMED1; Synonyms=IL1RL1L, IL1RL1LG; 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 [MRNA], TISSUE SPECIFICITY, AND POSSIBLE INTERACTION RP WITH IL1RL1. RC TISSUE=Glioblastoma; RX PubMed=8621446; DOI=10.1074/jbc.271.10.5784; RA Gayle M.A., Slack J.L., Bonnert T.P., Renshaw B.R., Sonoda G., Taguchi T., RA Testa J.R., Dower S.K., Sims J.E.; RT "Cloning of a putative ligand for the T1/ST2 receptor."; RL J. Biol. Chem. 271:5784-5789(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Melanoma; 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 PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 24-43. RC TISSUE=Leukemic T-cell; RX PubMed=19892738; DOI=10.1073/pnas.0908958106; RA Xu G., Shin S.B., Jaffrey S.R.; RT "Global profiling of protease cleavage sites by chemoselective labeling of RT protein N-termini."; RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009). RN [5] RP SUBCELLULAR LOCATION. RX PubMed=10852829; DOI=10.1242/jcs.113.13.2507; RA Emery G., Rojo M., Gruenberg J.; RT "Coupled transport of p24 family members."; RL J. Cell Sci. 113:2507-2516(2000). RN [6] RP SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=12237308; DOI=10.1074/jbc.m206989200; RA Jenne N., Frey K., Brugger B., Wieland F.T.; RT "Oligomeric state and stoichiometry of p24 proteins in the early secretory RT pathway."; RL J. Biol. Chem. 277:46504-46511(2002). RN [7] 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 [8] RP FUNCTION, INTERACTION WITH IL1RL1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP CYS-45 AND CYS-106. RX PubMed=23319592; DOI=10.1074/jbc.m112.403899; RA Connolly D.J., O'Neill L.A., McGettrick A.F.; RT "The GOLD domain-containing protein TMED1 is involved in interleukin-33 RT signaling."; RL J. Biol. Chem. 288:5616-5623(2013). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [10] RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER GLY-23, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [11] RP FUNCTION, AND INTERACTION WITH RNF26. RX PubMed=32614325; DOI=10.7554/elife.57306; RA Fenech E.J., Lari F., Charles P.D., Fischer R., Laetitia-Thezenas M., RA Bagola K., Paton A.W., Paton J.C., Gyrd-Hansen M., Kessler B.M., RA Christianson J.C.; RT "Interaction mapping of endoplasmic reticulum ubiquitin ligases identifies RT modulators of innate immune signalling."; RL Elife 9:0-0(2020). RN [12] RP VARIANT [LARGE SCALE ANALYSIS] ASN-102. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Potential role in vesicular protein trafficking, mainly in CC the early secretory pathway. May act as a cargo receptor at the lumenal CC side for incorporation of secretory cargo molecules into transport CC vesicles and may be involved in vesicle coat formation at the CC cytoplasmic side. Plays a positive role in IL-33-mediated IL-8 and IL-6 CC production by interacting with interleukin-33 receptor IL1RL1 CC (PubMed:23319592). Also plays a role in the modulation of innate immune CC signaling through the cGAS-STING pathway by interacting with RNF26 CC (PubMed:32614325). {ECO:0000269|PubMed:23319592, CC ECO:0000269|PubMed:32614325}. CC -!- SUBUNIT: Homodimer in endoplasmic reticulum, endoplasmic reticulum- CC Golgi intermediate compartment and cis-Golgi network. Interacts with CC IL1RL1 (PubMed:23319592). Interacts with RNF26; this interaction is CC important to modulate innate immune signaling through the cGAS-STING CC pathway (PubMed:32614325). {ECO:0000269|PubMed:12237308, CC ECO:0000269|PubMed:23319592, ECO:0000269|PubMed:32614325}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:8621446}; CC Single-pass type I membrane protein {ECO:0000255}. Endoplasmic CC reticulum membrane {ECO:0000269|PubMed:10852829, CC ECO:0000269|PubMed:12237308, ECO:0000269|PubMed:23319592}; Single-pass CC type I membrane protein {ECO:0000255}. Golgi apparatus, cis-Golgi CC network membrane {ECO:0000269|PubMed:10852829, CC ECO:0000269|PubMed:12237308}; Single-pass type I membrane protein CC {ECO:0000255}. Endoplasmic reticulum-Golgi intermediate compartment CC membrane {ECO:0000269|PubMed:12237308}; Single-pass type I membrane CC protein {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:8621446}. CC -!- MISCELLANEOUS: Found only in very low concentrations in the endoplasmic CC reticulum, Golgi apparatus and endoplasmic reticulum-Golgi intermediate CC compartment compared to other members of the EMP24/GP25L family. CC -!- SIMILARITY: Belongs to the EMP24/GP25L 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; U41804; AAC50419.1; -; mRNA. DR EMBL; AC007229; AAD23605.1; -; Genomic_DNA. DR EMBL; BC002443; AAH02443.1; -; mRNA. DR CCDS; CCDS12249.1; -. DR RefSeq; NP_006849.1; NM_006858.3. DR PDB; 7RRM; X-ray; 1.72 A; A/B/C=23-130. DR PDBsum; 7RRM; -. DR AlphaFoldDB; Q13445; -. DR SMR; Q13445; -. DR BioGRID; 116208; 93. DR IntAct; Q13445; 24. DR MINT; Q13445; -. DR STRING; 9606.ENSP00000214869; -. DR TCDB; 9.B.188.1.1; the transmembrane emp24 domain-containing protein (tmed) family. DR GlyGen; Q13445; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13445; -. DR PhosphoSitePlus; Q13445; -. DR SwissPalm; Q13445; -. DR BioMuta; TMED1; -. DR DMDM; 74739789; -. DR jPOST; Q13445; -. DR MassIVE; Q13445; -. DR PaxDb; 9606-ENSP00000214869; -. DR PeptideAtlas; Q13445; -. DR ProteomicsDB; 59453; -. DR Pumba; Q13445; -. DR TopDownProteomics; Q13445; -. DR Antibodypedia; 2281; 227 antibodies from 25 providers. DR DNASU; 11018; -. DR Ensembl; ENST00000214869.7; ENSP00000214869.1; ENSG00000099203.7. DR GeneID; 11018; -. DR KEGG; hsa:11018; -. DR MANE-Select; ENST00000214869.7; ENSP00000214869.1; NM_006858.4; NP_006849.1. DR UCSC; uc002mpy.5; human. DR AGR; HGNC:17291; -. DR CTD; 11018; -. DR DisGeNET; 11018; -. DR GeneCards; TMED1; -. DR HGNC; HGNC:17291; TMED1. DR HPA; ENSG00000099203; Low tissue specificity. DR MIM; 605395; gene. DR neXtProt; NX_Q13445; -. DR OpenTargets; ENSG00000099203; -. DR PharmGKB; PA134972147; -. DR VEuPathDB; HostDB:ENSG00000099203; -. DR eggNOG; KOG3287; Eukaryota. DR GeneTree; ENSGT00940000158445; -. DR HOGENOM; CLU_066963_0_0_1; -. DR InParanoid; Q13445; -. DR OMA; PAGRQEC; -. DR OrthoDB; 601480at2759; -. DR PhylomeDB; Q13445; -. DR TreeFam; TF313000; -. DR PathwayCommons; Q13445; -. DR SignaLink; Q13445; -. DR BioGRID-ORCS; 11018; 12 hits in 1156 CRISPR screens. DR ChiTaRS; TMED1; human. DR GeneWiki; TMED1; -. DR GenomeRNAi; 11018; -. DR Pharos; Q13445; Tbio. DR PRO; PR:Q13445; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q13445; Protein. DR Bgee; ENSG00000099203; Expressed in stromal cell of endometrium and 196 other cell types or tissues. DR ExpressionAtlas; Q13445; baseline and differential. DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IBA:GO_Central. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0038024; F:cargo receptor activity; IBA:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IBA:GO_Central. DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR InterPro; IPR015720; Emp24-like. DR InterPro; IPR009038; GOLD_dom. DR InterPro; IPR036598; GOLD_dom_sf. DR PANTHER; PTHR22811; TRANSMEMBRANE EMP24 DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR22811:SF40; TRANSMEMBRANE EMP24 DOMAIN-CONTAINING PROTEIN 1; 1. DR Pfam; PF01105; EMP24_GP25L; 1. DR SMART; SM01190; EMP24_GP25L; 1. DR SUPFAM; SSF101576; Supernatant protein factor (SPF), C-terminal domain; 1. DR PROSITE; PS50866; GOLD; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Coiled coil; Direct protein sequencing; KW Endoplasmic reticulum; Golgi apparatus; Immunity; Innate immunity; KW Membrane; Protein transport; Reference proteome; Signal; Transmembrane; KW Transmembrane helix; Transport. FT SIGNAL 1..23 FT /evidence="ECO:0000269|PubMed:19892738, FT ECO:0007744|PubMed:25944712" FT CHAIN 24..227 FT /note="Transmembrane emp24 domain-containing protein 1" FT /id="PRO_0000248019" FT TOPO_DOM 24..194 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 195..215 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 216..227 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 43..125 FT /note="GOLD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00096" FT COILED 145..170 FT /evidence="ECO:0000255" FT MOTIF 218..227 FT /note="COPI vesicle coat-binding" FT /evidence="ECO:0000255" FT MOTIF 218..219 FT /note="COPII vesicle coat-binding" FT /evidence="ECO:0000255" FT VARIANT 102 FT /note="D -> N (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036533" FT MUTAGEN 45 FT /note="C->S: Significant loss of interaction with IL1RL1." FT /evidence="ECO:0000269|PubMed:23319592" FT MUTAGEN 106 FT /note="C->S: Significant loss of interaction with IL1RL1." FT /evidence="ECO:0000269|PubMed:23319592" FT STRAND 30..38 FT /evidence="ECO:0007829|PDB:7RRM" FT STRAND 43..50 FT /evidence="ECO:0007829|PDB:7RRM" FT STRAND 55..65 FT /evidence="ECO:0007829|PDB:7RRM" FT STRAND 70..75 FT /evidence="ECO:0007829|PDB:7RRM" FT STRAND 81..97 FT /evidence="ECO:0007829|PDB:7RRM" FT STRAND 100..108 FT /evidence="ECO:0007829|PDB:7RRM" FT STRAND 116..125 FT /evidence="ECO:0007829|PDB:7RRM" SQ SEQUENCE 227 AA; 25206 MW; 058C5274E05F8575 CRC64; MMAAGAALAL ALWLLMPPVE VGGAGPPPIQ DGEFTFLLPA GRKQCFYQSA PANASLETEY QVIGGAGLDV DFTLESPQGV LLVSESRKAD GVHTVEPTEA GDYKLCFDNS FSTISEKLVF FELIFDSLQD DEEVEGWAEA VEPEEMLDVK MEDIKESIET MRTRLERSIQ MLTLLRAFEA RDRNLQEGNL ERVNFWSAVN VAVLLLVAVL QVCTLKRFFQ DKRPVPT //