TMED1_HUMAN
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 03-AUG-2022, entry version 158.
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}.
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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; 82.
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 EPD; Q13445; -.
DR jPOST; Q13445; -.
DR MassIVE; Q13445; -.
DR MaxQB; Q13445; -.
DR PaxDb; Q13445; -.
DR PeptideAtlas; Q13445; -.
DR PRIDE; Q13445; -.
DR ProteomicsDB; 59453; -.
DR TopDownProteomics; Q13445; -.
DR Antibodypedia; 2281; 215 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 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; EICFDNG; -.
DR OrthoDB; 1292519at2759; -.
DR PhylomeDB; Q13445; -.
DR TreeFam; TF313000; -.
DR PathwayCommons; Q13445; -.
DR SignaLink; Q13445; -.
DR BioGRID-ORCS; 11018; 12 hits in 1078 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 194 other tissues.
DR ExpressionAtlas; Q13445; baseline and differential.
DR Genevisible; Q13445; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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; PTHR22811; 1.
DR Pfam; PF01105; EMP24_GP25L; 1.
DR SMART; SM01190; EMP24_GP25L; 1.
DR SUPFAM; SSF101576; SSF101576; 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
