TMED9_HUMAN
ID TMED9_HUMAN Reviewed; 235 AA.
AC Q9BVK6; Q14437; Q8WZ61;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Transmembrane emp24 domain-containing protein 9;
DE AltName: Full=GMP25;
DE AltName: Full=Glycoprotein 25L2;
DE AltName: Full=p24 family protein alpha-2;
DE Short=p24alpha2;
DE AltName: Full=p25;
DE Flags: Precursor;
GN Name=TMED9; Synonyms=GP25L2;
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=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-235.
RC TISSUE=Liver;
RA Dominguez M., Fazel A., Parlati F., Bell A.W., Thomas D.Y.,
RA Bergeron J.J.M.;
RL Submitted (AUG-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-235.
RA Wang C., Li Y.;
RT "A novel human cDNA that shares sequence homology with Homo sapiens mRNAs
RT LOC96645 and gp25L2.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 129-138 AND 170-180, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [6]
RP GLYCOSYLATION, AND SUBUNIT.
RX PubMed=10359607; DOI=10.1091/mbc.10.6.1939;
RA Fullekrug J., Suganuma T., Tang B.L., Hong W., Storrie B., Nilsson T.;
RT "Localization and recycling of gp27 (hp24gamma3): complex formation with
RT other p24 family members.";
RL Mol. Biol. Cell 10:1939-1955(1999).
RN [7]
RP FUNCTION, AND 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 [8]
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 [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 232-LYS-LYS-233.
RX PubMed=14600267; DOI=10.1242/jcs.00802;
RA Emery G., Parton R.G., Rojo M., Gruenberg J.;
RT "The trans-membrane protein p25 forms highly specialized domains that
RT regulate membrane composition and dynamics.";
RL J. Cell Sci. 116:4821-4832(2003).
RN [10]
RP GLYCOSYLATION AT ASN-125.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [11]
RP INTERACTION WITH SPAST.
RX PubMed=15537668; DOI=10.1093/hmg/ddi003;
RA Reid E., Connell J.W., Edwards T.L., Duley S., Brown S.E., Sanderson C.M.;
RT "The hereditary spastic paraplegia protein spastin interacts with the
RT ESCRT-III complex-associated endosomal protein CHMP1B.";
RL Hum. Mol. Genet. 14:19-38(2005).
RN [12]
RP FUNCTION, AND INTERACTION WITH PTPN2.
RX PubMed=16595549; DOI=10.1242/jcs.02885;
RA Gupta V., Swarup G.;
RT "Evidence for a role of transmembrane protein p25 in localization of
RT protein tyrosine phosphatase TC48 to the ER.";
RL J. Cell Sci. 119:1703-1714(2006).
RN [13]
RP INTERACTION WITH COPG1.
RX PubMed=16940185; DOI=10.1128/mcb.01055-06;
RA Bethune J., Kol M., Hoffmann J., Reckmann I., Brugger B., Wieland F.;
RT "Coatomer, the coat protein of COPI transport vesicles, discriminates
RT endoplasmic reticulum residents from p24 proteins.";
RL Mol. Cell. Biol. 26:8011-8021(2006).
RN [14]
RP FUNCTION.
RX PubMed=18287528; DOI=10.1091/mbc.e07-10-0989;
RA Mitrovic S., Ben-Tekaya H., Koegler E., Gruenberg J., Hauri H.-P.;
RT "The cargo receptors Surf4, endoplasmic reticulum-Golgi intermediate
RT compartment (ERGIC)-53, and p25 are required to maintain the architecture
RT of ERGIC and Golgi.";
RL Mol. Biol. Cell 19:1976-1990(2008).
RN [15]
RP FUNCTION.
RX PubMed=19296914; DOI=10.1016/j.cellsig.2009.03.006;
RA Luo R., Ha V.L., Hayashi R., Randazzo P.A.;
RT "Arf GAP2 is positively regulated by coatomer and cargo.";
RL Cell. Signal. 21:1169-1179(2009).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-125.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [17]
RP INTERACTION WITH TMED5.
RX PubMed=19948005; DOI=10.1111/j.1600-0854.2009.01009.x;
RA Koegler E., Bonnon C., Waldmeier L., Mitrovic S., Halbeisen R., Hauri H.P.;
RT "p28, a novel ERGIC/cis Golgi protein, required for Golgi ribbon
RT formation.";
RL Traffic 11:70-89(2010).
RN [18]
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 [19]
RP INTERACTION WITH STX17.
RX PubMed=21545355; DOI=10.1042/bc20110006;
RA Muppirala M., Gupta V., Swarup G.;
RT "Syntaxin 17 cycles between the ER and ERGIC and is required to maintain
RT the architecture of ERGIC and Golgi.";
RL Biol. Cell 103:333-350(2011).
RN [20]
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).
CC -!- FUNCTION: Appears to be involved in vesicular protein trafficking,
CC mainly in the early secretory pathway. In COPI vesicle-mediated
CC retrograde transport involved in the coatomer recruitment to membranes
CC of the early secretory pathway. Increases coatomer-dependent activity
CC of ARFGAP2. Thought to play a crucial role in the specific retention of
CC p24 complexes in cis-Golgi membranes; specifically contributes to the
CC coupled localization of TMED2 and TMED10 in the cis-Golgi network. May
CC be involved in organization of intracellular membranes, such as of the
CC ER-Golgi intermediate compartment and the Golgi apparatus. Involved in
CC ER localization of PTPN2 isoform PTPB. {ECO:0000269|PubMed:10852829,
CC ECO:0000269|PubMed:14600267, ECO:0000269|PubMed:16595549,
CC ECO:0000269|PubMed:18287528, ECO:0000269|PubMed:19296914}.
CC -!- SUBUNIT: Monomer and homodimer in endoplasmic reticulum. Predominantly
CC monomeric and to lesser extent homodimeric in endoplasmic reticulum-
CC Golgi intermediate compartment and cis-Golgi network. Probably
CC oligomerizes with other members of the EMP24/GP25L family such as
CC TMED2, TMED7 and TMED10. Interacts with TMED5. Interacts (via C-
CC terminus) with COPG1; the interaction involves dimeric TMED9. Interacts
CC with PTPN2 and SPAST. Interacts with STX17; the interaction is direct.
CC {ECO:0000269|PubMed:10359607, ECO:0000269|PubMed:12237308,
CC ECO:0000269|PubMed:15537668, ECO:0000269|PubMed:16595549,
CC ECO:0000269|PubMed:16940185, ECO:0000269|PubMed:19948005,
CC ECO:0000269|PubMed:21545355}.
CC -!- INTERACTION:
CC Q9BVK6; O43315: AQP9; NbExp=3; IntAct=EBI-1056827, EBI-17444777;
CC Q9BVK6; O43736: ITM2A; NbExp=3; IntAct=EBI-1056827, EBI-2431769;
CC Q9BVK6; Q96GM1: PLPPR2; NbExp=3; IntAct=EBI-1056827, EBI-12955265;
CC Q9BVK6; P17706-1: PTPN2; NbExp=5; IntAct=EBI-1056827, EBI-4409481;
CC Q9BVK6; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-1056827, EBI-8652744;
CC Q9BVK6; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-1056827, EBI-2852148;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC I membrane protein. Golgi apparatus, cis-Golgi network membrane;
CC Single-pass type I membrane protein. Endoplasmic reticulum-Golgi
CC intermediate compartment membrane; Single-pass type I membrane protein.
CC Golgi apparatus, trans-Golgi network membrane {ECO:0000250}; Single-
CC pass type I membrane protein {ECO:0000250}. Note=Cycles between
CC compartments of the early secretatory pathway.
CC -!- PTM: N-linked glycosylated containing high mannose.
CC {ECO:0000269|PubMed:10359607, ECO:0000269|PubMed:12754519,
CC ECO:0000269|PubMed:19159218}.
CC -!- SIMILARITY: Belongs to the EMP24/GP25L family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL35268.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA62380.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC139795; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001123; AAH01123.2; -; mRNA.
DR EMBL; X90872; CAA62380.1; ALT_INIT; mRNA.
DR EMBL; AF441399; AAL35268.1; ALT_INIT; mRNA.
DR CCDS; CCDS4428.1; -.
DR RefSeq; NP_059980.2; NM_017510.5.
DR AlphaFoldDB; Q9BVK6; -.
DR SMR; Q9BVK6; -.
DR BioGRID; 120115; 128.
DR ELM; Q9BVK6; -.
DR IntAct; Q9BVK6; 56.
DR MINT; Q9BVK6; -.
DR STRING; 9606.ENSP00000330945; -.
DR GlyConnect; 1846; 4 N-Linked glycans (1 site).
DR GlyGen; Q9BVK6; 2 sites, 4 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q9BVK6; -.
DR MetOSite; Q9BVK6; -.
DR PhosphoSitePlus; Q9BVK6; -.
DR SwissPalm; Q9BVK6; -.
DR BioMuta; TMED9; -.
DR DMDM; 239938724; -.
DR EPD; Q9BVK6; -.
DR jPOST; Q9BVK6; -.
DR MassIVE; Q9BVK6; -.
DR MaxQB; Q9BVK6; -.
DR PaxDb; Q9BVK6; -.
DR PeptideAtlas; Q9BVK6; -.
DR PRIDE; Q9BVK6; -.
DR ProteomicsDB; 79214; -.
DR TopDownProteomics; Q9BVK6; -.
DR Antibodypedia; 29339; 165 antibodies from 24 providers.
DR DNASU; 54732; -.
DR Ensembl; ENST00000332598.7; ENSP00000330945.6; ENSG00000184840.12.
DR GeneID; 54732; -.
DR KEGG; hsa:54732; -.
DR MANE-Select; ENST00000332598.7; ENSP00000330945.6; NM_017510.6; NP_059980.2.
DR UCSC; uc003mhx.4; human.
DR CTD; 54732; -.
DR DisGeNET; 54732; -.
DR GeneCards; TMED9; -.
DR HGNC; HGNC:24878; TMED9.
DR HPA; ENSG00000184840; Low tissue specificity.
DR neXtProt; NX_Q9BVK6; -.
DR OpenTargets; ENSG00000184840; -.
DR PharmGKB; PA134881976; -.
DR VEuPathDB; HostDB:ENSG00000184840; -.
DR eggNOG; KOG1690; Eukaryota.
DR GeneTree; ENSGT00940000159747; -.
DR HOGENOM; CLU_066963_2_2_1; -.
DR InParanoid; Q9BVK6; -.
DR OMA; MSHRVRM; -.
DR OrthoDB; 1294924at2759; -.
DR PhylomeDB; Q9BVK6; -.
DR TreeFam; TF314123; -.
DR PathwayCommons; Q9BVK6; -.
DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport.
DR Reactome; R-HSA-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR SignaLink; Q9BVK6; -.
DR BioGRID-ORCS; 54732; 29 hits in 1081 CRISPR screens.
DR ChiTaRS; TMED9; human.
DR GenomeRNAi; 54732; -.
DR Pharos; Q9BVK6; Tbio.
DR PRO; PR:Q9BVK6; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9BVK6; protein.
DR Bgee; ENSG00000184840; Expressed in tendon of biceps brachii and 206 other tissues.
DR ExpressionAtlas; Q9BVK6; baseline and differential.
DR Genevisible; Q9BVK6; 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; TAS:Reactome.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR GO; GO:0030140; C:trans-Golgi network transport vesicle; TAS:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; TAS:Reactome.
DR GO; GO:0019905; F:syntaxin binding; IPI:UniProtKB.
DR GO; GO:0048205; P:COPI coating of Golgi vesicle; IMP:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0010638; P:positive regulation of organelle organization; IMP:UniProtKB.
DR InterPro; IPR015720; Emp24-like.
DR InterPro; IPR009038; GOLD_dom.
DR PANTHER; PTHR22811; PTHR22811; 1.
DR Pfam; PF01105; EMP24_GP25L; 1.
DR SMART; SM01190; EMP24_GP25L; 1.
DR PROSITE; PS50866; GOLD; 1.
PE 1: Evidence at protein level;
KW Acetylation; Coiled coil; Direct protein sequencing; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Membrane; Protein transport;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..37
FT /evidence="ECO:0000250"
FT CHAIN 38..235
FT /note="Transmembrane emp24 domain-containing protein 9"
FT /id="PRO_0000010396"
FT TOPO_DOM 38..202
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 47..145
FT /note="GOLD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00096"
FT REGION 121..160
FT /note="Required for interaction with STX17"
FT /evidence="ECO:0000269|PubMed:21545355"
FT COILED 154..184
FT /evidence="ECO:0000255"
FT MOTIF 228..235
FT /note="COPI vesicle coat-binding"
FT /evidence="ECO:0000255"
FT MOTIF 228..229
FT /note="COPII vesicle coat-binding"
FT /evidence="ECO:0000255"
FT MOD_RES 160
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KF1"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:19159218"
FT VARIANT 16
FT /note="T -> S (in dbSNP:rs57960711)"
FT /id="VAR_061178"
FT MUTAGEN 232..233
FT /note="KK->SS: Localization to plasma membrane and
FT endocytosis."
FT /evidence="ECO:0000269|PubMed:14600267"
FT CONFLICT 83
FT /note="L -> F (in Ref. 2; CAA62380)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="F -> C (in Ref. 2; CAA62380)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="Q -> E (in Ref. 2; CAA62380)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="Y -> C (in Ref. 3; AAL35268)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="A -> P (in Ref. 2; CAA62380)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 235 AA; 27277 MW; 9B6D2D517D9E77D8 CRC64;
MAVELGVLLV RPRPGTGLGR VMRTLLLVLW LATRGSALYF HIGETEKKCF IEEIPDETMV
IGNYRTQLYD KQREEYQPAT PGLGMFVEVK DPEDKVILAR QYGSEGRFTF TSHTPGEHQI
CLHSNSTKFS LFAGGMLRVH LDIQVGEHAN DYAEIAAKDK LSELQLRVRQ LVEQVEQIQK
EQNYQRWREE RFRQTSESTN QRVLWWSILQ TLILVAIGVW QMRHLKSFFE AKKLV
