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Protein

Transmembrane emp24 domain-containing protein 2

Gene

TMED2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in vesicular protein trafficking. Mainly functions in the early secretory pathway but also in post-Golgi membranes. Thought to act as cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and to be involved in vesicle coat formation at the cytoplasmic side. In COPII vesicle-mediated anterograde transport involved in the transport of GPI-anchored proteins and proposed to act together with TMED10 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER. Recognizes GPI anchors structural remodeled in the ER by PGAP1 and MPPE1. In COPI vesicle-mediated retrograde transport inhibits the GTPase-activating activity of ARFGAP1 towards ARF1 thus preventing immature uncoating and allowing cargo selection to take place. Involved in trafficking of G protein-coupled receptors (GPCRs). Regulates F2RL1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma membrane thus contributing to receptor resensitization. Facilitates CASR maturation and stabilization in the early secretory pathway and increases CASR plasma membrane targeting. Proposed to be involved in organization of intracellular membranes such as the maintenance of the Golgi apparatus. May also play a role in the biosynthesis of secreted cargo such as eventual processing.5 Publications

GO - Biological processi

  1. cargo loading into vesicle Source: UniProtKB
  2. COPI coating of Golgi vesicle Source: UniProtKB
  3. COPII vesicle coating Source: UniProtKB
  4. embryonic morphogenesis Source: Ensembl
  5. ER to Golgi vesicle-mediated transport Source: UniProtKB
  6. Golgi organization Source: UniProtKB
  7. intracellular protein transport Source: UniProtKB
  8. maternal placenta development Source: Ensembl
  9. negative regulation of GTPase activity Source: UniProtKB
  10. protein targeting to plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

ER-Golgi transport, Protein transport, Transport

Enzyme and pathway databases

ReactomeiREACT_118798. Pre-NOTCH Processing in Golgi.

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane emp24 domain-containing protein 2
Alternative name(s):
Membrane protein p24A
p24
p24 family protein beta-1
Short name:
p24beta1
Gene namesi
Name:TMED2
Synonyms:RNP24
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:16996. TMED2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 168148LumenalSequence AnalysisAdd
BLAST
Transmembranei169 – 18921HelicalSequence AnalysisAdd
BLAST
Topological domaini190 – 20112CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. COPI-coated vesicle Source: UniProtKB
  2. COPI-coated vesicle membrane Source: UniProtKB-SubCell
  3. endoplasmic reticulum Source: UniProtKB
  4. endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB
  5. endoplasmic reticulum-Golgi intermediate compartment membrane Source: UniProtKB-SubCell
  6. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  7. Golgi apparatus Source: UniProtKB
  8. Golgi cisterna membrane Source: UniProtKB-SubCell
  9. integral component of membrane Source: HGNC
  10. intracellular membrane-bounded organelle Source: HPA
  11. zymogen granule membrane Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi194 – 1952FF → AA: Disrupts association with coatomer; when associated with S-198-199-S. 2 Publications
Mutagenesisi194 – 1952FF → AA: Reduced surface and total expression of CASR. 2 Publications
Mutagenesisi198 – 1992RR → SS: Disrupts association with coatomer; when associated with A-194-195-A. 1 Publication
Mutagenesisi198 – 1992RR → SS: No inhibition of coatomer-dependent GTP hydrolysis. 1 Publication

Organism-specific databases

PharmGKBiPA142670796.

Polymorphism and mutation databases

BioMutaiTMED2.
DMDMi3914237.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence AnalysisAdd
BLAST
Chaini21 – 201181Transmembrane emp24 domain-containing protein 2PRO_0000010381Add
BLAST

Proteomic databases

MaxQBiQ15363.
PaxDbiQ15363.
PeptideAtlasiQ15363.
PRIDEiQ15363.

PTM databases

PhosphoSiteiQ15363.

Expressioni

Gene expression databases

BgeeiQ15363.
CleanExiHS_TMED2.
ExpressionAtlasiQ15363. baseline and differential.
GenevestigatoriQ15363.

Organism-specific databases

HPAiHPA014060.

Interactioni

Subunit structurei

Monomer and homodimer in the endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment and Golgi. Probably oligomerizes with other members of the EMP24/GP25L family such as TMED7, TMED9 and TMED10. Interacts with TMED10. Associates with the COPI vesicle coat (coatomer); TMED10:TMED2 heterotetramers are proposed to be involved in coatomer association. Interacts (via C-terminus) with COPG1; the interaction involves dimeric TMED2. Interacts with SEC23A; indicative for an association of TMED2 with the COPII vesicle coat. Interacts with ARF1 and ARFGAP1 (By similarity). Interacts with CD59, SEC24A, SEC24B, SEC24C, SEC24D and ATLA1. Interacts with KDELR1; the interaction is decreased by KDEL ligand (By similarity). Interacts with F2RL1; the interaction occurs at the Golgi apparatus. Interacts with CASR (immaturely glycosylated form); the interaction occurs in the endoplasmic reticulum-Golgi intermediate compartment or cis-Golgi. Interacts with F2RL1; the interaction occurs at the Golgi apparatus. Interacts with GORASP1 and GORASP2 (By similarity). Found in a complex composed at least of SURF4, TMED2 and TMED10.By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CASRP411803EBI-998485,EBI-4400127
CD59P139874EBI-998485,EBI-297972
F2RL1P550856EBI-998485,EBI-4303189
TMED10O355872EBI-998485,EBI-4405327From a different organism.
TMED10P497557EBI-998485,EBI-998422

Protein-protein interaction databases

BioGridi116158. 32 interactions.
IntActiQ15363. 31 interactions.
MINTiMINT-5000229.
STRINGi9606.ENSP00000262225.

Structurei

3D structure databases

ProteinModelPortaliQ15363.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 11283GOLDPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 181181Interaction with F2RL1Add
BLAST
Regioni118 – 15740Required for TMED10 and TMED2 cis-Golgi network localizationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili117 – 16751Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi194 – 2018COPI vesicle coat-bindingSequence Analysis
Motifi194 – 1952COPII vesicle coat-bindingSequence Analysis

Sequence similaritiesi

Belongs to the EMP24/GP25L family.Curated
Contains 1 GOLD domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG271196.
HOGENOMiHOG000160229.
HOVERGENiHBG105106.
InParanoidiQ15363.
OMAiNEEQCFF.
OrthoDBiEOG7RFTJP.
PhylomeDBiQ15363.
TreeFamiTF313000.

Family and domain databases

InterProiIPR009038. GOLD.
IPR015720. TMP21-related.
[Graphical view]
PANTHERiPTHR22811. PTHR22811. 1 hit.
PfamiPF01105. EMP24_GP25L. 1 hit.
[Graphical view]
SUPFAMiSSF101576. SSF101576. 1 hit.
PROSITEiPS50866. GOLD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15363-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVTLAELLVL LAALLATVSG YFVSIDAHAE ECFFERVTSG TKMGLIFEVA
60 70 80 90 100
EGGFLDIDVE ITGPDNKGIY KGDRESSGKY TFAAHMDGTY KFCFSNRMST
110 120 130 140 150
MTPKIVMFTI DIGEAPKGQD METEAHQNKL EEMINELAVA MTAVKHEQEY
160 170 180 190 200
MEVRERIHRA INDNTNSRVV LWSFFEALVL VAMTLGQIYY LKRFFEVRRV

V
Length:201
Mass (Da):22,761
Last modified:November 1, 1996 - v1
Checksum:iC452370E459DC894
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X92098 mRNA. Translation: CAA63069.1.
BC025957 mRNA. Translation: AAH25957.1.
CCDSiCCDS9250.1.
RefSeqiNP_006806.1. NM_006815.3.
UniGeneiHs.733403.

Genome annotation databases

EnsembliENST00000262225; ENSP00000262225; ENSG00000086598.
GeneIDi10959.
KEGGihsa:10959.
UCSCiuc001ufg.3. human.

Polymorphism and mutation databases

BioMutaiTMED2.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X92098 mRNA. Translation: CAA63069.1.
BC025957 mRNA. Translation: AAH25957.1.
CCDSiCCDS9250.1.
RefSeqiNP_006806.1. NM_006815.3.
UniGeneiHs.733403.

3D structure databases

ProteinModelPortaliQ15363.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116158. 32 interactions.
IntActiQ15363. 31 interactions.
MINTiMINT-5000229.
STRINGi9606.ENSP00000262225.

PTM databases

PhosphoSiteiQ15363.

Polymorphism and mutation databases

BioMutaiTMED2.
DMDMi3914237.

Proteomic databases

MaxQBiQ15363.
PaxDbiQ15363.
PeptideAtlasiQ15363.
PRIDEiQ15363.

Protocols and materials databases

DNASUi10959.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262225; ENSP00000262225; ENSG00000086598.
GeneIDi10959.
KEGGihsa:10959.
UCSCiuc001ufg.3. human.

Organism-specific databases

CTDi10959.
GeneCardsiGC12P124069.
HGNCiHGNC:16996. TMED2.
HPAiHPA014060.
neXtProtiNX_Q15363.
PharmGKBiPA142670796.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG271196.
HOGENOMiHOG000160229.
HOVERGENiHBG105106.
InParanoidiQ15363.
OMAiNEEQCFF.
OrthoDBiEOG7RFTJP.
PhylomeDBiQ15363.
TreeFamiTF313000.

Enzyme and pathway databases

ReactomeiREACT_118798. Pre-NOTCH Processing in Golgi.

Miscellaneous databases

ChiTaRSiTMED2. human.
GeneWikiiTMED2.
GenomeRNAii10959.
NextBioi41644.
PROiQ15363.

Gene expression databases

BgeeiQ15363.
CleanExiHS_TMED2.
ExpressionAtlasiQ15363. baseline and differential.
GenevestigatoriQ15363.

Family and domain databases

InterProiIPR009038. GOLD.
IPR015720. TMP21-related.
[Graphical view]
PANTHERiPTHR22811. PTHR22811. 1 hit.
PfamiPF01105. EMP24_GP25L. 1 hit.
[Graphical view]
SUPFAMiSSF101576. SSF101576. 1 hit.
PROSITEiPS50866. GOLD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Tmp21 and p24A, two type I proteins enriched in pancreatic microsomal membranes, are members of a protein family involved in vesicular trafficking."
    Blum R., Feick P., Puype M., Vandekerckhove J., Klengel R., Nastainczyk W., Schulz I.
    J. Biol. Chem. 271:17183-17189(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Muscle.
  3. "gp25L/emp24/p24 protein family members of the cis-Golgi network bind both COP I and II coatomer."
    Dominguez M., Dejgaard K., Fullekrug J., Dahan S., Fazel A., Paccaud J.P., Thomas D.Y., Bergeron J.J., Nilsson T.
    J. Cell Biol. 140:751-765(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, ASSOCIATION WITH COPI AND COPII VESICLE COAT.
  4. "Localization and recycling of gp27 (hp24gamma3): complex formation with other p24 family members."
    Fullekrug J., Suganuma T., Tang B.L., Hong W., Storrie B., Nilsson T.
    Mol. Biol. Cell 10:1939-1955(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  5. "Decoding of sorting signals by coatomer through a GTPase switch in the COPI coat complex."
    Goldberg J.
    Cell 100:671-679(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF 194-PHE-PHE-195 AND 198-ARG-ARG-199.
  6. "Coupled transport of p24 family members."
    Emery G., Rojo M., Gruenberg J.
    J. Cell Sci. 113:2507-2516(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  7. "Oligomeric state and stoichiometry of p24 proteins in the early secretory pathway."
    Jenne N., Frey K., Brugger B., Wieland F.T.
    J. Biol. Chem. 277:46504-46511(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, SUBUNIT.
  8. "Coatomer, the coat protein of COPI transport vesicles, discriminates endoplasmic reticulum residents from p24 proteins."
    Bethune J., Kol M., Hoffmann J., Reckmann I., Brugger B., Wieland F.
    Mol. Cell. Biol. 26:8011-8021(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH COPG1.
  9. "p24A, a type I transmembrane protein, controls ARF1-dependent resensitization of protease-activated receptor-2 by influence on receptor trafficking."
    Luo W., Wang Y., Reiser G.
    J. Biol. Chem. 282:30246-30255(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH F2RL1.
  10. "Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER/Golgi interface and Golgi morphogenesis."
    Namekawa M., Muriel M.-P., Janer A., Latouche M., Dauphin A., Debeir T., Martin E., Duyckaerts C., Prigent A., Depienne C., Sittler A., Brice A., Ruberg M.
    Mol. Cell. Neurosci. 35:1-13(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ATLA1.
  11. "The cargo receptors Surf4, endoplasmic reticulum-Golgi intermediate compartment (ERGIC)-53, and p25 are required to maintain the architecture of ERGIC and Golgi."
    Mitrovic S., Ben-Tekaya H., Koegler E., Gruenberg J., Hauri H.-P.
    Mol. Biol. Cell 19:1976-1990(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH SURF4 AND TMED10.
  12. "The cargo receptor p24A facilitates calcium sensing receptor maturation and stabilization in the early secretory pathway."
    Stepanchick A., Breitwieser G.E.
    Biochem. Biophys. Res. Commun. 395:136-140(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CASR, MUTAGENESIS OF 194-PHE-PHE-195.
  13. "Selective export of human GPI-anchored proteins from the endoplasmic reticulum."
    Bonnon C., Wendeler M.W., Paccaud J.P., Hauri H.P.
    J. Cell Sci. 123:1705-1715(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CD59; SEC24A; SEC24B; SEC24C AND SEC24D.
  14. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  15. "Proteinase-activated receptors, nucleotide P2Y receptors, and mu-opioid receptor-1B are under the control of the type I transmembrane proteins p23 and p24A in post-Golgi trafficking."
    Luo W., Wang Y., Reiser G.
    J. Neurochem. 117:71-81(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH F2R; P2RY4; P2RY11 AND OPRM1.
  16. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiTMED2_HUMAN
AccessioniPrimary (citable) accession number: Q15363
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: April 29, 2015
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Ectopic expression of TMED2 alone does not result in its proper cis-Golgi network localization. Coexpression of TMED10 is necessary, and coexpression of TMED3 and/or TMED9 is facilitating localization. Down-regulation of TMED10 expression reduces TMED2 protein level.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.