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Q15363 (TMED2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transmembrane emp24 domain-containing protein 2
Alternative name(s):
Membrane protein p24A
p24
p24 family protein beta-1
Short name=p24beta1
Gene names
Name:TMED2
Synonyms:RNP24
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length201 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.9 Ref.12 Ref.13 Ref.15

Subunit structure

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. Ref.4 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15

Subcellular location

Cytoplasmic vesicle membrane; Single-pass type I membrane protein. Cytoplasmic vesicleCOPI-coated vesicle membrane; Single-pass type I membrane protein. Golgi apparatuscis-Golgi network membrane; Single-pass type I membrane protein. Golgi apparatusGolgi stack membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endoplasmic reticulum-Golgi intermediate compartment membrane; Single-pass type I membrane protein. Note: Cycles between compartments of the early secretatory pathway. Ref.3 Ref.6 Ref.7

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.

Sequence similarities

Belongs to the EMP24/GP25L family.

Contains 1 GOLD domain.

Ontologies

Keywords
   Biological processER-Golgi transport
Protein transport
Transport
   Cellular componentCytoplasmic vesicle
Endoplasmic reticulum
Golgi apparatus
Membrane
   DomainCoiled coil
Signal
Transmembrane
Transmembrane helix
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processCOPI coating of Golgi vesicle

Traceable author statement Ref.5. Source: UniProtKB

COPII vesicle coating

Traceable author statement Ref.13. Source: UniProtKB

ER to Golgi vesicle-mediated transport

Traceable author statement Ref.13. Source: UniProtKB

Golgi organization

Inferred from mutant phenotype Ref.9. Source: UniProtKB

cargo loading into vesicle

Traceable author statement Ref.13. Source: UniProtKB

embryonic morphogenesis

Inferred from electronic annotation. Source: Ensembl

intracellular protein transport

Inferred from direct assay Ref.13. Source: UniProtKB

maternal placenta development

Inferred from electronic annotation. Source: Ensembl

negative regulation of GTPase activity

Inferred from direct assay Ref.5. Source: UniProtKB

protein targeting to plasma membrane

Inferred from direct assay Ref.12. Source: UniProtKB

   Cellular_componentCOPI-coated vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

COPI-coated vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Golgi apparatus

Inferred from direct assay Ref.7. Source: UniProtKB

Golgi cisterna membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum

Inferred from direct assay Ref.7. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum-Golgi intermediate compartment

Inferred from direct assay Ref.7. Source: UniProtKB

endoplasmic reticulum-Golgi intermediate compartment membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from sequence or structural similarity. Source: HGNC

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

zymogen granule membrane

Inferred from sequence or structural similarity. Source: HGNC

   Molecular_functionprotein binding

Inferred from physical interaction Ref.4Ref.7PubMed 16641999Ref.9Ref.11Ref.12Ref.13Ref.15. Source: IntAct

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 201181Transmembrane emp24 domain-containing protein 2
PRO_0000010381

Regions

Topological domain21 – 168148Lumenal Potential
Transmembrane169 – 18921Helical; Potential
Topological domain190 – 20112Cytoplasmic Potential
Domain30 – 11283GOLD
Region1 – 181181Interaction with F2RL1
Region118 – 15740Required for TMED10 and TMED2 cis-Golgi network localization
Coiled coil117 – 16751 Potential
Motif194 – 2018COPI vesicle coat-binding Potential
Motif194 – 1952COPII vesicle coat-binding Potential

Experimental info

Mutagenesis194 – 1952FF → AA: Disrupts association with coatomer; when associated with S-198-199-S. Ref.5 Ref.12
Mutagenesis194 – 1952FF → AA: Reduced surface and total expression of CASR. Ref.5 Ref.12
Mutagenesis198 – 1992RR → SS: Disrupts association with coatomer; when associated with A-194-195-A. Ref.5 Ref.12
Mutagenesis198 – 1992RR → SS: No inhibition of coatomer-dependent GTP hydrolysis. Ref.5 Ref.12

Sequences

Sequence LengthMass (Da)Tools
Q15363 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: C452370E459DC894

FASTA20122,761
        10         20         30         40         50         60 
MVTLAELLVL LAALLATVSG YFVSIDAHAE ECFFERVTSG TKMGLIFEVA EGGFLDIDVE 

        70         80         90        100        110        120 
ITGPDNKGIY KGDRESSGKY TFAAHMDGTY KFCFSNRMST MTPKIVMFTI DIGEAPKGQD 

       130        140        150        160        170        180 
METEAHQNKL EEMINELAVA MTAVKHEQEY MEVRERIHRA INDNTNSRVV LWSFFEALVL 

       190        200 
VAMTLGQIYY LKRFFEVRRV V 

« Hide

References

« Hide 'large scale' references
[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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X92098 mRNA. Translation: CAA63069.1.
BC025957 mRNA. Translation: AAH25957.1.
CCDSCCDS9250.1.
RefSeqNP_006806.1. NM_006815.3.
UniGeneHs.733403.

3D structure databases

ProteinModelPortalQ15363.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116158. 13 interactions.
IntActQ15363. 31 interactions.
MINTMINT-5000229.
STRING9606.ENSP00000262225.

PTM databases

PhosphoSiteQ15363.

Polymorphism databases

DMDM3914237.

Proteomic databases

MaxQBQ15363.
PaxDbQ15363.
PeptideAtlasQ15363.
PRIDEQ15363.

Protocols and materials databases

DNASU10959.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262225; ENSP00000262225; ENSG00000086598.
GeneID10959.
KEGGhsa:10959.
UCSCuc001ufg.3. human.

Organism-specific databases

CTD10959.
GeneCardsGC12P124069.
HGNCHGNC:16996. TMED2.
HPAHPA014060.
neXtProtNX_Q15363.
PharmGKBPA142670796.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG271196.
HOGENOMHOG000160229.
HOVERGENHBG105106.
InParanoidQ15363.
OMAEECFFDK.
OrthoDBEOG7RFTJP.
PhylomeDBQ15363.
TreeFamTF313000.

Gene expression databases

ArrayExpressQ15363.
BgeeQ15363.
CleanExHS_TMED2.
GenevestigatorQ15363.

Family and domain databases

InterProIPR009038. GOLD.
IPR015720. TMP21-related.
[Graphical view]
PANTHERPTHR22811. PTHR22811. 1 hit.
PfamPF01105. EMP24_GP25L. 1 hit.
[Graphical view]
SUPFAMSSF101576. SSF101576. 1 hit.
PROSITEPS50866. GOLD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTMED2. human.
GeneWikiTMED2.
GenomeRNAi10959.
NextBio41644.
PROQ15363.

Entry information

Entry nameTMED2_HUMAN
AccessionPrimary (citable) accession number: Q15363
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM