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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

  • cargo loading into vesicle Source: UniProtKB
  • COPI coating of Golgi vesicle Source: UniProtKB
  • COPII vesicle coating Source: UniProtKB
  • ER to Golgi vesicle-mediated transport Source: UniProtKB
  • Golgi organization Source: UniProtKB
  • heart looping Source: Ensembl
  • intracellular protein transport Source: UniProtKB
  • labyrinthine layer blood vessel development Source: Ensembl
  • maternal placenta development Source: Ensembl
  • multicellular organism growth Source: Ensembl
  • negative regulation of GTPase activity Source: UniProtKB
  • neural tube closure Source: Ensembl
  • positive regulation of gene expression Source: Ensembl
  • post-anal tail morphogenesis Source: Ensembl
  • protein targeting to plasma membrane Source: UniProtKB
  • retrograde vesicle-mediated transport, Golgi to ER Source: Reactome
  • somite rostral/caudal axis specification Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

ER-Golgi transport, Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000086598-MONOMER.
ReactomeiR-HSA-1912420. Pre-NOTCH Processing in Golgi.
R-HSA-204005. COPII (Coat Protein 2) Mediated Vesicle Transport.
R-HSA-5694530. Cargo concentration in the ER.
R-HSA-6807878. COPI-mediated anterograde transport.
R-HSA-6811434. COPI-dependent Golgi-to-ER retrograde traffic.

Protein family/group databases

TCDBi9.B.188.1.2. the transmembrane emp24 domain-containing protein (tmed) family.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:16996. TMED2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 168LumenalSequence analysisAdd BLAST148
Transmembranei169 – 189HelicalSequence analysisAdd BLAST21
Topological domaini190 – 201CytoplasmicSequence analysisAdd BLAST12

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi194 – 195FF → AA: Disrupts association with coatomer; when associated with S-198-199-S. 2 Publications2
Mutagenesisi194 – 195FF → AA: Reduced surface and total expression of CASR. 2 Publications2
Mutagenesisi198 – 199RR → SS: Disrupts association with coatomer; when associated with A-194-195-A. 1 Publication2
Mutagenesisi198 – 199RR → SS: No inhibition of coatomer-dependent GTP hydrolysis. 1 Publication2

Organism-specific databases

DisGeNETi10959.
OpenTargetsiENSG00000086598.
PharmGKBiPA142670796.

Polymorphism and mutation databases

BioMutaiTMED2.
DMDMi3914237.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001038121 – 201Transmembrane emp24 domain-containing protein 2Add BLAST181

Proteomic databases

EPDiQ15363.
PaxDbiQ15363.
PeptideAtlasiQ15363.
PRIDEiQ15363.
TopDownProteomicsiQ15363.

PTM databases

iPTMnetiQ15363.
PhosphoSitePlusiQ15363.

Expressioni

Gene expression databases

BgeeiENSG00000086598.
CleanExiHS_TMED2.
ExpressionAtlasiQ15363. baseline and differential.
GenevisibleiQ15363. HS.

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. 47 interactors.
IntActiQ15363. 35 interactors.
MINTiMINT-5000229.
STRINGi9606.ENSP00000262225.

Structurei

Secondary structure

1201
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 25Combined sources4
Beta strandi29 – 37Combined sources9
Beta strandi42 – 49Combined sources8
Beta strandi51 – 53Combined sources3
Beta strandi57 – 62Combined sources6
Beta strandi68 – 83Combined sources16
Beta strandi85 – 96Combined sources12
Beta strandi104 – 112Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5AZWX-ray1.50A/B19-114[»]
ProteinModelPortaliQ15363.
SMRiQ15363.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 112GOLDPROSITE-ProRule annotationAdd BLAST83

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 181Interaction with F2RL11 PublicationAdd BLAST181
Regioni118 – 157Required for TMED10 and TMED2 cis-Golgi network localizationAdd BLAST40

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili117 – 167Sequence analysisAdd BLAST51

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi194 – 201COPI vesicle coat-bindingSequence analysis8
Motifi194 – 195COPII vesicle coat-bindingSequence analysis2

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

eggNOGiKOG1692. Eukaryota.
ENOG410XQCK. LUCA.
GeneTreeiENSGT00670000097656.
HOGENOMiHOG000160229.
HOVERGENiHBG105106.
InParanoidiQ15363.
KOiK20347.
OMAiNEEQCFF.
OrthoDBiEOG091G0L5D.
PhylomeDBiQ15363.
TreeFamiTF313000.

Family and domain databases

InterProiIPR009038. GOLD_dom.
[Graphical view]
PfamiPF01105. EMP24_GP25L. 1 hit.
[Graphical view]
SMARTiSM01190. 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_001308374.1. NM_001321445.1.
NP_006806.1. NM_006815.3.
UniGeneiHs.733403.

Genome annotation databases

EnsembliENST00000262225; ENSP00000262225; ENSG00000086598.
GeneIDi10959.
KEGGihsa:10959.

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_001308374.1. NM_001321445.1.
NP_006806.1. NM_006815.3.
UniGeneiHs.733403.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5AZWX-ray1.50A/B19-114[»]
ProteinModelPortaliQ15363.
SMRiQ15363.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116158. 47 interactors.
IntActiQ15363. 35 interactors.
MINTiMINT-5000229.
STRINGi9606.ENSP00000262225.

Protein family/group databases

TCDBi9.B.188.1.2. the transmembrane emp24 domain-containing protein (tmed) family.

PTM databases

iPTMnetiQ15363.
PhosphoSitePlusiQ15363.

Polymorphism and mutation databases

BioMutaiTMED2.
DMDMi3914237.

Proteomic databases

EPDiQ15363.
PaxDbiQ15363.
PeptideAtlasiQ15363.
PRIDEiQ15363.
TopDownProteomicsiQ15363.

Protocols and materials databases

DNASUi10959.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262225; ENSP00000262225; ENSG00000086598.
GeneIDi10959.
KEGGihsa:10959.

Organism-specific databases

CTDi10959.
DisGeNETi10959.
GeneCardsiTMED2.
HGNCiHGNC:16996. TMED2.
HPAiHPA014060.
neXtProtiNX_Q15363.
OpenTargetsiENSG00000086598.
PharmGKBiPA142670796.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1692. Eukaryota.
ENOG410XQCK. LUCA.
GeneTreeiENSGT00670000097656.
HOGENOMiHOG000160229.
HOVERGENiHBG105106.
InParanoidiQ15363.
KOiK20347.
OMAiNEEQCFF.
OrthoDBiEOG091G0L5D.
PhylomeDBiQ15363.
TreeFamiTF313000.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000086598-MONOMER.
ReactomeiR-HSA-1912420. Pre-NOTCH Processing in Golgi.
R-HSA-204005. COPII (Coat Protein 2) Mediated Vesicle Transport.
R-HSA-5694530. Cargo concentration in the ER.
R-HSA-6807878. COPI-mediated anterograde transport.
R-HSA-6811434. COPI-dependent Golgi-to-ER retrograde traffic.

Miscellaneous databases

ChiTaRSiTMED2. human.
GeneWikiiTMED2.
GenomeRNAii10959.
PROiQ15363.

Gene expression databases

BgeeiENSG00000086598.
CleanExiHS_TMED2.
ExpressionAtlasiQ15363. baseline and differential.
GenevisibleiQ15363. HS.

Family and domain databases

InterProiIPR009038. GOLD_dom.
[Graphical view]
PfamiPF01105. EMP24_GP25L. 1 hit.
[Graphical view]
SMARTiSM01190. EMP24_GP25L. 1 hit.
[Graphical view]
SUPFAMiSSF101576. SSF101576. 1 hit.
PROSITEiPS50866. GOLD. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 145 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.