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Protein

Transmembrane emp24 domain-containing protein 10

Gene

TMED10

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

Functioni

Involved in vesicular protein trafficking. Mainly functions in the early secretory pathway. 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 TMED2 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 (By similarity). In COPI vesicle-mediated retrograde transport involved in the biogenesis of COPI vesicles and vesicle coat recruitment. On Golgi membranes, acts as primary receptor for ARF1-GDP which is involved in COPI-vesicle formation. Increases coatomer-dependent GTPase-activating activity of ARFGAP2. Involved in trafficking of G protein-coupled receptors (GPCRs). Regulates F2LR1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma membrane thus contributing to receptor resensitization. Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent of modulation of gamma-secretase activity). As part of the presenilin-dependent gamma-secretase complex regulates gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40 (Abeta40). Involved in organization of the Golgi apparatus.By similarity7 Publications

Miscellaneous

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

GO - Molecular functioni

  • protein-containing complex binding Source: Ensembl
  • syntaxin binding Source: UniProtKB

GO - Biological processi

  • cargo loading into vesicle Source: UniProtKB
  • COPI-coated vesicle budding 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: Ensembl
  • intracellular protein transport Source: UniProtKB
  • kidney development Source: Ensembl
  • protein complex oligomerization Source: Ensembl
  • regulated exocytosis Source: HGNC
  • regulation of amyloid-beta formation Source: UniProtKB
  • response to alkaloid Source: Ensembl
  • retrograde vesicle-mediated transport, Golgi to ER Source: UniProtKB
  • vesicle targeting, to, from or within Golgi Source: HGNC

Keywordsi

Biological processER-Golgi transport, Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-204005 COPII-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
SIGNORiP49755

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane emp24 domain-containing protein 10
Alternative name(s):
21 kDa transmembrane-trafficking protein
S31III125
Short name:
S31I125
Tmp-21-I
Transmembrane protein Tmp21
p23
p24 family protein delta-1
Short name:
p24delta1
p24delta
Gene namesi
Name:TMED10
Synonyms:TMP21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000170348.8
HGNCiHGNC:16998 TMED10
MIMi605406 gene
neXtProtiNX_P49755

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 185LumenalSequence analysisAdd BLAST154
Transmembranei186 – 206HelicalSequence analysisAdd BLAST21
Topological domaini207 – 219CytoplasmicSequence analysisAdd BLAST13

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi211 – 212FF → AA: Disrupts interaction with COPG1 and association with coatomer; when associated with 215-A-A-216. 3 Publications2
Mutagenesisi211 – 212FF → AA: No decrease in binding to COPG1. Disrupts interaction with SEC23A. 3 Publications2
Mutagenesisi215 – 216KK → AA: Disrupts interaction with COPG1 and association with coatomer; when associated with 211-A-A-212. 3 Publications2
Mutagenesisi215 – 216KK → AA: Significant reduction in binding to COPG1. 3 Publications2

Organism-specific databases

DisGeNETi10972
OpenTargetsiENSG00000170348
PharmGKBiPA128394579

Polymorphism and mutation databases

BioMutaiTMED10
DMDMi3915893

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Combined sources1 PublicationAdd BLAST31
ChainiPRO_000001039932 – 219Transmembrane emp24 domain-containing protein 10Add BLAST188

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei171Dimethylated arginine; alternateBy similarity1
Modified residuei171Omega-N-methylated arginine; alternateBy similarity1
Modified residuei176Dimethylated arginine; alternateBy similarity1
Modified residuei176Omega-N-methylated arginine; alternateBy similarity1
Glycosylationi179N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein, Methylation

Proteomic databases

EPDiP49755
MaxQBiP49755
PaxDbiP49755
PeptideAtlasiP49755
PRIDEiP49755
TopDownProteomicsiP49755

PTM databases

iPTMnetiP49755
PhosphoSitePlusiP49755
SwissPalmiP49755

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000170348
CleanExiHS_TMED10
ExpressionAtlasiP49755 baseline and differential
GenevisibleiP49755 HS

Organism-specific databases

HPAiCAB034442
CAB037251
HPA047139
HPA050539

Interactioni

Subunit structurei

Predominantly homodimeric and to lesser extent monomeric in endoplasmic reticulum. Homodimer and monomer in endoplasmic reticulum-Golgi intermediate compartment and cis-Golgi network. Probably oligomerizes with other members of the EMP24/GP25L family such as TMED2, TMED7 and TMED9. Interacts (via GOLD domain) with TMED2 (via GOLD domain). 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 TMED10. Interacts with ARF1 (GDP-bound); the interaction probably involves a TMED10 oligomer. Interacts with SEC23A; indicative for an association of TMED10 with the COPII vesicle coat. Interacts with CD59, SEC24B, SEC24C and SEC24D (By similarity). Interacts with MPPE1/PGAP5. Interacts with F2LR1. Interacts with KDELR2; the interaction is disrupted by KDELR2 ligand (By similarity). Found in a complex composed at least of SURF4, TMED2 and TMED10. Associates with the presenilin-dependent gamma-secretase complex. Interacts with STX17; the interaction is direct.By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • syntaxin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116169, 58 interactors
CORUMiP49755
ELMiP49755
IntActiP49755, 38 interactors
MINTiP49755
STRINGi9606.ENSP00000303145

Structurei

3D structure databases

ProteinModelPortaliP49755
SMRiP49755
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini41 – 193GOLDPROSITE-ProRule annotationAdd BLAST153

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 142Required for interaction with STX171 PublicationAdd BLAST142
Regioni147 – 178Required for TMED10 and TMED2 cis-Golgi network localizationAdd BLAST32
Regioni204 – 219Interaction with COPG1Add BLAST16
Regioni207 – 219Interaction with ARF11 PublicationAdd BLAST13

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi211 – 219COPI vesicle coat-binding9
Motifi211 – 212COPII vesicle coat-binding2

Domaini

The lumenal domain mediates localization to the plasma membrane by partially overriding the ER retention by the cytoplasmic domain.By similarity

Sequence similaritiesi

Belongs to the EMP24/GP25L family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1691 Eukaryota
ENOG410XTBQ LUCA
GeneTreeiENSGT00550000074954
HOVERGENiHBG107275
InParanoidiP49755
KOiK20352
OMAiFSMCCLI
OrthoDBiEOG091G0O9D
PhylomeDBiP49755
TreeFamiTF313729

Family and domain databases

InterProiView protein in InterPro
IPR009038 GOLD_dom
IPR015720 TMP21-related
PANTHERiPTHR22811 PTHR22811, 1 hit
PfamiView protein in Pfam
PF01105 EMP24_GP25L, 1 hit
SMARTiView protein in SMART
SM01190 EMP24_GP25L, 1 hit
PROSITEiView protein in PROSITE
PS50866 GOLD, 1 hit

Sequencei

Sequence statusi: Complete.

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

P49755-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGLSGPPAR RGPFPLALLL LFLLGPRLVL AISFHLPINS RKCLREEIHK
60 70 80 90 100
DLLVTGAYEI SDQSGGAGGL RSHLKITDSA GHILYSKEDA TKGKFAFTTE
110 120 130 140 150
DYDMFEVCFE SKGTGRIPDQ LVILDMKHGV EAKNYEEIAK VEKLKPLEVE
160 170 180 190 200
LRRLEDLSES IVNDFAYMKK REEEMRDTNE STNTRVLYFS IFSMFCLIGL
210
ATWQVFYLRR FFKAKKLIE
Length:219
Mass (Da):24,976
Last modified:December 15, 1998 - v2
Checksum:i0A0486BE65C4DBBB
GO

Sequence cautioni

The sequence AAC42003 differs from that shown. Reason: Frameshift at several positions.Curated
The sequence CAD66561 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti75K → R in CAD89913 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01205164S → Y. Corresponds to variant dbSNP:rs4929Ensembl.1
Natural variantiVAR_049111152R → G. Corresponds to variant dbSNP:rs17103066Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X97442 mRNA Translation: CAA66071.1
X97444 mRNA Translation: CAA66073.1
U61734 Genomic DNA Translation: AAB03625.1
L40397 mRNA Translation: AAC42003.1 Frameshift.
AJ004913 mRNA Translation: CAA06213.1
BX248754 mRNA Translation: CAD66561.1 Different initiation.
AK312384 mRNA Translation: BAG35302.1
AL832012 mRNA Translation: CAD89913.1
AC007055 Genomic DNA Translation: AAD31941.1
CH471061 Genomic DNA Translation: EAW81223.1
BC001496 mRNA Translation: AAH01496.1
BC001825 mRNA Translation: AAH01825.1
CCDSiCCDS9840.1
PIRiG01159
RefSeqiNP_006818.3, NM_006827.5
UniGeneiHs.74137

Genome annotation databases

EnsembliENST00000303575; ENSP00000303145; ENSG00000170348
GeneIDi10972
KEGGihsa:10972
UCSCiuc001xrm.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTMEDA_HUMAN
AccessioniPrimary (citable) accession number: P49755
Secondary accession number(s): B2R605
, Q15602, Q16536, Q86TC2, Q86TS5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 15, 1998
Last modified: May 23, 2018
This is version 174 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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