Q9BVK6 (TMED9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane emp24 domain-containing protein 9

Alternative name(s):
GMP25
Glycoprotein 25L2
p24 family protein alpha-2
Short name=p24alpha2
p25

Gene names

Name:	TMED9
Synonyms:	GP25L2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	235 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Appears to be involved in vesicular protein trafficking, mainly in the early secretory pathway. In COPI vesicle-mediated retrograde transport involved in the coatomer recruitment to membranes of the early secretory pathway. Increases coatomer-dependent activity of ARFGAP2. Thought to play a crucial role in the specific retention of p24 complexes in cis-Golgi membranes; specifically contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network. May be involved in organization of intracellular membranes, such as of the ER-Golgi intermediate compartment and the Golgi apparatus. Involved in ER localization of PTPN2 isoform PTPB. Ref.7 Ref.9 Ref.12 Ref.14 Ref.15
Subunit structure	Monomer and homodimer in endoplasmic reticulum. Predominantly monomeric and to lesser extent homodimeric 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 TMED10. Interacts with TMED5. Interacts (via C-terminus) with COPG1; the interaction involves dimeric TMED9. Interacts with PTPN2 and SPAST. Interacts with STX17; the interaction is direct. Ref.6 Ref.8 Ref.11 Ref.12 Ref.13 Ref.17 Ref.19
Subcellular location	Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus › cis-Golgi network membrane; Single-pass type I membrane protein. Endoplasmic reticulum-Golgi intermediate compartment membrane; Single-pass type I membrane protein. Golgi apparatus › trans-Golgi network membrane; Single-pass type I membrane protein By similarity. Note: Cycles between compartments of the early secretatory pathway. Ref.7 Ref.8 Ref.9
Post-translational modification	N-linked glycosylated containing high mannose. Ref.6 Ref.10
Sequence similarities	Belongs to the EMP24/GP25L family. Contains 1 GOLD domain.
Sequence caution	The sequence AAL35268.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence CAA62380.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil Signal Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	COPI coating of Golgi vesicle Inferred from mutant phenotype Ref.14. Source: UniProtKB Golgi organization Inferred from mutant phenotype Ref.14. Source: UniProtKB positive regulation of organelle organization Inferred from mutant phenotype Ref.14. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum Inferred from direct assay Ref.8. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum-Golgi intermediate compartment Inferred from direct assay Ref.8. Source: UniProtKB endoplasmic reticulum-Golgi intermediate compartment membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW trans-Golgi network transport vesicle Traceable author statement PubMed 9527489. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PTPN2	P17706-1	5	EBI-1056827,EBI-4409481

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 37	37	By similarity
	Chain	38 – 235	198	Transmembrane emp24 domain-containing protein 9		PRO_0000010396
Regions
	Topological domain	38 – 202	165	Lumenal Potential
	Transmembrane	203 – 222	20	Helical; Potential
	Topological domain	223 – 235	13	Cytoplasmic Potential
	Domain	47 – 145	99	GOLD
	Region	121 – 160	40	Required for interaction with STX17
	Coiled coil	154 – 184	31	Potential
	Motif	228 – 235	8	COPI vesicle coat-binding Potential
	Motif	228 – 229	2	COPII vesicle coat-binding Potential
Amino acid modifications
	Glycosylation	125	1	N-linked (GlcNAc...) Ref.10 Ref.16
Natural variations
	Natural variant	16	1	T → S. Corresponds to variant rs57960711 [ dbSNP | Ensembl ].		VAR_061178
Experimental info
	Mutagenesis	232 – 233	2	KK → SS: Localization to plasma membrane and endocytosis. Ref.9
	Sequence conflict	83	1	L → F in CAA62380. Ref.2
	Sequence conflict	86	1	F → C in CAA62380. Ref.2
	Sequence conflict	101	1	Q → E in CAA62380. Ref.2
	Sequence conflict	102	1	Y → C in AAL35268. Ref.3
	Sequence conflict	156	1	A → P in CAA62380. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9BVK6 [UniParc]. Last modified June 16, 2009. Version 2. Checksum: 9B6D2D517D9E77D8	FASTA	235	27,277
	10 20 30 40 50 60 MAVELGVLLV RPRPGTGLGR VMRTLLLVLW LATRGSALYF HIGETEKKCF IEEIPDETMV 70 80 90 100 110 120 IGNYRTQLYD KQREEYQPAT PGLGMFVEVK DPEDKVILAR QYGSEGRFTF TSHTPGEHQI 130 140 150 160 170 180 CLHSNSTKFS LFAGGMLRVH LDIQVGEHAN DYAEIAAKDK LSELQLRVRQ LVEQVEQIQK 190 200 210 220 230 EQNYQRWREE RFRQTSESTN QRVLWWSILQ TLILVAIGVW QMRHLKSFFE AKKLV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: Skin.
[3]	Dominguez M., Fazel A., Parlati F., Bell A.W., Thomas D.Y., Bergeron J.J.M. Submitted (AUG-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-235. Tissue: Liver.
[4]	"A novel human cDNA that shares sequence homology with Homo sapiens mRNAs LOC96645 and gp25L2." Wang C., Li Y. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-235.
[5]	Bienvenut W.V. Submitted (MAR-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 129-138 AND 170-180, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[6]	"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: GLYCOSYLATION, SUBUNIT.
[7]	"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: FUNCTION, SUBCELLULAR LOCATION.
[8]	"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.
[9]	"The trans-membrane protein p25 forms highly specialized domains that regulate membrane composition and dynamics." Emery G., Parton R.G., Rojo M., Gruenberg J. J. Cell Sci. 116:4821-4832(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 232-LYS-LYS-233.
[10]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-125.
[11]	"The hereditary spastic paraplegia protein spastin interacts with the ESCRT-III complex-associated endosomal protein CHMP1B." Reid E., Connell J.W., Edwards T.L., Duley S., Brown S.E., Sanderson C.M. Hum. Mol. Genet. 14:19-38(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPAST.
[12]	"Evidence for a role of transmembrane protein p25 in localization of protein tyrosine phosphatase TC48 to the ER." Gupta V., Swarup G. J. Cell Sci. 119:1703-1714(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PTPN2.
[13]	"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.
[14]	"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: FUNCTION.
[15]	"Arf GAP2 is positively regulated by coatomer and cargo." Luo R., Ha V.L., Hayashi R., Randazzo P.A. Cell. Signal. 21:1169-1179(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-125, MASS SPECTROMETRY. Tissue: Liver.
[17]	"p28, a novel ERGIC/cis Golgi protein, required for Golgi ribbon formation." Koegler E., Bonnon C., Waldmeier L., Mitrovic S., Halbeisen R., Hauri H.P. Traffic 11:70-89(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TMED5.
[18]	"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].
[19]	"Syntaxin 17 cycles between the ER and ERGIC and is required to maintain the architecture of ERGIC and Golgi." Muppirala M., Gupta V., Swarup G. Biol. Cell 103:333-350(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STX17.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC139795 Genomic DNA. No translation available. BC001123 mRNA. Translation: AAH01123.2. X90872 mRNA. Translation: CAA62380.1. Different initiation. AF441399 mRNA. Translation: AAL35268.1. Different initiation.
IPI	IPI00023542.
RefSeq	NP_059980.2. NM_017510.4.
UniGene	Hs.279929.
3D structure databases
ProteinModelPortal	Q9BVK6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BVK6. 20 interactions.
MINT	MINT-5001958.
STRING	9606.ENSP00000330945.
PTM databases
PhosphoSite	Q9BVK6.
Polymorphism databases
DMDM	239938724.
Proteomic databases
PaxDb	Q9BVK6.
PRIDE	Q9BVK6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000332598; ENSP00000330945; ENSG00000184840.
GeneID	54732.
KEGG	hsa:54732.
UCSC	uc003mhx.3. human.
Organism-specific databases
CTD	54732.
GeneCards	GC05P177019.
H-InvDB	HIX0005470.
HGNC	HGNC:24878. TMED9.
HPA	HPA014650.
neXtProt	NX_Q9BVK6.
PharmGKB	PA134881976.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG323830.
HOGENOM	HOG000160228.
HOVERGEN	HBG105357.
InParanoid	Q9BVK6.
OMA	VLWWSIV.
OrthoDB	EOG74BJT2.
PhylomeDB	Q9BVK6.
Gene expression databases
Bgee	Q9BVK6.
CleanEx	HS_TMED9.
Genevestigator	Q9BVK6.
Family and domain databases
InterPro	IPR009038. GOLD. [Graphical view]
Pfam	PF01105. EMP24_GP25L. 1 hit. [Graphical view]
PROSITE	PS50866. GOLD. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TMED9. human.
GenomeRNAi	54732.
NextBio	57312.
PRO	Q9BVK6.

Entry information

Entry name

TMED9_HUMAN

Accession

Primary (citable) accession number: Q9BVK6
Secondary accession number(s): Q14437, Q8WZ61

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	June 16, 2009
Last modified:	November 13, 2013
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.