Q92611 (EDEM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ER degradation-enhancing alpha-mannosidase-like 1

Gene names

Name:	EDEM1
Synonyms:	EDEM, KIAA0212

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	657 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. It is directly involved in endoplasmic reticulum-associated degradation (ERAD) and targets misfolded glycoproteins for degradation in an N-glycan-independent manner, probably by forming a complex with SEL1L. It lacks mannosidase activity. Ref.5 Ref.7 Ref.8
Subunit structure	Interacts with DERL2 and DERL3. Binds to SEL1L. Ref.6 Ref.8
Subcellular location	Endoplasmic reticulum membrane; Single-pass type II membrane protein Ref.7.
Sequence similarities	Belongs to the glycosyl hydrolase 47 family.
Sequence caution	The sequence BAA13203.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	ER-associated protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB post-translational protein modification Traceable author statement. Source: Reactome protein N-linked glycosylation via asparagine Traceable author statement. Source: Reactome protein folding Traceable author statement. Source: Reactome response to unfolded protein Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to endoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro mannosyl-oligosaccharide 1,2-alpha-mannosidase activity Inferred from electronic annotation. Source: InterPro misfolded protein binding Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BZW1	Q7L1Q6	1	EBI-1056336,EBI-1046727

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 657	657	ER degradation-enhancing alpha-mannosidase-like 1		PRO_0000210321
Regions
	Topological domain	1 – 4	4	Cytoplasmic Potential
	Transmembrane	5 – 25	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	26 – 657	632	Lumenal Potential
Amino acid modifications
	Glycosylation	181	1	N-linked (GlcNAc...) Potential
	Glycosylation	198	1	N-linked (GlcNAc...) Potential
	Glycosylation	299	1	N-linked (GlcNAc...) Potential
	Glycosylation	342	1	N-linked (GlcNAc...) Potential
	Glycosylation	624	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	225	1	E → Q: Normal affinity for misfolded glycoproteins, but impaired SEL1L binding. Ref.8
	Mutagenesis	370	1	D → N: Normal affinity for misfolded glycoproteins, but impaired SEL1L binding. Ref.8
	Mutagenesis	493	1	E → Q: Normal affinity for misfolded glycoproteins, but impaired SEL1L binding. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Q92611 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: E0097901B3BF02FB	FASTA	657	73,768
	10 20 30 40 50 60 MQWRALVLGL VLLRLGLHGV LWLVFGLGPS MGFYQRFPLS FGFQRLRSPD GPASPTSGPV 70 80 90 100 110 120 GRPGGVSGPS WLQPPGTGAA QSPRKAPRRP GPGMCGPANW GYVLGGRGRG PDEYEKRYSG 130 140 150 160 170 180 AFPPQLRAQM RDLARGMFVF GYDNYMAHAF PQDELNPIHC RGRGPDRGDP SNLNINDVLG 190 200 210 220 230 240 NYSLTLVDAL DTLAIMGNSS EFQKAVKLVI NTVSFDKDST VQVFEATIRV LGSLLSAHRI 250 260 270 280 290 300 ITDSKQPFGD MTIKDYDNEL LYMAHDLAVR LLPAFENTKT GIPYPRVNLK TGVPPDTNNE 310 320 330 340 350 360 TCTAGAGSLL VEFGILSRLL GDSTFEWVAR RAVKALWNLR SNDTGLLGNV VNIQTGHWVG 370 380 390 400 410 420 KQSGLGAGLD SFYEYLLKSY ILFGEKEDLE MFNAAYQSIQ NYLRRGREAC NEGEGDPPLY 430 440 450 460 470 480 VNVNMFSGQL MNTWIDSLQA FFPGLQVLIG DVEDAICLHA FYYAIWKRYG ALPERYNWQL 490 500 510 520 530 540 QAPDVLFYPL RPELVESTYL LYQATKNPFY LHVGMDILQS LEKYTKVKCG YATLHHVIDK 550 560 570 580 590 600 STEDRMESFF LSETCKYLYL LFDEDNPVHK SGTRYMFTTE GHIVSVDEHL RELPWKEFFS 610 620 630 640 650 EEGGQDQGGK SVHRPKPHEL KVINSSSNCN RVPDERRYSL PLKSIYMRQI DQMVGLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed: 9039502] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[5]	"Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle." Molinari M., Calanca V., Galli C., Lucca P., Paganetti P. Science 299:1397-1400(2003) [PubMed: 12610306] [Abstract] Cited for: FUNCTION.
[6]	"Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation." Oda Y., Okada T., Yoshida H., Kaufman R.J., Nagata K., Mori K. J. Cell Biol. 172:383-393(2006) [PubMed: 16449189] [Abstract] Cited for: INTERACTION WITH DERL2 AND DERL3.
[7]	"A dual role for EDEM1 in the processing of rod opsin." Kosmaoglou M., Kanuga N., Aguila M., Garriga P., Cheetham M.E. J. Cell Sci. 122:4465-4472(2009) [PubMed: 19934218] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex." Cormier J.H., Tamura T., Sunryd J.C., Hebert D.N. Mol. Cell 34:627-633(2009) [PubMed: 19524542] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLU-225; ASP-370 AND GLU-493, INTERACTION WITH SEL1L.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D86967 mRNA. Translation: BAA13203.2. Different initiation. AK292643 mRNA. Translation: BAF85332.1. CH471055 Genomic DNA. Translation: EAW63925.1. BC019088 mRNA. Translation: AAH19088.1.
IPI	IPI00005683.
RefSeq	NP_055489.1. NM_014674.2.
UniGene	Hs.224616.
3D structure databases
ProteinModelPortal	Q92611.
SMR	Q92611. Positions 124-587.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92611. 1 interaction.
MINT	MINT-3049027.
STRING	Q92611.
Protein family/group databases
CAZy	GH47. Glycoside Hydrolase Family 47.
Polymorphism databases
DMDM	17368550.
Proteomic databases
PRIDE	Q92611.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000256497; ENSP00000256497; ENSG00000134109.
GeneID	9695.
KEGG	hsa:9695.
UCSC	uc003bqi.1. human.
Organism-specific databases
CTD	9695.
GeneCards	GC03P005203.
H-InvDB	HIX0030794. HIX0200542.
HGNC	HGNC:18967. EDEM1.
HPA	HPA029565.
MIM	607673. gene.
neXtProt	NX_Q92611.
PharmGKB	PA128394554.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09744.
GeneTree	ENSGT00530000063069.
HOGENOM	HBG562188.
HOVERGEN	HBG051158.
InParanoid	Q92611.
OMA	AVKALWS.
OrthoDB	EOG4ZPDTW.
PhylomeDB	Q92611.
Enzyme and pathway databases
Reactome	REACT_15380. Diabetes pathways. REACT_17015. Metabolism of proteins.
Gene expression databases
ArrayExpress	Q92611.
Bgee	Q92611.
CleanEx	HS_EDEM1.
Genevestigator	Q92611.
GermOnline	ENSG00000134109. Homo sapiens.
Family and domain databases
InterPro	IPR001382. Glyco_hydro_47. [Graphical view]
Gene3D	G3DSA:1.50.10.50. Glyco_hydro_47. 1 hit.
KO	K10084.
PANTHER	PTHR11742. Glyco_hydro_47. 1 hit.
Pfam	PF01532. Glyco_hydro_47. 1 hit. [Graphical view]
PRINTS	PR00747. GLYHDRLASE47.
SUPFAM	SSF48225. Glyco_hydro_47. 1 hit.
ProtoNet	Search...
Other
NextBio	36427.
SOURCE	Search...

Entry information

Entry name

EDEM1_HUMAN

Accession

Primary (citable) accession number: Q92611
Secondary accession number(s): A8K9C8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	February 1, 1997
Last modified:	December 14, 2011
This is version 103 of the entry and version 1 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.