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Protein

ER degradation-enhancing alpha-mannosidase-like protein 1

Gene

EDEM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 has low mannosidase activity, catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2.4 Publications

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • mannosyl-oligosaccharide 1,2-alpha-mannosidase activity Source: ParkinsonsUK-UCL
  • misfolded protein binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Unfolded protein response

Enzyme and pathway databases

ReactomeiR-HSA-381038. XBP1(S) activates chaperone genes.
R-HSA-901032. ER Quality Control Compartment (ERQC).

Protein family/group databases

CAZyiGH47. Glycoside Hydrolase Family 47.

Names & Taxonomyi

Protein namesi
Recommended name:
ER degradation-enhancing alpha-mannosidase-like protein 1
Gene namesi
Name:EDEM1
Synonyms:EDEM, KIAA0212
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:18967. EDEM1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 44CytoplasmicSequence analysis
Transmembranei5 – 2521Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini26 – 657632LumenalSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi225 – 2251E → Q: Normal affinity for misfolded glycoproteins, but impaired SEL1L binding. 1 Publication
Mutagenesisi370 – 3701D → N: Normal affinity for misfolded glycoproteins, but impaired SEL1L binding. 1 Publication
Mutagenesisi493 – 4931E → Q: Normal affinity for misfolded glycoproteins, but impaired SEL1L binding. 1 Publication

Organism-specific databases

PharmGKBiPA128394554.

Polymorphism and mutation databases

BioMutaiEDEM1.
DMDMi17368550.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 657657ER degradation-enhancing alpha-mannosidase-like protein 1PRO_0000210321Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi181 – 1811N-linked (GlcNAc...)Sequence analysis
Glycosylationi198 – 1981N-linked (GlcNAc...)Sequence analysis
Glycosylationi299 – 2991N-linked (GlcNAc...)Sequence analysis
Glycosylationi342 – 3421N-linked (GlcNAc...)Sequence analysis
Glycosylationi624 – 6241N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ92611.
MaxQBiQ92611.
PaxDbiQ92611.
PRIDEiQ92611.

PTM databases

PhosphoSiteiQ92611.

Expressioni

Gene expression databases

BgeeiQ92611.
CleanExiHS_EDEM1.
ExpressionAtlasiQ92611. baseline and differential.
GenevisibleiQ92611. HS.

Organism-specific databases

HPAiHPA029565.

Interactioni

Subunit structurei

Interacts with DNAJC10 (By similarity). Interacts with DERL2 and DERL3. Binds to SEL1L.By similarity2 Publications

GO - Molecular functioni

  • misfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115047. 33 interactions.
IntActiQ92611. 9 interactions.
MINTiMINT-3049027.
STRINGi9606.ENSP00000256497.

Structurei

3D structure databases

ProteinModelPortaliQ92611.
SMRiQ92611. Positions 132-586.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glycosyl hydrolase 47 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2429. Eukaryota.
ENOG410XS6F. LUCA.
GeneTreeiENSGT00530000063069.
HOGENOMiHOG000004833.
HOVERGENiHBG051158.
InParanoidiQ92611.
KOiK10084.
OMAiELLYMAH.
OrthoDBiEOG7MWGWT.
PhylomeDBiQ92611.
TreeFamiTF300807.

Family and domain databases

Gene3Di1.50.10.50. 1 hit.
InterProiIPR001382. Glyco_hydro_47.
[Graphical view]
PfamiPF01532. Glyco_hydro_47. 1 hit.
[Graphical view]
PRINTSiPR00747. GLYHDRLASE47.
SUPFAMiSSF48225. SSF48225. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92611-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

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

DQMVGLI
Length:657
Mass (Da):73,768
Last modified:February 1, 1997 - v1
Checksum:iE0097901B3BF02FB
GO
Isoform 2 (identifier: Q92611-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-195: Missing.
     561-657: LFDEDNPVHK...RQIDQMVGLI → VCVLQDEPRNI

Note: No experimental confirmation available.
Show »
Length:376
Mass (Da):42,670
Checksum:i1C30323E865938D2
GO

Sequence cautioni

The sequence BAA13203.2 differs from that shown. Reason: Erroneous initiation. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 195195Missing in isoform 2. 1 PublicationVSP_056703Add
BLAST
Alternative sequencei561 – 65797LFDED…MVGLI → VCVLQDEPRNI in isoform 2. 1 PublicationVSP_056704Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86967 mRNA. Translation: BAA13203.2. Different initiation.
AK292643 mRNA. Translation: BAF85332.1.
AK302065 mRNA. Translation: BAG63455.1.
AC026202 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW63925.1.
BC019088 mRNA. Translation: AAH19088.1.
CCDSiCCDS33686.1. [Q92611-1]
RefSeqiNP_055489.1. NM_014674.2. [Q92611-1]
UniGeneiHs.224616.

Genome annotation databases

EnsembliENST00000256497; ENSP00000256497; ENSG00000134109. [Q92611-1]
ENST00000445686; ENSP00000394099; ENSG00000134109. [Q92611-2]
GeneIDi9695.
KEGGihsa:9695.
UCSCiuc003bqi.4. human. [Q92611-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86967 mRNA. Translation: BAA13203.2. Different initiation.
AK292643 mRNA. Translation: BAF85332.1.
AK302065 mRNA. Translation: BAG63455.1.
AC026202 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW63925.1.
BC019088 mRNA. Translation: AAH19088.1.
CCDSiCCDS33686.1. [Q92611-1]
RefSeqiNP_055489.1. NM_014674.2. [Q92611-1]
UniGeneiHs.224616.

3D structure databases

ProteinModelPortaliQ92611.
SMRiQ92611. Positions 132-586.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115047. 33 interactions.
IntActiQ92611. 9 interactions.
MINTiMINT-3049027.
STRINGi9606.ENSP00000256497.

Protein family/group databases

CAZyiGH47. Glycoside Hydrolase Family 47.

PTM databases

PhosphoSiteiQ92611.

Polymorphism and mutation databases

BioMutaiEDEM1.
DMDMi17368550.

Proteomic databases

EPDiQ92611.
MaxQBiQ92611.
PaxDbiQ92611.
PRIDEiQ92611.

Protocols and materials databases

DNASUi9695.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256497; ENSP00000256497; ENSG00000134109. [Q92611-1]
ENST00000445686; ENSP00000394099; ENSG00000134109. [Q92611-2]
GeneIDi9695.
KEGGihsa:9695.
UCSCiuc003bqi.4. human. [Q92611-1]

Organism-specific databases

CTDi9695.
GeneCardsiEDEM1.
H-InvDBHIX0030794.
HGNCiHGNC:18967. EDEM1.
HPAiHPA029565.
MIMi607673. gene.
neXtProtiNX_Q92611.
PharmGKBiPA128394554.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2429. Eukaryota.
ENOG410XS6F. LUCA.
GeneTreeiENSGT00530000063069.
HOGENOMiHOG000004833.
HOVERGENiHBG051158.
InParanoidiQ92611.
KOiK10084.
OMAiELLYMAH.
OrthoDBiEOG7MWGWT.
PhylomeDBiQ92611.
TreeFamiTF300807.

Enzyme and pathway databases

ReactomeiR-HSA-381038. XBP1(S) activates chaperone genes.
R-HSA-901032. ER Quality Control Compartment (ERQC).

Miscellaneous databases

ChiTaRSiEDEM1. human.
GeneWikiiEDEM1.
GenomeRNAii9695.
NextBioi35476023.
PROiQ92611.
SOURCEiSearch...

Gene expression databases

BgeeiQ92611.
CleanExiHS_EDEM1.
ExpressionAtlasiQ92611. baseline and differential.
GenevisibleiQ92611. HS.

Family and domain databases

Gene3Di1.50.10.50. 1 hit.
InterProiIPR001382. Glyco_hydro_47.
[Graphical view]
PfamiPF01532. Glyco_hydro_47. 1 hit.
[Graphical view]
PRINTSiPR00747. GLYHDRLASE47.
SUPFAMiSSF48225. SSF48225. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Testis and Thymus.
  3. "The DNA sequence, annotation and analysis of human chromosome 3."
    Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
    , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
    Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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] (ISOFORM 1).
    Tissue: Skin.
  6. "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] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DERL2 AND DERL3.
  8. Cited for: FUNCTION, SUBCELLULAR LOCATION.
  9. "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] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF GLU-225; ASP-370 AND GLU-493, INTERACTION WITH SEL1L.
  10. "EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step."
    Ninagawa S., Okada T., Sumitomo Y., Kamiya Y., Kato K., Horimoto S., Ishikawa T., Takeda S., Sakuma T., Yamamoto T., Mori K.
    J. Cell Biol. 206:347-356(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiEDEM1_HUMAN
AccessioniPrimary (citable) accession number: Q92611
Secondary accession number(s): A8K9C8, B4DXP3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: February 1, 1997
Last modified: May 11, 2016
This is version 146 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. 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.