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Q9BUN8 (DERL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Derlin-1
Alternative name(s):
Degradation in endoplasmic reticulum protein 1
Short name=DERtrin-1
Der1-like protein 1
Gene names
Name:DERL1
Synonyms:DER1
ORF Names:UNQ243/PRO276
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length251 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by forming a channel that allows the retrotranslocation of misfolded proteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and the degradation substrate. In case of infection by cytomegaloviruses, it plays a central role in the export from the ER and subsequent degradation of MHC class I heavy chains via its interaction with US11 viral protein, which recognizes and associates with MHC class I heavy chains. Also participates in the degradation process of misfolded cytomegalovirus US2 protein. Ref.5 Ref.6

Subunit structure

Forms homo- and heterooligomers with DERL2 and DERL3; binding to DERL3 is poorer than that between DERL2 and DERL3. Interacts with AMFR, VIMP/SELS, SEL1L, SELK, SYVN1 and VCP, as well as with SEL1L-SYVN1 and VCP-VIMP protein complexes; this interaction is weaker than that observed between DERL2 and these complexes. Interacts with the cytomegalovirus US11 protein. Interacts with NGLY1 and YOD1. Does not bind to EDEM1. Interacts with DNAJB9 and RNF103. Part of a complex which includes CANX, DERL1, DERL2, DDOST/OST48, RPN1, RPN2, SELK, VIMP, STT3A AND VCP. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.5 Ref.6 Ref.10 Ref.11.

Tissue specificity

Ubiquitous. Ref.5 Ref.11

Induction

Up-regulated in response to endoplasmic reticulum stress via the ERN1-XBP1 pathway of the unfolded protein response (UPR) By similarity.

Sequence similarities

Belongs to the derlin family.

Ontologies

Keywords
   Biological processHost-virus interaction
Protein transport
Transport
Unfolded protein response
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processER-associated ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.6. Source: UniProtKB

endoplasmic reticulum unfolded protein response

Inferred from direct assay Ref.6. Source: UniProtKB

establishment of protein localization

Traceable author statement Ref.6. Source: UniProtKB

intracellular transport of viral protein in host cell

Traceable author statement Ref.6. Source: UniProtKB

response to unfolded protein

Inferred from mutant phenotype Ref.5. Source: MGI

retrograde protein transport, ER to cytosol

Inferred from direct assay Ref.6. Source: UniProtKB

   Cellular_componentearly endosome

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from direct assay Ref.5. Source: UniProtKB

integral component of endoplasmic reticulum membrane

Inferred from direct assay Ref.6. Source: UniProtKB

integral component of membrane

Inferred from direct assay Ref.5. Source: MGI

late endosome

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionMHC class I protein binding

Inferred from direct assay Ref.5. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.6Ref.12Ref.14. Source: UniProtKB

receptor activity

Non-traceable author statement Ref.6. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BCAP31P515723EBI-398977,EBI-77683
CFTRP135692EBI-398977,EBI-349854

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BUN8-1)

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.
Isoform 2 (identifier: Q9BUN8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     170-189: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.17
Chain2 – 251250Derlin-1
PRO_0000219042

Regions

Topological domain2 – 2221Cytoplasmic Potential
Transmembrane23 – 4321Helical; Name=1; Potential
Topological domain44 – 5916Lumenal Potential
Transmembrane60 – 8021Helical; Name=2; Potential
Topological domain81 – 10525Cytoplasmic Potential
Transmembrane106 – 12621Helical; Name=3; Potential
Topological domain127 – 15428Lumenal Potential
Transmembrane155 – 17521Helical; Name=4; Potential
Topological domain176 – 25176Cytoplasmic Potential

Amino acid modifications

Modified residue21N-acetylserine Ref.17
Modified residue2021Phosphothreonine Ref.13

Natural variations

Alternative sequence170 – 18920Missing in isoform 2.
VSP_041329
Natural variant1711I → V.
Corresponds to variant rs2272722 [ dbSNP | Ensembl ].
VAR_019516

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 4A6E0DB68D9AF244

FASTA25128,801
        10         20         30         40         50         60 
MSDIGDWFRS IPAITRYWFA ATVAVPLVGK LGLISPAYLF LWPEAFLYRF QIWRPITATF 

        70         80         90        100        110        120 
YFPVGPGTGF LYLVNLYFLY QYSTRLETGA FDGRPADYLF MLLFNWICIV ITGLAMDMQL 

       130        140        150        160        170        180 
LMIPLIMSVL YVWAQLNRDM IVSFWFGTRF KACYLPWVIL GFNYIIGGSV INELIGNLVG 

       190        200        210        220        230        240 
HLYFFLMFRY PMDLGGRNFL STPQFLYRWL PSRRGGVSGF GVPPASMRRA ADQNGGGGRH 

       250 
NWGQGFRLGD Q 

« Hide

Isoform 2 [UniParc].

Checksum: E0D0982FDD620F1F
Show »

FASTA23126,423

References

« Hide 'large scale' references
[1]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[2]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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: Lymph.
[4]"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. expand/collapse author list , 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] OF 47-131 (ISOFORM 2).
Tissue: Esophagus.
[5]"A membrane protein required for dislocation of misfolded proteins from the ER."
Lilley B.N., Ploegh H.L.
Nature 429:834-840(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, TISSUE SPECIFICITY, INTERACTION WITH US11.
[6]"A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol."
Ye Y., Shibata Y., Yun C., Ron D., Rapoport T.A.
Nature 429:841-847(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH US11 AND VIMP.
[7]"The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway."
Schulze A., Standera S., Buerger E., Kikkert M., van Voorden S., Wiertz E., Koning F., Kloetzel P.-M., Seeger M.
J. Mol. Biol. 354:1021-1027(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH VCP AND SYVN1.
[8]"The retrotranslocation protein derlin-1 binds peptide:N-glycanase to the endoplasmic reticulum."
Katiyar S., Joshi S., Lennarz W.J.
Mol. Biol. Cell 16:4584-4594(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NGLY1.
[9]"Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane."
Ye Y., Shibata Y., Kikkert M., van Voorden S., Wiertz E., Rapoport T.A.
Proc. Natl. Acad. Sci. U.S.A. 102:14132-14138(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: HOMOOLIGOMERIZATION, INTERACTION WITH AMFR; SYVN1; VCP AND VIMP.
[10]"Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane."
Lilley B.N., Ploegh H.L.
Proc. Natl. Acad. Sci. U.S.A. 102:14296-14301(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, OLIGOMERIZATION, INTERACTION WITH VIMP; VCP; SEL1L AND SYVN1.
[11]"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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH DERL3 AND VCP.
[12]"Ubiquitin ligase Kf-1 is involved in the endoplasmic reticulum-associated degradation pathway."
Maruyama Y., Yamada M., Takahashi K., Yamada M.
Biochem. Biophys. Res. Commun. 374:737-741(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RNF103.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER."
Ernst R., Mueller B., Ploegh H.L., Schlieker C.
Mol. Cell 36:28-38(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH YOD1.
[15]"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].
[16]"Selenoprotein K binds multiprotein complexes and is involved in the regulation of endoplasmic reticulum homeostasis."
Shchedrina V.A., Everley R.A., Zhang Y., Gygi S.P., Hatfield D.L., Gladyshev V.N.
J. Biol. Chem. 286:42937-42948(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SELK AND VIMP, IDENTIFICATION IN A COMPLEX WITH CANX; DERL2; DDOST; RPN1; RPN2; SELK; STT3A; VCP AND VIMP.
[17]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY358818 mRNA. Translation: AAQ89177.1.
AC104316 Genomic DNA. No translation available.
BC002457 mRNA. Translation: AAH02457.1.
AK124086 mRNA. Translation: BAG54003.1.
CCDSCCDS47915.1. [Q9BUN8-2]
CCDS6337.1. [Q9BUN8-1]
RefSeqNP_001128143.1. NM_001134671.2. [Q9BUN8-2]
NP_077271.1. NM_024295.5. [Q9BUN8-1]
UniGeneHs.241576.

3D structure databases

ProteinModelPortalQ9BUN8.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122559. 40 interactions.
IntActQ9BUN8. 8 interactions.
STRING9606.ENSP00000259512.

Protein family/group databases

TCDB3.A.16.1.1. the endoplasmic reticular retrotranslocon (er-rt) family.

PTM databases

PhosphoSiteQ9BUN8.

Polymorphism databases

DMDM50400630.

Proteomic databases

MaxQBQ9BUN8.
PaxDbQ9BUN8.
PRIDEQ9BUN8.

Protocols and materials databases

DNASU79139.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000259512; ENSP00000259512; ENSG00000136986. [Q9BUN8-1]
ENST00000405944; ENSP00000384289; ENSG00000136986. [Q9BUN8-2]
GeneID79139.
KEGGhsa:79139.
UCSCuc003ypl.3. human. [Q9BUN8-1]
uc003ypm.3. human. [Q9BUN8-2]

Organism-specific databases

CTD79139.
GeneCardsGC08M124094.
HGNCHGNC:28454. DERL1.
HPAHPA016562.
MIM608813. gene.
neXtProtNX_Q9BUN8.
PharmGKBPA134926638.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5291.
HOGENOMHOG000200949.
HOVERGENHBG105143.
InParanoidQ9BUN8.
KOK11519.
OMAYIWCQLN.
OrthoDBEOG7353XM.
PhylomeDBQ9BUN8.
TreeFamTF354297.

Gene expression databases

ArrayExpressQ9BUN8.
BgeeQ9BUN8.
CleanExHS_DERL1.
GenevestigatorQ9BUN8.

Family and domain databases

InterProIPR007599. DER1.
[Graphical view]
PANTHERPTHR11009. PTHR11009. 1 hit.
PfamPF04511. DER1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi79139.
NextBio68017.
PROQ9BUN8.
SOURCESearch...

Entry information

Entry nameDERL1_HUMAN
AccessionPrimary (citable) accession number: Q9BUN8
Secondary accession number(s): B3KW41, E9PH19
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM