Q9BUN8 (DERL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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 › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	251 AA.
Sequence status	Complete.
Protein existence	Evidence 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, 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 RNF103. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14
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 process	Host-virus interaction Protein transport Transport Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER-associated protein catabolic process Inferred from direct assay Ref.6. Source: UniProtKB endoplasmic reticulum unfolded protein response Inferred from direct assay Ref.6. Source: UniProtKB intracellular transport of viral proteins in host cell Traceable author statement Ref.6. Source: UniProtKB retrograde protein transport, ER to cytosol Inferred from direct assay Ref.6. Source: UniProtKB
Cellular_component	early endosome Inferred from electronic annotation. Source: Compara integral to endoplasmic reticulum membrane Inferred from direct assay Ref.6. Source: UniProtKB late endosome Inferred from electronic annotation. Source: Compara
Molecular_function	MHC class I protein binding Inferred from direct assay Ref.5. Source: UniProtKB receptor activity Non-traceable author statement Ref.6. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCAP31	P51572	3	EBI-398977,EBI-77683
CFTR	P13569	2	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 251	251	Derlin-1		PRO_0000219042
Regions
	Topological domain	1 – 22	22	Cytoplasmic Potential
	Transmembrane	23 – 43	21	Helical; Name=1; Potential
	Topological domain	44 – 59	16	Lumenal Potential
	Transmembrane	60 – 80	21	Helical; Name=2; Potential
	Topological domain	81 – 105	25	Cytoplasmic Potential
	Transmembrane	106 – 126	21	Helical; Name=3; Potential
	Topological domain	127 – 154	28	Lumenal Potential
	Transmembrane	155 – 175	21	Helical; Name=4; Potential
	Topological domain	176 – 251	76	Cytoplasmic Potential
Amino acid modifications
	Modified residue	202	1	Phosphothreonine Ref.13
Natural variations
	Alternative sequence	170 – 189	20	Missing in isoform 2.		VSP_041329
	Natural variant	171	1	I → V. Corresponds to variant rs2272722 [ dbSNP | Ensembl ].		VAR_019516

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 4A6E0DB68D9AF244	FASTA	251	28,801
	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
	Isoform 2 [UniParc]. Checksum: E0D0982FDD620F1F	FASTA	231	26,423
	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 GFNYIIGGSY PMDLGGRNFL 190 200 210 220 230 STPQFLYRWL PSRRGGVSGF GVPPASMRRA ADQNGGGGRH NWGQGFRLGD Q

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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].
+	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.
IPI	IPI00013271. IPI00902975.
RefSeq	NP_001128143.1. NM_001134671.2. NP_077271.1. NM_024295.5.
UniGene	Hs.241576.
3D structure databases
ProteinModelPortal	Q9BUN8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BUN8. 8 interactions.
STRING	9606.ENSP00000259512.
Protein family/group databases
TCDB	3.A.16.1.1. endoplasmic reticular retrotranslocon (ER-RT) family.
PTM databases
PhosphoSite	Q9BUN8.
Polymorphism databases
DMDM	50400630.
Proteomic databases
PaxDb	Q9BUN8.
PRIDE	Q9BUN8.
Protocols and materials databases
DNASU	79139.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000259512; ENSP00000259512; ENSG00000136986. ENST00000405944; ENSP00000384289; ENSG00000136986.
GeneID	79139.
KEGG	hsa:79139.
UCSC	uc003ypl.2. human. uc003ypm.2. human.
Organism-specific databases
CTD	79139.
GeneCards	GC08M124094.
HGNC	HGNC:28454. DERL1.
HPA	HPA016562.
MIM	608813. gene.
neXtProt	NX_Q9BUN8.
PharmGKB	PA134926638.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5291.
HOGENOM	HOG000200949.
HOVERGEN	HBG105143.
InParanoid	Q9BUN8.
KO	K11519.
OMA	YIWCQLN.
OrthoDB	EOG47H5QT.
PhylomeDB	Q9BUN8.
Gene expression databases
ArrayExpress	Q9BUN8.
Bgee	Q9BUN8.
CleanEx	HS_DERL1.
Genevestigator	Q9BUN8.
GermOnline	ENSG00000136986. Homo sapiens.
Family and domain databases
InterPro	IPR007599. DER1. [Graphical view]
PANTHER	PTHR11009. PTHR11009. 1 hit.
Pfam	PF04511. DER1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	79139.
NextBio	68017.
SOURCE	Search...

Entry information

Entry name

DERL1_HUMAN

Accession

Primary (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:	April 3, 2013
This is version 100 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.