Reviewed, UniProtKB/Swiss-Prot Q9GZP9 (DERL2_HUMAN)

Names and origin

Protein names

Recommended name:
    Derlin-2
Alternative name(s):
    Der1-like protein 2
    Degradation in endoplasmic reticulum protein 2
      Short name=DERtrin-2
    F-LAN-1
    F-LANa

Gene names

Name:	DERL2
Synonyms:	DER2, FLANA
ORF Names:	CGI-101, SBBI53

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	239 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal glycoproteins, but not that of misfolded nonglycoproteins. May act by forming a channel that allows the retrotranslocation of misfolded glycoproteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and the degradation substrate. In contrast to DERL1, it is not involved in the degradation of MHC class I heavy chains following infection by cytomegaloviruses. May play a role in cell proliferation. Ref.6 Ref.7 Ref.8
Subunit structure	Forms homo- and heterooligomers with DERL3 and, to a lesser extent, with DERL1. Interacts with SELS, VCP and EDEM1. Mediates association between VCP and EDEM1, as well as that between VCP and the degradation substrate. Interacts with the SEL1L/SYVN1 and VCP/SELS protein complexes. Ref.7 Ref.8
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Ref.6 Ref.8
Tissue specificity	Ubiquitous. Overexpressed in various hepatocarcinomas. Ref.8 Ref.1
Induction	Up-regulated in response to ER stress via the ERN1-XBP1 pathway of the unfolded protein response (UPR) By similarity.
Sequence similarities	Belongs to the derlin family.
Sequence caution	The sequence AAD34096.1 differs from that shown. Reason: Frameshift at positions 122, 128 and 136.

Ontologies

Keywords
Biological process	Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane
Domain	Transmembrane
Gene Ontology (GO)
Biological process	ER-associated protein catabolic process Ref.8 Inferred from mutant phenotype. Source: UniProtKB endoplasmic reticulum unfolded protein response Ref.8 Inferred from direct assay. Source: UniProtKB positive regulation of cell growth Ref.1 Inferred from direct assay. Source: UniProtKB positive regulation of cell proliferation Ref.1 Inferred from direct assay. Source: UniProtKB retrograde protein transport, ER to cytosol Ref.8 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	integral to endoplasmic reticulum membrane Ref.8 Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 239	239	Derlin-2		PRO_0000219045
Regions
	Topological domain	1 – 57	57	Cytoplasmic Potential
	Transmembrane	58 – 78	21	1 Potential
	Topological domain	79 – 96	18	Lumenal Potential
	Transmembrane	97 – 117	21	2 Potential
	Topological domain	118 – 150	33	Cytoplasmic Potential
	Transmembrane	151 – 171	21	3 Potential
	Topological domain	172	1	Lumenal Potential
	Transmembrane	173 – 193	21	4 Potential
	Topological domain	194 – 239	46	Cytoplasmic Potential

Sequences

	Sequence		Length	Mass (Da)
	Q9GZP9-1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: CAA228487C3CCB5C	FASTA	239	27,567
	10 20 30 40 50 60 MAYQSLRLEY LQIPPVSRAY TTACVLTTAA VQLELITPFQ LYFNPELIFK HFQIWRLITN 70 80 90 100 110 120 FLFFGPVGFN FLFNMIFLYR YCRMLEEGSF RGRTADFVFM FLFGGFLMTL FGLFVSLVFL 130 140 150 160 170 180 GQAFTIMLVY VWSRRNPYVR MNFFGLLNFQ APFLPWVLMG FSLLLGNSII VDLLGIAVGH 190 200 210 220 230 IYFFLEDVFP NQPGGIRILK TPSILKAIFD TPDEDPNYNP LPEERPGGFA WGEGQRLGG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of F-LANa, upregulated in human liver cancer." Ying H., Yu Y., Xu Y. Biochem. Biophys. Res. Commun. 286:394-400(2001) [PubMed: 11500051] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics." Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C. Genome Res. 10:703-713(2000) [PubMed: 10810093] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	Zhang W., Wan T., Cao X. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Dendritic cell.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"A membrane protein required for dislocation of misfolded proteins from the ER." Lilley B.N., Ploegh H.L. Nature 429:834-840(2004) [PubMed: 15215855] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]	"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: 16186509] [Abstract] Cited for: FUNCTION, OLIGOMERIZATION, INTERACTION WITH SELS; SEL1L AND SYVN1.
[8]	"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: FUNCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, TISSUE SPECIFICITY, INDUCTION, OLIGOMERIZATION, INTERACTION WITH VCP AND EDEM1.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF132289 mRNA. Translation: AAG43049.1. AF208065 mRNA. Translation: AAL14869.1. AF151859 mRNA. Translation: AAD34096.1. Frameshift. AF242523 mRNA. Translation: AAF99603.1. CR457202 mRNA. Translation: CAG33483.1. BC010890 mRNA. Translation: AAH10890.1.
IPI	IPI00304264.
PIR	JC7752.
RefSeq	NP_057125.2.
UniGene	Hs.286131
3D structure databases
ModBase	Search...
Proteomic databases
PeptideAtlas	Q9GZP9.
PRIDE	Q9GZP9.
Genome annotation databases
Ensembl	ENSG00000072849. Homo sapiens. [Contig view]
GeneID	51009.
KEGG	hsa:51009.
Organism-specific databases
GeneCards	GC17M005311.
H-InvDB	HIX0013472.
HGNC	HGNC:17943. DERL2.
MIM	610304. gene.
PharmGKB	PA134896343.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9GZP9.
HOVERGEN	Q9GZP9.
OMA	Q9GZP9. ITRAYTT.
Gene expression databases
ArrayExpress	Q9GZP9.
Bgee	Q9GZP9.
CleanEx	HS_DERL2.
GermOnline	ENSG00000072849. Homo sapiens.
Family and domain databases
InterPro	IPR007599. DER1. [Graphical view]
PANTHER	PTHR11009. DER1. 1 hit.
Pfam	PF04511. DER1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	53490.
SOURCE	Search...

Entry information

Entry name

DERL2_HUMAN

Accession

Primary (citable) accession number: Q9GZP9
Secondary accession number(s): Q9Y3A7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	March 1, 2001
Last modified:	June 16, 2009
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)