Q96Q80 (DERL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Derlin-3

Alternative name(s):
Degradation in endoplasmic reticulum protein 3
Short name=DERtrin-3
Der1-like protein 3

Gene names

Name:	DERL3
Synonyms:	C22orf14, DER3, LLN2

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	235 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 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. Ref.7 Ref.8
Subunit structure	Forms homo- and heterooligomers with DERL2 and, to a lesser extent, with DERL1. Interacts with VCP and EDEM1. Ref.7
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.7.
Tissue specificity	Unlike DERL1 and DERL2, restricted to several tissues. Expressed at high levels in placenta, pancreas, spleen and small intestine. Ref.7
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
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER-associated protein catabolic process Inferred from mutant phenotype Ref.8. Source: UniProtKB endoplasmic reticulum unfolded protein response Inferred from direct assay Ref.7. Source: UniProtKB protein N-linked glycosylation via asparagine Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	integral to endoplasmic reticulum membrane Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96Q80-1)

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: Q96Q80-2)

The sequence of this isoform differs from the canonical sequence as follows:
     206-235: KLLLDAPAEDPNYLPLPEEQPGPHLPPPQQ → GLQSSKAPAGSSLTIWTQQSQGGPGTAGELAAPS

Note: No experimental confirmation available.

Isoform 3 (identifier: Q96Q80-3)

The sequence of this isoform differs from the canonical sequence as follows:
     206-235: KLLLDAPAEDPNYLPLPEEQPGPHLPPPQQ → LATAQQCPHRTGPSAGDFRAARPQLAVA

Note: No experimental confirmation available.

Isoform 4 (identifier: Q96Q80-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-74: Missing.
     110-205: LLGLLGSLFF...KRLLQTPGFL → VSFPQALEPR...LCSTRAPPHR

Note: No experimental confirmation available.

Isoform 5 (identifier: Q96Q80-5)

The sequence of this isoform differs from the canonical sequence as follows:
     206-235: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 235	235	Derlin-3		PRO_0000219048
Regions
	Topological domain	1 – 22	22	Cytoplasmic Potential
	Transmembrane	23 – 43	21	Helical; Name=1; Potential
	Topological domain	44 – 58	15	Lumenal Potential
	Transmembrane	59 – 79	21	Helical; Name=2; Potential
	Topological domain	80 – 98	19	Cytoplasmic Potential
	Transmembrane	99 – 119	21	Helical; Name=3; Potential
	Topological domain	120 – 157	38	Lumenal Potential
	Transmembrane	158 – 178	21	Helical; Name=4; Potential
	Topological domain	179 – 235	57	Cytoplasmic Potential
Natural variations
	Alternative sequence	1 – 74	74	Missing in isoform 4.		VSP_011086
	Alternative sequence	110 – 205	96	LLGLL…TPGFL → VSFPQALEPRARAPRRPACV GPGANTAMPERDTVAVSSLV CVEGPLCAQLQGSGLDLQCC MQNTKPRTKEPGTVPALGAH GLLAAAGQLHPRGPAGDCGG PYLLLPGGRLPQPAWRQEAP ADPWLPVSVESPPSLSPPSE GSPPMGTCAGLCSTRAPPHR in isoform 4.		VSP_011087
	Alternative sequence	206 – 235	30	KLLLD…PPPQQ → GLQSSKAPAGSSLTIWTQQS QGGPGTAGELAAPS in isoform 2.		VSP_011088
	Alternative sequence	206 – 235	30	KLLLD…PPPQQ → LATAQQCPHRTGPSAGDFRA ARPQLAVA in isoform 3.		VSP_011089
	Alternative sequence	206 – 235	30	Missing in isoform 5.		VSP_046330
	Natural variant	149	1	F → L. Ref.2 Corresponds to variant rs3177243 [ dbSNP | Ensembl ].		VAR_048897
	Natural variant	211	1	A → V. Ref.3 Corresponds to variant rs1128127 [ dbSNP | Ensembl ].		VAR_019517

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 19, 2004. Version 2. Checksum: 2DC5F02487C4B824	FASTA	235	26,679
	10 20 30 40 50 60 MAWQGLAAEF LQVPAVTRAY TAACVLTTAA VQLELLSPFQ LYFNPHLVFR KFQVWRLVTN 70 80 90 100 110 120 FLFFGPLGFS FFFNMLFVFR YCRMLEEGSF RGRTADFVFM FLFGGVLMTL LGLLGSLFFL 130 140 150 160 170 180 GQALMAMLVY VWSRRSPRVR VNFFGLLTFQ APFLPWALMG FSLLLGNSIL VDLLGIAVGH 190 200 210 220 230 IYYFLEDVFP NQPGGKRLLQ TPGFLKLLLD APAEDPNYLP LPEEQPGPHL PPPQQ
	Isoform 2 [UniParc]. Checksum: 7297772E29193957	FASTA	239	26,605
	10 20 30 40 50 60 MAWQGLAAEF LQVPAVTRAY TAACVLTTAA VQLELLSPFQ LYFNPHLVFR KFQVWRLVTN 70 80 90 100 110 120 FLFFGPLGFS FFFNMLFVFR YCRMLEEGSF RGRTADFVFM FLFGGVLMTL LGLLGSLFFL 130 140 150 160 170 180 GQALMAMLVY VWSRRSPRVR VNFFGLLTFQ APFLPWALMG FSLLLGNSIL VDLLGIAVGH 190 200 210 220 230 IYYFLEDVFP NQPGGKRLLQ TPGFLGLQSS KAPAGSSLTI WTQQSQGGPG TAGELAAPS
	Isoform 3 [UniParc]. Checksum: 98A860411ED2C73B	FASTA	233	26,255
	10 20 30 40 50 60 MAWQGLAAEF LQVPAVTRAY TAACVLTTAA VQLELLSPFQ LYFNPHLVFR KFQVWRLVTN 70 80 90 100 110 120 FLFFGPLGFS FFFNMLFVFR YCRMLEEGSF RGRTADFVFM FLFGGVLMTL LGLLGSLFFL 130 140 150 160 170 180 GQALMAMLVY VWSRRSPRVR VNFFGLLTFQ APFLPWALMG FSLLLGNSIL VDLLGIAVGH 190 200 210 220 230 IYYFLEDVFP NQPGGKRLLQ TPGFLLATAQ QCPHRTGPSA GDFRAARPQL AVA
	Isoform 4 [UniParc]. Checksum: 30576E135EC94D48	FASTA	225	23,859
	10 20 30 40 50 60 MLFVFRYCRM LEEGSFRGRT ADFVFMFLFG GVLMTVSFPQ ALEPRARAPR RPACVGPGAN 70 80 90 100 110 120 TAMPERDTVA VSSLVCVEGP LCAQLQGSGL DLQCCMQNTK PRTKEPGTVP ALGAHGLLAA 130 140 150 160 170 180 AGQLHPRGPA GDCGGPYLLL PGGRLPQPAW RQEAPADPWL PVSVESPPSL SPPSEGSPPM 190 200 210 220 GTCAGLCSTR APPHRKLLLD APAEDPNYLP LPEEQPGPHL PPPQQ
	Isoform 5 [UniParc]. Checksum: E125D7D2EDBB8031	FASTA	205	23,382
	10 20 30 40 50 60 MAWQGLAAEF LQVPAVTRAY TAACVLTTAA VQLELLSPFQ LYFNPHLVFR KFQVWRLVTN 70 80 90 100 110 120 FLFFGPLGFS FFFNMLFVFR YCRMLEEGSF RGRTADFVFM FLFGGVLMTL LGLLGSLFFL 130 140 150 160 170 180 GQALMAMLVY VWSRRSPRVR VNFFGLLTFQ APFLPWALMG FSLLLGNSIL VDLLGIAVGH 190 200 IYYFLEDVFP NQPGGKRLLQ TPGFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a novel member of the NADH oxidoreductase complex I subunit homolog." Shimizu N., Minosima S., Kawasaki K., Sasaki T. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 3).
[2]	The European IMAGE consortium Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), VARIANT LEU-149.
[3]	"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] (ISOFORM 4), VARIANT VAL-211. Tissue: Testis.
[4]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Placenta.
[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: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, OLIGOMERIZATION, INTERACTION WITH VCP AND EDEM1.
[8]	"STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein." Sato T., Sako Y., Sho M., Momohara M., Suico M.A., Shuto T., Nishitoh H., Okiyoneda T., Kokame K., Kaneko M., Taura M., Miyata M., Chosa K., Koga T., Morino-Koga S., Wada I., Kai H. Mol. Cell 47:99-110(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ERAD PATHWAY.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB049213 Genomic DNA. Translation: BAB68409.1. AL389876 mRNA. No translation available. AK125830 mRNA. Translation: BAC86311.1. CR456372 mRNA. Translation: CAG30258.1. AP000350 Genomic DNA. No translation available. BC057830 mRNA. Translation: AAH57830.1.
IPI	IPI00430406. IPI00430407. IPI00430408. IPI00430409. IPI00878606.
RefSeq	NP_001002862.1. NM_001002862.2. NP_001129223.1. NM_001135751.1. NP_940842.2. NM_198440.3.
UniGene	Hs.593679.
3D structure databases
ProteinModelPortal	Q96Q80.
SMR	Q96Q80. Positions 14-187.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000384744.
Polymorphism databases
DMDM	50400613.
Proteomic databases
PaxDb	Q96Q80.
PRIDE	Q96Q80.
Protocols and materials databases
DNASU	91319.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000318109; ENSP00000315303; ENSG00000099958. ENST00000406855; ENSP00000384744; ENSG00000099958. ENST00000476077; ENSP00000419399; ENSG00000099958.
GeneID	91319.
KEGG	hsa:91319.
UCSC	uc002zyh.3. human. uc002zyj.3. human. uc002zyk.4. human.
Organism-specific databases
CTD	91319.
GeneCards	GC22M024176.
HGNC	HGNC:14236. DERL3.
HPA	CAB037234.
MIM	610305. gene.
neXtProt	NX_Q96Q80.
PharmGKB	PA25883.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5291.
HOGENOM	HOG000200948.
HOVERGEN	HBG051338.
KO	K13989.
OMA	TAMLVYV.
Gene expression databases
ArrayExpress	Q96Q80.
Bgee	Q96Q80.
CleanEx	HS_DERL3.
Genevestigator	Q96Q80.
GermOnline	ENSG00000099958. 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	91319.
NextBio	77178.
SOURCE	Search...

Entry information

Entry name

DERL3_HUMAN

Accession

Primary (citable) accession number: Q96Q80
Secondary accession number(s): F2Z3B6 , Q6ICJ6, Q6PEX0, Q6ZUB5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	July 19, 2004
Last modified:	May 1, 2013
This is version 88 of the entry and version 2 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.