U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

KDELR2 KDEL endoplasmic reticulum protein retention receptor 2 [ Homo sapiens (human) ]

Gene ID: 11014, updated on 5-Mar-2024

Summary

Go to the top of the page Help
Official Symbol
KDELR2provided by HGNC
Official Full Name
KDEL endoplasmic reticulum protein retention receptor 2provided by HGNC
Primary source
HGNC:HGNC:6305
See related
Ensembl:ENSG00000136240 MIM:609024; AllianceGenome:HGNC:6305
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ELP1; OI21; ELP-1; ERD2.2
Summary
Retention of resident soluble proteins in the lumen of the endoplasmic reticulum (ER) is achieved in both yeast and animal cells by their continual retrieval from the cis-Golgi, or a pre-Golgi compartment. Sorting of these proteins is dependent on a C-terminal tetrapeptide signal, usually lys-asp-glu-leu (KDEL) in animal cells, and his-asp-glu-leu (HDEL) in S. cerevisiae. This process is mediated by a receptor that recognizes, and binds the tetrapeptide-containing protein, and returns it to the ER. In yeast, the sorting receptor encoded by a single gene, ERD2, is a seven-transmembrane protein. Unlike yeast, several human homologs of the ERD2 gene, constituting the KDEL receptor gene family, have been described. KDELR2 was the second member of the family to be identified, and it encodes a protein which is 83% identical to the KDELR1 gene product. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in placenta (RPKM 79.8), stomach (RPKM 78.5) and 25 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
7p22.1
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (6461089..6484152, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (6580398..6603413, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (6500720..6523783, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17942 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25621 Neighboring gene Rac family small GTPase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25622 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:6449304-6449840 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:6454955-6455531 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:6464151-6464650 Neighboring gene diacylglycerol lipase beta Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25623 Neighboring gene MPRA-validated peak6358 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25624 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25625 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25626 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17943 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17944 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17945 Neighboring gene ribosomal protein L31 pseudogene 34 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17946 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17947 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17948 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17949 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17950 Neighboring gene uncharacterized LOC101927325 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25627 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25628 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25629 Neighboring gene Grid2 interacting protein

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. KDELR2 promotes breast cancer proliferation via HDAC3-mediated cell cycle progression. Wei H, et al. Cancer Commun (Lond), 2021 Sep. PMID 34146461, Free PMC Article
  2. Two novel bi-allelic KDELR2 missense variants cause osteogenesis imperfecta with neurodevelopmental features. Efthymiou S, et al. Am J Med Genet A, 2021 Jul. PMID 33964184, Free PMC Article
  3. KDELR2 Competes with Measles Virus Envelope Proteins for Cellular Chaperones Reducing Their Chaperone-Mediated Cell Surface Transport. Tiwarekar V, et al. Viruses, 2019 Jan 4. PMID 30621148, Free PMC Article
  4. Endoplasmic reticulum resident proteins of normal human dermal fibroblasts are the major targets for oxidative stress induced by hydrogen peroxide. van der Vlies D, et al. Biochem J, 2002 Sep 15. PMID 12071860, Free PMC Article
  5. A brefeldin A-like phenotype is induced by the overexpression of a human ERD-2-like protein, ELP-1. Hsu VW, et al. Cell, 1992 May 15. PMID 1316805, Free PMC Article

See all (48) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Two novel bi-allelic KDELR2 missense variants cause osteogenesis imperfecta with neurodevelopmental features.
    Title: Two novel bi-allelic KDELR2 missense variants cause osteogenesis imperfecta with neurodevelopmental features.
  2. KDELR2 promotes breast cancer proliferation via HDAC3-mediated cell cycle progression.
    Title: KDELR2 promotes breast cancer proliferation via HDAC3-mediated cell cycle progression.
  3. KDELR2 is an unfavorable prognostic biomarker and regulates CCND1 to promote tumor progression in glioma.
    Title: KDELR2 is an unfavorable prognostic biomarker and regulates CCND1 to promote tumor progression in glioma.
  4. Interaction between KDELR2 and HSP47 as a Key Determinant in Osteogenesis Imperfecta Caused by Bi-allelic Variants in KDELR2.
    Title: Interaction between KDELR2 and HSP47 as a Key Determinant in Osteogenesis Imperfecta Caused by Bi-allelic Variants in KDELR2.
  5. Cell-type-specific differences in KDEL receptor clustering in mammalian cells.
    Title: Cell-type-specific differences in KDEL receptor clustering in mammalian cells.
  6. KDELR2 is a target gene downstream of HIF1-alpha driving the malignancy of glioblastoma.
    Title: KDELR2 Promotes Glioblastoma Tumorigenesis Targeted by HIF1a via mTOR Signaling Pathway.
  7. Our data indicate that KDELR2 competes with measles virus (MV) envelope proteins for binding to calnexin and GRP78/Bip, and that this interaction limits the availability of the chaperones for MV proteins, causing the reduction of virus spread and titers.
    Title: KDELR2 Competes with Measles Virus Envelope Proteins for Cellular Chaperones Reducing Their Chaperone-Mediated Cell Surface Transport.
  8. show that Golgi-based, KDEL receptor-dependent signalling promotes lysosome repositioning to the perinuclear area, involving a complex process intertwined to autophagy, lipid-droplet turnover and Golgi-mediated secretion.
    Title: KDEL receptor regulates secretion by lysosome relocation- and autophagy-dependent modulation of lipid-droplet turnover.
  9. A Golgi-based KDELR-dependent signalling pathway controls invadopodia-dependent extracellular matrix degradation.
    Title: A Golgi-based KDELR-dependent signalling pathway controls extracellular matrix degradation.
  10. Hrr25 protein kinase directly modifies Elp1 on two sites and we provide evidence that phosphorylation plays a positive role in the tRNA modification
    Title: Phosphorylation of Elp1 by Hrr25 is required for elongator-dependent tRNA modification in yeast.
Submit: New GeneRIF Correction

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Osteogenesis imperfecta, type 21
MedGen: C5436875 OMIM: 619131 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts.
EBI GWAS Catalog

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Potential readthrough

Included gene: DAGLB

Homology

Clone Names

  • FLJ45532

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ER retention sequence binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables KDEL sequence binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in endoplasmic reticulum to Golgi vesicle-mediated transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in maintenance of protein localization in endoplasmic reticulum IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein retention in ER lumen IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein transport IEA
Inferred from Electronic Annotation
more info
  
involved_in retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
colocalizes_with COPI-coated vesicle membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in Golgi membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in Golgi membrane TAS
Traceable Author Statement
more info
  
is_active_in cis-Golgi network IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in transport vesicle TAS
Traceable Author Statement
more info
  

General protein information

Go to the top of the page Help
Preferred Names
ER lumen protein-retaining receptor 2
Names
(Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2
ERD-2-like protein
ERD2-like protein 1
KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2
KDEL receptor 2

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001100603.2 → NP_001094073.1  ER lumen protein-retaining receptor 2 isoform 2

    See identical proteins and their annotated locations for NP_001094073.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the coding region, compared to variant 1, which results in a frameshift, compared to variant 1. The encoded isoform (2) has a longer and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AC072052, AK124072, BC071982
    Consensus CDS
    CCDS43550.1
    UniProtKB/Swiss-Prot
    P33947
    Related
    ENSP00000420501.1, ENST00000490996.1
    Conserved Domains (1) summary
    pfam00810
    Location:28 → 119
    ER_lumen_recept; ER lumen protein retaining receptor

  2. NM_006854.4 → NP_006845.1  ER lumen protein-retaining receptor 2 isoform 1

    See identical proteins and their annotated locations for NP_006845.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC072052, AK124072, AL547016, DA713413
    Consensus CDS
    CCDS5351.1
    UniProtKB/Swiss-Prot
    A4D2P4, P33947, Q6IPC5, Q96E30
    Related
    ENSP00000258739.4, ENST00000258739.9
    Conserved Domains (1) summary
    pfam00810
    Location:28 → 169
    ER_lumen_recept; ER lumen protein retaining receptor

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    6461089..6484152 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    6580398..6603413 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P33947.1 GenPept UniProtKB/Swiss-Prot:P33947

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous