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    CRELD2 cysteine rich with EGF like domains 2 [ Homo sapiens (human) ]

    Gene ID: 79174, updated on 6-Jun-2024

    Summary

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    Official Symbol
    CRELD2provided by HGNC
    Official Full Name
    cysteine rich with EGF like domains 2provided by HGNC
    Primary source
    HGNC:HGNC:28150
    See related
    Ensembl:ENSG00000184164 MIM:607171; AllianceGenome:HGNC:28150
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    Predicted to enable calcium ion binding activity and protein disulfide isomerase activity. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in thyroid (RPKM 19.3), testis (RPKM 9.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CRELD2 in Genome Data Viewer
    Location:
    22q13.33
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (49918634..49927537)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (50423116..50432198)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (50312282..50321185)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124905147 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50250325-50250985 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50252588-50253125 Neighboring gene zinc finger BED-type containing 4 Neighboring gene ALG12 alpha-1,6-mannosyltransferase Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19282 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50281931-50282432 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50294104-50294824 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50294825-50295544 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50295545-50296264 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13928 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13929 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50316438-50317008 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50317009-50317578 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19284 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19286 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19285 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19287 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13930 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19288 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13931 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13932 Neighboring gene Sharpr-MPRA regulatory region 8073 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50336353-50337079 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50337080-50337805 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50340469-50341056 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50343989-50344576 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50344577-50345162 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50346923-50347508 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13935 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13936 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13937 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13938 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13939 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13940 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13941 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50358856-50359356 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19289 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19290 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13942 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19291 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19292 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13943 Neighboring gene microRNA 6821 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13944 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19293 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19294 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19295 Neighboring gene Pim-3 proto-oncogene, serine/threonine kinase Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50421116-50422037 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50437830-50438788 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50438789-50439748 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50439749-50440706 Neighboring gene interleukin 17 receptor E like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13945 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13946 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50451079-50451679

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

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    Related articles in PubMed

    1. CRELD2, endoplasmic reticulum stress, and human diseases. Tang Q, et al. Front Endocrinol (Lausanne), 2023. PMID 36936176, Free PMC Article
    2. Characterization of V-ATPase inhibitor-induced secretion of cysteine-rich with EGF-like domains 2. Oh-hashi K, et al. Cell Biol Toxicol, 2014 Jun. PMID 24687431
    3. CRELD2: gene mapping, alternate splicing, and comparative genomic identification of the promoter region. Maslen CL, et al. Gene, 2006 Nov 1. PMID 16919896
    4. Creld2 function during unfolded protein response is essential for liver metabolism homeostasis. Kern P, et al. FASEB J, 2021 Oct. PMID 34549824
    5. ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism. Boyle ST, et al. Nat Cell Biol, 2020 Jul. PMID 32451439

    See all (32) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CRELD2, endoplasmic reticulum stress, and human diseases.
      Title: CRELD2, endoplasmic reticulum stress, and human diseases.
    2. Creld2 function during unfolded protein response is essential for liver metabolism homeostasis.
      Title: Creld2 function during unfolded protein response is essential for liver metabolism homeostasis.
    3. ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism.
      Title: ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism.
    4. intravesicular acidification by V-ATPase regulates the secretion of CRELD2 without relying on the balance of intracellular calcium ions and the expression of endoplasmic reticulum chaperones such as GRP78 and protein disulfide isomerase.
      Title: Characterization of V-ATPase inhibitor-induced secretion of cysteine-rich with EGF-like domains 2.
    5. We demonstrate that Armet and Creld2 are genotype-specific ER stress response proteins with substrate specificities, and that aggregation of mutant matrilin-3 is a key disease trigger in MED that could be exploited as a potential therapeutic target
      Title: Armet/Manf and Creld2 are components of a specialized ER stress response provoked by inappropriate formation of disulphide bonds: implications for genetic skeletal diseases.
    6. results strongly suggest that Creld2 may be directly regulated by BMP9 and ER stress response may play an important role in regulating osteogenic differentiation
      Title: Endoplasmic reticulum (ER) stress inducible factor cysteine-rich with EGF-like domains 2 (Creld2) is an important mediator of BMP9-regulated osteogenic differentiation of mesenchymal stem cells.
    7. Mapping of CRELD2 by FISH shows that it maps to 22q13 rather than the GenBank reported locus of 22p13.
      Title: CRELD2: gene mapping, alternate splicing, and comparative genomic identification of the promoter region.
    8. CRELD2 can act as a specific regulator of alpha4beta2 nAChR expression
      Title: The cysteine-rich with EGF-like domains 2 (CRELD2) protein interacts with the large cytoplasmic domain of human neuronal nicotinic acetylcholine receptor alpha4 and beta2 subunits.
    Submit: New GeneRIF Correction

    Phenotypes

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

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ44190, FLJ98733, MGC11256, DKFZp667O055

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein disulfide isomerase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular space IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    protein disulfide isomerase CRELD2
    Names
    cysteine-rich with EGF-like domain protein 2
    NP_001128573.1
    NP_001271246.1
    NP_001271247.1
    NP_077300.3
    XP_005261794.1
    XP_005261795.1
    XP_011528674.1
    XP_054181883.1
    XP_054181884.1
    XP_054181885.1

    NCBI Reference Sequences (RefSeq)

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    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_001135101.3 → NP_001128573.1  protein disulfide isomerase CRELD2 isoform a precursor

      See identical proteins and their annotated locations for NP_001128573.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a, also known as CRELD2-epsilon).
      Source sequence(s)
      BI462292, DQ470679
      Consensus CDS
      CCDS46730.1
      UniProtKB/Swiss-Prot
      Q6UXH1
      Related
      ENSP00000383938.3, ENST00000404488.7
      Conserved Domains (3) summary
      smart00261
      Location:304 → 344
      FU; Furin-like repeats
      pfam11938
      Location:31 → 120
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl00057
      Location:337 → 377
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

    2. NM_001284317.2 → NP_001271246.1  protein disulfide isomerase CRELD2 isoform c precursor

      See identical proteins and their annotated locations for NP_001271246.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) lacks two alternate in-frame exons in the central coding region, compared to variant 1, resulting in an isoform (c, also known as CRELD2-gamma) that is shorter than isoform a.
      Source sequence(s)
      BI462292, BQ003113, DQ470677
      Consensus CDS
      CCDS63516.1
      UniProtKB/Swiss-Prot
      Q6UXH1
      Related
      ENSP00000384111.3, ENST00000403427.3
      Conserved Domains (3) summary
      pfam03302
      Location:197 → 266
      VSP; Giardia variant-specific surface protein
      pfam11938
      Location:31 → 120
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl00057
      Location:260 → 300
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

    3. NM_001284318.2 → NP_001271247.1  protein disulfide isomerase CRELD2 isoform d precursor

      See identical proteins and their annotated locations for NP_001271247.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (d, also known as CRELD2-alpha) that is shorter than isoform a.
      Source sequence(s)
      BC002894, BI462292, BQ003113
      Consensus CDS
      CCDS63515.1
      UniProtKB/Swiss-Prot
      Q6UXH1
      Related
      ENSP00000386034.3, ENST00000407217.7
      Conserved Domains (3) summary
      smart00261
      Location:194 → 230
      FU; Furin-like repeats
      pfam11938
      Location:31 → 120
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl00057
      Location:256 → 296
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

    4. NM_024324.5 → NP_077300.3  protein disulfide isomerase CRELD2 isoform b precursor

      See identical proteins and their annotated locations for NP_077300.3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (b, also known as CRELD2-delta) that is shorter than isoform a.
      Source sequence(s)
      AY358355, BI462292
      Consensus CDS
      CCDS14082.1
      UniProtKB/Swiss-Prot
      A5GZA2, A5GZA3, A5GZA4, A5GZA5, A5GZA6, Q4W0V0, Q6UXH1, Q86UC0, Q9BU47
      Related
      ENSP00000332223.4, ENST00000328268.9
      Conserved Domains (3) summary
      smart00261
      Location:194 → 230
      FU; Furin-like repeats
      pfam11938
      Location:31 → 120
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl00057
      Location:288 → 328
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

    RNA

    1. NR_104295.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) lacks an exon and uses an alternate splice site in the central region, compared to variant 1. This variant is represented as non-coding because use of the expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK308692, AL671710, BI462292, BQ003113

    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_000022.11 Reference GRCh38.p14 Primary Assembly

      Range
      49918634..49927537
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005261737.4 → XP_005261794.1  protein disulfide isomerase CRELD2 isoform X1

      Conserved Domains (3) summary
      smart00261
      Location:305 → 345
      FU; Furin-like repeats
      pfam11938
      Location:31 → 120
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl00057
      Location:338 → 378
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

    2. XM_005261738.6 → XP_005261795.1  protein disulfide isomerase CRELD2 isoform X2

      See identical proteins and their annotated locations for XP_005261795.1

      UniProtKB/Swiss-Prot
      Q6UXH1
      Related
      ENST00000483652.5
      Conserved Domains (3) summary
      smart00261
      Location:194 → 230
      FU; Furin-like repeats
      pfam11938
      Location:31 → 120
      DUF3456; TLR4 regulator and MIR-interacting MSAP
      cl00057
      Location:288 → 328
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

    3. XM_011530372.4 → XP_011528674.1  protein disulfide isomerase CRELD2 isoform X3

      UniProtKB/TrEMBL
      A6PWM2
      Related
      ENSP00000387769.1, ENST00000450207.5
      Conserved Domains (1) summary
      pfam11938
      Location:31 → 120
      DUF3456; TLR4 regulator and MIR-interacting MSAP

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060946.1 Alternate T2T-CHM13v2.0

      Range
      50423116..50432198
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054325908.1 → XP_054181883.1  protein disulfide isomerase CRELD2 isoform X1

    2. XM_054325909.1 → XP_054181884.1  protein disulfide isomerase CRELD2 isoform X2

    3. XM_054325910.1 → XP_054181885.1  protein disulfide isomerase CRELD2 isoform X3

      UniProtKB/TrEMBL
      A6PWM2
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6UXH1.1 GenPept UniProtKB/Swiss-Prot:Q6UXH1

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