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    KREMEN2 kringle containing transmembrane protein 2 [ Homo sapiens (human) ]

    Gene ID: 79412, updated on 5-Mar-2024

    Summary

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    Official Symbol
    KREMEN2provided by HGNC
    Official Full Name
    kringle containing transmembrane protein 2provided by HGNC
    Primary source
    HGNC:HGNC:18797
    See related
    Ensembl:ENSG00000131650 MIM:609899; AllianceGenome:HGNC:18797
    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
    KRM2
    Summary
    This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor. A similar protein in mouse functions interacts with with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein forms a ternary membrane complex with DKK1 and the WNT receptor lipoprotein receptor-related protein 6 (LRP6), and induces rapid endocytosis and removal of LRP6 from the plasma membrane. It contains extracellular kringle, WSC, and CUB domains. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
    Expression
    Biased expression in skin (RPKM 2.2), brain (RPKM 0.7) and 7 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    16p13.3
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (2964275..2968380)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (2990954..2995059)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (3014276..3018381)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene FLYWCH-type zinc finger 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:2974631-2975496 Neighboring gene ribosomal protein L23a pseudogene 86 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr16:2978151-2978660 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:2988192-2988805 Neighboring gene uncharacterized LOC105371055 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3005307-3006228 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3006229-3007148 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10287 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3011513-3012510 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3012511-3013508 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7088 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7089 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3015093-3016052 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3018331-3019320 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7093 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7092 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7094 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7095 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:3021603-3022419 Neighboring gene progestin and adipoQ receptor family member 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3029137-3030013 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3030014-3030889 Neighboring gene protein kinase, membrane associated tyrosine/threonine 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3030890-3031766 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:3032811-3033312 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7098 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:3033737-3033923 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:3037455-3038406 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:3038407-3039356 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:3043721-3044222 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:3045542-3046514 Neighboring gene glycine rich extracellular protein 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:3048182-3048682 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:3048683-3049183 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:3051481-3052017

    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. Kremen1-induced cell death is regulated by homo- and heterodimerization. Sumia I, et al. Cell Death Discov, 2019. PMID 31069116, Free PMC Article
    2. Differential expression of DKK-1 binding receptors on stromal cells and myeloma cells results in their distinct response to secreted DKK-1 in myeloma. Dun X, et al. Mol Cancer, 2010 Sep 16. PMID 20846389, Free PMC Article
    3. Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Mao B, et al. Nature, 2002 Jun 6. PMID 12050670
    4. Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2. Gu Y, et al. Cell Res, 2022 Jan. PMID 34837059, Free PMC Article
    5. A Role for Mitochondrial Translation in Promotion of Viability in K-Ras Mutant Cells. Martin TD, et al. Cell Rep, 2017 Jul 11. PMID 28700943, Free PMC Article

    See all (14) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. KREMEN2 is upregulated in cancers, consistent with its role in inhibiting Kremen1-induced cell death
      Title: Kremen1-induced cell death is regulated by homo- and heterodimerization.
    2. The mRNA expression levels of DKK-1 binding receptor LRP5/6 and Krm1/2 in SCs from patients with MM were significantly higher than those in myeloma cells and in SCs from healthy donors.
      Title: Differential expression of DKK-1 binding receptors on stromal cells and myeloma cells results in their distinct response to secreted DKK-1 in myeloma.
    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

    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

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Homology

    Clone Names

    • MGC10791, MGC16709

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in limb development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in multicellular organism development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of ossification ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in early endosome membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    kremen protein 2
    Names
    dickkopf receptor 2
    kringle domain-containing transmembrane protein 2
    kringle-containing protein marking the eye and the nose

    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_001253725.2 → NP_001240654.1  kremen protein 2 isoform e precursor

      See identical proteins and their annotated locations for NP_001240654.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) has multiple differences in the coding region, compared to variant 1, one of which results in a translational frameshift. The resulting protein (isoform e) has a distinct C-terminus and is shorter than isoform d.
      Source sequence(s)
      AC004235, AK075033, AK223422
      Consensus CDS
      CCDS58413.1
      UniProtKB/TrEMBL
      Q53F67
      Related
      ENSP00000459878.1, ENST00000575885.5
      Conserved Domains (3) summary
      smart00130
      Location:34 → 119
      KR; Kringle domain
      cd00041
      Location:180 → 285
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
      cl02568
      Location:124 → 165
      WSC; WSC domain

    2. NM_001253726.2 → NP_001240655.1  kremen protein 2 isoform f precursor

      See identical proteins and their annotated locations for NP_001240655.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform f), compared to isoform d.
      Source sequence(s)
      AK301953, BC003533
      Consensus CDS
      CCDS58412.1
      UniProtKB/TrEMBL
      Q53F67
      Related
      ENSP00000461860.1, ENST00000571007.5
      Conserved Domains (3) summary
      cd00041
      Location:180 → 285
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
      cd00108
      Location:35 → 119
      KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...
      cl02568
      Location:124 → 165
      WSC; WSC domain

    3. NM_024507.4 → NP_078783.1  kremen protein 2 isoform b precursor

      See identical proteins and their annotated locations for NP_078783.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2), also called kremen2b, lacks an exon in the 3' coding region compared to variant 4, resulting in a frameshift. The encoded isoform (b) is shorter and has a distinct C-terminus compared to isoform d.
      Source sequence(s)
      BC003533, BC009383
      Consensus CDS
      CCDS10484.1
      UniProtKB/TrEMBL
      Q53F67
      Related
      ENSP00000322079.6, ENST00000319500.11
      Conserved Domains (3) summary
      smart00130
      Location:34 → 119
      KR; Kringle domain
      cd00041
      Location:219 → 324
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
      pfam01822
      Location:124 → 205
      WSC; WSC domain

    4. NM_172229.3 → NP_757384.1  kremen protein 2 isoform d precursor

      See identical proteins and their annotated locations for NP_757384.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (d).
      Source sequence(s)
      AB086405, BC003533, BC009383
      Consensus CDS
      CCDS10483.1
      UniProtKB/Swiss-Prot
      B4DXF6, I3L2S2, Q8N2J4, Q8NCW0, Q8NCW1, Q96GL8, Q9BTP9
      UniProtKB/TrEMBL
      Q53F67
      Related
      ENSP00000304422.5, ENST00000303746.10
      Conserved Domains (3) summary
      cd00041
      Location:219 → 324
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
      cd00108
      Location:35 → 119
      KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...
      pfam01822
      Location:124 → 205
      WSC; WSC domain

    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_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      2964275..2968380
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      2990954..2995059
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_145347.1: Suppressed sequence

      Description
      NM_145347.1: This RefSeq was temporarily suppressed because currently there is insufficient data to support this transcript.

    2. NM_145348.1: Suppressed sequence

      Description
      NM_145348.1: This RefSeq was temporarily suppressed because currently there is insufficient data to support this transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8NCW0.1 GenPept UniProtKB/Swiss-Prot:Q8NCW0

    Gene LinkOut

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

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