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    CEMIP2 cell migration inducing hyaluronidase 2 [ Homo sapiens (human) ]

    Gene ID: 23670, updated on 3-Nov-2024

    Summary

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    Official Symbol
    CEMIP2provided by HGNC
    Official Full Name
    cell migration inducing hyaluronidase 2provided by HGNC
    Primary source
    HGNC:HGNC:11869
    See related
    Ensembl:ENSG00000135048 MIM:605835; AllianceGenome:HGNC:11869
    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
    TMEM2
    Summary
    This gene encodes a type II transmembrane protein that belongs to the interferon-induced transmembrane (IFITM) protein superfamily. The encoded protein functions as a cell surface hyaluronidase that cleaves extracellular high molecular weight hyaluronan into intermediate size fragments before internalization and degradation in the lysosome. It also has an interferon-mediated antiviral function in humans through activation of the JAK STAT signaling pathway. The activation of this gene by transcription factor SOX4 in breast cancer cells has been shown to mediate the pathological effects of SOX4 on cancer progression. Naturally occurring mutations in this gene are associated with autosomal recessive non-syndromic hearing loss. [provided by RefSeq, Mar 2017]
    Expression
    Broad expression in placenta (RPKM 42.4), gall bladder (RPKM 25.8) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CEMIP2 in Genome Data Viewer
    Location:
    9q21.13
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (71683366..71769466, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (83833547..83919992, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (74298282..74383429, complement)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene transient receptor potential cation channel subfamily M member 3 Neighboring gene uncharacterized LOC107987079 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:74167128-74167628 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:74167629-74168129 Neighboring gene ribosomal protein L35a pseudogene 21 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr9:74304891-74306090 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:74358750-74359614 Neighboring gene NANOG hESC enhancer GRCh37_chr9:74368830-74369517 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:74371765-74372408 Neighboring gene HNF1 motif-containing MPRA enhancer 224 Neighboring gene hESC enhancers GRCh37_chr9:74383087-74383768 and GRCh37_chr9:74383769-74384450 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:74408684-74409233 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:74409234-74409782 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28454 Neighboring gene glucosamine-6-phosphate deaminase 2 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19945 Neighboring gene abhydrolase domain containing 17B, depalmitoylase

    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 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. miR-518a-3p Suppresses Triple-Negative Breast Cancer Invasion and Migration Through Regulation of TMEM2. Gan L, et al. Technol Cancer Res Treat, 2020 Jan-Dec. PMID 33251982, Free PMC Article
    2. TMEM2 expression is downregulated as bladder cancer invades the muscle layer. Yoneyama MS, et al. Biochem Biophys Res Commun, 2022 Jul 12. PMID 35525055
    3. Transcriptome alterations in HepG2 cells induced by shRNA knockdown and overexpression of TMEM2 gene. Jia X, et al. Biosci Biotechnol Biochem, 2020 Aug. PMID 32326855
    4. TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK-STAT signaling pathway. Zhu X, et al. Cell Death Dis, 2016 Jun 2. PMID 27253403, Free PMC Article
    5. The small interferon-induced transmembrane genes and proteins. Siegrist F, et al. J Interferon Cytokine Res, 2011 Jan. PMID 21166591

    See all (64) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. HRD1-induced TMEM2 ubiquitination promotes ER stress-mediated apoptosis through a non-canonical pathway in intestinal ischemia/reperfusion.
      Title: HRD1-induced TMEM2 ubiquitination promotes ER stress-mediated apoptosis through a non-canonical pathway in intestinal ischemia/reperfusion.
    2. TMEM2 is a bona fide hyaluronidase possessing intrinsic catalytic activity.
      Title: TMEM2 is a bona fide hyaluronidase possessing intrinsic catalytic activity.
    3. Human TMEM2 is not a catalytic hyaluronidase, but a regulator of hyaluronan metabolism via HYBID (KIAA1199/CEMIP) and HAS2 expression.
      Title: Human TMEM2 is not a catalytic hyaluronidase, but a regulator of hyaluronan metabolism via HYBID (KIAA1199/CEMIP) and HAS2 expression.
    4. Concurrent Overexpression of Two Hyaluronidases, KIAA1199 and TMEM2, Strongly Predicts Shorter Survival After Resection in Pancreatic Ductal Adenocarcinoma.
      Title: Concurrent Overexpression of Two Hyaluronidases, KIAA1199 and TMEM2, Strongly Predicts Shorter Survival After Resection in Pancreatic Ductal Adenocarcinoma.
    5. Expression and regulation of recently discovered hyaluronidases, HYBID and TMEM2, in chondrocytes from knee osteoarthritic cartilage.
      Title: Expression and regulation of recently discovered hyaluronidases, HYBID and TMEM2, in chondrocytes from knee osteoarthritic cartilage.
    6. TMEM2 expression is downregulated as bladder cancer invades the muscle layer.
      Title: TMEM2 expression is downregulated as bladder cancer invades the muscle layer.
    7. miR-518a-3p Suppresses Triple-Negative Breast Cancer Invasion and Migration Through Regulation of TMEM2.
      Title: miR-518a-3p Suppresses Triple-Negative Breast Cancer Invasion and Migration Through Regulation of TMEM2.
    8. Transcriptome alterations in HepG2 cells induced by shRNA knockdown and overexpression of TMEM2 gene.
      Title: Transcriptome alterations in HepG2 cells induced by shRNA knockdown and overexpression of TMEM2 gene.
    9. ectopic expression of human TMEM2 in C. elegans protected animals from endoplasmic reticulum stress and increased both longevity and pathogen resistance.
      Title: The Hyaluronidase, TMEM2, Promotes ER Homeostasis and Longevity Independent of the UPR(ER).
    10. Findings indicate that hyaluronan-binding protein (HYBID) is indispensable for KIAA1199 (CEMIP)-mediated hyaluronan-B (HA) depolymerization in skin fibroblasts, but transmembrane protein 2 (TMEM2) is not involved in the HYBID-mediated process as a catalytic hyaluronidase.
      Title: The role and regulation of TMEM2 (transmembrane protein 2) in HYBID (hyaluronan (HA)-binding protein involved in HA depolymerization/ KIAA1199/CEMIP)-mediated HA depolymerization in human skin fibroblasts.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cadherin binding HDA PubMed 
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables carbohydrate binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables hyalurononglucosaminidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT enables hyalurononglucosaminidase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in angiogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in hyaluronan catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of sprouting angiogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cell surface hyaluronidase CEMIP2
    Names
    cell surface hyaluronidase
    transmembrane protein 2
    NP_001129292.1
    NP_001336713.1
    NP_037522.1
    XP_005251926.1
    XP_047279092.1
    XP_047279093.1
    XP_054218563.1
    XP_054218564.1

    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.

    Genomic

    1. NG_053053.1 RefSeqGene

      Range
      6020..91167
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001135820.2 → NP_001129292.1  cell surface hyaluronidase CEMIP2 isoform b

      See identical proteins and their annotated locations for NP_001129292.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
      Source sequence(s)
      AB037833, AK075370, CA418327, DA865249
      Consensus CDS
      CCDS47979.1
      UniProtKB/Swiss-Prot
      Q9UHN6
      Related
      ENSP00000366266.5, ENST00000377066.9
      Conserved Domains (3) summary
      cd13938
      Location:220 → 387
      PANDER_like_TMEM2; PANDER-like domain of the transmembrane protein TMEM2
      pfam10162
      Location:123 → 244
      G8; G8 domain
      pfam15711
      Location:1181 → 1270
      ILEI; Interleukin-like EMT inducer

    2. NM_001349784.2 → NP_001336713.1  cell surface hyaluronidase CEMIP2 isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, uses an alternate splice site, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (c) has a shorter N-terminus compared to isoform a.
      Source sequence(s)
      BC144510, CA418327, CR990222
      Conserved Domains (1) summary
      pfam15711
      Location:606 → 690
      ILEI; Interleukin-like EMT inducer

    3. NM_013390.3 → NP_037522.1  cell surface hyaluronidase CEMIP2 isoform a

      See identical proteins and their annotated locations for NP_037522.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AB037833, AK075370, CA418327, DA865249
      Consensus CDS
      CCDS6638.1
      UniProtKB/Swiss-Prot
      A6H8W9, B2RTQ6, Q5T838, Q5T839, Q5T840, Q5T841, Q8NBP6, Q9P2D5, Q9UHN6
      Related
      ENSP00000366243.4, ENST00000377044.9
      Conserved Domains (3) summary
      cd13938
      Location:220 → 387
      PANDER_like_TMEM2; PANDER-like domain of the transmembrane protein TMEM2
      pfam10162
      Location:123 → 244
      G8; G8 domain
      pfam15711
      Location:1244 → 1333
      ILEI; Interleukin-like EMT inducer

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      71683366..71769466 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047423136.1 → XP_047279092.1  cell surface hyaluronidase CEMIP2 isoform X2

    2. XM_005251869.5 → XP_005251926.1  cell surface hyaluronidase CEMIP2 isoform X1

      See identical proteins and their annotated locations for XP_005251926.1

      UniProtKB/Swiss-Prot
      A6H8W9, B2RTQ6, Q5T838, Q5T839, Q5T840, Q5T841, Q8NBP6, Q9P2D5, Q9UHN6
      Conserved Domains (3) summary
      cd13938
      Location:220 → 387
      PANDER_like_TMEM2; PANDER-like domain of the transmembrane protein TMEM2
      pfam10162
      Location:123 → 244
      G8; G8 domain
      pfam15711
      Location:1244 → 1333
      ILEI; Interleukin-like EMT inducer

    3. XM_047423137.1 → XP_047279093.1  cell surface hyaluronidase CEMIP2 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      83833547..83919992 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054362588.1 → XP_054218563.1  cell surface hyaluronidase CEMIP2 isoform X1

      UniProtKB/Swiss-Prot
      A6H8W9, B2RTQ6, Q5T838, Q5T839, Q5T840, Q5T841, Q8NBP6, Q9P2D5, Q9UHN6

    2. XM_054362589.1 → XP_054218564.1  cell surface hyaluronidase CEMIP2 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UHN6.1 GenPept UniProtKB/Swiss-Prot:Q9UHN6

    Gene LinkOut

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

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