CEMIP2 Gene

Name	cell migration inducing hyaluronidase 2
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CEMIP2, also known as transmembrane protein 2 (TMEM2), is emerging as a context‐dependent regulator of hyaluronan (HA) homeostasis and extracellular matrix (ECM) remodeling. In murine models, TMEM2 has been shown to act as a cell‐surface hyaluronidase that degrades high molecular weight HA into approximately 5‐kDa fragments in a calcium‐dependent manner, a property that underlies its essential role in systemic HA turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, in breast cancer cells TMEM2 is transcriptionally activated by the developmental factor SOX4, thereby promoting proinvasive and promigratory phenotypes that favor metastatic colonization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Notably, however, in human contexts such as skin fibroblasts and osteoarthritic synovium the expression of TMEM2 remains largely unchanged compared to normal tissues, and HA degradation in these settings appears to be predominantly mediated by the paralog HYBID/CEMIP rather than by TMEM2—suggesting that the catalytic role of TMEM2 may be restricted or regulated differently in human cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition to its potential enzymatic activity, TMEM2 has been implicated in the regulation of cell adhesion; for instance, in gliomas, TMEM2 localizes to focal adhesions and directly interacts with integrins to modulate cell–substrate attachment and migration, further contributing to tumor cell invasiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CEMIP2/TMEM2 functions in a multifaceted and tissue‐specific fashion. In certain developmental and murine systems, it acts catalytically to regulate HA catabolism and ECM turnover, while in other contexts its role shifts toward modulating cell adhesion and migration—especially in tumor progression. This context‐dependency underscores the complexity of ECM regulation and the varied contributions of CEMIP2 to both physiological and pathological processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hayato Yamamoto, Yuki Tobisawa, Toshihiro Inubushi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mammalian homolog of the zebrafish transmembrane protein 2 (TMEM2) is the long-sought-after cell-surface hyaluronidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.770149"}], "href": "https://doi.org/10.1074/jbc.M116.770149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28246172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28246172"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuki Tobisawa, Naoki Fujita, Hayato Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cell surface hyaluronidase TMEM2 is essential for systemic hyaluronan catabolism and turnover."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2021.101281"}], "href": "https://doi.org/10.1016/j.jbc.2021.101281"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34624311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34624311"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hyeseung Lee, Hani Goodarzi, Sohail F Tavazoie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-15-2322"}], "href": "https://doi.org/10.1158/0008-5472.CAN-15-2322"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27328729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27328729"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuta Yoshino, Masakazu Goto, Hideaki Hara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.09.097"}], "href": "https://doi.org/10.1016/j.bbrc.2018.09.097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30241936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30241936"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jun Shiozawa, Susana de Vega, Mehmet Z Cilek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Implication of HYBID (Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization) in Hyaluronan Degradation by Synovial Fibroblasts in Patients with Knee Osteoarthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2020.01.003"}], "href": "https://doi.org/10.1016/j.ajpath.2020.01.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32084364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32084364"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Qiuyi Jiang, Xinzhuang Wang, Quan Yang, et al. "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "TMEM2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Combined with "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "IDH"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and 1p19q in Refining Molecular Subtypes for Predicting Survival of Patients with Glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Cell Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/dna.2020.6384"}], "href": "https://doi.org/10.1089/dna.2020.6384"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34735293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34735293"}]}]}]}
NCBI Gene ID	23670
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CEMIP2 has 5,607 functional associations with biological entities spanning 6 categories (chemical, functional term, phrase or reference, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 46 datasets.

Click the + buttons to view associations for CEMIP2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CEMIP2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CEMIP2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CEMIP2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CEMIP2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CEMIP2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CEMIP2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CEMIP2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CEMIP2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CEMIP2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CEMIP2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CEMIP2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CEMIP2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CEMIP2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CEMIP2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CEMIP2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CEMIP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CEMIP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	GlyGen Glycosylated Proteins	ligands (chemical) binding CEMIP2 protein from the GlyGen Glycosylated Proteins dataset.
	GO Biological Process Annotations 2023	biological processes involving CEMIP2 gene from the curated GO Biological Process Annotations 2023 dataset.
	GO Biological Process Annotations 2025	biological processes involving CEMIP2 gene from the curated GO Biological Process Annotations2025 dataset.
	GO Cellular Component Annotations 2023	cellular components containing CEMIP2 protein from the curated GO Cellular Component Annotations 2023 dataset.
	GO Cellular Component Annotations 2025	cellular components containing CEMIP2 protein from the curated GO Cellular Component Annotations 2025 dataset.
	GO Molecular Function Annotations 2023	molecular functions performed by CEMIP2 gene from the curated GO Molecular Function Annotations 2023 dataset.
	GO Molecular Function Annotations 2025	molecular functions performed by CEMIP2 gene from the curated GO Molecular Function Annotations 2025 dataset.
	GTEx eQTL 2025	SNPs regulating expression of CEMIP2 gene from the GTEx eQTL 2025 dataset.
	GTEx Tissue Gene Expression Profiles 2023	tissues with high or low expression of CEMIP2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
	GTEx Tissue-Specific Aging Signatures	tissue samples with high or low expression of CEMIP2 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
	GWAS Catalog SNP-Phenotype Associations 2025	phenotypes associated with CEMIP2 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
	HuBMAP Azimuth Cell Type Annotations	cell types associated with CEMIP2 gene from the HuBMAP Azimuth Cell Type Annotations dataset.
	JASPAR Predicted Human Transcription Factor Targets 2025	transcription factors regulating expression of CEMIP2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
	JASPAR Predicted Mouse Transcription Factor Targets 2025	transcription factors regulating expression of CEMIP2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
	LINCS L1000 CMAP Chemical Perturbation Consensus Signatures	small molecule perturbations changing expression of CEMIP2 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
	LINCS L1000 CMAP CRISPR Knockout Consensus Signatures	gene perturbations changing expression of CEMIP2 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
	MoTrPAC Rat Endurance Exercise Training	tissue samples with high or low expression of CEMIP2 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
	NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles	drug perturbations changing expression of CEMIP2 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
	PFOCR Pathway Figure Associations 2023	pathways involving CEMIP2 protein from the PFOCR Pathway Figure Associations 2023 dataset.
	Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures	gene perturbations changing expression of CEMIP2 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset.
	Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures	gene perturbations changing expression of CEMIP2 gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset.
	Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures	gene perturbations changing expression of CEMIP2 gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset.
	Rummagene Transcription Factor Associations 2026	transcription factors regulating expression of CEMIP2 gene from the Rummagene Transcription Factor Associations 2026 dataset.
	RummaGEO Drug Perturbation Signatures	drug perturbations changing expression of CEMIP2 gene from the RummaGEO Drug Perturbation Signatures dataset.
	RummaGEO Gene Perturbation Signatures	gene perturbations changing expression of CEMIP2 gene from the RummaGEO Gene Perturbation Signatures dataset.
	Sci-Plex Drug Perturbation Signatures	drug perturbations changing expression of CEMIP2 gene from the Sci-Plex Drug Perturbation Signatures dataset.
	Tahoe Therapeutics Tahoe 100M Perturbation Atlas	drug perturbations changing expression of CEMIP2 gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset.
	TISSUES Curated Tissue Protein Expression Evidence Scores 2025	tissues with high expression of CEMIP2 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
	TISSUES Experimental Tissue Protein Expression Evidence Scores 2025	tissues with high expression of CEMIP2 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
	TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025	tissues co-occuring with CEMIP2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.