Details for: MXRA8

Gene ID: 54587

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MXRA8

Ensembl ID: ENSG00000162576

Description: matrix remodeling associated 8

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • bronchus fibroblast of lung CL2000093
    CSI 28.59
    rCSI 23.23%
    PRS 96.22
  • skin fibroblast CL0002620
    CSI 19.46
    rCSI 16.78%
    PRS 96.09
  • tracheobronchial smooth muscle cell CL0019019
    CSI 17.33
    rCSI 30.55%
    PRS 97.52
  • keratocyte CL0002363
    CSI 13.52
    rCSI 32.51%
    PRS 96.49
  • intestinal epithelial cell CL0002563
    CSI 11.52
    rCSI 12.04%
    PRS 94.73
  • fibroblast of lung CL0002553
    CSI 11.52
    rCSI 10.72%
    PRS 97.24
  • myofibroblast cell CL0000186
    CSI 8.35
    rCSI 11.56%
    PRS 94.46
  • alveolar adventitial fibroblast CL4028006
    CSI 8.17
    rCSI 12.9%
    PRS 97.09
  • adventitial cell CL0002503
    CSI 6.51
    rCSI 15.54%
    PRS 97.56
  • alveolar type 1 fibroblast cell CL4028004
    CSI 6.35
    rCSI 6.95%
    PRS 97.23
  • cardiac neuron CL0010022
    CSI 5.59
    rCSI 17.9%
    PRS 95.55
  • interstitial cell of Cajal CL0002088
    CSI 5.51
    rCSI 7.02%
    PRS 98.04
  • fibroblast of breast CL4006000
    CSI 5.51
    rCSI 23.17%
    PRS 97.45
  • extravillous trophoblast CL0008036
    CSI 5.28
    rCSI 6.53%
    PRS 95.02
  • smooth muscle cell CL0000192
    CSI 5.24
    rCSI 12.5%
    PRS 93.01
  • stromal cell of ovary CL0002132
    CSI 5.02
    rCSI 13.8%
    PRS 97.47
  • ependymal cell CL0000065
    CSI 4.9
    rCSI 9.94%
    PRS 84.2
  • glioblast CL0000030
    CSI 4.81
    rCSI 7.67%
    PRS 91.63
  • podocyte CL0000653
    CSI 4.62
    rCSI 20.52%
    PRS 96.03
  • vascular associated smooth muscle cell CL0000359
    CSI 4.52
    rCSI 14.67%
    PRS 95.72
  • neural crest cell CL0011012
    CSI 4.37
    rCSI 3.45%
    PRS 93.18
  • fibroblast of cardiac tissue CL0002548
    CSI 4.34
    rCSI 20.79%
    PRS 96.87
  • pancreatic stellate cell CL0002410
    CSI 4.34
    rCSI 25.24%
    PRS 96.74
  • lung pericyte CL0009089
    CSI 3.97
    rCSI 10.48%
    PRS 97.93
  • enteric smooth muscle cell CL0002504
    CSI 3.85
    rCSI 5.49%
    PRS 96.48
  • hepatic stellate cell CL0000632
    CSI 3.74
    rCSI 14.03%
    PRS 94.5
  • tendon cell CL0000388
    CSI 3.73
    rCSI 9.7%
    PRS 97.42
  • chondrocyte CL0000138
    CSI 3.55
    rCSI 5.65%
    PRS 93.58
  • Schwann cell CL0002573
    CSI 3.41
    rCSI 9.7%
    PRS 94.14
  • perivascular cell CL4033054
    CSI 3.13
    rCSI 4.28%
    PRS 97.87
  • mononuclear phagocyte CL0000113
    CSI 3.07
    rCSI 6.76%
    PRS 97.62
  • stromal cell CL0000499
    CSI 3.05
    rCSI 8.58%
    PRS 94.26
  • peripheral nervous system neuron CL2000032
    CSI 2.74
    rCSI 3.73%
    PRS 92.6
  • adipocyte CL0000136
    CSI 2.66
    rCSI 3.41%
    PRS 91.38
  • myeloid leukocyte CL0000766
    CSI 2.6
    rCSI 2.39%
    PRS 97.22
  • placental villous trophoblast CL2000060
    CSI 2.45
    rCSI 3.79%
    PRS 95.04
  • mesenchymal stem cell of adipose tissue CL0002570
    CSI 2.43
    rCSI 13.56%
    PRS 97.1
  • mesodermal cell CL0000222
    CSI 2.35
    rCSI 2.82%
    PRS 96.36
  • mesenchymal cell CL0008019
    CSI 2.31
    rCSI 5.88%
    PRS 94.32
  • glial cell CL0000125
    CSI 2.15
    rCSI 8.2%
    PRS 92.03
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.06
    rCSI 1.98%
    PRS 95.22
  • syncytiotrophoblast cell CL0000525
    CSI 1.74
    rCSI 5%
    PRS 95.7
  • basal cell CL0000646
    CSI 1.58
    rCSI 2.11%
    PRS 94.24
  • parietal epithelial cell CL1000452
    CSI 1.46
    rCSI 3.91%
    PRS 93.45
  • uterine smooth muscle cell CL0002601
    CSI 1.42
    rCSI 9.34%
    PRS 97.41
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.21
    rCSI 3.49%
    PRS 95.83
  • odontoblast CL0000060
    CSI 1.18
    rCSI 26.74%
    PRS 98.55
  • osteoblast CL0000062
    CSI 0.86
    rCSI 21.36%
    PRS 98.13
  • brain vascular cell CL4023072
    CSI 0.82
    rCSI 8.5%
    PRS 91.75
  • blood vessel smooth muscle cell CL0019018
    CSI 0.49
    rCSI 3.98%
    PRS 95.56
  • mesenchymal lymphangioblast CL0005021
    CSI 0.38
    rCSI 9.91%
    PRS 97.75
  • mesenchymal stem cell CL0000134
    CSI 0.21
    rCSI 2.33%
    PRS 97.38

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Matrix Remodeling Associated 8, [MXRA8](/details-gene/54587), is a protein-coding gene located on chromosome 1p36.33. It encodes a cell surface protein belonging to the immunoglobulin superfamily. Functionally, [MXRA8](/details-gene/54587) is recognized as a critical receptor for multiple arthritogenic alphaviruses, including the chikungunya virus, playing a key role in viral entry ([Link](https://doi.org/10.1038/s41586-018-0121-3)). Beyond its role in virology, it is implicated in fundamental cellular processes such as `[Cell adhesion](/details-cell/GO:0007155)` and tissue development, including the inhibition of osteoclast differentiation and angiogenesis ([Link](https://doi.org/10.1002/jbmr.1632), [Link](https://doi.org/10.1093/cvr/cvt019)). Expression data highlights its prominence in mesenchymal and stromal cell lineages, particularly various fibroblast populations and smooth muscle cells, suggesting a significant role in the maintenance and remodeling of connective tissues. ## Cellular Roles and Expression Landscape The expression profile of [MXRA8](/details-gene/54587) underscores its importance in structural and connective tissues. **Overall**, the gene shows the highest significance in mesenchymal cell types. It is a particularly strong marker for [bronchus fibroblast of lung](/details-cell/CL2000093) (CSI: 28.59), [skin fibroblast](/details-cell/CL0002620) (CSI: 19.46), and [fibroblast of lung](/details-cell/CL0002553) (CSI: 11.52), indicating a central role in the biology of these stromal cells across different organs. Its high significance in [tracheobronchial smooth muscle cell](/details-cell/CL0019019) (CSI: 17.33) and [smooth muscle cell](/details-cell/CL0000192) (CSI: 5.24) further reinforces its association with contractile and structural tissues. Beyond these primary cell types, [MXRA8](/details-gene/54587) is also significantly expressed in specialized cells such as [keratocytes](/details-cell/CL0002363) in the cornea and [intestinal epithelial cell](/details-cell/CL0002563), suggesting diverse functions in tissue barrier integrity and maintenance. The collective expression pattern points towards a role for [MXRA8](/details-gene/54587) in mediating cell-cell and cell-matrix interactions that are fundamental to tissue architecture and response to injury or infection. ## Pathways and Molecular Function The functional annotations for [MXRA8](/details-gene/54587) are consistent with its role as a cell surface protein involved in tissue dynamics. Its participation in `[Cell adhesion](/details-cell/GO:0007155)` and its localization to the `[Cell surface](/details-cell/GO:0009986)` and `[Bicellular tight junction](/details-cell/GO:0005923)` are central to its function in maintaining tissue structure. Research has demonstrated its ability to inhibit angiogenesis and osteoclast differentiation, suggesting a regulatory role in tissue remodeling processes ([Link](https://doi.org/10.1093/cvr/cvt019), [Link](https://doi.org/10.1002/jbmr.1632)). At the molecular level, the gene is involved in protein metabolism pathways, including `[Metabolism of proteins](/details-cell/R-HSA-392499)` and `[Post-translational protein modification](/details-cell/R-HSA-597592)`, indicating that the MXRA8 protein itself undergoes significant processing to become functional. Its most clinically relevant function is as a viral receptor, where its `[Protein binding](/details-cell/GO:0005515)` capacity is exploited by alphaviruses to gain entry into host cells, a finding that places it at the critical interface between host-pathogen interactions ([Link](https://doi.org/10.1038/s41586-018-0121-3)). ## Research Directions The dual role of [MXRA8](/details-gene/54587) as both a viral entry factor and a regulator of tissue remodeling presents several compelling avenues for future research. Its high expression in [fibroblast of lung](/details-cell/CL0002553) populations is particularly notable, given the lung is a primary site for both viral infections and fibrotic diseases. ### Proposed Hypotheses: 1. Given its high expression in multiple fibroblast populations and its documented role in modulating angiogenesis and cell differentiation, [MXRA8](/details-gene/54587) signaling may be a critical determinant in the pathogenesis of fibrotic diseases. Dysregulation of [MXRA8](/details-gene/54587) expression or function in lung fibroblasts could contribute to the excessive matrix deposition seen in idiopathic pulmonary fibrosis. 2. The expression level of [MXRA8](/details-gene/54587) on synovial fibroblasts and other joint-associated stromal cells likely dictates tissue tropism and disease severity for arthritogenic alphaviruses like Chikungunya. Genetic or environmental factors that alter its expression could explain the variability in joint pathology observed among infected individuals. ### Key Experiment: To test the hypothesis that [MXRA8](/details-gene/54587) is involved in lung fibrosis (Hypothesis 1), a murine model of bleomycin-induced pulmonary fibrosis could be utilized. Mxra8 knockout mice and wild-type controls would be administered bleomycin to induce lung injury. The development of fibrosis would be compared between genotypes by quantifying collagen deposition via hydroxyproline assays and visualizing tissue architecture with Masson's trichrome staining. Furthermore, lung fibroblasts could be isolated from both groups to assess their activation state (e.g., alpha-SMA expression) and proliferative capacity *in vitro*. ### Therapeutic Potential: As a cell surface receptor, [MXRA8](/details-gene/54587) represents a highly attractive therapeutic target. In the context of alphaviral infections, it is a prime candidate for **inhibition**. The development of blocking monoclonal antibodies or a soluble decoy receptor based on the MXRA8 ectodomain could prevent viral entry and serve as a potent antiviral therapeutic. In the context of fibrosis, its therapeutic potential is more complex and would depend on whether its activity is pro- or anti-fibrotic. If it proves to be a negative regulator of fibroblast activation, developing an agonist to enhance its natural function could be a novel anti-fibrotic strategy. The specific expression pattern on stromal cells suggests that targeting [MXRA8](/details-gene/54587) could offer a focused therapeutic approach with potentially fewer off-target effects than broadly acting anti-fibrotic agents.

Genular Protein ID: 1225037199

Symbol: MXRA8_HUMAN

Name: Matrix remodeling-associated protein 8

UniProtKB Accession Codes:

Q9BRK3 B3KTR6 B4DE34 Q5TA39 Q96KC3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 4 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 2 RefSeq 5 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14603461

Title: Limitrin, a novel immunoglobulin superfamily protein localized to glia limitans formed by astrocyte endfeet.

PubMed ID: 14603461

DOI: 10.1002/glia.10279

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 22492581

Title: DICAM inhibits osteoclast differentiation through attenuation of the integrin alphaVbeta3 pathway.

PubMed ID: 22492581

DOI: 10.1002/jbmr.1632

PubMed ID: 23386276

Title: DICAM inhibits angiogenesis via suppression of AKT and p38 MAP kinase signalling.

PubMed ID: 23386276

DOI: 10.1093/cvr/cvt019

PubMed ID: 26091039

Title: A single kinase generates the majority of the secreted phosphoproteome.

PubMed ID: 26091039

DOI: 10.1016/j.cell.2015.05.028

PubMed ID: 29769725

Title: Mxra8 is a receptor for multiple arthritogenic alphaviruses.

PubMed ID: 29769725

DOI: 10.1038/s41586-018-0121-3

Sequence Information:

  • Length: 442
  • Mass: 49132
  • Checksum: B08F89D726222CA1
  • Sequence:
    • MALPSRILLW KLVLLQSSAV LLHSGSSVPA AAGSSVVSES AVSWEAGARA VLRCQSPRMV 
WTQDRLHDRQ RVLHWDLRGP GGGPARRLLD LYSAGEQRVY EARDRGRLEL SASAFDDGNF 
SLLIRAVEET DAGLYTCNLH HHYCHLYESL AVRLEVTDGP PATPAYWDGE KEVLAVARGA 
PALLTCVNRG HVWTDRHVEE AQQVVHWDRQ PPGVPHDRAD RLLDLYASGE RRAYGPLFLR 
DRVAVGADAF ERGDFSLRIE PLEVADEGTY SCHLHHHYCG LHERRVFHLT VAEPHAEPPP 
RGSPGNGSSH SGAPGPDPTL ARGHNVINVI VPESRAHFFQ QLGYVLATLL LFILLLVTVL 
LAARRRRGGY EYSDQKSGKS KGKDVNLAEF AVAAGDQMLY RSEDIQLDYK NNILKERAEL 
AHSPLPAKYI DLDKGFRKEN CK