Details for: TRIML2

Gene ID: 205860

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: TRIML2

Ensembl ID: ENSG00000179046

Description: tripartite motif family like 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • extravillous trophoblast CL0008036
    CSI 5.29
    rCSI 6.54%
    PRS 99.46

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 [TRIML2](/details-gene/205860) (tripartite motif family like 2) is a protein-coding gene located on chromosome 4q35.2. As a member of the tripartite motif (TRIM) family, it functions as an E3 ubiquitin ligase, playing roles in [protein ubiquitination](/details-go/GO0016567) and the [innate immune response](/details-go/GO0045087). Expression data indicates that [TRIML2](/details-gene/205860) has a highly specialized role, with its expression being a significant and defining feature of [extravillous trophoblast](/details-cell/CL0008036) cells, which are critical for placental development and maternal-fetal immune tolerance. The gene's initial characterization was supported by large-scale cDNA sequencing and genome annotation projects [Link](https://doi.org/10.1038/nature03466), [Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504). ## Cellular Roles and Expression Landscape The expression profile of [TRIML2](/details-gene/205860) suggests a highly specific function rather than a ubiquitous role. **Overall**, the gene's significance is exceptionally high and narrowly focused within [extravillous trophoblast](/details-cell/CL0008036) cells (CSI: 5.29). This strong, cell-type-specific signal indicates that [TRIML2](/details-gene/205860) is not merely active in these cells but may serve as a key marker that defines their unique biological identity. [Extravillous trophoblast](/details-cell/CL0008036) cells are instrumental in embryo implantation and uterine artery remodeling, processes requiring controlled invasion and immune modulation. The high significance of [TRIML2](/details-gene/205860) in this context points towards a crucial role in regulating the molecular machinery that governs these specialized placental functions. ## Pathways and Molecular Function Functional annotations for [TRIML2](/details-gene/205860) align with its proposed role in specialized cellular processes. Its primary molecular function is categorized as [ubiquitin protein ligase activity](/details-go/GO0061630), which involves tagging other proteins with ubiquitin for degradation or signaling. This activity is a central mechanism for controlling protein levels and is integral to the biological process of [protein ubiquitination](/details-go/GO0016567). This E3 ligase function is likely directed at substrates involved in the [innate immune response](/details-go/GO0045087) and the [regulation of gene expression](/details-go/GO0010468). In the context of its specific expression in [extravillous trophoblast](/details-cell/CL0008036) cells, this suggests [TRIML2](/details-gene/205860) may help establish the unique immune-privileged environment at the maternal-fetal interface. By regulating protein stability, it could modulate signaling pathways that prevent maternal immune rejection of the semi-allogeneic fetus. The protein is known to operate within the [cytoplasm](/details-go/GO0005737) and engage in [protein binding](/details-go/GO0005515), including with identical protein molecules ([identical protein binding](/details-go/GO0042802)). ## Research Directions The highly specific expression of [TRIML2](/details-gene/205860) in a cell type critical for pregnancy presents several avenues for future investigation. **Proposed Hypotheses:** 1. [TRIML2](/details-gene/205860) functions as a master regulator of trophoblast invasion by ubiquitinating and promoting the degradation of proteins that inhibit cell migration and tissue remodeling. Its dysregulation could therefore be a contributing factor in pregnancy disorders characterized by poor placentation, such as pre-eclampsia. 2. As an E3 ligase involved in innate immunity, [TRIML2](/details-gene/205860) may specifically target and degrade components of inflammatory signaling pathways (e.g., TLR or RLR pathways) within [extravillous trophoblast](/details-cell/CL0008036) cells, thereby actively maintaining a state of immune tolerance at the maternal-fetal interface. **Experimental Approach:** To test the first hypothesis, a compelling experiment would involve the use of human trophoblast stem cells (TSCs). CRISPR-Cas9 could be used to generate a [TRIML2](/details-gene/205860) knockout TSC line. These knockout cells and their wild-type counterparts would then be differentiated into syncytiotrophoblasts and extravillous trophoblasts. The invasive capacity of the differentiated extravillous trophoblasts could be quantitatively assessed using a Matrigel invasion assay. Concurrently, unbiased mass spectrometry-based proteomics (e.g., Ub-clipping or UbiSite) could be performed on both cell lines to identify specific protein substrates of [TRIML2](/details-gene/205860) whose ubiquitination status and abundance change upon its knockout. **Therapeutic Potential:** Based on current data, the therapeutic potential of targeting [TRIML2](/details-gene/205860) is likely confined to pregnancy-related pathologies. If loss-of-function is linked to conditions like pre-eclampsia, developing strategies to enhance or restore its E3 ligase activity or expression could be a potential therapeutic avenue. Conversely, if its overexpression is associated with overly invasive placental conditions like placenta accreta, targeted inhibition might be beneficial. However, its immediate value may lie as a highly specific biomarker for assessing [extravillous trophoblast](/details-cell/CL0008036) health and function during pregnancy.

Genular Protein ID: 4002977593

Symbol: TRIMM_HUMAN

Name: SPRY domain-containing protein 6

UniProtKB Accession Codes:

Q8N7C3 B7Z6J6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 4 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 8 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 5 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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

Sequence Information:

  • Length: 437
  • Mass: 49893
  • Checksum: BC2532BEF2CA551F
  • Sequence:
    • MSKRLSPQLQ HNITEDAYCE THLEPTRLFC DVDQITLCSK CFQSQEHKHH MVCGIQEAAE 
NYRKLFQEIL NTSREKLEAA KSILTDEQER MAMIQEEEQN FKKMIESEYS MRLRLLNEEC 
EQNLQRQQEC ISDLNLRETL LNQAIKLATE LEEMFQEMLQ RLGRVGRENM EKLKESEARA 
SEQVRSLLKL IVELEKKCGE GTLALLKNAK YSLERSKSLL LEHLEPAHIT DLSLCHIRGL 
SSMFRVLQRH LTLDPETAHP CLALSEDLRT MRLRHGQQDG AGNPERLDFS AMVLAAESFT 
SGRHYWEVDV EKATRWQVGI YHGSADAKGS TARASGEKVL LTGSVMGTEW TLWVFPPLKR 
LFLEKKLDTV GVFLDCEHGQ ISFYNVTEMS LIYNFSHCAF QGALRPVFSL CIPNGDTSPD 
SLTILQHGPS CDATVSP

Genular Protein ID: 70878963

Symbol: B7ZLC3_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7ZLC3

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Gene3D 1 HOGENOM 1 InterPro 7 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 2 PeptideAtlas 1 Pfam 2 PhylomeDB 1 RefSeq 1 SAM 1 SMART 2 SUPFAM 1 UCSC 1

Citations:

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

Sequence Information:

  • Length: 412
  • Mass: 46866
  • Checksum: C073C24BC632DECA
  • Sequence:
    • MVCGIQEAAE NYRKLFQEIL NTSREKLEAA KSILTDEQER MAMIQEEEQN FKKMIESEYS 
MRLRLLNEEC EQNLQRQQEC ISDLNLRETL LNQAIKLATE LEEMFQEMLQ RLGRVGRENM 
EKLKESEARA SEQVRSLLKL IVELEKKCGE GTLALLKCLD LEIRPPELRE MNFCCAEATQ 
SMNAKYSLER SKSLLLEHLE PAHITDLSLC HIRGLSSMFR VLQRHLTLDP ETAHPCLALS 
EDLRTMRLRH GQQDGAGNPE RLDFSAMVLA AESFTSGRHY WEVDVEKATR WQVGIYHGSA 
DAKGSTARAS GEKVLLTGSV MGTEWTLWVF PPLKRLFLEK KLDTVGVFLD CEHGQISFYN 
VTEMSLIYNF SHCAFQGALR PVFSLCIPNG DTSPDSLTIL QHGPSCDATV SP