Details for: MICALL1

Gene ID: 85377

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: MICALL1

Ensembl ID: ENSG00000100139

Description: MICAL like 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • cerebral cortex endothelial cell CL1001602
    CSI 3.4
    rCSI 5.88%
    PRS 96
  • epithelial cell CL0000066
    CSI 2.65
    rCSI 4.07%
    PRS 91.46
  • extravillous trophoblast CL0008036
    CSI 2.49
    rCSI 3.08%
    PRS 97.04
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.4
    rCSI 2.99%
    PRS 92.25
  • placental villous trophoblast CL2000060
    CSI 2.2
    rCSI 3.4%
    PRS 97.04
  • enteric smooth muscle cell CL0002504
    CSI 2.04
    rCSI 2.9%
    PRS 98.3
  • club cell CL0000158
    CSI 1.98
    rCSI 2.91%
    PRS 96.7
  • cardiac endothelial cell CL0010008
    CSI 1.91
    rCSI 7.7%
    PRS 98.19
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.81
    rCSI 4.6%
    PRS 96.09
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.77
    rCSI 2.97%
    PRS 93.74
  • neural progenitor cell CL0011020
    CSI 1.65
    rCSI 7.24%
    PRS 91.89

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.

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  • 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)

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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 [MICALL1](/details-gene/85377) (MICAL like 1) is a protein-coding gene located on chromosome 22q13.1. It encodes a member of the MICAL (Molecule Interacting with CasL) family of flavoprotein oxidoreductases. Functionally, [MICALL1](/details-gene/85377) is a key regulator of intracellular membrane trafficking, particularly involved in processes such as [endocytosis](/details-go/GO:0006897) and [endocytic recycling](/details-go/GO:0032456). **Overall**, expression data indicates its highest significance in various endothelial and epithelial cell types, including [cerebral cortex endothelial cell](/details-cell/CL1001602) and general [epithelial cell](/details-cell/CL0000066), as well as in specific neuronal populations. This expression pattern, combined with its established molecular functions, suggests a critical role in maintaining cellular transport, barrier function, and receptor dynamics across multiple tissues. ## Cellular Roles and Expression Landscape The expression profile of [MICALL1](/details-gene/85377) highlights its importance in cells that form structural barriers and engage in high levels of molecular transport. **Overall**, the gene shows the highest significance in endothelial cells, as evidenced by its top rank in [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 3.40) and high significance in [cardiac endothelial cell](/details-cell/CL0010008) (CSI: 1.91). This suggests a conserved role in regulating endothelial trafficking, which is critical for processes like transcytosis and angiogenesis. A second major functional group where [MICALL1](/details-gene/85377) is prominent is epithelial and trophoblastic cells. It is highly significant in general [epithelial cell](/details-cell/CL0000066) (CSI: 2.65), [extravillous trophoblast](/details-cell/CL0008036) (CSI: 2.49), [placental villous trophoblast](/details-cell/CL2000060) (CSI: 2.20), [club cell](/details-cell/CL0000158) of the lung (CSI: 1.98), and [kidney connecting tubule epithelial cell](/details-cell/CL1000768) (CSI: 1.81). This pattern points to a fundamental role in maintaining the integrity and transport functions of epithelial linings in diverse organs. Furthermore, [MICALL1](/details-gene/85377) shows a specialized role within the nervous system, with notable significance in specific inhibitory neuron subtypes, including [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 2.40) and [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) (CSI: 1.77), as well as in [neural progenitor cell](/details-cell/CL0011020) (CSI: 1.65). This is consistent with its documented involvement in [neuron projection development](/details-go/GO:0031175) and suggests it contributes to the complex trafficking of synaptic components. ## Pathways and Molecular Function The functional annotations for [MICALL1](/details-gene/85377) strongly corroborate its role as a central component of the endosomal system. It is localized to the [cytoplasmic side of endosome membrane](/details-go/GO:0010009), including [early endosome](/details-go/GO:0005769), [late endosome](/details-go/GO:0005770), and [recycling endosome membrane](/details-go/GO:0055038). Its primary biological processes revolve around membrane dynamics, including [endocytosis](/details-go/GO:0006897), [receptor-mediated endocytosis](/details-go/GO:0006898), and particularly [endocytic recycling](/details-go/GO:0032456). At the molecular level, [MICALL1](/details-gene/85377) acts as a scaffolding or adaptor protein, evidenced by its binding capabilities to [cadherins](/details-go/GO:0045296), [phosphatidic acid](/details-go/GO:0070300), and [small gtpases](/details-go/GO:0031267). Research has demonstrated that MICAL-L1 serves as a hub on tubular recycling endosomes, connecting Rab and Arf family GTPases to regulate receptor recycling ([Link](https://doi.org/10.1091/mbc.e09-06-0535); [Link](https://doi.org/10.1111/j.1600-0854.2011.01294.x)). For instance, it has been specifically implicated in mediating the endocytosis and subsequent trafficking of the epidermal growth factor receptor (EGFR), a critical process for modulating cell signaling ([Link](https://doi.org/10.1091/mbc.e11-01-0030)). This function is consistent with its high expression in epithelial cells, where receptor turnover is crucial for homeostasis and response to stimuli. ## Research Directions The widespread yet specific expression of [MICALL1](/details-gene/85377) in barrier and neuronal cells, combined with its central role in endosomal trafficking, suggests it may be a critical node in both physiological and pathological processes. ### Proposed Hypotheses: 1. **Hypothesis 1:** Given its top significance in [cerebral cortex endothelial cell](/details-cell/CL1001602) and its function in [cadherin binding](/details-go/GO:0045296) and endocytosis, [MICALL1](/details-gene/85377) is a critical regulator of blood-brain barrier (BBB) integrity by controlling the endocytic turnover of adherens and tight junction proteins. Dysregulation of [MICALL1](/details-gene/85377) could therefore contribute to BBB breakdown in neurological diseases. 2. **Hypothesis 2:** In [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), [MICALL1](/details-gene/85377) specifically modulates the surface expression and recycling of GABA receptors or associated synaptic machinery. Altered [MICALL1](/details-gene/85377) function in these neurons could lead to imbalances in cortical excitation/inhibition, a hallmark of conditions like epilepsy or schizophrenia. ### Experimental Approach: To test Hypothesis 1, an *in vitro* model of the BBB could be established using primary human brain microvascular endothelial cells. [MICALL1](/details-gene/85377) expression could be knocked down using CRISPR-Cas9 or siRNA. The consequences would be assayed by measuring transendothelial electrical resistance (TEER) to assess barrier permeability and by using immunofluorescence and surface biotinylation assays to quantify the localization and turnover rates of key junctional proteins like VE-cadherin and Claudin-5. ### Therapeutic Potential: [MICALL1](/details-gene/85377) presents a complex but potentially valuable therapeutic target. As a regulator of receptor endocytosis, its **inhibition** could be beneficial in cancers characterized by overexpression and signaling of growth factor receptors like EGFR. By preventing receptor recycling to the plasma membrane, inhibitors could enhance the efficacy of receptor-blocking antibodies. Conversely, its role in BBB maintenance suggests that modulating [MICALL1](/details-gene/85377) activity could be a strategy to transiently increase BBB permeability, thereby improving drug delivery to the central nervous system. Because it is an intracellular scaffolding protein without a known enzymatic active site that is easily targeted, developing small molecule inhibitors would be challenging, suggesting that gene-level therapies may be a more viable, albeit complex, long-term strategy.

Genular Protein ID: 2812116311

Symbol: MILK1_HUMAN

Name: MICAL-like protein 1

UniProtKB Accession Codes:

Q8N3F8 Q5TI16 Q7RTP5 Q8N3N8 Q9BVL9 Q9BY92 Q9UH43 Q9UH44 Q9UH45

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 18 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 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 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 21795389

Title: MICAL-like1 mediates epidermal growth factor receptor endocytosis.

PubMed ID: 21795389

DOI: 10.1091/mbc.e11-01-0030

PubMed ID: 15461802

Title: A genome annotation-driven approach to cloning the human ORFeome.

PubMed ID: 15461802

DOI: 10.1186/gb-2004-5-10-r84

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 11258795

Title: Identification of novel transcribed sequences on human chromosome 22 by expressed sequence tag mapping.

PubMed ID: 11258795

DOI: 10.1093/dnares/8.1.1

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: 12110185

Title: MICALs, a family of conserved flavoprotein oxidoreductases, function in plexin-mediated axonal repulsion.

PubMed ID: 12110185

DOI: 10.1016/s0092-8674(02)00794-8

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19864458

Title: MICAL-L1 links EHD1 to tubular recycling endosomes and regulates receptor recycling.

PubMed ID: 19864458

DOI: 10.1091/mbc.e09-06-0535

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20801876

Title: Collapsin response mediator protein-2 (Crmp2) regulates trafficking by linking endocytic regulatory proteins to dynein motors.

PubMed ID: 20801876

DOI: 10.1074/jbc.c110.166066

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21951725

Title: MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a.

PubMed ID: 21951725

DOI: 10.1111/j.1600-0854.2011.01294.x

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 23596323

Title: Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis.

PubMed ID: 23596323

DOI: 10.1091/mbc.e13-01-0026

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 20106972

Title: Mechanism for the selective interaction of C-terminal Eps15 homology domain proteins with specific Asn-Pro-Phe-containing partners.

PubMed ID: 20106972

DOI: 10.1074/jbc.m109.045666

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 863
  • Mass: 93441
  • Checksum: 755E3B57C6037292
  • Sequence:
    • MAGPRGALLA WCRRQCEGYR GVEIRDLSSS FRDGLAFCAI LHRHRPDLLD FDSLSKDNVF 
ENNRLAFEVA EKELGIPALL DPNDMVSMSV PDCLSIMTYV SQYYNHFCSP GQAGVSPPRK 
GLAPCSPPSV APTPVEPEDV AQGEELSSGS LSEQGTGQTP SSTCAACQQH VHLVQRYLAD 
GRLYHRHCFR CRRCSSTLLP GAYENGPEEG TFVCAEHCAR LGPGTRSGTR PGPFSQPKQQ 
HQQQLAEDAK DVPGGGPSSS APAGAEADGP KASPEARPQI PTKPRVPGKL QELASPPAGR 
PTPAPRKASE STTPAPPTPR PRSSLQQENL VEQAGSSSLV NGRLHELPVP KPRGTPKPSE 
GTPAPRKDPP WITLVQAEPK KKPAPLPPSS SPGPPSQDSR QVENGGTEEV AQPSPTASLE 
SKPYNPFEEE EEDKEEEAPA APSLATSPAL GHPESTPKSL HPWYGITPTS SPKTKKRPAP 
RAPSASPLAL HASRLSHSEP PSATPSPALS VESLSSESAS QTAGAELLEP PAVPKSSSEP 
AVHAPGTPGN PVSLSTNSSL ASSGELVEPR VEQMPQASPG LAPRTRGSSG PQPAKPCSGA 
TPTPLLLVGD RSPVPSPGSS SPQLQVKSSC KENPFNRKPS PAASPATKKA TKGSKPVRPP 
APGHGFPLIK RKVQADQYIP EEDIHGEMDT IERRLDALEH RGVLLEEKLR GGLNEGREDD 
MLVDWFKLIH EKHLLVRRES ELIYVFKQQN LEQRQADVEY ELRCLLNKPE KDWTEEDRAR 
EKVLMQELVT LIEQRNAIIN CLDEDRQREE EEDKMLEAMI KKKEFQREAE PEGKKKGKFK 
TMKMLKLLGN KRDAKSKSPR DKS