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9.B.129.1.1
Megalencephalic leukoencephalopathy with subcortical cysts 1 homologue, MLC1. May interact with several ion and water channels and cause channelopathies (Brignone et al. 2015). The disease is a progressive cerebral white matter disease in children caused by mutations in the MLC1 gene. This disease is histopathologically characterized by myelin splitting and intramyelinic vacuole formation. MLC1 is mainly expressed in the brain and leukocytes. MLC1 contains an even number (probably 8) TMSs and is expressed in distal astroglial processes in perivascular, subependymal, and subpial regions, possibly suggesting a role in transport across the blood-brain and brain-cerebrospinal fluid barriers. Astrocytes are of fundamental importance in maintaining the structural and functional integrity of neural tissue (Boor et al. 2005). GlialCAM/MLC1 may form a functional unit (Pérez-Rius et al. 2019).  Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures, suggesting a role for astrocytes in volume regulation in epilepsy (Dubey et al. 2018). Depolarization causes the formation of a ternary complex between GlialCAM, MLC1 and ClC-2 in astrocytes (Sirisi et al. 2017). MLC1 depends on the fluid mosaic membrane which has been reviewed (Nicolson and Ferreira de Mattos 2022).  

Accession Number:Q15049
Protein Name:Membrane protein MLC1
Length:377
Molecular Weight:41141.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:8
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

Entrez Gene ID: 23209   
KEGG: hsa:23209   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0016323 C:basolateral plasma membrane
GO:0005901 C:caveola
GO:0005911 C:cell-cell junction
GO:0031410 C:cytoplasmic vesicle
GO:0005769 C:early endosome
GO:0005783 C:endoplasmic reticulum
GO:0016021 C:integral to membrane
GO:0000299 C:integral to membrane of membrane fraction
GO:0005764 C:lysosome
GO:0048471 C:perinuclear region of cytoplasm
GO:0055037 C:recycling endosome
GO:0005216 F:ion channel activity
GO:0008565 F:protein transporter activity
GO:0072584 P:caveolin-mediated endocytosis
GO:0071397 P:cellular response to cholesterol
GO:0032388 P:positive regulation of intracellular transport
GO:0051259 P:protein oligomerization
GO:0047484 P:regulation of response to osmotic stress

References (13)

[1] “A missense mutation in a novel gene encoding a putative cation channel is associated with catatonic schizophrenia in a large pedigree.”  Meyer J.et.al.   11326298
[2] “Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1.”  Nomura N.et.al.   7584026
[3] “Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.”  Nakajima D.et.al.   12168954
[4] “A genome annotation-driven approach to cloning the human ORFeome.”  Collins J.E.et.al.   15461802
[5] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[6] “The DNA sequence of human chromosome 22.”  Dunham I.et.al.   10591208
[7] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[8] “Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.”  Gevaert K.et.al.   12665801
[9] “Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations.”  Lanciotti A.et.al.   22328087
[10] “Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts.”  Leegwater P.A.J.et.al.   11254442
[11] “Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts.”  Leegwater P.A.J.et.al.   11935341
[12] “Megalencephalic leukoencephalopathy with subcortical cysts; a founder effect in Israeli patients and a higher than expected carrier rate among Libyan Jews.”  Ben-Zeev B.et.al.   12189496
[13] “Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1.”  Ilja Boor P.K.et.al.   16652334

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MTQEPFREEL AYDRMPTLER GRQDPASYAP DAKPSDLQLS KRLPPCFSHK TWVFSVLMGS 
61:	CLLVTSGFSL YLGNVFPAEM DYLRCAAGSC IPSAIVSFTV SRRNANVIPN FQILFVSTFA 
121:	VTTTCLIWFG CKLVLNPSAI NINFNLILLL LLELLMAATV IIAARSSEED CKKKKGSMSD 
181:	SANILDEVPF PARVLKSYSV VEVIAGISAV LGGIIALNVD DSVSGPHLSV TFFWILVACF 
241:	PSAIASHVAA ECPSKCLVEV LIAISSLTSP LLFTASGYLS FSIMRIVEMF KDYPPAIKPS 
301:	YDVLLLLLLL VLLLQAGLNT GTAIQCVRFK VSARLQGASW DTQNGPQERL AGEVARSPLK 
361:	EFDKEKAWRA VVVQMAQ