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FLASH GENE

Symbol

PLP1

contributors: mct - updated : 20-01-2015

HGNC name	proteolipid protein 1
HGNC id	9086

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	PMDX Pelizaeus-Merzbacher disease, type 1 SPG2 spastic paraplegia 2
Location	Xq22.2      Physical location : 103.031.438 - 103.047.545
Synonym name	lipophilin
	major myelin proteolipid protein
Synonym symbol(s)	PLP, PMD, SPG2, PLP/DM20

DNA

TYPE	functioning gene
STRUCTURE	16.11 kb     8 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	promoter is responsible for driving expression of one of the major components of myelin--PLP and its splice variant DM-20 (
	PLP1promoter activity is not restricted to the myelinating cell lineage, but rather, has widespread activity both during embryonic and early postnatal development in the CNS (

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	see DXS178

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_199478 7 splicing 2933 NP_955772 - 242 express predominantly in oligodendrocytes 2011 21572962 also called DM20 deletion of part of exon 3 DM20 is found mainly as a monomer presence of a 35 AA sequence within the intracellular loop of PLP that is absent in DM20 NM_000533 7 splicing 3038 NP_000524 - 277 - 2006 16774974 also called PLP exists as both a monomer and a disulfide-linked dimer presence of a 35 AA sequence within the intracellular loop of PLP that is absent in DM20 NM_001128834 8 - 3148 NP_001122306 - 277 - 2006 16774974

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine     moderately Nervous brain       highly Homo sapiens Reproductive male system testis     moderately Homo sapiens Skin/Tegument skin       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central white matter     Homo sapiens Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Nervous oligodendrocyte Homo sapiens Reproductive Leydig cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES		Hydrophilic
STRUCTURE

motifs/domains	hydrophobic membrane protein with four putative membrane spanning domains (4TM)
	two extracellular loop regions, EC1 and EC2, that interact with the opposing membrane in myelin

HOMOLOGY

interspecies

homolog to murine Plp

Homologene

FAMILY	myelin proteolipid protein family
	tetraspan membrane protein family

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,organelle,lysosome
text	VAMP3 and VAMP7 colocalize with the major myelin proteolipid protein (PLP1) in recycling endosomes and late endosomes/lysosomes, respectively

basic FUNCTION	tetraspanin, major myelin protein from the central nervous system
	playing an important role in the formation or maintenance of the multilamellar structure of myelin
	involved in axonal-glial interactions
	may have functions not only in oligodendrocytes but also in neurons and could be implicated in axono-glial communication
	inhibits oligodendrocyte precursor cells (OPCs) differentiation and its effect is mediated through the ERK signaling cascade
	inhibits OPC differentiation through the ERK cascade, possibly leading to dysmyelination
	while PLP1 can co-exist with MPZ in peripheral nervous system (PNS) myelin, PLP1 cannot replace MPZ as the major structural protein of PNS myelin

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

sensory transduction/vision

a component

INTERACTION

DNA

RNA

small molecule

protein	developmental changes in HNRNPH2/HNRNPF associated with oligodendrocytes (OLs) differentiation synergistically regulate PLP1 alternative splicing and a G-rich enhancer participates in the regulation
	HNRNPH2 and HNRNPF regulate PLP1 splicing by recruiting U1snRNP and HNRNPH2 plays a primary role in PLP1 splice site selection
	interaction of PLP1 and MAL2 in oligodendrocytic cells
	interaction with VAMP7 (VAMP7 controls exocytosis of PLP1 from late endosomal/lysosomal organelles as part of a transcytosis pathway)
	ZFYVE27 interact with other hereditary spastic paraplegia-related proteins including myelin proteolipid protein 1 (PLP1), atlastin-1 (SPG3A), REEP1, REEP5 (similar to REEP1), KIF5A, KIF5B, KIF5C

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

PMDX , SPG2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       in neuroaxonal injury with neurologic deficit constitutional       loss of function in axonal degeneration

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	myelin-deficient (MD) rats, which carry a mutation in the Plp gene, exhibit lethal hypoxic ventilatory depression
	lowering toxic Plp1 overexpression via a progesterone antagonist ameliorates axonal loss and the disease phenotype in Plp1 transgenic mice
	mice with Plp1 gene duplication model the most common form of Pelizaeus-Merzbacher disease (PMD), a CNS disease in which patients may suffer respiratory complications