PLP1

Protein identityUniProt · HPA

UniProt accession

P60201

Gene

PLP1

Ensembl

ENSG00000123560

Chromosome

X

Canonical length

277 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters

OverviewNCBI Gene

This gene encodes a transmembrane proteolipid protein that is the predominant component of myelin. The encoded protein may play a role in the compaction, stabilization, and maintenance of myelin sheaths, as well as in oligodendrocyte development and axonal survival. Mutations in this gene cause Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Alternatively splicing results in multiple transcript variants, including the DM20 splice variant. [provided by RefSeq, Feb 2015]

Canonical amino-acid sequenceUniProt

277 residues, UniProt reviewed canonical sequence.

>P60201|PLP1
     1  MGLLECCARC LVGAPFASLV ATGLCFFGVA LFCGCGHEAL TGTEKLIETY FSKNYQDYEY
    61  LINVIHAFQY VIYGTASFFF LYGALLLAEG FYTTGAVRQI FGDYKTTICG KGLSATVTGG
   121  QKGRGSRGQH QAHSLERVCH CLGKWLGHPD KFVGITYALT VVWLLVFACS AVPVYIYFNT
   181  WTTCQSIAFP SKTSASIGSL CADARMYGVL PWNAFPGKVC GSNLLSICKT AEFQMTFHLF
   241  IAAFVGAAAT LVSLLTFMIA ATYNFAVLKL MGRGTKF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PLP1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

4

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

10,196 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PLP1.

Disease | AllUniProt

Conditions PLP1 is implicated in, by any mechanism.

• Leukodystrophy, hypomyelinating, 1 (HLD1) MIM:312080
• Spastic paraplegia 2, X-linked (SPG2) MIM:312920

Disease | GeneticClinVar

172 pathogenic / likely-pathogenic of 482 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pelizaeus-Merzbacher disease
• Hereditary spastic paraplegia 2
• Inborn genetic diseases
• Thyroid cancer, nonmedullary, 1
• Pelizaeus-Merzbacher disease, connatal

Disease | ImmuneIEDB

Conditions an epitope on PLP1 was assayed in.

• multiple sclerosis B and T cell
• amyotrophic lateral sclerosis B cell
• central nervous system disease T cell

ReferencesPubMed · IEDB

Publications for PLP1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.36

gnomAD pLI

0.93

gnomAD missense Z

2.04

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• astrocyte development
• axon development
• axon ensheathment
• central nervous system myelination
• chemical synaptic transmission
• inflammatory response
• long-chain fatty acid biosynthetic process
• positive regulation of gene expression
• substantia nigra development

Molecular functions

• identical protein binding
• structural constituent of myelin sheath
• structural molecule activity

Cellular components

• myelin sheath
• plasma membrane
• synapse

Protein domainsUniProt · Pfam · InterPro

• Myelin proteolipid protein PLP
• Myelin proteolipid protein PLP, conserved site
• Myelin proteolipid protein (PLP or lipophilin)

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Hereditary spastic paraplegia
• Leukodystrophy
• Lipoprotein
• Membrane
• Neurodegeneration
• Palmitate
• Phosphoprotein
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of PLP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MAL
• BCL2L13
• CREB3L1