Mlph melanophilin [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mlphprovided by MGI
Official Full Name: melanophilinprovided by MGI
Primary source: MGI:MGI:2176380
See related: Ensembl:ENSMUSG00000026303 AllianceGenome:MGI:2176380
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: ln; l1Rk3; Slac-2a; D1Wsu84e; l(1)-3Rk; 2210418F23Rik; 5031433I09Rik
Summary: Enables cytoskeletal protein binding activity and small GTPase binding activity. Acts upstream of or within melanocyte differentiation; melanosome localization; and protein targeting. Located in cytoskeleton and melanosome. Part of unconventional myosin complex. Is expressed in several structures, including genitourinary system; gut; liver; lung; and spleen. Human ortholog(s) of this gene implicated in Griscelli syndrome type 3. Orthologous to human MLPH (melanophilin). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in stomach adult (RPKM 29.6), colon adult (RPKM 16.0) and 9 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 D; 1 45.73 cM

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (90842750..90878864)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (90915024..90951142)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Regulation of Melanophilin (Mlph) gene expression by the glucocorticoid receptor (GR).
Title: Regulation of Melanophilin (Mlph) gene expression by the glucocorticoid receptor (GR).
propose that Rab36 stimulates RILPL2 to interact with the myosin-5a GTD; this interaction then induces exposure of the melanophilin-binding site in the GTD, enabling melanophilin to interact with the GTD and activate myosin-5a motor activity
Title: The cargo adaptor proteins RILPL2 and melanophilin co-regulate myosin-5a motor activity.
When actin and microtubules were present simultaneously, melanophilin's phosphorylation state enforced track selection of the Rab27a/melanophilin/myosin Va transport complex.
Title: Myosin Va's adaptor protein melanophilin enforces track selection on the microtubule and actin networks in vitro.
The results showed that Rab27A(Q78L) is unable to localize on mature melanosomes and that its inhibitory activity on melanosome transport is completely dependent on its binding to the Rab27A effector Slac2-a/melanophilin.
Title: The GTPase-deficient Rab27A(Q78L) mutant inhibits melanosome transport in melanocytes through trapping of Rab27A effector protein Slac2-a/melanophilin in their cytosol: development of a novel melanosome-targetinG tag.
Data show at the single-molecule level that melanophilin (Mlph) increases the number of processively moving myoVa motors by 17-fold.
Title: More than just a cargo adapter, melanophilin prolongs and slows processive runs of myosin Va.
Data suggest that Rab27a and Rab27b regulate distinct steps in the bone marrow-derived mast cells (BMMC) degranulation pathway, with Rab27a/Mlph/MyoVa regulating cortical actin stability upstream of Rab27a/b/Munc13-4-dependent granule exocytosis.
Title: Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion.
structural basis for the exclusive association of Slac2-a with the Rab27 subfamily.
Title: Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases.
Data suggest that Mlph is targeted to and/or stabilised on melanosomes by Rab27a, and then recruits MyoVa, which provides additional stability to the complex and allows melanosomes to transfer from MT to actin-based transport.
Title: Rab27a and MyoVa are the primary Mlph interactors regulating melanosome transport in melanocytes.
The transcript levels of melanophilin, a protein involved in vesicular trafficking in melanocytes, are rapidly increased by aldosterone in cortical collecting duct cells
Title: Melanophilin, a novel aldosterone-induced gene in mouse cortical collecting duct cells.
analysis of the minimal myosin Va binding site within an intrinsically unstructured domain of melanophilin
Title: Identification of a minimal myosin Va binding site within an intrinsically unstructured domain of melanophilin.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Spontaneous (1)
Chemically induced (ENU) (2)
Endonuclease-mediated (3)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW228792 (e-PCR)
- UniSTS:178435

Mlph (e-PCR), detects polymorphism
- UniSTS:259187

D1Wsu84e (e-PCR), detects polymorphism
- UniSTS:142286

PMC56945P1 (e-PCR)
- UniSTS:273360

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables actin binding	IBA Inferred from Biological aspect of Ancestor more info
enables actin binding	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables microtubule plus-end binding	IDA Inferred from Direct Assay more info	PubMed
enables microtubule plus-end binding	IPI Inferred from Physical Interaction more info	PubMed
enables molecular adaptor activity	EXP Inferred from Experiment more info	PubMed
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables myosin V binding	IPI Inferred from Physical Interaction more info	PubMed
enables myosin binding	IBA Inferred from Biological aspect of Ancestor more info
enables myosin binding	IDA Inferred from Direct Assay more info	PubMed
enables myosin binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	ISO Inferred from Sequence Orthology more info
enables small GTPase binding	IDA Inferred from Direct Assay more info	PubMed
enables small GTPase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in intracellular protein transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within melanocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within melanosome localization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within pigmentation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein targeting	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in actin cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
is_active_in cortical actin cytoskeleton	IBA Inferred from Biological aspect of Ancestor more info
located_in cortical actin cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in melanosome	IDA Inferred from Direct Assay more info	PubMed
located_in melanosome	TAS Traceable Author Statement more info	PubMed
located_in microtubule organizing center	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in stress fiber	IDA Inferred from Direct Assay more info	PubMed
part_of unconventional myosin complex	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: melanophilin

Names: exophilin-3; leaden protein; slaC2-a; slp homolog lacking C2 domains a; synaptotagmin-like protein 2a

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_053015.3 → NP_443748.2 melanophilin

See identical proteins and their annotated locations for NP_443748.2

Status: VALIDATED

Source sequence(s)

AC118682, AK019883, AK148274

Consensus CDS

CCDS15155.1

UniProtKB/TrEMBL

A0A0R4J075, B9EKA5

Related

ENSMUSP00000027528.7, ENSMUST00000027528.7

Conserved Domains (2) summary

pfam02318
Location:8 → 125

FYVE_2; FYVE-type zinc finger

pfam04698
Location:445 → 497

Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000067.7 Reference GRCm39 C57BL/6J

Range

90842750..90878864

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006529231.5 → XP_006529294.1 melanophilin isoform X1

UniProtKB/TrEMBL

B9EKA5

Conserved Domains (2) summary

pfam02318
Location:8 → 125

FYVE_2; FYVE-type zinc finger

pfam04698
Location:444 → 496

Rab_eff_C; Rab effector MyRIP/melanophilin C-terminus