Affinage

MLPH

Melanophilin · UniProt Q9BV36

Length
600 aa
Mass
65.9 kDa
Annotated
2026-06-10
100 papers in source corpus 1 papers cited in narrative 1 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MLPH (melanophilin), the human ortholog of the murine leaden (ln) gene, functions in the pathway controlling dendritic melanocyte morphology and pigment granule distribution (PMID:3410303). Loss of ln function produces adendritic melanocytes and a diluted coat color, and this phenotype is partially suppressed by the unlinked dilute suppressor gene dsu, establishing genetic epistasis that places ln downstream within a melanocyte morphology pathway (PMID:3410303). Beyond this in vivo genetic placement, no molecular mechanism, partners, or biochemical activity for MLPH has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 1988 Medium

    Established that the leaden gene controls melanocyte dendricity and acts in a defined genetic pathway with the dilute suppressor locus, rather than affecting pigment synthesis alone.

    Evidence Genetic epistasis and coat-color suppression assays with melanocyte morphology examination in single- and double-mutant mice, plus linkage mapping

    PMID:3410303

    Open questions at the time
    • No molecular identity of the leaden gene product or its biochemical activity determined
    • Mechanism by which dsu suppresses the ln phenotype unknown
    • No direct evidence linking the murine phenotype to human MLPH function

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular function, binding partners, subcellular localization, and biochemical mechanism by which MLPH controls melanocyte morphology and pigment granule distribution remain uncharacterized in the available corpus.
  • No protein-level mechanism, interactors, or localization data in the timeline
  • No structural or biochemical characterization
  • Relationship between ln and dsu gene products at the molecular level unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 The murine leaden (ln) gene (ortholog of human MLPH/melanophilin) controls melanocyte morphology; ln/ln melanocytes are adendritic, and the dilute suppressor gene dsu can partially restore normal dendritic melanocyte morphology in ln/ln mice, indicating genetic epistasis between dsu and ln in the melanocyte morphology pathway. Genetic mapping placed dsu and ln on chromosome 1, approximately 9 cM apart. Genetic epistasis analysis, coat-color suppression assay, melanocyte morphology examination in double-mutant mice, genetic linkage mapping Genetics Medium 3410303

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1984 Two new monoclonal antibodies (LN-1, LN-2) reactive in B5 formalin-fixed, paraffin-embedded tissues with follicular center and mantle zone human B lymphocytes and derived tumors. Journal of immunology (Baltimore, Md. : 1950) 283 6376628
2006 Activation and cross-talk between Akt, NF-kappaB, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78. The Journal of biological chemistry 228 16543232
2005 Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK. The Journal of biological chemistry 152 15908432
2020 Retrograde migration supplies resident memory T cells to lung-draining LN after influenza infection. The Journal of experimental medicine 115 32568362
2007 Synthesis, crystal structure and DNA-binding studies of the Ln(III) complex with 6-hydroxychromone-3-carbaldehyde benzoyl hydrazone. Journal of inorganic biochemistry 114 17692381
2012 Ln is a key regulator of leaflet shape and number of seeds per pod in soybean. The Plant cell 93 23243125
2009 Isolation of antipodal (-)-versicolamide B and notoamides L-N from a marine-derived Aspergillus sp. Organic letters 90 19281134
2020 Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration. Theranostics 89 32724468
1981 Characterization of an established human malignant glioma cell line: LN-18. Acta neuropathologica 85 7211194
2020 Ultrasensitive Fluorescent miRNA Biosensor Based on a "Sandwich" Oligonucleotide Hybridization and Fluorescence Resonance Energy Transfer Process Using an Ln(III)-MOF and Ag Nanoparticles for Early Cancer Diagnosis: Application of Central Composite Design. ACS applied materials & interfaces 77 32207913
1997 LN-2 (CD74). A marker to distinguish atypical fibroxanthoma from malignant fibrous histiocytoma. Cancer 74 9179057
2006 Equilibrium and formation/dissociation kinetics of some Ln(III)PCTA complexes. Inorganic chemistry 67 17083226
2013 Contribution of the PI3K/MMPs/Ln-5γ2 and EphA2/FAK/Paxillin signaling pathways to tumor growth and vasculogenic mimicry of gallbladder carcinomas. International journal of oncology 63 23588386
2012 Fluoridated HAp:Ln3+ (Ln = Eu or Tb) nanoparticles for cell-imaging. Nanoscale 63 23076865
2000 Is ferromagnetism an intrinsic property of the CuII/GdIII couple? 2. Structures and magnetic properties of novel trinuclear complexes with mu-phenolato-mu-oximato (Cu-Ln-Cu) cores (Ln = La, Ce, Gd). Inorganic chemistry 63 11151500
2008 A two-step model for Langerhans cell migration to skin-draining LN. European journal of immunology 57 18991275
2015 Phenylbutyrate-a pan-HDAC inhibitor-suppresses proliferation of glioblastoma LN-229 cell line. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 56 26260271
1988 The murine dilute suppressor gene dsu suppresses the coat-color phenotype of three pigment mutations that alter melanocyte morphology, d, ash and ln. Genetics 56 3410303
1988 Age- and sex-specific pediatric reference intervals: study design and methods illustrated by measurement of serum proteins with the Behring LN Nephelometer. Clinical chemistry 55 3261214
2022 Safety and Efficacy of Belimumab in Patients with Lupus Nephritis: Open-Label Extension of BLISS-LN Study. Clinical journal of the American Society of Nephrology : CJASN 54 36302567
2008 A single point mutation in the LN domain of LAMA2 causes muscular dystrophy and peripheral amyelination. Journal of cell science 51 18430779
2006 Heterobimetallic Zn(II)-Ln(III) phenylene-bridged schiff base complexes, computational studies, and evidence for singlet energy transfer as the main pathway in the sensitization of near-infrared Nd3+ luminescence. Inorganic chemistry 51 17083231
2012 Interleukin-1β and transforming growth factor-β cooperate to induce neurosphere formation and increase tumorigenicity of adherent LN-229 glioma cells. Stem cell research & therapy 48 22330721
2006 Genetic similarities and differences between lobular in situ neoplasia (LN) and invasive lobular carcinoma of the breast. Virchows Archiv : an international journal of pathology 48 16612623
2002 Unequivocal synthetic pathway to heterodinuclear (4f,4f') complexes: magnetic study of relevant (Ln(III), Gd(III)) and (Gd(III), Ln(III)) complexes. Chemistry (Weinheim an der Bergstrasse, Germany) 48 12203324
2014 Norcantharidin inhibits tumor growth and vasculogenic mimicry of human gallbladder carcinomas by suppression of the PI3-K/MMPs/Ln-5γ2 signaling pathway. BMC cancer 47 24628713
2006 Synthesis, characterization, and DNA-binding properties of the Ln(III) complexes with 6-hydroxy chromone-3-carbaldehyde-(2'-hydroxy) benzoyl hydrazone. Bioorganic & medicinal chemistry 46 16781158
2014 Distinct functions of the laminin β LN domain and collagen IV during cardiac extracellular matrix formation and stabilization of alary muscle attachments revealed by EMS mutagenesis in Drosophila. BMC developmental biology 45 24935095
2010 Para-derivatized pybox ligands as sensitizers in highly luminescent Ln(III) complexes. Inorganic chemistry 44 20809608
2005 Syntheses, structures, and magnetic properties of diphenoxo-bridged M(II)Ln(III) complexes derived from N,N'-ethylenebis(3-ethoxysalicylaldiimine) (M = Cu or Ni; Ln = Ce-Yb): observation of surprisingly strong exchange interactions. Inorganic chemistry 43 15877435
2009 [Ln(DPA)(3)](3-) is a convenient paramagnetic shift reagent for protein NMR studies. Journal of the American Chemical Society 42 19585996
2011 Molecular and Biological Characterization of Chinese Sacbrood Virus LN Isolate. Comparative and functional genomics 41 21527980
2008 Synthesis, crystal structure, antioxidant activities and DNA-binding studies of the Ln(III) complexes with 7-methoxychromone-3-carbaldehyde-(4'-hydroxy) benzoyl hydrazone. European journal of medicinal chemistry 39 19038478
2017 Association of LN Evaluation with Survival in Women Aged 70 Years or Older With Clinically Node-Negative Hormone Receptor Positive Breast Cancer. Annals of surgical oncology 38 28766195
1989 Astrocytes and microglia in human brain share an epitope recognized by a B-lymphocyte-specific monoclonal antibody (LN-1). The American journal of pathology 38 2476034
2010 Syntheses, crystal and electronic structures, and physical properties of quaternary semiconductors: Ln2Mn3Sb4S12 (Ln = Pr, Nd, Sm, Gd). Inorganic chemistry 37 20509606
1988 Antigenic phenotype of Langerhans cell histiocytosis: an immunohistochemical study demonstrating the value of LN-2, LN-3, and vimentin. Human pathology 37 2973428
2011 Stability and structural evolution of Ce(IV)(1-x)Ln(III)(x)O(2-x/2) solid solutions: a coupled μ-Raman/XRD approach. Inorganic chemistry 35 21714501
2009 Synthesis, characterization, DNA binding properties and antioxidant activity of Ln(III) complexes with hesperetin-4-one-(benzoyl) hydrazone. European journal of medicinal chemistry 33 19615791
1988 Immunohistochemical characterization of two new monoclonal antibodies (LN-4, LN-5) reactive with human macrophage subsets and derived malignancies in B5-fixed, paraffin-embedded tissues. Blood 33 3281719
2016 LN-1-255, a penicillanic acid sulfone able to inhibit the class D carbapenemase OXA-48. The Journal of antimicrobial chemotherapy 32 27125555
2017 Microsolvation of the pyrrole cation (Py+) with nonpolar and polar ligands: infrared spectra of Py+-Ln with L = Ar, N2, and H2O (n ≤ 3). Physical chemistry chemical physics : PCCP 31 28106189
2004 Potentiation of signal transduction mitogenesis and cellular proliferation upon binding of receptor-recognized forms of alpha2-macroglobulin to 1-LN prostate cancer cells. Cellular signalling 30 14709337
2014 Prediction of thyroid extracapsular extension with cervical lymph node metastases (ECE-LN) by CEUS and BRAF expression in papillary thyroid carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 24863948
2006 Diagnostic value of two reagent strips (Multistix 8 SG and Combur 2 LN) in cirrhotic patients with spontaneous bacterial peritonitis and symptomatic bacterascites. Gastroenterologie clinique et biologique 27 16633312
1993 Plasminogen activator and metalloprotease activities of Du-145, PC-3, and 1-LN-PC-3-1A human prostate tumors grown in nude mice: correlation with tumor invasive behavior. Cellular & molecular biology research 26 7951414
2020 MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori- induced gastric ulcer or progression to gastric cancer. Microbial pathogenesis 25 32795593
2012 A novel anti-tumor agent, Ln(III) 2-thioacetate benzothiazole induces anti-angiogenic effect and cell death in cancer cell lines. European journal of medicinal chemistry 25 22424613
2019 High in vitro and in vivo antitumor activities of Ln(III) complexes with mixed 5,7-dichloro-2-methyl-8-quinolinol and 4,4'-dimethyl-2,2'-bipyridyl chelating ligands. European journal of medicinal chemistry 24 30870791
2000 Selective upregulated expression of the alpha2-macroglobulin signaling receptor in highly metastatic 1-LN prostate carcinoma cells. Archives of biochemistry and biophysics 24 11097186
2002 Tissue factor is the receptor for plasminogen type 1 on 1-LN human prostate cancer cells. Blood 23 12036889
2014 Di-ethylhexylphthalate (DEHP) modulates cell invasion, migration and anchorage independent growth through targeting S100P in LN-229 glioblastoma cells. International journal of environmental research and public health 20 24821384
2005 Association of plasminogen with dipeptidyl peptidase IV and Na+/H+ exchanger isoform NHE3 regulates invasion of human 1-LN prostate tumor cells. The Journal of biological chemistry 20 15911629
2017 Confirmation of the pleiotropic control of leaflet shape and number of seeds per pod by the Ln gene in induced soybean mutants. Breeding science 19 29085246
2016 Correlative near-infrared light and cathodoluminescence microscopy using Y2O3:Ln, Yb (Ln = Tm, Er) nanophosphors for multiscale, multicolour bioimaging. Scientific reports 19 27185264
2007 Establishment and characterization of androgen-independent human prostate cancer cell lines, LN-REC4 and LNCaP-SF, from LNCaP. International journal of urology : official journal of the Japanese Urological Association 19 17430262
2023 Lanthanides as Calcium Mimetic Species in Calcium-Signaling/Buffering Proteins: The Effect of Lanthanide Type on the Ca2+/Ln3+ Competition. International journal of molecular sciences 18 37047269
2022 Curcumin piperidone derivatives induce anti-proliferative and anti-migratory effects in LN-18 human glioblastoma cells. Scientific reports 18 35907913
2016 Perovskite-Like Polar Lanthanide Formate Frameworks of [NH2NH3][Ln(HCOO)4] (Ln = Tb-Lu and Y): Synthesis, Structures, Magnetism, and Anisotropic Thermal Expansion. Inorganic chemistry 18 27366822
2011 Engineering [Ln(DPA)3] 3- binding sites in proteins: a widely applicable method for tagging proteins with lanthanide ions. Journal of biomolecular NMR 18 21786031
2001 Death receptor-independent cytochrome c release and caspase activation mediate thymidine kinase plus ganciclovir-mediated cytotoxicity in LN-18 and LN-229 human malignant glioma cells. Gene therapy 18 11313826
1982 Mode of action of LN 1643 (a triphenylbromoethylene antiestrogen): probable mediation by the estrogen receptor and high affinity metabolite. Biochemical pharmacology 18 7150347
2021 SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer. OncoTargets and therapy 17 34335030
2019 Multifunctional NaLnF4@MOF-Ln Nanocomposites with Dual-Mode Luminescence for Drug Delivery and Cell Imaging. Nanomaterials (Basel, Switzerland) 17 31500216
2015 Ln(3+)-doped hydroxyapatite nanocrystals: controllable synthesis and cell imaging. Physical chemistry chemical physics : PCCP 17 26190155
2014 (BMI)3LnCl6 crystals as models for the coordination environment of LnCl3 (Ln = Sm, Eu, Dy, Er, Yb) in 1-butyl-3-methylimidazolium chloride ionic-liquid solution. Inorganic chemistry 17 24849287
2012 Naphthomycins L-N, ansamycin antibiotics from Streptomyces sp. CS. Journal of natural products 17 22742732
2022 A novel regulatory complex mediated by Lanata (Ln) controls multicellular trichome formation in tomato. The New phytologist 16 36102042
2010 Syntheses, structures, and magnetic properties of diphenoxo-bridged Cu(II)Ln(III) and Ni(II)(low-spin)Ln(III) compounds derived from a compartmental ligand (Ln = Ce-Yb). Inorganic chemistry 16 20812685
2009 PFT-alpha inhibits antibody-induced activation of p53 and pro-apoptotic signaling in 1-LN prostate cancer cells. Biochemical and biophysical research communications 16 19913499
2007 Mature DC from skin and skin-draining LN retain the ability to acquire and efficiently present targeted antigen. European journal of immunology 16 17407099
2004 Cell surface adenosine deaminase binds and stimulates plasminogen activation on 1-LN human prostate cancer cells. The Journal of biological chemistry 16 15016824
2022 Ln2 (SeO3 )2 (SO4 )(H2 O)2 (Ln=Sm, Dy, Yb): A Mixed-Ligand Pathway to New Lanthanide(III) Multifunctional Materials Featuring Nonlinear Optical and Magnetic Anisotropy Properties. Angewandte Chemie (International ed. in English) 15 36194725
2016 High glucose regulates LN expression in human liver sinusoidal endothelial cells through ROS/integrin αvβ3 pathway. Environmental toxicology and pharmacology 15 26896612
2024 GC/MS and LC/MS serum metabolomic analysis of Chinese LN patients. Scientific reports 14 38233574
2021 LN Monocytes Limit DC-Poly I:C Induced Cytotoxic T Cell Response via IL-10 and Induction of Suppressor CD4 T Cells. Frontiers in immunology 14 34691085
2021 ln RNA LINC01234 promotes triple-negative breast cancer progression through regulating the miR-429/SYNJ1 axis. American journal of translational research 14 34786067
2009 Crystal structures, DNA-binding studies and antioxidant activities of the Ln(III) complexes with 7-methoxychromone- 3-carbaldehyde-isonicotinoyl hydrazone. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 14 19404747
2009 Homeostatic proliferation of naïve CD8+ T cells depends on CD62L/L-selectin-mediated homing to peripheral LN. European journal of immunology 14 19658092
2010 Grafting of peralkylated Ln(II)Al(III) heterobimetallic complexes onto periodic mesoporous silica KIT-6. Dalton transactions (Cambridge, England : 2003) 13 20683527
2008 Towards inert and preorganized d-block-containing receptors for trivalent lanthanides: the synthesis and characterization of triple-helical monometallic Os(II) and bimetallic Os(II)-Ln(III) complexes. Dalton transactions (Cambridge, England : 2003) 13 18615212
2001 Heteroleptic lanthanide compounds with chalcogenolate ligands: reduction of PhNNPh/PhEEPh (E = Se or Te) mixtures with Ln (Ln = Ho, Er, Tm, Yb). Thermolysis can give LnN or LnE. Inorganic chemistry 13 11195372
2023 Stabilization Of The CN3 5- Anion In Recoverable High-pressure Ln3 O2 (CN3 ) (Ln=La, Eu, Gd, Tb, Ho, Yb) Oxoguanidinates. Angewandte Chemie (International ed. in English) 12 37768278
2021 Na-Ln Heterometallic Coordination Polymers: Structure Modulation by Na+ Concentration and Efficient Detection to Tetracycline Antibiotics and 4-(Phenylazo)aniline. Inorganic chemistry 12 34015217
2016 Expression of Tim4 in Glioma and its Regulatory Role in LN-18 Glioma Cells. Medical science monitor : international medical journal of experimental and clinical research 12 26741116
2016 Targeted Stealth Polymer Capsules Encapsulating Ln3+-Doped LaVO4 Nanoparticles for Bioimaging Applications. ACS biomaterials science & engineering 12 33434986
2014 LaF3:Ln mesoporous spheres: controllable synthesis, tunable luminescence and application for dual-modal chemo-/photo-thermal therapy. Nanoscale 12 25359551
2019 Novel NIR LaGaO3:Cr3+,Ln3+ (Ln = Yb, Nd, Er) phosphors via energy transfer for C-Si-based solar cells. Dalton transactions (Cambridge, England : 2003) 11 31290880
2018 Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 11 30522103
2013 Polar and magnetic layered A-site and rock salt B-site-ordered NaLnFeWO6 (Ln = La, Nd) perovskites. Inorganic chemistry 11 24138134
2020 Mitochondria-localizing dicarbohydrazide Ln complexes and their mechanism of in vitro anticancer activity. Dalton transactions (Cambridge, England : 2003) 10 32175553
2020 CTRP13 attenuates the expression of LN and CAV-1 Induced by high glucose via CaMKKβ/AMPK pathway in rLSECs. Aging 10 32554851
2020 Development of Sentinel LN Imaging with a Combination of HAase Based on a Comprehensive Analysis of the Intra-lymphatic Kinetics of LPs. Molecular therapy : the journal of the American Society of Gene Therapy 10 32966771
2018 Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients. Oncotarget 10 29632639
2017 Ln polyoxocations: yttrium oxide solution speciation & solution deposited thin films. Dalton transactions (Cambridge, England : 2003) 10 28009880
2009 Synthesis, characterization and DNA-binding properties of Ln(III) complexes with 6-ethoxy chromone-3-carbaldehyde benzoyl hydrazone. Journal of fluorescence 10 19370403
2007 Synthesis, characterization, DNA-binding properties of the Ln(III) complexes with 6-hydroxy chromone-3-carbaldehyde-(4'-hydroxy) benzoyl hydrazone. Journal of fluorescence 10 18074203
2021 LN-Derived Fibroblastic Reticular Cells and Their Impact on T Cell Response-A Systematic Review. Cells 9 34068712
2019 Well-tuned white-light-emitting behaviours in multicenter-Ln polyoxometalate derivatives: A photoluminescence property and energy transfer pathway study. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 9 31252209
2014 Caspase-activated DNase is necessary and sufficient for oligonucleosomal DNA breakdown, but not for chromatin disassembly during caspase-dependent apoptosis of LN-18 glioblastoma cells. The Journal of biological chemistry 9 24838313

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