Property Summary

NCBI Gene PubMed Count 39
PubMed Score 25.81
PubTator Score 30.19

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (2)

Disease Target Count P-value
psoriasis 6685 5.5e-25
Disease Target Count Z-score Confidence
Blepharitis 5 4.575 2.3
Dry eye syndrome 14 3.973 2.0
Dacryoadenitis 7 3.308 1.7

Synonym

Accession Q9GZZ8
Symbols

Gene

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

Pathway (1)

Protein-protein Interaction (9)

Gene RIF (39)

PMID Text
26670139 cytoprotective effect of lacritin is mediated through Cyclooxygenase-2 (COX-2).
24942736 the C terminus of lacritin is multifunctional by dose and proteolytic processing and appears to play a key role in the innate protection of the eye
23769845 Genomic analysis expands the number of predicted lacritin orthologs, and suggests that secondary structure may be largely conserved. All currently known tear proteins predicted to be extracellular by GEO are assembled, and functions summarized.
23748026 Lacritin is a component of vampire bat saliva, as detected by mass spectrometry.
23640897 Lacritin rapidly and transiently accelerates autophagy to rid stressed cells of aggregated proteins. Lacritin also restores oxidative phosphorylation. LC3-II, in the absence of autophagic inhibitor, decreases as a consequence of rapidly increased flux.
23504321 Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity.
23482462 Lacritin stimulates tear protein secretion from lacrimal acinar cells stressed with inflammatory cytokines, however under the same conditions carbachol is completely ineffective. Inflammatory cytokines are elevated in dry eye, the most common eye disease. The implication is that topical lacritin might be an effective therapeutic for dry eye.
23425695 Tissue transglutaminase promotes crosslinking of lacritin between K82 or K85 and Q106 - the latter residing in the SDC1 binding domain of lacritin necessary for cell targeting, thus inactivating lacritin. Tissue transglutaminase is thought to be upregulated in dry eye, the most common eye disease.
23422824 Lacritin protein yields were improved primarily by hydrophobic or salt bridge mutagenesis and less so by elimination of rare codons.
23308132 Lacritin is 10-fold less in tears from individuals suffering from fungal keratitis, and is barely detectable in the initial stage of infection by Fusarium solani. Fungal keratitis accounts for half of all corneal ulcers in Africa and India.
23272196 Study involving 129 dry eye disease patients and 73 healthy controls, revealing significantly less tear lacritin in 95% of patients. Lacritin was one of seven proteins downregulated
22956620 Lacritin mRNA is the 24st most abundant in the lacrimal gland of Wolfring. Lacritin protein is detected by immunofluorescence.
22918641 A direct ELISA was established to estimate lacritin levels in tears. An ELISA estimate of 4.2 ng lacritin per 100 ng total tear protein did not vary significantly among individuals of different ages (18 - 52 years), or gender.
22871838 Horse lacritin is 45% identical to human, and shares a predicted amphipathic alpha helix important for cell targeting.
22736608 iTRAQ analysis suggests that lacritin is selectively deficient in tears of patients with aqueous deficient dry eye.
20375347 Monkey lacrimal acinar cells release lacritin upon carbachol stimulation. Pro-secretory signaling involves PKC and calcium, but not MAPK.
19770725 Lacritin was found to be decreased in tears of patients with contact lens related dry eye.
19714880 In tears of patients with climatic droplet keratopathy, N-linked glycosylation of lacritin is decreased, although the quantity of lacritin is unaltered.
18334948 Lacritin from tears is deposited on all contact lenses tested, and one of 19 tear proteins identified.
17850790 Lacritin was detected in monkey tear fluid. Among monkey ocular tissues, lacritin mRNA is highly expressed highly in lacrimal gland, somewhat less so in conjunctiva and meibomian gland, and slightly in corneal epithelium.
16982797 Heparanase cleavage of SDC1 heparan sulfate chains is required for lacritin binding. This mechanism therefore forms a novel off/on switch for lacritin-dependent mitogenesis.
16982797 Lacritin binds a form of SDC1 that lacks or contains short heparan sulfate chains, as revealed by gel filtration of chemically cleaved chains. Also by binding studies with FGF2 purified SDC1 with or without heparitinase digestion.
16982797 Lacritin mitogenesis and COX2 expression is abrogated when SDC1 (but not SDC2) is depleted by siRNA. Similarly siRNA depletion of HPSE1 (but not HPSE2) knocks out lacritin mitogenesis and can be rescued by exogenous HPSE1.
16982797 Lacritin binds human SDC1, but not human SDC2 or SDC4. Lacritin C-5, C-10, N-15, N-24, but not C-25 binds SDC1. C-15 weakly binds. Thus the C-terminal mitogenic and SDC1 binding domains appear to be the same.
16923831 Lacritin-dependent mitogenesis is abrogated by siRNA depletion of NFATC1, mTOR and STIM1, but not TRPC1. Also cyclosporin and rapamycin inhibit. This same pattern is observed in affect on lacritin-stimulated COX2 mRNA expression.
16923831 Lacritin signaling drives the formation of a Golgi PKCalpha/PLD1/PLCgamma2 complex.
16923831 Lacritin calcium signaling is inhibited by pertussis toxin, U73122 and Go 6976.
16923831 Lacritin displays restricted cell target specificity in a screen of 17 different cell types. It targets rat lacrimal acinar, human corneal epithelial (HCE-T), human salivary ductal (HSG) and human embryonal kidney cells (HEK293).
16923831 Lacritin's C-terminus is required for mitogenesis. C-10 is fully active, C-15 has approximately half the activity and C-20 is inactive.
16923831 Lacritin's signaling and mitogenic responses are biphasic (1- 10 nM dose optimum). Its biphasic signaling includes rapid PKCalpha dephosphorylation, and PLD1, calcineurin and NFATC1 activation.
16865190 Lacritin is detected in human tears by mass spectometry from patients with pterygium.
16488965 Lacritin is detected by MS in meibomian gland secretions.
15952718 Lacritin is one of nine tear proteins downregulated in patients suffering from blepharitis, or inflammation of the eyelid often associated with dry eye.
15851553 Lacritin is the sixth most common transcript in the human lacrimal gland based on EST sequencing, and is one of twenty-nine 'lacrimal preferred' genes.
14574570 expressed in human breast tumors, breast cancer cell lines, and normal breast
12613904 Lacritin gene maps near but not within triple A syndome region. Alacrimia in triple a syndrome not due to mutation in lacritin gene.
11419941 Lacritin binds several basment membrane components (collagen IV, nidogen, fibronectin, laminin-1). Also vitronectin, but not collagen I or heparin. Yet it is secreted apically and possibly may form non-covalent complexes with tear fibronectin.
11419941 Lacritin is detected in human tears and promotes tear secretion in vitro when added to rat lacrimal acinar cells via a pathway apparently independent of the M3 receptor. It is mitogenic at low ng/ml levels for salivary ductal cells.
11419941 Tissue microarray of seventy-five different human tissues, including mammary gland, detected expression only in lacrimal acinar and salivary ductal cells. Thyroid immunostaining was equivocal. These data agree with Clonetech RNA dot blot analysis.

AA Sequence

MKFTTLLFLAAVAGALVYAEDASSDSTGADPAQEAGTSKPNEEISGPAEPASPPETTTTAQETSAAAVQG      1 - 70
TAKVTSSRQELNPLKSIVEKSILLTEQALAKAGKGMHGGVPGGKQFIENGSEFAQKLLKKFSLLKPWA       71 - 138
//

Text Mined References (40)

PMID Year Title
26670139 2015 Lacritin Salvages Human Corneal Epithelial Cells from Lipopolysaccharide Induced Cell Death.
25946035 2015 Human Basal Tear Peptidome Characterization by CID, HCD, and ETD Followed by in Silico and in Vitro Analyses for Antimicrobial Peptide Identification.
25530855 2014 Lacritin-mediated regeneration of the corneal epithelia by protein polymer nanoparticles.
25481446 2015 A thermo-responsive protein treatment for dry eyes.
25034600 2014 Topical administration of lacritin is a novel therapy for aqueous-deficient dry eye disease.
24942736 2014 A cleavage-potentiated fragment of tear lacritin is bactericidal.
23769845 2013 Lacritin and the tear proteome as natural replacement therapy for dry eye.
23748026 2013 Dracula's children: molecular evolution of vampire bat venom.
23640897 2013 Lacritin rescues stressed epithelia via rapid forkhead box O3 (FOXO3)-associated autophagy that restores metabolism.
23580065 2013 Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naïve to therapy.
23504321 2013 Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity.
23482462 2013 Lacritin-induced secretion of tear proteins from cultured monkey lacrimal acinar cells.
23425695 2013 Tissue transglutaminase is a negative regulator of monomeric lacritin bioactivity.
23422824 2013 Conserved regional 3' grouping of rare codons in the coding sequence of ocular prosecretory mitogen lacritin.
23308132 2013 Pathogen induced changes in the protein profile of human tears from Fusarium keratitis patients.
23272196 2012 Lacrimal proline rich 4 (LPRR4) protein in the tear fluid is a potential biomarker of dry eye syndrome.
22956620 2012 Gene expression in human accessory lacrimal glands of Wolfring.
22918641 2012 Tear lacritin levels by age, sex, and time of day in healthy adults.
22871838 2012 Detection of prosecretory mitogen lacritin in nonprimate tears primarily as a C-terminal-like fragment.
22736608 2012 iTRAQ quantitative proteomics in the analysis of tears in dry eye patients.
22664934 2012 Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach.
20375347 2010 Mechanism for carbachol-induced secretion of lacritin in cultured monkey lacrimal acinar cells.
19770725 2009 Mass spectrometry-based proteomic analyses in contact lens-related dry eye.
19714880 2009 Quantitative analysis of N-linked glycoproteins in tear fluid of climatic droplet keratopathy by glycopeptide capture and iTRAQ.
18840430 2009 Lacritin and other new proteins of the lacrimal functional unit.
18334948 2008 Mass spectrometry-based proteomic analyses of contact lens deposition.
17850790 2007 Establishment of an appropriate animal model for lacritin studies: cloning and characterization of lacritin in monkey eyes.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
16982797 2006 Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin.
16923831 2006 Restricted epithelial proliferation by lacritin via PKCalpha-dependent NFAT and mTOR pathways.
16865190 2006 Characterisation of human tear proteins using high-resolution mass spectrometry.
16740002 2006 Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry.
16488965 2006 Proteomic analysis of human meibomian gland secretions.
15952718 Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis.
15851553 2005 The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14574570 2003 Expression of a novel lacrimal gland gene lacritin in human breast tissues.
12613904 2002 Genetic separation of the human lacritin gene ("LACRT") and triple A (Allgrove) syndrome on 12q13.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11419941 2001 cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland.