Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Small proline-rich protein 1 is the major component of the cell envelope of normal human oral keratinocytes.
Differentially expressed late constituents of the epidermal cornified envelope.
Characterization of human loricrin. Structure and function of a new class of epidermal cell envelope proteins.
-
Human loricrin is incorporated into the cornified cell envelope through N-epsilon-(gamma-glutamyl)lysine isodipeptide cross-links.
"Furthermore, we have isolated four peptides from purified human cell envelopes that contain recognizable loricrin sequences and which are cross-linked by the N epsilon-(gamma-glutamyl)lysine isodipeptide bond."
-
Loricrin is highly insoluble partly because of disulfide cross-linking.
"We show that unlike all other putative protein components of the cell envelope, loricrins are highly insoluble, due at least in part to cross-linking by disulfide bonds."
-
Isopeptide attachment to the cornified envelope explains loricrin's extraordinary insolubility and scarcity as a monomer in epidermal extracts.
"The presence of such bonds thus affords an explanation for the extraordinary insolubility of loricrin by cross-linking to the cell envelope and can also explain the low steady-state levels of monomeric loricrin in cytoskeletal extracts of epidermis."
The proteins elafin, filaggrin, keratin intermediate filaments, loricrin, and small proline-rich proteins 1 and 2 are isodipeptide cross-linked components of the human epidermal cornified cell envelope.
-
Loricrin is the dominant cross-linked protein in the outer portion of purified human epidermal cornified envelopes.
"Based on these data, most (94% molar mass) of the outer third of CE structure consists of intra- and interchain cross-linked loricrin, admixed with SPR1 and SPR2 proteins as bridging cross-links between loricrin."
-
Human envelope assembly includes loricrin cross-links to SPR proteins, elafin, keratins, and filaggrin.
"In addition, cross-links involving loricrin and keratins 1, 2e, and 10 or filaggrin were recovered in both levels."
Biochemical, structural, and transglutaminase substrate properties of human loricrin, the major epidermal cornified cell envelope protein.
-
Loricrin is a major cornified-envelope barrier protein in terminally differentiated epidermal keratinocytes.
"Loricrin is the major protein of the cornified cell envelope of terminally differentiated epidermal keratinocytes which functions as a physical barrier."
-
Epidermal transglutaminases 1, 2, and 3 use loricrin as a substrate, with TGase 3 favoring intrachain and TGase 1 favoring interchain cross-links.
"The transglutaminase (TGase) 1, 2, and 3 enzymes expressed during epidermal differentiation utilized loricrin in vitro as a complete substrate, but the types of cross-linking were different. The TGase 3 reaction favored certain lysines and glutamines by forming mostly intrachain cross-links, whereas TGase 1 formed mostly large oligomeric complexes by interchain cross-links involving different lysines and glutamines."
-
The in-vitro acceptor and donor residues closely match cross-link sites observed in vivo.
"Together, the glutamines and lysines used in vitro are almost identical to those seen in vivo."
Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein.
-
Loricrin-null mice show delayed embryonic skin-barrier formation.
"These mice showed a delay in the formation of the skin barrier in embryonic development."
-
Cornified envelopes from loricrin-null mice are more susceptible to mechanical stress.
"Isolated mutant CEs were more easily fragmented by sonication in vitro, indicating a greater susceptibility to mechanical stress."
-
Loricrin loss does not abolish steady-state epidermal permeability-barrier function in the knockout mice.
"Nevertheless, we did not detect impaired epidermal barrier function in these mice."
-
Increased expression of other envelope components is one mechanism that compensates for loricrin loss.
"At least one of the compensatory mechanisms preventing a more severe skin phenotype in newborn Lor(-/-) mice is an increase in the expression of other CE components, such as SPRRP2D and SPRRP2H, members of the family of "small proline rich proteins""
A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome.
-
A human LORICRIN frameshift disrupts the glycine- and glutamine/lysine-rich C-terminal region and is predicted to impair cornification.
"Sequencing of the loricrin gene revealed an insertion that shifts the translation frame of the C-terminal Gly- and Gln/Lys-rich domains, and is likely to impair cornification."
Transgenic mice expressing a mutant form of loricrin reveal the molecular basis of the skin diseases, Vohwinkel syndrome and progressive symmetric erythrokeratoderma.
-
A disease-like C-terminal mutant accumulates in keratinocyte nuclei and cytoplasm instead of the cornified envelope.
"Immunofluorescence and immunoelectron microscopy showed the mutant loricrin protein in the nucleus and cytoplasm of epidermal keratinocytes, but did not detect the protein in the cornified cell envelope."
-
Nuclear deposition of mutant loricrin interferes with late epidermal differentiation and produces a Vohwinkel-syndrome-like phenotype.
"Thus, deposition of the mutant protein in the nucleus appears to interfere with late stages of epidermal differentiation, resulting in a VS-like phenotype."
-
The mutant C terminus gains a nuclear localization signal, distinguishing toxic mutant behavior from normal loricrin function.
"Transfection experiments indicated that the COOH-terminal domain of the mutant loricrin contains a nuclear localization signal."
UniProt entry P23490 (LORI_HUMAN), Loricrin
-
UniProt describes loricrin as a major keratinocyte cell-envelope protein.
"Major keratinocyte cell envelope protein."
-
UniProt reports cytoplasmic and nucleoplasmic localization.
"Cytoplasm. Nucleus, nucleoplasm."
-
UniProt records loricrin as a transglutaminase substrate.
"Substrate of transglutaminases."
-
UniProt records glutamine-lysine cross-links to other loricrin molecules and SPRR proteins.
"Some glutamines and lysines are cross-linked to other loricrin molecules and to SPRRs proteins."
-
UniProt records intermolecular and intramolecular disulfide bonds.
"Contains inter- or intramolecular disulfide-bonds."
Lamellar bodies bind the early cornified envelope
Reinforcement of the Cornified Envelope
Late envelope proteins bind cornified envelope:CDSN
CDSN binds the cornified envelope
Plasma membrane resorption