LORI_HUMAN
ID LORI_HUMAN Reviewed; 312 AA.
AC P23490; Q5T869; Q5XKF8;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Loricrin {ECO:0000305};
GN Name=LORICRIN {ECO:0000312|HGNC:HGNC:6663}; Synonyms=LOR, LRN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GLN-LYS CROSS-LINKS,
RP AND VARIANT SER-GLY-GLY-GLY-189 INS.
RC TISSUE=Foreskin;
RX PubMed=2007607; DOI=10.1016/s0021-9258(18)38163-8;
RA Hohl D., Mehrel T., Lichti U., Turner M.L., Roop D.R., Steinert P.M.;
RT "Characterization of human loricrin. Structure and function of a new class
RT of epidermal cell envelope proteins.";
RL J. Biol. Chem. 266:6626-6636(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-GLY-GLY-GLY-189 INS.
RX PubMed=1355480; DOI=10.1016/s0021-9258(19)37152-2;
RA Yoneda K., Hohl D., McBride O.W., Wang M., Cehrs K.U., Idler W.W.,
RA Steinert P.M.;
RT "The human loricrin gene.";
RL J. Biol. Chem. 267:18060-18066(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLY-29 AND
RP SER-GLY-GLY-GLY-189 INS.
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INVOLVEMENT IN VSI.
RX PubMed=9326323; DOI=10.1086/515518;
RA Ishida-Yamamoto A., McGrath J.A., Lam H., Iizuka H., Friedman R.A.,
RA Christiano A.M.;
RT "The molecular pathology of progressive symmetric erythrokeratoderma: a
RT frameshift mutation in the loricrin gene and perturbations in the cornified
RT cell envelope.";
RL Am. J. Hum. Genet. 61:581-589(1997).
RN [6]
RP GLN-LYS CROSS-LINKS WITH SPRR PROTEINS.
RX PubMed=10066784; DOI=10.1074/jbc.274.11.7226;
RA Candi E., Tarcsa E., Idler W.W., Kartasova T., Marekov L.N., Steinert P.M.;
RT "Transglutaminase cross-linking properties of the small proline-rich 1
RT family of cornified cell envelope proteins. Integration with loricrin.";
RL J. Biol. Chem. 274:7226-7237(1999).
RN [7]
RP INVOLVEMENT IN VSI.
RX PubMed=12072018; DOI=10.1046/j.1365-2230.2002.01031.x;
RA O'Driscoll J., Muston G.C., McGrath J.A., Lam H.M., Ashworth J.,
RA Christiano A.M.;
RT "A recurrent mutation in the loricrin gene underlies the ichthyotic variant
RT of Vohwinkel syndrome.";
RL Clin. Exp. Dermatol. 27:243-246(2002).
RN [8]
RP INVOLVEMENT IN VSI.
RX PubMed=12615358; DOI=10.1016/s0923-1811(02)00143-3;
RA Ishida-Yamamoto A.;
RT "Loricrin keratoderma: a novel disease entity characterized by nuclear
RT accumulation of mutant loricrin.";
RL J. Dermatol. Sci. 31:3-8(2003).
CC -!- FUNCTION: Major keratinocyte cell envelope protein.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleoplasm.
CC -!- PTM: Substrate of transglutaminases. Some glutamines and lysines are
CC cross-linked to other loricrin molecules and to SPRRs proteins.
CC -!- PTM: Contains inter- or intramolecular disulfide-bonds. {ECO:0000305}.
CC -!- DISEASE: Vohwinkel syndrome with ichthyosis (VSI) [MIM:604117]: A
CC variant form of Vohwinkel syndrome without hearing loss and associated
CC with ichthyosiform dermatosis. Clinical features include palmoplantar
CC keratoderma, pseudoainhum and ichthyosis. Compact hyperkeratosis with
CC round retained nuclei and hypergranulosis is observed on skin biopsies.
CC {ECO:0000269|PubMed:12072018, ECO:0000269|PubMed:12615358,
CC ECO:0000269|PubMed:9326323}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; M61120; AAA36180.1; -; mRNA.
DR EMBL; M94077; AAA36181.1; -; Genomic_DNA.
DR EMBL; AL161636; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034690; AAH34690.1; -; mRNA.
DR EMBL; BC108290; AAI08291.1; -; mRNA.
DR CCDS; CCDS30870.1; -.
DR PIR; A38743; A38743.
DR RefSeq; NP_000418.2; NM_000427.2.
DR AlphaFoldDB; P23490; -.
DR BioGRID; 110198; 39.
DR IntAct; P23490; 7.
DR MINT; P23490; -.
DR STRING; 9606.ENSP00000357731; -.
DR GlyGen; P23490; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P23490; -.
DR PhosphoSitePlus; P23490; -.
DR BioMuta; LOR; -.
DR DMDM; 215274015; -.
DR MassIVE; P23490; -.
DR PaxDb; P23490; -.
DR PeptideAtlas; P23490; -.
DR PRIDE; P23490; -.
DR ProteomicsDB; 54114; -.
DR Antibodypedia; 20374; 83 antibodies from 25 providers.
DR DNASU; 4014; -.
DR Ensembl; ENST00000368742.4; ENSP00000357731.3; ENSG00000203782.6.
DR GeneID; 4014; -.
DR KEGG; hsa:4014; -.
DR MANE-Select; ENST00000368742.4; ENSP00000357731.3; NM_000427.3; NP_000418.2.
DR UCSC; uc001fbm.4; human.
DR CTD; 4014; -.
DR DisGeNET; 4014; -.
DR GeneCards; LORICRIN; -.
DR HGNC; HGNC:6663; LORICRIN.
DR HPA; ENSG00000203782; Tissue enriched (skin).
DR MalaCards; LORICRIN; -.
DR MIM; 152445; gene.
DR MIM; 604117; phenotype.
DR neXtProt; NX_P23490; -.
DR OpenTargets; ENSG00000203782; -.
DR Orphanet; 79395; Keratoderma hereditarium mutilans with ichthyosis.
DR Orphanet; 316; Progressive symmetric erythrokeratodermia.
DR VEuPathDB; HostDB:ENSG00000203782; -.
DR eggNOG; ENOG502RU07; Eukaryota.
DR GeneTree; ENSGT01050000248066; -.
DR HOGENOM; CLU_891260_0_0_1; -.
DR InParanoid; P23490; -.
DR OMA; FKTAQYL; -.
DR OrthoDB; 48717at2759; -.
DR PathwayCommons; P23490; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P23490; -.
DR SIGNOR; P23490; -.
DR BioGRID-ORCS; 4014; 13 hits in 1068 CRISPR screens.
DR ChiTaRS; LOR; human.
DR GeneWiki; Loricrin; -.
DR GenomeRNAi; 4014; -.
DR Pharos; P23490; Tbio.
DR PRO; PR:P23490; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P23490; protein.
DR Bgee; ENSG00000203782; Expressed in upper arm skin and 90 other tissues.
DR Genevisible; P23490; HS.
DR GO; GO:0001533; C:cornified envelope; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0030280; F:structural constituent of skin epidermis; IDA:CAFA.
DR GO; GO:0031424; P:keratinization; IEA:UniProtKB-KW.
DR GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB.
DR GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB.
DR InterPro; IPR031700; Loricrin.
DR PANTHER; PTHR39228; PTHR39228; 2.
DR Pfam; PF15847; Loricrin; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Direct protein sequencing; Disulfide bond; Ichthyosis;
KW Isopeptide bond; Keratinization; Nucleus; Palmoplantar keratoderma;
KW Reference proteome; Repeat.
FT CHAIN 1..312
FT /note="Loricrin"
FT /id="PRO_0000084458"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..312
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 89
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-154); alternate"
FT /evidence="ECO:0000269|PubMed:10066784"
FT CROSSLNK 89
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-216); alternate"
FT /evidence="ECO:0000269|PubMed:10066784"
FT CROSSLNK 154
FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT with K-89)"
FT /evidence="ECO:0000269|PubMed:10066784"
FT CROSSLNK 212
FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT with K-312)"
FT /evidence="ECO:0000269|PubMed:10066784"
FT CROSSLNK 213
FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT with K-312)"
FT /evidence="ECO:0000269|PubMed:10066784"
FT CROSSLNK 216
FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT with K-89)"
FT /evidence="ECO:0000269|PubMed:10066784"
FT CROSSLNK 312
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-212); alternate"
FT /evidence="ECO:0000269|PubMed:10066784"
FT CROSSLNK 312
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-213); alternate"
FT /evidence="ECO:0000269|PubMed:10066784"
FT VARIANT 29
FT /note="S -> G (in dbSNP:rs6661601)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047712"
FT VARIANT 189
FT /note="Y -> YSGGG (in dbSNP:rs11275959)"
FT /evidence="ECO:0000269|PubMed:1355480,
FT ECO:0000269|PubMed:2007607"
FT /id="VAR_065891"
FT VARIANT 285
FT /note="S -> F (in dbSNP:rs56816110)"
FT /id="VAR_061676"
FT CONFLICT 29
FT /note="S -> T (in Ref. 1; AAA36180, 2; AAA36181 and 4;
FT AAH34690/AAI08291)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 312 AA; 25761 MW; A64248C3E4FD698E CRC64;
MSYQKKQPTP QPPVDCVKTS GGGGGGGGSG GGGCGFFGGG GSGGGSSGSG CGYSGGGGYS
GGGCGGGSSG GGGGGGIGGC GGGSGGSVKY SGGGGSSGGG SGCFSSGGGG SGCFSSGGGG
SSGGGSGCFS SGGGGSSGGG SGCFSSGGGG FSGQAVQCQS YGGVSSGGSS GGGSGCFSSG
GGGGSVCGYS GGGSGCGGGS SGGSGSGYVS SQQVTQTSCA PQPSYGGGSS GGGGSGGSGC
FSSGGGGGSS GCGGGSSGIG SGCIISGGGS VCGGGSSGGG GGGSSVGGSG SGKGVPICHQ
TQQKQAPTWP SK
