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   27-MAR-2024, entry version 176.
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; 44.
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; 9606-ENSP00000357731; -.
DR   PeptideAtlas; P23490; -.
DR   ProteomicsDB; 54114; -.
DR   Pumba; P23490; -.
DR   Antibodypedia; 20374; 102 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   AGR; HGNC:6663; -.
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; GQAVQCQ; -.
DR   PathwayCommons; P23490; -.
DR   Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR   SignaLink; P23490; -.
DR   SIGNOR; P23490; -.
DR   BioGRID-ORCS; 4014; 18 hits in 1142 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 cell types or tissues.
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; LORICRIN; 1.
DR   PANTHER; PTHR39228:SF2; LORICRIN; 1.
DR   Pfam; PF15847; Loricrin; 1.
DR   PRINTS; PR01228; EGGSHELL.
DR   Genevisible; P23490; HS.
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
//