ID   INVO_HUMAN              Reviewed;         585 AA.
AC   P07476; Q5T7P4;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   28-JUL-2009, sequence version 2.
DT   27-MAR-2024, entry version 199.
DE   RecName: Full=Involucrin;
GN   Name=IVL;
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 [GENOMIC DNA], AND VARIANTS GLN-227; SER-236 AND
RP   GLU-237.
RX   PubMed=2873896; DOI=10.1016/0092-8674(86)90884-6;
RA   Eckert R.L., Green H.;
RT   "Structure and evolution of the human involucrin gene.";
RL   Cell 46:583-589(1986).
RN   [2]
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLN-227; SER-236 AND
RP   GLU-237.
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   [4]
RP   PROTEIN SEQUENCE OF 281-290.
RC   TISSUE=Keratinocyte;
RX   PubMed=9115270; DOI=10.1074/jbc.272.18.12035;
RA   Robinson N.A., Lapic S., Welter J.F., Eckert R.L.;
RT   "S100A11, S100A10, annexin I, desmosomal proteins, small proline-rich
RT   proteins, plasminogen activator inhibitor-2, and involucrin are components
RT   of the cornified envelope of cultured human epidermal keratinocytes.";
RL   J. Biol. Chem. 272:12035-12046(1997).
RN   [5]
RP   STRUCTURAL STUDIES.
RX   PubMed=1601889; DOI=10.1016/s0021-9258(19)49829-3;
RA   Yaffe M.B., Beegen H., Eckert R.L.;
RT   "Biophysical characterization of involucrin reveals a molecule ideally
RT   suited to function as an intermolecular cross-bridge of the keratinocyte
RT   cornified envelope.";
RL   J. Biol. Chem. 267:12233-12238(1992).
RN   [6]
RP   GLN-LYS CROSS-LINK.
RX   PubMed=2461365; DOI=10.1016/s0021-9258(19)81327-3;
RA   Simon M., Green H.;
RT   "The glutamine residues reactive in transglutaminase-catalyzed cross-
RT   linking of involucrin.";
RL   J. Biol. Chem. 263:18093-18098(1988).
RN   [7]
RP   LIPIDATION AT GLN-79; GLN-118 AND GLN-133.
RX   PubMed=9651377; DOI=10.1074/jbc.273.28.17763;
RA   Marekov L.N., Steinert P.M.;
RT   "Ceramides are bound to structural proteins of the human foreskin epidermal
RT   cornified cell envelope.";
RL   J. Biol. Chem. 273:17763-17770(1998).
RN   [8]
RP   INTERACTION WITH INVOLUCRIN.
RX   PubMed=15147942; DOI=10.1016/j.bbrc.2004.04.109;
RA   Michibata H., Chiba H., Wakimoto K., Seishima M., Kawasaki S., Okubo K.,
RA   Mitsui H., Torii H., Imai Y.;
RT   "Identification and characterization of a novel component of the cornified
RT   envelope, cornifelin.";
RL   Biochem. Biophys. Res. Commun. 318:803-813(2004).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
CC   -!- FUNCTION: Part of the insoluble cornified cell envelope (CE) of
CC       stratified squamous epithelia.
CC   -!- SUBUNIT: Directly or indirectly cross-linked to cornifelin (CNFN).
CC   -!- INTERACTION:
CC       P07476; Q96AP0: ACD; NbExp=2; IntAct=EBI-11307220, EBI-717666;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Constituent of the scaffolding of
CC       the cornified envelope.
CC   -!- TISSUE SPECIFICITY: Keratinocytes of epidermis and other stratified
CC       squamous epithelia.
CC   -!- PTM: Substrate of transglutaminase. Some glutamines and lysines are
CC       cross-linked to other involucrin molecules, to other proteins such as
CC       keratin, desmoplakin, periplakin and envoplakin, and to lipids like
CC       omega-hydroxyceramide.
CC   -!- SIMILARITY: Belongs to the involucrin family. {ECO:0000305}.
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DR   EMBL; M13903; AAA59186.1; -; Genomic_DNA.
DR   EMBL; AL162596; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC046391; AAH46391.1; -; mRNA.
DR   CCDS; CCDS1030.1; -.
DR   PIR; A24168; A24168.
DR   RefSeq; NP_005538.2; NM_005547.2.
DR   AlphaFoldDB; P07476; -.
DR   BioGRID; 109917; 177.
DR   IntAct; P07476; 32.
DR   MINT; P07476; -.
DR   STRING; 9606.ENSP00000357753; -.
DR   GlyGen; P07476; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; P07476; -.
DR   PhosphoSitePlus; P07476; -.
DR   BioMuta; IVL; -.
DR   DMDM; 254763301; -.
DR   EPD; P07476; -.
DR   MassIVE; P07476; -.
DR   MaxQB; P07476; -.
DR   PaxDb; 9606-ENSP00000357753; -.
DR   PeptideAtlas; P07476; -.
DR   PRIDE; P07476; -.
DR   ProteomicsDB; 52005; -.
DR   Antibodypedia; 3703; 826 antibodies from 39 providers.
DR   DNASU; 3713; -.
DR   Ensembl; ENST00000368764.4; ENSP00000357753.3; ENSG00000163207.7.
DR   GeneID; 3713; -.
DR   KEGG; hsa:3713; -.
DR   MANE-Select; ENST00000368764.4; ENSP00000357753.3; NM_005547.4; NP_005538.2.
DR   UCSC; uc001fau.4; human.
DR   AGR; HGNC:6187; -.
DR   CTD; 3713; -.
DR   DisGeNET; 3713; -.
DR   GeneCards; IVL; -.
DR   HGNC; HGNC:6187; IVL.
DR   HPA; ENSG00000163207; Group enriched (cervix, esophagus, salivary gland, skin, vagina).
DR   MIM; 147360; gene.
DR   neXtProt; NX_P07476; -.
DR   OpenTargets; ENSG00000163207; -.
DR   PharmGKB; PA29985; -.
DR   VEuPathDB; HostDB:ENSG00000163207; -.
DR   eggNOG; ENOG502S84Y; Eukaryota.
DR   GeneTree; ENSGT00940000164168; -.
DR   HOGENOM; CLU_017743_0_0_1; -.
DR   InParanoid; P07476; -.
DR   OMA; GASRINY; -.
DR   OrthoDB; 4741756at2759; -.
DR   PhylomeDB; P07476; -.
DR   TreeFam; TF340025; -.
DR   PathwayCommons; P07476; -.
DR   Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR   SignaLink; P07476; -.
DR   SIGNOR; P07476; -.
DR   BioGRID-ORCS; 3713; 13 hits in 1147 CRISPR screens.
DR   ChiTaRS; IVL; human.
DR   GeneWiki; Involucrin; -.
DR   GenomeRNAi; 3713; -.
DR   Pharos; P07476; Tbio.
DR   PRO; PR:P07476; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P07476; Protein.
DR   Bgee; ENSG00000163207; Expressed in cervix squamous epithelium and 113 other cell types or tissues.
DR   GO; GO:0005813; C:centrosome; IDA:HPA.
DR   GO; GO:0001533; C:cornified envelope; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0016604; C:nuclear body; IDA:HPA.
DR   GO; GO:0018153; P:isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine; TAS:UniProtKB.
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   GO; GO:0010224; P:response to UV-B; IDA:UniProtKB.
DR   InterPro; IPR019743; Involucrin_CS.
DR   InterPro; IPR019571; Involucrin_N.
DR   InterPro; IPR000354; Involucrin_rpt.
DR   Pfam; PF00904; Involucrin; 39.
DR   Pfam; PF10583; Involucrin_N; 1.
DR   PROSITE; PS00795; INVOLUCRIN; 1.
DR   Genevisible; P07476; HS.
PE   1: Evidence at protein level;
KW   Cytoplasm; Direct protein sequencing; Isopeptide bond; Keratinization;
KW   Lipoprotein; Reference proteome; Repeat.
FT   CHAIN           1..585
FT                   /note="Involucrin"
FT                   /id="PRO_0000159736"
FT   REPEAT          153..162
FT                   /note="1"
FT   REPEAT          163..172
FT                   /note="2"
FT   REPEAT          173..182
FT                   /note="3"
FT   REPEAT          183..192
FT                   /note="4"
FT   REPEAT          193..202
FT                   /note="5"
FT   REPEAT          203..212
FT                   /note="6"
FT   REPEAT          213..222
FT                   /note="7"
FT   REPEAT          223..232
FT                   /note="8"
FT   REPEAT          233..242
FT                   /note="9"
FT   REPEAT          243..252
FT                   /note="10"
FT   REPEAT          253..262
FT                   /note="11"
FT   REPEAT          263..272
FT                   /note="12"
FT   REPEAT          273..282
FT                   /note="13"
FT   REPEAT          283..292
FT                   /note="14"
FT   REPEAT          293..302
FT                   /note="15"
FT   REPEAT          303..312
FT                   /note="16"
FT   REPEAT          313..322
FT                   /note="17"
FT   REPEAT          323..332
FT                   /note="18"
FT   REPEAT          333..342
FT                   /note="19"
FT   REPEAT          343..352
FT                   /note="20"
FT   REPEAT          353..362
FT                   /note="21"
FT   REPEAT          363..372
FT                   /note="22"
FT   REPEAT          373..382
FT                   /note="23"
FT   REPEAT          383..392
FT                   /note="24; approximate"
FT   REPEAT          393..402
FT                   /note="25"
FT   REPEAT          403..412
FT                   /note="26"
FT   REPEAT          413..422
FT                   /note="27"
FT   REPEAT          423..432
FT                   /note="28"
FT   REPEAT          433..442
FT                   /note="29"
FT   REPEAT          443..452
FT                   /note="30"
FT   REPEAT          453..462
FT                   /note="31"
FT   REPEAT          463..472
FT                   /note="32"
FT   REPEAT          473..482
FT                   /note="33"
FT   REPEAT          483..492
FT                   /note="34"
FT   REPEAT          493..502
FT                   /note="35"
FT   REPEAT          503..512
FT                   /note="36; approximate"
FT   REPEAT          513..522
FT                   /note="37"
FT   REPEAT          523..532
FT                   /note="38"
FT   REPEAT          533..542
FT                   /note="39; approximate"
FT   REGION          1..132
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          149..540
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          153..542
FT                   /note="39 X 10 AA approximate tandem repeats of [LP]-[EKG]-
FT                   [LHVYQEK]-[PLSQE]-[EQDV]-[QHEKRGA]-Q-[EMVQLP]-[GKLE]-
FT                   [QHVNLD]"
FT   COMPBIAS        1..35
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        55..132
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        149..174
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        182..259
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        260..274
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        337..361
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        365..379
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        380..395
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        415..441
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        442..463
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        464..489
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        501..531
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   LIPID           79
FT                   /note="Omega-hydroxyceramide glutamate ester"
FT                   /evidence="ECO:0000305|PubMed:9651377"
FT   LIPID           118
FT                   /note="Omega-hydroxyceramide glutamate ester"
FT                   /evidence="ECO:0000305|PubMed:9651377"
FT   LIPID           133
FT                   /note="Omega-hydroxyceramide glutamate ester"
FT                   /evidence="ECO:0000305|PubMed:9651377"
FT   CROSSLNK        496
FT                   /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT                   with K-? in other proteins)"
FT   VARIANT         113
FT                   /note="T -> A (in dbSNP:rs2229496)"
FT                   /id="VAR_029019"
FT   VARIANT         166
FT                   /note="L -> P (in dbSNP:rs11205133)"
FT                   /id="VAR_029020"
FT   VARIANT         174
FT                   /note="K -> E (in dbSNP:rs12035307)"
FT                   /id="VAR_029021"
FT   VARIANT         227
FT                   /note="E -> Q (in dbSNP:rs11807064)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:2873896"
FT                   /id="VAR_058411"
FT   VARIANT         236
FT                   /note="P -> S (in dbSNP:rs17855670)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:2873896"
FT                   /id="VAR_058412"
FT   VARIANT         237
FT                   /note="Q -> E (in dbSNP:rs7520711)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:2873896"
FT                   /id="VAR_029022"
FT   VARIANT         312
FT                   /note="Q -> K (in dbSNP:rs11205137)"
FT                   /id="VAR_029023"
FT   VARIANT         480
FT                   /note="V -> L (in dbSNP:rs7545520)"
FT                   /id="VAR_029024"
SQ   SEQUENCE   585 AA;  68479 MW;  775D2AFB90F647E8 CRC64;
     MSQQHTLPVT LSPALSQELL KTVPPPVNTH QEQMKQPTPL PPPCQKVPVE LPVEVPSKQE
     EKHMTAVKGL PEQECEQQQK EPQEQELQQQ HWEQHEEYQK AENPEQQLKQ EKTQRDQQLN
     KQLEEEKKLL DQQLDQELVK RDEQLGMKKE QLLELPEQQE GHLKHLEQQE GQLKHPEQQE
     GQLELPEQQE GQLELPEQQE GQLELPEQQE GQLELPEQQE GQLELPEQQE GQLELPQQQE
     GQLELSEQQE GQLELSEQQE GQLKHLEHQE GQLEVPEEQM GQLKYLEQQE GQLKHLDQQE
     KQPELPEQQM GQLKHLEQQE GQPKHLEQQE GQLEQLEEQE GQLKHLEQQE GQLEHLEHQE
     GQLGLPEQQV LQLKQLEKQQ GQPKHLEEEE GQLKHLVQQE GQLKHLVQQE GQLEQQERQV
     EHLEQQVGQL KHLEEQEGQL KHLEQQQGQL EVPEQQVGQP KNLEQEEKQL ELPEQQEGQV
     KHLEKQEAQL ELPEQQVGQP KHLEQQEKHL EHPEQQDGQL KHLEQQEGQL KDLEQQKGQL
     EQPVFAPAPG QVQDIQPALP TKGEVLLPVE HQQQKQEVQW PPKHK
//