INVO_HUMAN
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 03-AUG-2022, entry version 190.
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; 174.
DR IntAct; P07476; 32.
DR MINT; P07476; -.
DR STRING; 9606.ENSP00000357753; -.
DR iPTMnet; P07476; -.
DR PhosphoSitePlus; P07476; -.
DR BioMuta; IVL; -.
DR DMDM; 254763301; -.
DR EPD; P07476; -.
DR MassIVE; P07476; -.
DR MaxQB; P07476; -.
DR PaxDb; P07476; -.
DR PeptideAtlas; P07476; -.
DR PRIDE; P07476; -.
DR ProteomicsDB; 52005; -.
DR Antibodypedia; 3703; 775 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 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; QESHEPD; -.
DR OrthoDB; 1397136at2759; -.
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 1069 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 tissues.
DR Genevisible; P07476; HS.
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 DisProt; DP00221; -.
DR InterPro; IPR002360; Involucrin.
DR InterPro; IPR019743; Involucrin_CS.
DR InterPro; IPR019571; Involucrin_N.
DR InterPro; IPR000354; Involucrin_rpt.
DR PANTHER; PTHR36910:SF9; PTHR36910:SF9; 2.
DR Pfam; PF00904; Involucrin; 40.
DR Pfam; PF10583; Involucrin_N; 1.
DR PROSITE; PS00795; INVOLUCRIN; 1.
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
