P07476 (INVO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Involucrin

Gene names

Name:

IVL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	585 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia.
Subunit structure	Directly or indirectly cross-linked to cornifelin (CNFN).
Subcellular location	Cytoplasm. Note: Constituent of the scaffolding of the cornified envelope.
Tissue specificity	Keratinocytes of epidermis and other stratified squamous epithelia.
Post-translational modification	Substrate of transglutaminase. Some glutamines and lysines are cross-linked to other involucrin molecules, to other proteins such as keratin, desmoplakin, periplakin and envoplakin, and to lipids like omega-hydroxyceramide.
Sequence similarities	Belongs to the involucrin family.

Ontologies

Keywords
Biological process	Keratinization
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Isopeptide bond Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine Traceable author statement Ref.5. Source: UniProtKB keratinization Inferred from electronic annotation. Source: UniProtKB-KW keratinocyte differentiation Inferred from direct assay PubMed 10908733. Source: UniProtKB response to UV-B Inferred from direct assay PubMed 16639001. Source: UniProtKB
Cellular_component	cornified envelope Inferred from direct assay PubMed 10908733. Source: UniProtKB cytoplasm Inferred from direct assay PubMed 16639001PubMed 42494. Source: UniProtKB
Molecular_function	protein binding, bridging Inferred from direct assay PubMed 10908733. Source: UniProtKB structural molecule activity Inferred from direct assay PubMed 10908733PubMed 42494. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 585

585

Involucrin

PRO_0000159736

Regions

Repeat

153 – 162

10

1

Repeat

163 – 172

10

2

Repeat

173 – 182

10

3

Repeat

183 – 192

10

4

Repeat

193 – 202

10

5

Repeat

203 – 212

10

6

Repeat

213 – 222

10

7

Repeat

223 – 232

10

8

Repeat

233 – 242

10

9

Repeat

243 – 252

10

10

Repeat

253 – 262

10

11

Repeat

263 – 272

10

12

Repeat

273 – 282

10

13

Repeat

283 – 292

10

14

Repeat

293 – 302

10

15

Repeat

303 – 312

10

16

Repeat

313 – 322

10

17

Repeat

323 – 332

10

18

Repeat

333 – 342

10

19

Repeat

343 – 352

10

20

Repeat

353 – 362

10

21

Repeat

363 – 372

10

22

Repeat

373 – 382

10

23

Repeat

383 – 392

10

24; approximate

Repeat

393 – 402

10

25

Repeat

403 – 412

10

26

Repeat

413 – 422

10

27

Repeat

423 – 432

10

28

Repeat

433 – 442

10

29

Repeat

443 – 452

10

30

Repeat

453 – 462

10

31

Repeat

463 – 472

10

32

Repeat

473 – 482

10

33

Repeat

483 – 492

10

34

Repeat

493 – 502

10

35

Repeat

503 – 512

10

36; approximate

Repeat

513 – 522

10

37

Repeat

523 – 532

10

38

Repeat

533 – 542

10

39; approximate

Region

153 – 542

390

39 X 10 AA approximate tandem repeats of [LP]-[EKG]-[LHVYQEK]-[PLSQE]-[EQDV]-[QHEKRGA]-Q-[EMVQLP]-[GKLE]-[QHVNLD]

Amino acid modifications

Lipidation

79

1

Omega-hydroxyceramide glutamate ester Probable

Lipidation

90

1

Omega-hydroxyceramide glutamate ester Probable

Lipidation

118

1

Omega-hydroxyceramide glutamate ester Probable

Lipidation

133

1

Omega-hydroxyceramide glutamate ester Probable

Cross-link

496

Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-? in other proteins)

Natural variations

Natural variant

113

1

T → A.
Corresponds to variant rs2229496 [ dbSNP | Ensembl ].

VAR_029019

Natural variant

166

1

L → P.
Corresponds to variant rs11205133 [ dbSNP | Ensembl ].

VAR_029020

Natural variant

174

1

K → E.
Corresponds to variant rs12035307 [ dbSNP | Ensembl ].

VAR_029021

Natural variant

227

1

E → Q. Ref.1 Ref.3
Corresponds to variant rs11807064 [ dbSNP | Ensembl ].

VAR_058411

Natural variant

236

1

P → S. Ref.1 Ref.3
Corresponds to variant rs17855670 [ dbSNP | Ensembl ].

VAR_058412

Natural variant

237

1

Q → E. Ref.1 Ref.3
Corresponds to variant rs7520711 [ dbSNP | Ensembl ].

VAR_029022

Natural variant

312

1

Q → K.
Corresponds to variant rs11205137 [ dbSNP | Ensembl ].

VAR_029023

Natural variant

480

1

V → L.
Corresponds to variant rs7545520 [ dbSNP | Ensembl ].

VAR_029024

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

585

Helix Strand Turn

Details...

Helix

313 – 318

6

Helix

323 – 328

6

Helix

333 – 338

6

Helix

343 – 348

6

Helix

353 – 358

6

Sequences

	Sequence		Length	Mass (Da)
	P07476 [UniParc]. Last modified July 28, 2009. Version 2. Checksum: 775D2AFB90F647E8	FASTA	585	68,479
	10 20 30 40 50 60 MSQQHTLPVT LSPALSQELL KTVPPPVNTH QEQMKQPTPL PPPCQKVPVE LPVEVPSKQE 70 80 90 100 110 120 EKHMTAVKGL PEQECEQQQK EPQEQELQQQ HWEQHEEYQK AENPEQQLKQ EKTQRDQQLN 130 140 150 160 170 180 KQLEEEKKLL DQQLDQELVK RDEQLGMKKE QLLELPEQQE GHLKHLEQQE GQLKHPEQQE 190 200 210 220 230 240 GQLELPEQQE GQLELPEQQE GQLELPEQQE GQLELPEQQE GQLELPEQQE GQLELPQQQE 250 260 270 280 290 300 GQLELSEQQE GQLELSEQQE GQLKHLEHQE GQLEVPEEQM GQLKYLEQQE GQLKHLDQQE 310 320 330 340 350 360 KQPELPEQQM GQLKHLEQQE GQPKHLEQQE GQLEQLEEQE GQLKHLEQQE GQLEHLEHQE 370 380 390 400 410 420 GQLGLPEQQV LQLKQLEKQQ GQPKHLEEEE GQLKHLVQQE GQLKHLVQQE GQLEQQERQV 430 440 450 460 470 480 EHLEQQVGQL KHLEEQEGQL KHLEQQQGQL EVPEQQVGQP KNLEQEEKQL ELPEQQEGQV 490 500 510 520 530 540 KHLEKQEAQL ELPEQQVGQP KHLEQQEKHL EHPEQQDGQL KHLEQQEGQL KDLEQQKGQL 550 560 570 580 EQPVFAPAPG QVQDIQPALP TKGEVLLPVE HQQQKQEVQW PPKHK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and evolution of the human involucrin gene." Eckert R.L., Green H. Cell 46:583-589(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-227; SER-236 AND GLU-237.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLN-227; SER-236 AND GLU-237. Tissue: Skin.
[4]	"S100A11, S100A10, annexin I, desmosomal proteins, small proline-rich proteins, plasminogen activator inhibitor-2, and involucrin are components of the cornified envelope of cultured human epidermal keratinocytes." Robinson N.A., Lapic S., Welter J.F., Eckert R.L. J. Biol. Chem. 272:12035-12046(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 281-290. Tissue: Keratinocyte.
[5]	"Biophysical characterization of involucrin reveals a molecule ideally suited to function as an intermolecular cross-bridge of the keratinocyte cornified envelope." Yaffe M.B., Beegen H., Eckert R.L. J. Biol. Chem. 267:12233-12238(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURAL STUDIES.
[6]	"The glutamine residues reactive in transglutaminase-catalyzed cross-linking of involucrin." Simon M., Green H. J. Biol. Chem. 263:18093-18098(1988) [PubMed] [Europe PMC] [Abstract] Cited for: GLN-LYS CROSS-LINK.
[7]	"Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope." Marekov L.N., Steinert P.M. J. Biol. Chem. 273:17763-17770(1998) [PubMed] [Europe PMC] [Abstract] Cited for: LIPIDATION.
[8]	"Identification and characterization of a novel component of the cornified envelope, cornifelin." Michibata H., Chiba H., Wakimoto K., Seishima M., Kawasaki S., Okubo K., Mitsui H., Torii H., Imai Y. Biochem. Biophys. Res. Commun. 318:803-813(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INVOLUCRIN.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M13903 Genomic DNA. Translation: AAA59186.1.
AL162596 Genomic DNA. Translation: CAI19553.1.
BC046391 mRNA. Translation: AAH46391.1.

IPI

IPI00011692.

PIR

A24168.

RefSeq

NP_005538.2. NM_005547.2.

UniGene

Hs.516439.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EU0	model	-	A	312-361	[»]

DisProt

DP00221.

ProteinModelPortal

P07476.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000357753.

PTM databases

PhosphoSite

P07476.

Polymorphism databases

DMDM

254763301.

Proteomic databases

PaxDb

P07476.

PRIDE

P07476.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368764; ENSP00000357753; ENSG00000163207.

GeneID

3713.

KEGG

hsa:3713.

UCSC

uc001fau.3. human.

Organism-specific databases

CTD

3713.

GeneCards

GC01P152881.

H-InvDB

HIX0023860.

HGNC

HGNC:6187. IVL.

HPA

CAB002243.

MIM

147360. gene.

neXtProt

NX_P07476.

PharmGKB

PA29985.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG80441.

HOVERGEN

HBG006166.

InParanoid

P07476.

OMA

LEHPEQQ.

OrthoDB

EOG4S4PHX.

Gene expression databases

Bgee

P07476.

CleanEx

HS_IVL.

Genevestigator

P07476.

GermOnline

ENSG00000163207. Homo sapiens.

Family and domain databases

InterPro

IPR002360. Involucrin.
IPR019743. Involucrin_CS.
IPR019571. Involucrin_N.
IPR000354. Involucrin_rpt.
[Graphical view]

PANTHER

PTHR13905. PTHR13905. 1 hit.

Pfam

PF00904. Involucrin. 40 hits.
PF10583. Involucrin_N. 1 hit.
[Graphical view]

PROSITE

PS00795. INVOLUCRIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

IVL. human.

GenomeRNAi

3713.

NextBio

14551.

SOURCE

Search...

Entry information

Entry name

INVO_HUMAN

Accession

Primary (citable) accession number: P07476
Secondary accession number(s): Q5T7P4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	July 28, 2009
Last modified:	April 3, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.