ID   FILA2_HUMAN             Reviewed;        2391 AA.
AC   Q5D862; Q9H4U1;
DT   29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   29-MAR-2005, sequence version 1.
DT   27-MAR-2024, entry version 154.
DE   RecName: Full=Filaggrin-2;
DE            Short=FLG-2;
DE   AltName: Full=Intermediate filament-associated and psoriasis-susceptibility protein;
DE            Short=Ifapsoriasin;
GN   Name=FLG2; Synonyms=IFPS;
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], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP   INDUCTION BY CALCIUM.
RC   TISSUE=Foreskin keratinocyte;
RX   PubMed=19384417; DOI=10.1371/journal.pone.0005227;
RA   Wu Z., Hansmann B., Meyer-Hoffert U., Glaser R., Schroder J.M.;
RT   "Molecular identification and expression analysis of filaggrin-2, a member
RT   of the S100 fused-type protein family.";
RL   PLoS ONE 4:E5227-E5227(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Listwan P., Rothnagel J.A.;
RT   "Identification and partial characterization of the human homolog of mouse
RT   flg-2.";
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
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   PROTEIN SEQUENCE OF 7-17 AND 40-46, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   TISSUE=Cervix carcinoma;
RA   Bienvenut W.V., Calvo F., Kolch W.;
RL   Submitted (MAR-2008) to UniProtKB.
RN   [5]
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).
RN   [6]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, CLEAVAGE BY CAPN1, AND
RP   DEIMINATION BY PADI1/2/3.
RX   PubMed=21531719; DOI=10.1074/jbc.m110.197400;
RA   Hsu C.Y., Henry J., Raymond A.A., Mechin M.C., Pendaries V., Nassar D.,
RA   Hansmann B., Balica S., Burlet-Schiltz O., Schmitt A.M., Takahara H.,
RA   Paul C., Serre G., Simon M.;
RT   "Deimination of human filaggrin-2 promotes its proteolysis by calpain 1.";
RL   J. Biol. Chem. 286:23222-23233(2011).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [8]
RP   INVOLVEMENT IN PSS6, AND VARIANT PSS6 211-SER--HIS-2391 DEL.
RX   PubMed=28884927; DOI=10.1002/ajmg.a.38468;
RA   Alfares A., Al-Khenaizan S., Al Mutairi F.;
RT   "Peeling skin syndrome associated with novel variant in FLG2 gene.";
RL   Am. J. Med. Genet. A 173:3201-3204(2017).
RN   [9]
RP   FUNCTION, INVOLVEMENT IN PSS6, VARIANT PSS6 355-TYR--HIS-2391 DEL, AND
RP   CHARACTERIZATION OF VARIANT PSS6 355-TYR--HIS-2391 DEL.
RX   PubMed=29758285; DOI=10.1016/j.jid.2018.04.032;
RA   Mohamad J., Sarig O., Godsel L.M., Peled A., Malchin N., Bochner R.,
RA   Vodo D., Rabinowitz T., Pavlovsky M., Taiber S., Fried M.,
RA   Eskin-Schwartz M., Assi S., Shomron N., Uitto J., Koetsier J.L.,
RA   Bergman R., Green K.J., Sprecher E.;
RT   "Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the
RT   Cornified Cell Layers and Causes Peeling Skin Syndrome Type A.";
RL   J. Invest. Dermatol. 138:1736-1743(2018).
RN   [10]
RP   FUNCTION, INVOLVEMENT IN PSS6, VARIANT PSS6 211-SER--HIS-2391 DEL, AND
RP   CHARACTERIZATION OF VARIANT PSS6 211-SER--HIS-2391 DEL.
RX   PubMed=29505760; DOI=10.1016/j.jid.2018.01.038;
RA   Bolling M.C., Jan S.Z., Pasmooij A.M.G., Lemmink H.H., Franke L.H.,
RA   Yenamandra V.K., Sinke R.J., van den Akker P.C., Jonkman M.F.;
RT   "Generalized Ichthyotic Peeling Skin Syndrome due to FLG2 Mutations.";
RL   J. Invest. Dermatol. 138:1881-1884(2018).
RN   [11]
RP   VARIANTS THR-12 AND VAL-1450.
RX   PubMed=32341456; DOI=10.1038/s10038-020-0758-2;
RA   Nakashima M., Kato M., Matsukura M., Kira R., Ngu L.H., Lichtenbelt K.D.,
RA   van Gassen K.L.I., Mitsuhashi S., Saitsu H., Matsumoto N.;
RT   "De novo variants in CUL3 are associated with global developmental delays
RT   with or without infantile spasms.";
RL   J. Hum. Genet. 65:727-734(2020).
CC   -!- FUNCTION: Essential for normal cell-cell adhesion in the cornified cell
CC       layers (PubMed:29758285). Important for proper integrity and mechanical
CC       strength of the stratum corneum of the epidermis (PubMed:29505760).
CC       {ECO:0000269|PubMed:29505760, ECO:0000269|PubMed:29758285}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19384417}.
CC       Cytoplasmic granule {ECO:0000269|PubMed:19384417}. Note=In the stratum
CC       corneum of the epidermis, dispersed diffusely throughout the cytoplasm,
CC       while in the stratum granulosum, localized within keratohyalin granules
CC       (PubMed:19384417) (PubMed:21531719). In granular keratinocytes and in
CC       lower corneocytes, colocalizes with calpain-1/CAPN1.
CC       {ECO:0000269|PubMed:19384417, ECO:0000269|PubMed:21531719}.
CC   -!- TISSUE SPECIFICITY: Expressed in skin, thymus, stomach and placenta,
CC       but not detected in heart, brain, liver, lung, bone marrow, small
CC       intestine, spleen, prostate, colon, adrenal gland, kidney, pancreas,
CC       mammary gland, bladder, thyroid, salivary gland and trachea. Weakly
CC       expressed in esophagus, tonsils and testis (at protein level). In the
CC       skin, strongly expressed in the upper stratum granulosum and lower
CC       stratum corneum, but not detected in the upper stratum corneum (at
CC       protein level) (PubMed:19384417) (PubMed:21531719). In scalp hair
CC       follicles, mainly restricted within the granular and cornified cells
CC       surrounding the infundibular outer root sheath, with weak expression in
CC       central and proximal outer root sheath (at protein level). Tends to be
CC       down-regulated in sporiatic lesions compared to non-lesional skin inthe
CC       same patients (PubMed:19384417). {ECO:0000269|PubMed:19384417,
CC       ECO:0000269|PubMed:21531719}.
CC   -!- INDUCTION: In cultured foreskin fibroblasts, up-regulated in response
CC       to Ca(2+) stimulation. {ECO:0000269|PubMed:19384417}.
CC   -!- PTM: Deiminated by PADI1, PADI2 or PADI3 in vitro. The deiminated form
CC       is degraded by calpain-1/CAPN1 more quickly and into shorter peptides
CC       than the intact protein. {ECO:0000269|PubMed:21531719}.
CC   -!- PTM: May be processed by calpain-1/CAPN1 in the uppermost epidermal
CC       layers. {ECO:0000269|PubMed:21531719}.
CC   -!- DISEASE: Peeling skin syndrome 6 (PSS6) [MIM:618084]: A form of peeling
CC       skin syndrome, a genodermatosis characterized by generalized,
CC       continuous shedding of the outer layers of the epidermis. Two main PSS
CC       subtypes have been suggested. Patients with non-inflammatory PSS (type
CC       A) manifest white scaling, with painless and easy removal of the skin,
CC       irritation when in contact with water, dust and sand, and no history of
CC       erythema, pruritis or atopy. Inflammatory PSS (type B) is associated
CC       with generalized erythema, pruritus and atopy. It is an ichthyosiform
CC       erythroderma characterized by lifelong patchy peeling of the entire
CC       skin with onset at birth or shortly after. Several patients have been
CC       reported with high IgE levels. PSS6 patients manifest generalized
CC       ichthyotic dry skin, and bullous peeling lesions on the trunk and limbs
CC       at sites of minor trauma. Skin symptoms are exacerbated by warmth and
CC       humidity. PSS6 inheritance is autosomal recessive.
CC       {ECO:0000269|PubMed:28884927, ECO:0000269|PubMed:29505760,
CC       ECO:0000269|PubMed:29758285}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the S100-fused protein family. {ECO:0000305}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the S-100 family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AY827490; AAX12417.1; -; mRNA.
DR   EMBL; DQ118293; AAZ99029.1; -; Genomic_DNA.
DR   EMBL; AL356504; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS30861.1; -.
DR   RefSeq; NP_001014364.1; NM_001014342.2.
DR   AlphaFoldDB; Q5D862; -.
DR   SMR; Q5D862; -.
DR   BioGRID; 132815; 128.
DR   IntAct; Q5D862; 33.
DR   MINT; Q5D862; -.
DR   STRING; 9606.ENSP00000373370; -.
DR   GlyGen; Q5D862; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q5D862; -.
DR   PhosphoSitePlus; Q5D862; -.
DR   SwissPalm; Q5D862; -.
DR   BioMuta; FLG2; -.
DR   DMDM; 74755309; -.
DR   jPOST; Q5D862; -.
DR   MassIVE; Q5D862; -.
DR   PaxDb; 9606-ENSP00000373370; -.
DR   PeptideAtlas; Q5D862; -.
DR   ProteomicsDB; 62742; -.
DR   Antibodypedia; 34087; 69 antibodies from 12 providers.
DR   DNASU; 388698; -.
DR   Ensembl; ENST00000388718.5; ENSP00000373370.4; ENSG00000143520.6.
DR   GeneID; 388698; -.
DR   KEGG; hsa:388698; -.
DR   MANE-Select; ENST00000388718.5; ENSP00000373370.4; NM_001014342.3; NP_001014364.1.
DR   UCSC; uc001ezw.5; human.
DR   AGR; HGNC:33276; -.
DR   CTD; 388698; -.
DR   DisGeNET; 388698; -.
DR   GeneCards; FLG2; -.
DR   HGNC; HGNC:33276; FLG2.
DR   HPA; ENSG00000143520; Tissue enriched (skin).
DR   MalaCards; FLG2; -.
DR   MIM; 616284; gene.
DR   MIM; 618084; phenotype.
DR   neXtProt; NX_Q5D862; -.
DR   OpenTargets; ENSG00000143520; -.
DR   Orphanet; 263548; Peeling skin syndrome type A.
DR   PharmGKB; PA162388694; -.
DR   VEuPathDB; HostDB:ENSG00000143520; -.
DR   eggNOG; ENOG502QQH0; Eukaryota.
DR   GeneTree; ENSGT00940000154467; -.
DR   HOGENOM; CLU_234089_0_0_1; -.
DR   InParanoid; Q5D862; -.
DR   OMA; AGLWDGW; -.
DR   OrthoDB; 4642904at2759; -.
DR   PhylomeDB; Q5D862; -.
DR   TreeFam; TF338665; -.
DR   PathwayCommons; Q5D862; -.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   SignaLink; Q5D862; -.
DR   BioGRID-ORCS; 388698; 11 hits in 1144 CRISPR screens.
DR   GenomeRNAi; 388698; -.
DR   Pharos; Q5D862; Tbio.
DR   PRO; PR:Q5D862; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q5D862; Protein.
DR   Bgee; ENSG00000143520; Expressed in upper leg skin and 81 other cell types or tissues.
DR   GO; GO:0001533; C:cornified envelope; IBA:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0036457; C:keratohyalin granule; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR   GO; GO:0007155; P:cell adhesion; IMP:UniProtKB.
DR   GO; GO:0048730; P:epidermis morphogenesis; IMP:UniProtKB.
DR   GO; GO:0061436; P:establishment of skin barrier; IEP:UniProtKB.
DR   CDD; cd00213; S-100; 1.
DR   Gene3D; 1.10.238.10; EF-hand; 1.
DR   InterPro; IPR011992; EF-hand-dom_pair.
DR   InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR   InterPro; IPR002048; EF_hand_dom.
DR   InterPro; IPR003303; Filaggrin.
DR   InterPro; IPR034325; S-100_dom.
DR   InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR   InterPro; IPR013787; S100_Ca-bd_sub.
DR   PANTHER; PTHR22571:SF24; FILAGGRIN-2; 1.
DR   PANTHER; PTHR22571; FILAGGRIN-RELATED; 1.
DR   Pfam; PF01023; S_100; 1.
DR   PRINTS; PR00487; FILAGGRIN.
DR   SMART; SM01394; S_100; 1.
DR   SUPFAM; SSF47473; EF-hand; 1.
DR   PROSITE; PS00018; EF_HAND_1; 1.
DR   PROSITE; PS50222; EF_HAND_2; 2.
DR   PROSITE; PS00303; S100_CABP; 1.
DR   UCD-2DPAGE; Q5D862; -.
DR   Genevisible; Q5D862; HS.
PE   1: Evidence at protein level;
KW   Calcium; Cytoplasm; Direct protein sequencing; Disease variant;
KW   Metal-binding; Phosphoprotein; Reference proteome; Repeat.
FT   CHAIN           1..2391
FT                   /note="Filaggrin-2"
FT                   /id="PRO_0000331454"
FT   DOMAIN          8..43
FT                   /note="EF-hand 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          49..84
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   REPEAT          245..289
FT                   /note="Filaggrin 1"
FT   REPEAT          421..466
FT                   /note="Filaggrin 2"
FT   REPEAT          1019..1051
FT                   /note="Filaggrin 3"
FT   REPEAT          1097..1141
FT                   /note="Filaggrin 4"
FT   REPEAT          1455..1510
FT                   /note="Filaggrin 5"
FT   REPEAT          1607..1662
FT                   /note="Filaggrin 6"
FT   REPEAT          1757..1812
FT                   /note="Filaggrin 7"
FT   REPEAT          1928..1964
FT                   /note="Filaggrin 8"
FT   REPEAT          1984..2039
FT                   /note="Filaggrin 9"
FT   REPEAT          2134..2189
FT                   /note="Filaggrin 10"
FT   REGION          1..81
FT                   /note="S-100-like"
FT                   /evidence="ECO:0000250"
FT   REGION          96..275
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          349..369
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          406..2391
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        120..145
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        160..185
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        198..219
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        220..234
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        245..275
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        406..1266
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1267..1295
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1296..1312
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1326..1344
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1345..1363
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1364..1379
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1393..1421
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1434..1474
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1486..1500
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1501..1515
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1516..1531
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1532..1547
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1548..1573
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1574..1621
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1622..1650
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1651..1667
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1668..1701
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1709..1750
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1751..1773
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1774..1800
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1807..1835
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1849..1877
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1878..1894
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1903..1925
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1926..1985
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2001..2027
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2028..2044
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2045..2061
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2076..2102
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2115..2177
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2178..2194
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2195..2252
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2265..2327
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2365..2391
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         62
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         64
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         66
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         68
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         73
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   MOD_RES         1276
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1427
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1428
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1504
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1505
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1579
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1656
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1657
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1800
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1807
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1883
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1884
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         1959
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   MOD_RES         2034
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q2VIS4"
FT   VARIANT         12
FT                   /note="I -> T (in dbSNP:rs774342933)"
FT                   /evidence="ECO:0000269|PubMed:32341456"
FT                   /id="VAR_085409"
FT   VARIANT         41
FT                   /note="L -> F (in dbSNP:rs3818831)"
FT                   /id="VAR_042868"
FT   VARIANT         107
FT                   /note="R -> Q (in dbSNP:rs2282304)"
FT                   /id="VAR_042869"
FT   VARIANT         137
FT                   /note="G -> E (in dbSNP:rs6587667)"
FT                   /id="VAR_042870"
FT   VARIANT         211..2391
FT                   /note="Missing (in PSS6; reduced protein abundance in
FT                   patient's skin)"
FT                   /evidence="ECO:0000269|PubMed:28884927,
FT                   ECO:0000269|PubMed:29505760"
FT                   /id="VAR_081283"
FT   VARIANT         276
FT                   /note="R -> Q (in dbSNP:rs2282303)"
FT                   /id="VAR_042871"
FT   VARIANT         298
FT                   /note="C -> S (in dbSNP:rs2282302)"
FT                   /id="VAR_042872"
FT   VARIANT         355..2391
FT                   /note="Missing (in PSS6; reduced protein abundance in
FT                   patient's skin)"
FT                   /evidence="ECO:0000269|PubMed:29758285"
FT                   /id="VAR_081284"
FT   VARIANT         723
FT                   /note="E -> K (in dbSNP:rs16842865)"
FT                   /id="VAR_042873"
FT   VARIANT         881
FT                   /note="Y -> S (in dbSNP:rs79239476)"
FT                   /id="VAR_042874"
FT   VARIANT         958
FT                   /note="S -> Y (in dbSNP:rs12411129)"
FT                   /id="VAR_059173"
FT   VARIANT         1249
FT                   /note="H -> R (in dbSNP:rs16833974)"
FT                   /id="VAR_042875"
FT   VARIANT         1450
FT                   /note="A -> V"
FT                   /evidence="ECO:0000269|PubMed:32341456"
FT                   /id="VAR_085410"
FT   VARIANT         1992
FT                   /note="E -> D (in dbSNP:rs1858484)"
FT                   /id="VAR_042876"
FT   VARIANT         2239
FT                   /note="Q -> H (in dbSNP:rs12736606)"
FT                   /id="VAR_042877"
SQ   SEQUENCE   2391 AA;  248073 MW;  8BC74DE89E0DDC05 CRC64;
     MTDLLRSVVT VIDVFYKYTK QDGECGTLSK GELKELLEKE LHPVLKNPDD PDTVDVIMHM
     LDRDHDRRLD FTEFLLMIFK LTMACNKVLS KEYCKASGSK KHRRGHRHQE EESETEEDEE
     DTPGHKSGYR HSSWSEGEEH GYSSGHSRGT VKCRHGSNSR RLGRQGNLSS SGNQEGSQKR
     YHRSSCGHSW SGGKDRHGSS SVELRERINK SHISPSRESG EEYESGSGSN SWERKGHGGL
     SCGLETSGHE SNSTQSRIRE QKLGSSCSGS GDSGRRSHAC GYSNSSGCGR PQNASSSCQS
     HRFGGQGNQF SYIQSGCQSG IKGGQGHGCV SGGQPSGCGQ PESNPCSQSY SQRGYGAREN
     GQPQNCGGQW RTGSSQSSCC GQYGSGGSQS CSNGQHEYGS CGRFSNSSSS NEFSKCDQYG
     SGSSQSTSFE QHGTGLSQSS GFEQHVCGSG QTCGQHESTS SQSLGYDQHG SSSGKTSGFG
     QHGSGSGQSS GFGQCGSGSG QSSGFGQHGS VSGQSSGFGQ HGSVSGQSSG FGQHESRSRQ
     SSYGQHGSGS SQSSGYGQYG SRETSGFGQH GLGSGQSTGF GQYGSGSGQS SGFGQHGSGS
     GQSSGFGQHE SRSGQSSYGQ HSSGSSQSSG YGQHGSRQTS GFGQHGSGSS QSTGFGQYGS
     GSGQSSGFGQ HVSGSGQSSG FGQHESRSGH SSYGQHGFGS SQSSGYGQHG SSSGQTSGFG
     QHELSSGQSS SFGQHGSGSG QSSGFGQHGS GSGQSSGFGQ HESRSGQSSY GQHSSGSSQS
     SGYGQHGSRQ TSGFGQHGSG SSQSTGFGQY GSGSGQSAGF GQHGSGSGQS SGFGQHESRS
     HQSSYGQHGS GSSQSSGYGQ HGSSSGQTSG FGQHRSSSGQ YSGFGQHGSG SGQSSGFGQH
     GTGSGQYSGF GQHESRSHQS SYGQHGSGSS QSSGYGQHGS SSGQTFGFGQ HRSGSGQSSG
     FGQHGSGSGQ SSGFGQHESG SGKSSGFGQH ESRSSQSNYG QHGSGSSQSS GYGQHGSSSG
     QTTGFGQHRS SSGQYSGFGQ HGSGSDQSSG FGQHGTGSGQ SSGFGQYESR SRQSSYGQHG
     SGSSQSSGYG QHGSNSGQTS GFGQHRPGSG QSSGFGQYGS GSGQSSGFGQ HGSGTGKSSG
     FAQHEYRSGQ SSYGQHGTGS SQSSGCGQHE SGSGPTTSFG QHVSGSDNFS SSGQHISDSG
     QSTGFGQYGS GSGQSTGLGQ GESQQVESGS TVHGRQETTH GQTINTTRHS QSGQGQSTQT
     GSRVTRRRRS SQSENSDSEV HSKVSHRHSE HIHTQAGSHY PKSGSTVRRR QGTTHGQRGD
     TTRHGHSGHG QSTQTGSRTS GRQRFSHSDA TDSEVHSGVS HRPHSQEQTH SQAGSQHGES
     ESTVHERHET TYGQTGEATG HGHSGHGQST QRGSRTTGRR GSGHSESSDS EVHSGGSHRP
     QSQEQTHGQA GSQHGESGST VHGRHGTTHG QTGDTTRHAH YHHGKSTQRG SSTTGRRGSG
     HSESSDSEVH SGGSHTHSGH THGQSGSQHG ESESIIHDRH RITHGQTGDT TRHSYSGHEQ
     TTQTGSRTTG RQRTSHSEST DSEVHSGGSH RPHSREHTYG QAGSQHEEPE FTVHERHGTT
     HGQIGDTTGH SHSGHGQSTQ RGSRTTGRQR SSHSESSDSE VHSGVSHTHT GHTHGQAGSQ
     HGQSESIVPE RHGTTHGQTG DTTRHAHYHH GLTTQTGSRT TGRRGSGHSE YSDSEGYSGV
     SHTHSGHTHG QARSQHGESE SIVHERHGTI HGQTGDTTRH AHSGHGQSTQ TGSRTTGRRS
     SGHSEYSDSE GHSGFSQRPH SRGHTHGQAG SQHGESESIV DERHGTTHGQ TGDTSGHSQS
     GHGQSTQSGS STTGRRRSGH SESSDSEVHS GGSHTHSGHT HSQARSQHGE SESTVHKRHQ
     TTHGQTGDTT EHGHPSHGQT IQTGSRTTGR RGSGHSEYSD SEGPSGVSHT HSGHTHGQAG
     SHYPESGSSV HERHGTTHGQ TADTTRHGHS GHGQSTQRGS RTTGRRASGH SEYSDSEGHS
     GVSHTHSGHA HGQAGSQHGE SGSSVHERHG TTHGQTGDTT RHAHSGHGQS TQRGSRTAGR
     RGSGHSESSD SEVHSGVSHT HSGHTYGQAR SQHGESGSAI HGRQGTIHGQ TGDTTRHGQS
     GHGQSTQTGS RTTGRQRSSH SESSDSEVHS EASPTHSGHT HSQAGSRHGQ SGSSGHGRQG
     TTHGQTGDTT RHAHYGYGQS TQRGSRTTGR RGSGHSESSD SEVHSWGSHT HSGHIQGQAG
     SQQRQPGSTV HGRLETTHGQ TGDTTRHGHS GYGQSTQTGS RSSRASHFQS HSSERQRHGS
     SQVWKHGSYG PAEYDYGHTG YGPSGGSRKS ISNSHLSWST DSTANKQLSR H
//