FILA2_HUMAN
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 03-AUG-2022, entry version 145.
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 TYR-355--HIS-2391 DEL, AND
RP CHARACTERIZATION OF VARIANT PSS6 TYR-355--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}.
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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; 110.
DR IntAct; Q5D862; 31.
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 BioMuta; FLG2; -.
DR DMDM; 74755309; -.
DR UCD-2DPAGE; Q5D862; -.
DR jPOST; Q5D862; -.
DR MassIVE; Q5D862; -.
DR PaxDb; Q5D862; -.
DR PeptideAtlas; Q5D862; -.
DR PRIDE; Q5D862; -.
DR ProteomicsDB; 62742; -.
DR Antibodypedia; 34087; 55 antibodies from 11 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 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; TRHGHSG; -.
DR OrthoDB; 482595at2759; -.
DR PhylomeDB; Q5D862; -.
DR TreeFam; TF338665; -.
DR PathwayCommons; Q5D862; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q5D862; -.
DR BioGRID-ORCS; 388698; 9 hits in 1064 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 tissues.
DR Genevisible; Q5D862; HS.
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 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 Pfam; PF01023; S_100; 1.
DR PRINTS; PR00487; FILAGGRIN.
DR SMART; SM01394; S_100; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS00303; S100_CABP; 1.
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
