UniProt functional annotation for P20930



	UniProt functional annotation for P20930

UniProt code: P20930.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis.

Subcellular location: Cytoplasmic granule {ECO:0000269|PubMed:16710414}. Note=In the stratum granulosum of the epidermis, localized within keratohyalin granules (PubMed:1429717). In granular keratinocytes and in lower corneocytes, colocalizes with calpain-1/CAPN1 (PubMed:21531719). {ECO:0000269|PubMed:1429717, ECO:0000269|PubMed:21531719}.

Tissue specificity: Expressed in skin, thymus, stomach, tonsils, testis, placenta, kidney, pancreas, mammary gland, bladder, thyroid, salivary gland and trachea, but not detected in heart, brain, liver, lung, bone marrow, small intestine, spleen, prostate, colon, or adrenal gland (PubMed:19384417). In the skin, mainly expressed in stratum granulosum of the epidermis (PubMed:1429717) (PubMed:19384417). {ECO:0000269|PubMed:1429717, ECO:0000269|PubMed:19384417}.

Induction: In cultured foreskin fibroblasts, up-regulated in response to Ca(2+) stimulation. {ECO:0000269|PubMed:19384417}.

Ptm: Filaggrin is initially synthesized as a large, insoluble, highly phosphorylated precursor containing many tandem copies of 324 AA, which are not separated by large linker sequences. During terminal differentiation it is dephosphorylated and proteolytically cleaved. The N-terminal of the mature protein is heterogeneous, and is blocked by the formation of pyroglutamate.

Ptm: Undergoes deimination of some arginine residues (citrullination). {ECO:0000269|PubMed:8780679}.

Disease: Ichthyosis vulgaris (VI) [MIM:146700]: The most common form of ichthyosis inherited as an autosomal dominant trait. It is characterized by palmar hyperlinearity, keratosis pilaris and a fine scale that is most prominent over the lower abdomen, arms, and legs. Ichthyosis vulgaris is characterized histologically by absent or reduced keratohyalin granules in the epidermis and mild hyperkeratosis. The disease can be associated with frequent asthma, eczema or hay fever. {ECO:0000269|PubMed:16444271}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Dermatitis atopic 2 (ATOD2) [MIM:605803]: Atopic dermatitis is a complex, inflammatory disease with multiple alleles at several loci thought to be involved in the pathogenesis. It commonly begins in infancy or early childhood and is characterized by a chronic relapsing form of skin inflammation, a disturbance of epidermal barrier function that culminates in dry skin, and IgE-mediated sensitization to food and environmental allergens. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. {ECO:0000269|PubMed:16550169, ECO:0000269|PubMed:16815158, ECO:0000269|PubMed:17030239, ECO:0000269|PubMed:17291859}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity: Belongs to the S100-fused protein family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis.


Subcellular location:		Cytoplasmic granule {ECO:0000269\|PubMed:16710414}. Note=In the stratum granulosum of the epidermis, localized within keratohyalin granules (PubMed:1429717). In granular keratinocytes and in lower corneocytes, colocalizes with calpain-1/CAPN1 (PubMed:21531719). {ECO:0000269\|PubMed:1429717, ECO:0000269\|PubMed:21531719}.
Tissue specificity:		Expressed in skin, thymus, stomach, tonsils, testis, placenta, kidney, pancreas, mammary gland, bladder, thyroid, salivary gland and trachea, but not detected in heart, brain, liver, lung, bone marrow, small intestine, spleen, prostate, colon, or adrenal gland (PubMed:19384417). In the skin, mainly expressed in stratum granulosum of the epidermis (PubMed:1429717) (PubMed:19384417). {ECO:0000269\|PubMed:1429717, ECO:0000269\|PubMed:19384417}.
Induction:		In cultured foreskin fibroblasts, up-regulated in response to Ca(2+) stimulation. {ECO:0000269\|PubMed:19384417}.
Ptm:		Filaggrin is initially synthesized as a large, insoluble, highly phosphorylated precursor containing many tandem copies of 324 AA, which are not separated by large linker sequences. During terminal differentiation it is dephosphorylated and proteolytically cleaved. The N-terminal of the mature protein is heterogeneous, and is blocked by the formation of pyroglutamate.
Ptm:		Undergoes deimination of some arginine residues (citrullination). {ECO:0000269\|PubMed:8780679}.
Disease:		Ichthyosis vulgaris (VI) [MIM:146700]: The most common form of ichthyosis inherited as an autosomal dominant trait. It is characterized by palmar hyperlinearity, keratosis pilaris and a fine scale that is most prominent over the lower abdomen, arms, and legs. Ichthyosis vulgaris is characterized histologically by absent or reduced keratohyalin granules in the epidermis and mild hyperkeratosis. The disease can be associated with frequent asthma, eczema or hay fever. {ECO:0000269\|PubMed:16444271}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Dermatitis atopic 2 (ATOD2) [MIM:605803]: Atopic dermatitis is a complex, inflammatory disease with multiple alleles at several loci thought to be involved in the pathogenesis. It commonly begins in infancy or early childhood and is characterized by a chronic relapsing form of skin inflammation, a disturbance of epidermal barrier function that culminates in dry skin, and IgE-mediated sensitization to food and environmental allergens. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. {ECO:0000269\|PubMed:16550169, ECO:0000269\|PubMed:16815158, ECO:0000269\|PubMed:17030239, ECO:0000269\|PubMed:17291859}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Similarity:		Belongs to the S100-fused protein family. {ECO:0000305}.