UniProt functional annotation for P04264



	UniProt functional annotation for P04264

UniProt code: P04264.

Organism: Homo sapiens (Human).

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

Function: May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity receptor for kininogen-1/HMWK. {ECO:0000269|PubMed:17956333, ECO:0000269|PubMed:21544310}.

Subunit: Heterotetramer of two type I and two type II keratins. Heterodimer with KRT10 (PubMed:27595935). Two heterodimers of KRT1 and KRT10 form a heterotetramer (PubMed:27595935). Interacts with ITGB1 in the presence of RACK1 and SRC, and with RACK1 (PubMed:17956333). Interacts with C1QBP; the association represents a cell surface kininogen receptor (PubMed:21544310). Interacts with EPPK1; interaction is dependent of higher-order structure of intermediate filament (PubMed:16923132). {ECO:0000269|PubMed:16923132, ECO:0000269|PubMed:17956333, ECO:0000269|PubMed:21544310, ECO:0000269|PubMed:27595935}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:17956333}. Note=Located on plasma membrane of neuroblastoma NMB7 cells.

Tissue specificity: The source of this protein is neonatal foreskin. The 67-kDa type II keratins are expressed in terminally differentiating epidermis.

Ptm: Undergoes deimination of some arginine residues (citrullination). {ECO:0000269|PubMed:11841545, ECO:0000269|PubMed:8780679}.

Polymorphism: There are two size variants of KRT1, termed allele 1A and allele 1B with allelic frequencies of 0.61 and 0.39. Allele 1B lacks 7 residues compared to allele 1A.

Disease: Epidermolytic hyperkeratosis (EHK) [MIM:113800]: An autosomal dominant skin disorder characterized by widespread blistering and an ichthyotic erythroderma at birth that persist into adulthood. Histologically there is a diffuse epidermolytic degeneration in the lower spinous layer of the epidermis. Within a few weeks from birth, erythroderma and blister formation diminish and hyperkeratoses develop. {ECO:0000269|PubMed:10232403, ECO:0000269|PubMed:10688370, ECO:0000269|PubMed:10844506, ECO:0000269|PubMed:11531804, ECO:0000269|PubMed:12406348, ECO:0000269|PubMed:1380725, ECO:0000269|PubMed:1381288, ECO:0000269|PubMed:21271994, ECO:0000269|PubMed:7507151, ECO:0000269|PubMed:7507152, ECO:0000269|PubMed:7512983, ECO:0000269|PubMed:9856846}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Ichthyosis hystrix, Curth-Macklin type (IHCM) [MIM:146590]: A genodermatosis with severe verrucous hyperkeratosis. Affected individuals manifest congenital verrucous black scale on the scalp, neck, and limbs with truncal erythema, palmoplantar keratoderma and keratoses on the lips, ears, nipples and buttocks. {ECO:0000269|PubMed:11286616}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Keratoderma, palmoplantar, non-epidermolytic (NEPPK) [MIM:600962]: A dermatological disorder characterized by well- demarcated hyperkeratosis is present over the palms and soles. A red band is frequently present at the periphery of the keratosis. It is usually non-transgredient, with a sharp demarcation of the lesions at the wrists. {ECO:0000269|PubMed:11286630, ECO:0000269|PubMed:7528239}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Ichthyosis annular epidermolytic (AEI) [MIM:607602]: A skin disorder resembling bullous congenital ichthyosiform erythroderma. Affected individuals present with bullous ichthyosis in early childhood and hyperkeratotic lichenified plaques in the flexural areas and extensor surfaces at later ages. The feature that distinguishes AEI from BCIE is dramatic episodes of flares of annular polycyclic plaques with scale, which coalesce to involve most of the body surface and can persist for several weeks or even months. {ECO:0000269|PubMed:10053007, ECO:0000269|PubMed:10597140}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Keratoderma, palmoplantar, striate 3 (SPPK3) [MIM:607654]: A dermatological disorder characterized by thickening of the stratum corneum and epidermal layers on palms and soles. There is no involvement of non-palmoplantar skin, and both hair and nails are normal. {ECO:0000269|PubMed:11982762}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).

Similarity: Belongs to the intermediate filament family. {ECO:0000255|PROSITE-ProRule:PRU01188}.

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:		May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity receptor for kininogen-1/HMWK. {ECO:0000269\|PubMed:17956333, ECO:0000269\|PubMed:21544310}.


Subunit:		Heterotetramer of two type I and two type II keratins. Heterodimer with KRT10 (PubMed:27595935). Two heterodimers of KRT1 and KRT10 form a heterotetramer (PubMed:27595935). Interacts with ITGB1 in the presence of RACK1 and SRC, and with RACK1 (PubMed:17956333). Interacts with C1QBP; the association represents a cell surface kininogen receptor (PubMed:21544310). Interacts with EPPK1; interaction is dependent of higher-order structure of intermediate filament (PubMed:16923132). {ECO:0000269\|PubMed:16923132, ECO:0000269\|PubMed:17956333, ECO:0000269\|PubMed:21544310, ECO:0000269\|PubMed:27595935}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:17956333}. Note=Located on plasma membrane of neuroblastoma NMB7 cells.
Tissue specificity:		The source of this protein is neonatal foreskin. The 67-kDa type II keratins are expressed in terminally differentiating epidermis.
Ptm:		Undergoes deimination of some arginine residues (citrullination). {ECO:0000269\|PubMed:11841545, ECO:0000269\|PubMed:8780679}.
Polymorphism:		There are two size variants of KRT1, termed allele 1A and allele 1B with allelic frequencies of 0.61 and 0.39. Allele 1B lacks 7 residues compared to allele 1A.
Disease:		Epidermolytic hyperkeratosis (EHK) [MIM:113800]: An autosomal dominant skin disorder characterized by widespread blistering and an ichthyotic erythroderma at birth that persist into adulthood. Histologically there is a diffuse epidermolytic degeneration in the lower spinous layer of the epidermis. Within a few weeks from birth, erythroderma and blister formation diminish and hyperkeratoses develop. {ECO:0000269\|PubMed:10232403, ECO:0000269\|PubMed:10688370, ECO:0000269\|PubMed:10844506, ECO:0000269\|PubMed:11531804, ECO:0000269\|PubMed:12406348, ECO:0000269\|PubMed:1380725, ECO:0000269\|PubMed:1381288, ECO:0000269\|PubMed:21271994, ECO:0000269\|PubMed:7507151, ECO:0000269\|PubMed:7507152, ECO:0000269\|PubMed:7512983, ECO:0000269\|PubMed:9856846}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Ichthyosis hystrix, Curth-Macklin type (IHCM) [MIM:146590]: A genodermatosis with severe verrucous hyperkeratosis. Affected individuals manifest congenital verrucous black scale on the scalp, neck, and limbs with truncal erythema, palmoplantar keratoderma and keratoses on the lips, ears, nipples and buttocks. {ECO:0000269\|PubMed:11286616}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Keratoderma, palmoplantar, non-epidermolytic (NEPPK) [MIM:600962]: A dermatological disorder characterized by well- demarcated hyperkeratosis is present over the palms and soles. A red band is frequently present at the periphery of the keratosis. It is usually non-transgredient, with a sharp demarcation of the lesions at the wrists. {ECO:0000269\|PubMed:11286630, ECO:0000269\|PubMed:7528239}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Ichthyosis annular epidermolytic (AEI) [MIM:607602]: A skin disorder resembling bullous congenital ichthyosiform erythroderma. Affected individuals present with bullous ichthyosis in early childhood and hyperkeratotic lichenified plaques in the flexural areas and extensor surfaces at later ages. The feature that distinguishes AEI from BCIE is dramatic episodes of flares of annular polycyclic plaques with scale, which coalesce to involve most of the body surface and can persist for several weeks or even months. {ECO:0000269\|PubMed:10053007, ECO:0000269\|PubMed:10597140}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Keratoderma, palmoplantar, striate 3 (SPPK3) [MIM:607654]: A dermatological disorder characterized by thickening of the stratum corneum and epidermal layers on palms and soles. There is no involvement of non-palmoplantar skin, and both hair and nails are normal. {ECO:0000269\|PubMed:11982762}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
Similarity:		Belongs to the intermediate filament family. {ECO:0000255\|PROSITE-ProRule:PRU01188}.