UniProt functional annotation for O94885



	UniProt functional annotation for O94885

UniProt code: O94885.

Organism: Homo sapiens (Human).

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

Function: Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation. It acts as a scaffold molecule to assemble a molecular complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby facilitating NF-kappa-B signaling activation (PubMed:23776175). Regulates TRAF6 and MAP3K7 ubiquitination (PubMed:23776175). Involved in the regulation of cell mobility (PubMed:23333244, PubMed:23776175, PubMed:25315659). Regulates lipolysaccharide (LPS)-induced endothelial cell migration (PubMed:23776175). Is involved in the regulation of skin pigmentation through the control of melanocyte migration in the epidermis (PubMed:23333244). {ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:23776175, ECO:0000269|PubMed:25315659}.

Subunit: Interacts with GNAS (PubMed:23333244). Interacts with IQGAP1 (PubMed:23333244). Interacts with TRAF6 (via C-terminus); the interaction is LPS-dependent (PubMed:23776175). Interacts with MAP3K7, CHUK and IKBKB (PubMed:23776175). {ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:23776175}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:23333244}.

Tissue specificity: Expressed ubiquitously, with highest levels in lung, placenta, spleen and thymus. Down-regulated in the majority (74%) of breast tumors in comparison with corresponding normal breast epithelial tissues. Expressed in the epidermis, epidermal keratinocytes, dermal fibroblasts and melanocytes (PubMed:23333244, PubMed:26203640). {ECO:0000269|PubMed:12771949, ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:26203640}.

Disease: Dyschromatosis universalis hereditaria 1 (DUH1) [MIM:127500]: A form of dyschromatosis universalis, an autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body, that appear in infancy or early childhood. The trunk and extremities are the dominant sites of abnormal pigmentation. Facial lesions can be seen in 50% of affected individuals, but involvement of palms and soles is unusual. Abnormalities of hair and nails have also been reported. Dyschromatosis universalis hereditaria may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications. {ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:26203640, ECO:0000269|PubMed:27659786, ECO:0000269|PubMed:27840890, ECO:0000269|PubMed:27885802, ECO:0000269|PubMed:29956681}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma (CAPOK) [MIM:618373]: An autosomal recessive genodermatosis characterized by hypo- and hyperpigmented macular skin lesions, progressive alopecia, palmoplantar keratoderma, dystrophic nails, teeth abnormalities and a predisposition to squamous cell carcinoma. {ECO:0000269|PubMed:25315659}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=BAA34510.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB14909.1; Type=Erroneous initiation; Evidence={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:		Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation. It acts as a scaffold molecule to assemble a molecular complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby facilitating NF-kappa-B signaling activation (PubMed:23776175). Regulates TRAF6 and MAP3K7 ubiquitination (PubMed:23776175). Involved in the regulation of cell mobility (PubMed:23333244, PubMed:23776175, PubMed:25315659). Regulates lipolysaccharide (LPS)-induced endothelial cell migration (PubMed:23776175). Is involved in the regulation of skin pigmentation through the control of melanocyte migration in the epidermis (PubMed:23333244). {ECO:0000269\|PubMed:23333244, ECO:0000269\|PubMed:23776175, ECO:0000269\|PubMed:25315659}.


Subunit:		Interacts with GNAS (PubMed:23333244). Interacts with IQGAP1 (PubMed:23333244). Interacts with TRAF6 (via C-terminus); the interaction is LPS-dependent (PubMed:23776175). Interacts with MAP3K7, CHUK and IKBKB (PubMed:23776175). {ECO:0000269\|PubMed:23333244, ECO:0000269\|PubMed:23776175}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:23333244}.
Tissue specificity:		Expressed ubiquitously, with highest levels in lung, placenta, spleen and thymus. Down-regulated in the majority (74%) of breast tumors in comparison with corresponding normal breast epithelial tissues. Expressed in the epidermis, epidermal keratinocytes, dermal fibroblasts and melanocytes (PubMed:23333244, PubMed:26203640). {ECO:0000269\|PubMed:12771949, ECO:0000269\|PubMed:23333244, ECO:0000269\|PubMed:26203640}.
Disease:		Dyschromatosis universalis hereditaria 1 (DUH1) [MIM:127500]: A form of dyschromatosis universalis, an autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body, that appear in infancy or early childhood. The trunk and extremities are the dominant sites of abnormal pigmentation. Facial lesions can be seen in 50% of affected individuals, but involvement of palms and soles is unusual. Abnormalities of hair and nails have also been reported. Dyschromatosis universalis hereditaria may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications. {ECO:0000269\|PubMed:23333244, ECO:0000269\|PubMed:26203640, ECO:0000269\|PubMed:27659786, ECO:0000269\|PubMed:27840890, ECO:0000269\|PubMed:27885802, ECO:0000269\|PubMed:29956681}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma (CAPOK) [MIM:618373]: An autosomal recessive genodermatosis characterized by hypo- and hyperpigmented macular skin lesions, progressive alopecia, palmoplantar keratoderma, dystrophic nails, teeth abnormalities and a predisposition to squamous cell carcinoma. {ECO:0000269\|PubMed:25315659}. Note=The disease may be caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=BAA34510.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB14909.1; Type=Erroneous initiation; Evidence={ECO:0000305};