UniProt functional annotation for P16112



	UniProt functional annotation for P16112

UniProt code: P16112.

Organism: Homo sapiens (Human).

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

Function: This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region.

Subunit: Interacts with FBLN1 (By similarity). Interacts with COMP. {ECO:0000250, ECO:0000269|PubMed:17588949}.

Subcellular location: Secreted, extracellular space, extracellular matrix {ECO:0000250}.

Tissue specificity: Restricted to cartilages. {ECO:0000269|PubMed:7524681}.

Developmental stage: Expression was detected in chondrocytes throughout the developing skeleton.

Domain: Two globular domains, G1 and G2, comprise the N-terminus of the proteoglycan, while another globular region, G3, makes up the C- terminus. G1 contains Link domains and thus consists of three disulfide-bonded loop structures designated as the A, B, B' motifs. G2 is similar to G1. The keratan sulfate (KS) and the chondroitin sulfate (CS) attachment domains lie between G2 and G3.

Ptm: Contains mostly chondroitin sulfate, but also keratan sulfate chains, N-linked and O-linked oligosaccharides. The release of aggrecan fragments from articular cartilage into the synovial fluid at all stages of human osteoarthritis is the result of cleavage by aggrecanase. {ECO:0000269|PubMed:1569188, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:7574678}.

Disease: Spondyloepiphyseal dysplasia type Kimberley (SEDK) [MIM:608361]: Spondyloepiphyseal dysplasias are a heterogeneous group of congenital chondrodysplasias that specifically affect epiphyses and vertebrae. The autosomal dominant SEDK is associated with premature degenerative arthropathy. {ECO:0000269|PubMed:16080123}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Spondyloepimetaphyseal dysplasia, aggrecan type (SEMDAG) [MIM:612813]: A bone disease characterized by severe short stature, macrocephaly, severe midface hypoplasia, short neck, barrel chest and brachydactyly. The radiological findings comprise long bones with generalized irregular epiphyses with widened metaphyses, especially at the knees, platyspondyly, and multiple cervical-vertebral clefts. {ECO:0000269|PubMed:19110214}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Short stature and advanced bone age, with or without early- onset osteoarthritis and/or osteochondritis dissecans (SSOAOD) [MIM:165800]: An autosomal dominant disease characterized by short stature, advanced bone maturation, early-onset osteoarthritis, and mild dysmorphic features consisting of midface hypoplasia, brachydactyly, broad great toes, and lumbar lordosis. Other features include intervertebral disk disease and osteochondritis dissecans. Osteochondritis dissecans is defined as a separation of cartilage and subchondral bone from the surrounding tissue. {ECO:0000269|PubMed:20137779}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the aggrecan/versican proteoglycan 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:		This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region.


Subunit:		Interacts with FBLN1 (By similarity). Interacts with COMP. {ECO:0000250, ECO:0000269\|PubMed:17588949}.
Subcellular location:		Secreted, extracellular space, extracellular matrix {ECO:0000250}.
Tissue specificity:		Restricted to cartilages. {ECO:0000269\|PubMed:7524681}.
Developmental stage:		Expression was detected in chondrocytes throughout the developing skeleton.
Domain:		Two globular domains, G1 and G2, comprise the N-terminus of the proteoglycan, while another globular region, G3, makes up the C- terminus. G1 contains Link domains and thus consists of three disulfide-bonded loop structures designated as the A, B, B' motifs. G2 is similar to G1. The keratan sulfate (KS) and the chondroitin sulfate (CS) attachment domains lie between G2 and G3.
Ptm:		Contains mostly chondroitin sulfate, but also keratan sulfate chains, N-linked and O-linked oligosaccharides. The release of aggrecan fragments from articular cartilage into the synovial fluid at all stages of human osteoarthritis is the result of cleavage by aggrecanase. {ECO:0000269\|PubMed:1569188, ECO:0000269\|PubMed:16335952, ECO:0000269\|PubMed:7574678}.
Disease:		Spondyloepiphyseal dysplasia type Kimberley (SEDK) [MIM:608361]: Spondyloepiphyseal dysplasias are a heterogeneous group of congenital chondrodysplasias that specifically affect epiphyses and vertebrae. The autosomal dominant SEDK is associated with premature degenerative arthropathy. {ECO:0000269\|PubMed:16080123}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Spondyloepimetaphyseal dysplasia, aggrecan type (SEMDAG) [MIM:612813]: A bone disease characterized by severe short stature, macrocephaly, severe midface hypoplasia, short neck, barrel chest and brachydactyly. The radiological findings comprise long bones with generalized irregular epiphyses with widened metaphyses, especially at the knees, platyspondyly, and multiple cervical-vertebral clefts. {ECO:0000269\|PubMed:19110214}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Short stature and advanced bone age, with or without early- onset osteoarthritis and/or osteochondritis dissecans (SSOAOD) [MIM:165800]: An autosomal dominant disease characterized by short stature, advanced bone maturation, early-onset osteoarthritis, and mild dysmorphic features consisting of midface hypoplasia, brachydactyly, broad great toes, and lumbar lordosis. Other features include intervertebral disk disease and osteochondritis dissecans. Osteochondritis dissecans is defined as a separation of cartilage and subchondral bone from the surrounding tissue. {ECO:0000269\|PubMed:20137779}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the aggrecan/versican proteoglycan family. {ECO:0000305}.