UniProt functional annotation for Q01974



	UniProt functional annotation for Q01974

UniProt code: Q01974.

Organism: Homo sapiens (Human).

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

Function: Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development (By similarity). Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation (PubMed:17717073). In contrast, has also been shown to have very little tyrosine kinase activity in vitro. May act as a receptor for wnt ligand WNT5A which may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443). {ECO:0000250|UniProtKB:Q9Z138, ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:25029443}.

Catalytic activity: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:17717073};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:17717073};

Subunit: Homodimer; promotes osteogenesis. Binds YWHAB (PubMed:17717073). Interacts with WTIP (By similarity). {ECO:0000250|UniProtKB:Q9Z138, ECO:0000269|PubMed:17717073}.

Subcellular location: Cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.

Developmental stage: Expressed at high levels during early embryonic development. The expression levels drop strongly around day 16 and there are only very low levels in adult tissues.

Disease: Brachydactyly B1 (BDB1) [MIM:113000]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type B1 the middle phalanges are short but in addition the terminal phalanges are rudimentary or absent. Both fingers and toes are affected. The thumbs and big toes are usually deformed. Symphalangism is also a feature. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Robinow syndrome, autosomal recessive 1 (RRS1) [MIM:268310]: A recessive form of Robinow syndrome, a disease characterized by short- limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia. The clinical signs are generally far more severe in recessive cases, particularly skeletal abnormalities. All patients with the recessive form suffer from vertebral segmentation abnormalities, resulting in scoliosis and chest deformities. Rib fusions are considered to be characteristic of the autosomal recessive form. Patients can also present brachydactyly, with extensive aplasia/hypoplasia of the phalanges and metacarpals/metatarsals, and brachy-syn-polydactyly of the hands and oligodactyly of the feet. {ECO:0000269|PubMed:10932186, ECO:0000269|PubMed:10932187}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. ROR subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.

Sequence caution: Sequence=BAD92391.1; 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:		Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development (By similarity). Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation (PubMed:17717073). In contrast, has also been shown to have very little tyrosine kinase activity in vitro. May act as a receptor for wnt ligand WNT5A which may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443). {ECO:0000250\|UniProtKB:Q9Z138, ECO:0000269\|PubMed:17717073, ECO:0000269\|PubMed:25029443}.


Catalytic activity:		Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255\|PROSITE-ProRule:PRU10028, ECO:0000269\|PubMed:17717073};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:17717073};
Subunit:		Homodimer; promotes osteogenesis. Binds YWHAB (PubMed:17717073). Interacts with WTIP (By similarity). {ECO:0000250\|UniProtKB:Q9Z138, ECO:0000269\|PubMed:17717073}.
Subcellular location:		Cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
Developmental stage:		Expressed at high levels during early embryonic development. The expression levels drop strongly around day 16 and there are only very low levels in adult tissues.
Disease:		Brachydactyly B1 (BDB1) [MIM:113000]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type B1 the middle phalanges are short but in addition the terminal phalanges are rudimentary or absent. Both fingers and toes are affected. The thumbs and big toes are usually deformed. Symphalangism is also a feature. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Robinow syndrome, autosomal recessive 1 (RRS1) [MIM:268310]: A recessive form of Robinow syndrome, a disease characterized by short- limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia. The clinical signs are generally far more severe in recessive cases, particularly skeletal abnormalities. All patients with the recessive form suffer from vertebral segmentation abnormalities, resulting in scoliosis and chest deformities. Rib fusions are considered to be characteristic of the autosomal recessive form. Patients can also present brachydactyly, with extensive aplasia/hypoplasia of the phalanges and metacarpals/metatarsals, and brachy-syn-polydactyly of the hands and oligodactyly of the feet. {ECO:0000269\|PubMed:10932186, ECO:0000269\|PubMed:10932187}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the protein kinase superfamily. Tyr protein kinase family. ROR subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Sequence caution:		Sequence=BAD92391.1; Type=Erroneous initiation; Evidence={ECO:0000305};