UniProt functional annotation for P43146



	UniProt functional annotation for P43146

UniProt code: P43146.

Organism: Homo sapiens (Human).

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

Function: Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene. {ECO:0000269|PubMed:8187090, ECO:0000269|PubMed:8861902}.

Subunit: Interacts with the cytoplasmic part of UNC5A, UNC5B, UNC5C and probably UNC5D (By similarity). Interacts with DSCAM (By similarity). Interacts with PTK2/FAK1 and MAPK1 (By similarity). Interacts with NTN1 (By similarity). Interacts with MYO10 (PubMed:21642953). Interacts with CBLN4; this interaction can be competed by NTN1 (By similarity). Interacts with SIAH1 and SIAH2 (PubMed:9334332). {ECO:0000250|UniProtKB:P70211, ECO:0000250|UniProtKB:Q63155, ECO:0000269|PubMed:21642953, ECO:0000269|PubMed:9334332}.

Subcellular location: Membrane; Single-pass type I membrane protein.

Tissue specificity: Found in axons of the central and peripheral nervous system and in differentiated cell types of the intestine. Not expressed in colorectal tumor cells that lost their capacity to differentiate into mucus producing cells. {ECO:0000269|PubMed:7926722}.

Ptm: Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation. {ECO:0000269|PubMed:9334332}.

Disease: Mirror movements 1 (MRMV1) [MIM:157600]: A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. Some MRMV1 patients have agenesis of the corpus callosum. {ECO:0000269|PubMed:20431009, ECO:0000269|PubMed:28250454}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Gaze palsy, familial horizontal, with progressive scoliosis, 2, with impaired intellectual development (HGPPS2) [MIM:617542]: An autosomal recessive neurologic disorder characterized by global developmental delay, delayed walking, intellectual disability, horizontal gaze palsy, and childhood-onset progressive scoliosis. {ECO:0000269|PubMed:28250456}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Inactivation of DCC due to allelic deletion and/or point mutations is related to lymphatic and hematogenous metastatic tumor dissemination.

Similarity: Belongs to the immunoglobulin superfamily. DCC family. {ECO:0000305}.

Sequence caution: Sequence=AAA52175.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAA52177.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAA52179.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAA52180.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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:		Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene. {ECO:0000269\|PubMed:8187090, ECO:0000269\|PubMed:8861902}.


Subunit:		Interacts with the cytoplasmic part of UNC5A, UNC5B, UNC5C and probably UNC5D (By similarity). Interacts with DSCAM (By similarity). Interacts with PTK2/FAK1 and MAPK1 (By similarity). Interacts with NTN1 (By similarity). Interacts with MYO10 (PubMed:21642953). Interacts with CBLN4; this interaction can be competed by NTN1 (By similarity). Interacts with SIAH1 and SIAH2 (PubMed:9334332). {ECO:0000250\|UniProtKB:P70211, ECO:0000250\|UniProtKB:Q63155, ECO:0000269\|PubMed:21642953, ECO:0000269\|PubMed:9334332}.
Subcellular location:		Membrane; Single-pass type I membrane protein.
Tissue specificity:		Found in axons of the central and peripheral nervous system and in differentiated cell types of the intestine. Not expressed in colorectal tumor cells that lost their capacity to differentiate into mucus producing cells. {ECO:0000269\|PubMed:7926722}.
Ptm:		Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation. {ECO:0000269\|PubMed:9334332}.
Disease:		Mirror movements 1 (MRMV1) [MIM:157600]: A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. Some MRMV1 patients have agenesis of the corpus callosum. {ECO:0000269\|PubMed:20431009, ECO:0000269\|PubMed:28250454}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Gaze palsy, familial horizontal, with progressive scoliosis, 2, with impaired intellectual development (HGPPS2) [MIM:617542]: An autosomal recessive neurologic disorder characterized by global developmental delay, delayed walking, intellectual disability, horizontal gaze palsy, and childhood-onset progressive scoliosis. {ECO:0000269\|PubMed:28250456}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Inactivation of DCC due to allelic deletion and/or point mutations is related to lymphatic and hematogenous metastatic tumor dissemination.
Similarity:		Belongs to the immunoglobulin superfamily. DCC family. {ECO:0000305}.
Sequence caution:		Sequence=AAA52175.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAA52177.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAA52179.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAA52180.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};