UniProt functional annotation for O75147



	UniProt functional annotation for O75147

UniProt code: O75147.

Organism: Homo sapiens (Human).

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

Function: Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer (PubMed:24793695, PubMed:24793696). Acts as a regulator of the Cul7-RING(FBXW8) ubiquitin-protein ligase, playing a critical role in the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. Required to localize CUL7 to the Golgi apparatus in neurons. {ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}.

Subunit: Component of the 3M complex, composed of core components CUL7, CCDC8 and OBSL1. Interacts with CCDC8. Interacts with CUL7; the interaction is direct. Interacts with FBXW8. Interacts (via N-terminal Ig-like domain) with TTN/titin (via C-terminal Ig-like domain); the interaction is direct. {ECO:0000269|PubMed:20133654, ECO:0000269|PubMed:20489725, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:21737058, ECO:0000269|PubMed:24793695}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:24793695}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:24793695}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:24793695}. Golgi apparatus {ECO:0000269|PubMed:21572988}. Note=Colocalizes with CUL7 at the Golgi apparatus in neurons (PubMed:21572988).

Tissue specificity: Widely expressed, with predominant levels found in the heart. {ECO:0000269|PubMed:17289344}.

Disease: 3M syndrome 2 (3M2) [MIM:612921]: An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies. {ECO:0000269|PubMed:19481195, ECO:0000269|PubMed:23018678}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=AAH07201.1; Type=Erroneous initiation; Note=Extended 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:		Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer (PubMed:24793695, PubMed:24793696). Acts as a regulator of the Cul7-RING(FBXW8) ubiquitin-protein ligase, playing a critical role in the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. Required to localize CUL7 to the Golgi apparatus in neurons. {ECO:0000269\|PubMed:21572988, ECO:0000269\|PubMed:24793695, ECO:0000269\|PubMed:24793696}.


Subunit:		Component of the 3M complex, composed of core components CUL7, CCDC8 and OBSL1. Interacts with CCDC8. Interacts with CUL7; the interaction is direct. Interacts with FBXW8. Interacts (via N-terminal Ig-like domain) with TTN/titin (via C-terminal Ig-like domain); the interaction is direct. {ECO:0000269\|PubMed:20133654, ECO:0000269\|PubMed:20489725, ECO:0000269\|PubMed:21572988, ECO:0000269\|PubMed:21737058, ECO:0000269\|PubMed:24793695}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:24793695}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:24793695}. Cytoplasm, perinuclear region {ECO:0000269\|PubMed:24793695}. Golgi apparatus {ECO:0000269\|PubMed:21572988}. Note=Colocalizes with CUL7 at the Golgi apparatus in neurons (PubMed:21572988).
Tissue specificity:		Widely expressed, with predominant levels found in the heart. {ECO:0000269\|PubMed:17289344}.
Disease:		3M syndrome 2 (3M2) [MIM:612921]: An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies. {ECO:0000269\|PubMed:19481195, ECO:0000269\|PubMed:23018678}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=AAH07201.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};