UniProt functional annotation for P81274



	UniProt functional annotation for P81274

UniProt code: P81274.

Organism: Homo sapiens (Human).

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

Function: Plays an important role in mitotic spindle pole organization via its interaction with NUMA1 (PubMed:11781568, PubMed:15632202, PubMed:21816348). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays also an important role in asymmetric cell divisions (PubMed:21816348). Has guanine nucleotide dissociation inhibitor (GDI) activity towards G(i) alpha proteins, such as GNAI1 and GNAI3, and thereby regulates their activity (By similarity). {ECO:0000250|UniProtKB:Q8VDU0, ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22327364}.

Subunit: Interacts with the dynein-dynactin complex; this interaction is inhibited in a PLK1-dependent manner (PubMed:22327364). Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (PubMed:26766442). Interacts with LLGL2 (PubMed:15632202). Interacts (via TPR repeat region) with INSC/inscuteable (PubMed:16458856, PubMed:22074847). Interacts (via TPR repeat region) with NUMA1 (via C- terminus); this interaction is direct, inhibited in a PLK1-dependent manner, prevents the binding of NUMA1 with SPAG5 and promotes spindle pole organization (PubMed:11781568, PubMed:22327364, PubMed:27462074). INSC and NUMA1 compete for the same binding site, but INSC has higher affinity and can displace NUMA1 (in vitro) (PubMed:22074847). Interacts with GNAI2 (PubMed:8973305). Interacts (via GoLoco domains) with the GDP-bound form of GNAI1 and GNAI3; has much lower affinity for the GTP- bound form. Interaction with GDP-bound GNAI3 strongly enhances the affinity for NUMA1 (By similarity). Interacts (via TPR repeat region) with FRMPD1 (PubMed:22074847). INSC and FRMPD1 compete for the same binding site, but INSC has higher affinity and can displace FRMPD1 (in vitro) (By similarity). Interacts (via TPR repeat region) with FRMPD4 (PubMed:22074847, PubMed:25664792). Identified in a complex with INSC and F2RL2/Par3 (PubMed:16458856). Interacts with TASOR (By similarity). {ECO:0000250|UniProtKB:Q8VDU0, ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:16458856, ECO:0000269|PubMed:22074847, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:25664792, ECO:0000269|PubMed:26766442, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:8973305}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:22074847}. Cytoplasm, cell cortex {ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22074847, ECO:0000269|PubMed:22327364}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:21816348}. Lateral cell membrane {ECO:0000269|PubMed:26766442}. Note=Localizes in the cytoplasm during interphase and at cell cortex during metaphase (PubMed:11781568, PubMed:15632202, PubMed:22074847). Colocalizes with NUMA1 to mitotic spindle poles (PubMed:11781568, PubMed:21816348). Localized at the central and lateral cell cortex regions in a RanGTP-dependent manner (PubMed:22327364). In horizontally retinal progenitor dividing cells, localized to the lateral cortical region. In vertically retinal progenitor dividing cells, localized at the polar cortical region (By similarity). {ECO:0000250|UniProtKB:Q8VDU0, ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22074847, ECO:0000269|PubMed:22327364}.

Tissue specificity: Ubiquitously expressed.

Disease: Chudley-McCullough syndrome (CMCS) [MIM:604213]: An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal. {ECO:0000269|PubMed:20602914, ECO:0000269|PubMed:22578326}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Dysfunction of LGN is associated with the phenotype of multiple micronuclei due to chromosomal mis-segregation and defect in cell division through mis-localization of mitotic spindle regulator protein NUMA1. {ECO:0000305}.

Similarity: Belongs to the GPSM family. {ECO:0000305}.

Sequence caution: Sequence=AAB40385.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH27732.1; 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:		Plays an important role in mitotic spindle pole organization via its interaction with NUMA1 (PubMed:11781568, PubMed:15632202, PubMed:21816348). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays also an important role in asymmetric cell divisions (PubMed:21816348). Has guanine nucleotide dissociation inhibitor (GDI) activity towards G(i) alpha proteins, such as GNAI1 and GNAI3, and thereby regulates their activity (By similarity). {ECO:0000250\|UniProtKB:Q8VDU0, ECO:0000269\|PubMed:11781568, ECO:0000269\|PubMed:15632202, ECO:0000269\|PubMed:21816348, ECO:0000269\|PubMed:22327364}.


Subunit:		Interacts with the dynein-dynactin complex; this interaction is inhibited in a PLK1-dependent manner (PubMed:22327364). Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (PubMed:26766442). Interacts with LLGL2 (PubMed:15632202). Interacts (via TPR repeat region) with INSC/inscuteable (PubMed:16458856, PubMed:22074847). Interacts (via TPR repeat region) with NUMA1 (via C- terminus); this interaction is direct, inhibited in a PLK1-dependent manner, prevents the binding of NUMA1 with SPAG5 and promotes spindle pole organization (PubMed:11781568, PubMed:22327364, PubMed:27462074). INSC and NUMA1 compete for the same binding site, but INSC has higher affinity and can displace NUMA1 (in vitro) (PubMed:22074847). Interacts with GNAI2 (PubMed:8973305). Interacts (via GoLoco domains) with the GDP-bound form of GNAI1 and GNAI3; has much lower affinity for the GTP- bound form. Interaction with GDP-bound GNAI3 strongly enhances the affinity for NUMA1 (By similarity). Interacts (via TPR repeat region) with FRMPD1 (PubMed:22074847). INSC and FRMPD1 compete for the same binding site, but INSC has higher affinity and can displace FRMPD1 (in vitro) (By similarity). Interacts (via TPR repeat region) with FRMPD4 (PubMed:22074847, PubMed:25664792). Identified in a complex with INSC and F2RL2/Par3 (PubMed:16458856). Interacts with TASOR (By similarity). {ECO:0000250\|UniProtKB:Q8VDU0, ECO:0000269\|PubMed:11781568, ECO:0000269\|PubMed:15632202, ECO:0000269\|PubMed:16458856, ECO:0000269\|PubMed:22074847, ECO:0000269\|PubMed:22327364, ECO:0000269\|PubMed:25664792, ECO:0000269\|PubMed:26766442, ECO:0000269\|PubMed:27462074, ECO:0000269\|PubMed:8973305}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:11781568, ECO:0000269\|PubMed:15632202, ECO:0000269\|PubMed:22074847}. Cytoplasm, cell cortex {ECO:0000269\|PubMed:15632202, ECO:0000269\|PubMed:21816348, ECO:0000269\|PubMed:22074847, ECO:0000269\|PubMed:22327364}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269\|PubMed:11781568, ECO:0000269\|PubMed:21816348}. Lateral cell membrane {ECO:0000269\|PubMed:26766442}. Note=Localizes in the cytoplasm during interphase and at cell cortex during metaphase (PubMed:11781568, PubMed:15632202, PubMed:22074847). Colocalizes with NUMA1 to mitotic spindle poles (PubMed:11781568, PubMed:21816348). Localized at the central and lateral cell cortex regions in a RanGTP-dependent manner (PubMed:22327364). In horizontally retinal progenitor dividing cells, localized to the lateral cortical region. In vertically retinal progenitor dividing cells, localized at the polar cortical region (By similarity). {ECO:0000250\|UniProtKB:Q8VDU0, ECO:0000269\|PubMed:11781568, ECO:0000269\|PubMed:15632202, ECO:0000269\|PubMed:21816348, ECO:0000269\|PubMed:22074847, ECO:0000269\|PubMed:22327364}.
Tissue specificity:		Ubiquitously expressed.
Disease:		Chudley-McCullough syndrome (CMCS) [MIM:604213]: An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal. {ECO:0000269\|PubMed:20602914, ECO:0000269\|PubMed:22578326}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Dysfunction of LGN is associated with the phenotype of multiple micronuclei due to chromosomal mis-segregation and defect in cell division through mis-localization of mitotic spindle regulator protein NUMA1. {ECO:0000305}.
Similarity:		Belongs to the GPSM family. {ECO:0000305}.
Sequence caution:		Sequence=AAB40385.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH27732.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};