UniProt functional annotation for Q96PY6



	UniProt functional annotation for Q96PY6

UniProt code: Q96PY6.

Organism: Homo sapiens (Human).

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

Function: Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:20230784). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:20230784). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:21211617}.

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:20230784};

Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:20230784};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;

Subunit: Binds to CBY2 (By similarity). Found in a complex with CFAP410, NEK1 and SPATA7 (PubMed:26167768). Interacts with CFAP410 (PubMed:26167768). Interacts (via Ser-1052 phosphorylated form) with 14-3-3 proteins (By similarity). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:26167768}.

Subcellular location: Nucleus {ECO:0000269|PubMed:15604234, ECO:0000305|PubMed:21211617}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:P51954}. Cytoplasm {ECO:0000269|PubMed:18843199}. Note=Associated with the pericentriolar material (PubMed:21211617). Localizes to centrosome during interphase and mitosis (By similarity). Translocated from cytoplasm to discrete nuclear foci at sites of DNA damage (PubMed:15604234). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:15604234, ECO:0000269|PubMed:21211617}.

Tissue specificity: High fetal expression in the brain and kidney. {ECO:0000269|PubMed:21211617}.

Disease: Short-rib thoracic dysplasia 6 with or without polydactyly (SRTD6) [MIM:263520]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer- Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:22499340}. Note=The disease is caused by variants affecting the gene represented in this entry. In some cases NEK1 mutations result in disease phenotype in the presence of mutations in DYNC2H1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617). {ECO:0000269|PubMed:21211617}.

Disease: Amyotrophic lateral sclerosis 24 (ALS24) [MIM:617892]: A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269|PubMed:26945885, ECO:0000269|PubMed:27455347}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity: Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAH15147.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAB15207.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB55209.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB67794.1; 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:		Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:20230784). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:20230784). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617). {ECO:0000250\|UniProtKB:P51954, ECO:0000269\|PubMed:20230784, ECO:0000269\|PubMed:21211617}.


Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269\|PubMed:20230784};
Catalytic activity:		Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269\|PubMed:20230784};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Subunit:		Binds to CBY2 (By similarity). Found in a complex with CFAP410, NEK1 and SPATA7 (PubMed:26167768). Interacts with CFAP410 (PubMed:26167768). Interacts (via Ser-1052 phosphorylated form) with 14-3-3 proteins (By similarity). {ECO:0000250\|UniProtKB:P51954, ECO:0000269\|PubMed:26167768}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:15604234, ECO:0000305\|PubMed:21211617}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250\|UniProtKB:P51954}. Cytoplasm {ECO:0000269\|PubMed:18843199}. Note=Associated with the pericentriolar material (PubMed:21211617). Localizes to centrosome during interphase and mitosis (By similarity). Translocated from cytoplasm to discrete nuclear foci at sites of DNA damage (PubMed:15604234). {ECO:0000250\|UniProtKB:P51954, ECO:0000269\|PubMed:15604234, ECO:0000269\|PubMed:21211617}.
Tissue specificity:		High fetal expression in the brain and kidney. {ECO:0000269\|PubMed:21211617}.
Disease:		Short-rib thoracic dysplasia 6 with or without polydactyly (SRTD6) [MIM:263520]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer- Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269\|PubMed:22499340}. Note=The disease is caused by variants affecting the gene represented in this entry. In some cases NEK1 mutations result in disease phenotype in the presence of mutations in DYNC2H1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617). {ECO:0000269\|PubMed:21211617}.
Disease:		Amyotrophic lateral sclerosis 24 (ALS24) [MIM:617892]: A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269\|PubMed:26945885, ECO:0000269\|PubMed:27455347}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Similarity:		Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAH15147.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAB15207.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB55209.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB67794.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};