UniProt functional annotation for P63005



	UniProt functional annotation for P63005

UniProt code: P63005.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates to the PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule- dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. Also required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet-activating factor (PAF) by removing the acetyl group at the SN-2 position. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (By similarity). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (PubMed:17330141). {ECO:0000250|UniProtKB:P43033, ECO:0000250|UniProtKB:P43034, ECO:0000255|HAMAP-Rule:MF_03141, ECO:0000269|PubMed:11056530, ECO:0000269|PubMed:11344260, ECO:0000269|PubMed:12796778, ECO:0000269|PubMed:12911752, ECO:0000269|PubMed:14507966, ECO:0000269|PubMed:14578885, ECO:0000269|PubMed:14691133, ECO:0000269|PubMed:15173193, ECO:0000269|PubMed:15473966, ECO:0000269|PubMed:16107726, ECO:0000269|PubMed:16203747, ECO:0000269|PubMed:16369480, ECO:0000269|PubMed:16481446, ECO:0000269|PubMed:17330141}.

Subunit: Component of the cytosolic PAF-AH (I) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity. Interacts with the catalytic dimer of PAF-AH (I) heterotetrameric enzyme: interacts with PAFAH1B2 homodimer (alpha2/alpha2 homodimer), PAFAH1B3 homodimer (alpha1/alpha1 homodimer) and PAFAH1B2-PAFAH1B3 heterodimer (alpha2/alpha1 heterodimer) (PubMed:11344260, PubMed:12885786, PubMed:16481446). Can self-associate (PubMed:11163259, PubMed:11344260, PubMed:12885786, PubMed:15572112). Interacts with DCX, dynein, dynactin, IQGAP1, KATNB1, NDE1, NDEL1, NUDC, and RSN (PubMed:11001923, PubMed:11056530, PubMed:11163258, PubMed:11163259, PubMed:11163260, PubMed:11231056, PubMed:11940666, PubMed:12885786, PubMed:15173193, PubMed:15473966, PubMed:15473967, PubMed:15572112, PubMed:16203747, PubMed:16291865, PubMed:16481446, PubMed:16369480). Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling (PubMed:14578885). Interacts with INTS13 (PubMed:23097494). Interacts with DCDC1 (By similarity). Interacts with DISC1, and this interaction is enhanced by NDEL1 (By similarity). {ECO:0000250|UniProtKB:P43034, ECO:0000269|PubMed:11001923, ECO:0000269|PubMed:11056530, ECO:0000269|PubMed:11163258, ECO:0000269|PubMed:11163259, ECO:0000269|PubMed:11163260, ECO:0000269|PubMed:11231056, ECO:0000269|PubMed:11344260, ECO:0000269|PubMed:11940666, ECO:0000269|PubMed:12885786, ECO:0000269|PubMed:14578885, ECO:0000269|PubMed:15173193, ECO:0000269|PubMed:15473966, ECO:0000269|PubMed:15473967, ECO:0000269|PubMed:15572112, ECO:0000269|PubMed:16203747, ECO:0000269|PubMed:16291865, ECO:0000269|PubMed:16369480, ECO:0000269|PubMed:16481446, ECO:0000269|PubMed:23097494}.

Subcellular location: Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Nucleus membrane {ECO:0000255|HAMAP-Rule:MF_03141}. Note=May localize to the nuclear membrane (By similarity). Localizes to the plus end of microtubules and to the centrosome. Redistributes to axons during neuronal development. Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes. {ECO:0000250}.

Tissue specificity: Highly expressed in brain, particularly the hippocampus and the olfactory bulb. Also highly expressed in testis, including all seminiferous tubule cell types, all types of spermatogenic and Sertoli cells, and meiotically dividing and elongating spermatids. Expressed at lower levels in heart, kidney, large intestine, liver, lung, ovary, small intestine and spleen. {ECO:0000269|PubMed:11163259, ECO:0000269|PubMed:11163260, ECO:0000269|PubMed:12551946}.

Developmental stage: Embryonic expression begins prior to the blastocyst stage, when maternally expressed protein is depleted. By 10.5 dpc, expression is abundant in the developing central and peripheral nervous systems. Major sites of expression include the neuroepithelium of the fore-, mid-, and hindbrain, the spinal cord, the dorsal root and the cranial ganglia. By 13.5 dpc, highly expressed in neuroblasts as well as postmitotic neurons of the cortical plate. After completion of neuronal migration expression remains high in the cortex. Also expressed in the testis from P8. {ECO:0000269|PubMed:11001923, ECO:0000269|PubMed:11056530, ECO:0000269|PubMed:11163259, ECO:0000269|PubMed:11231056, ECO:0000269|PubMed:11344260, ECO:0000269|PubMed:12950100, ECO:0000269|PubMed:15147871, ECO:0000269|PubMed:15473966}.

Domain: Dimerization mediated by the LisH domain may be required to activate dynein. {ECO:0000255|HAMAP-Rule:MF_03141, ECO:0000269|PubMed:15274919, ECO:0000269|PubMed:16258276}.

Disruption phenotype: Double heterozygous PAFAH1B1 and homozygous VLDLR knockout mice present no obvious cortical layering defects (PubMed:17330141). Double heterozygous PAFAH1B1 and homozygous LRP8 knockout mice display a reeler-like phenotype in the forebrain consisting of the inversion of cortical layers and hippocampal disorganization (PubMed:17330141). {ECO:0000269|PubMed:17330141}.

Miscellaneous: Originally the subunits of the type I platelet- activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1), beta (PAFAH1B2) and gamma (PAFAH1B3) (By similarity). Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and alpha1 (PAFAH1B3) respectively (By similarity). {ECO:0000250|UniProtKB:P43034, ECO:0000250|UniProtKB:P68402, ECO:0000250|UniProtKB:Q15102, ECO:0000250|UniProtKB:Q29460}.

Similarity: Belongs to the WD repeat LIS1/nudF family. {ECO:0000255|HAMAP-Rule:MF_03141}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates to the PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule- dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. Also required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet-activating factor (PAF) by removing the acetyl group at the SN-2 position. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (By similarity). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (PubMed:17330141). {ECO:0000250\|UniProtKB:P43033, ECO:0000250\|UniProtKB:P43034, ECO:0000255\|HAMAP-Rule:MF_03141, ECO:0000269\|PubMed:11056530, ECO:0000269\|PubMed:11344260, ECO:0000269\|PubMed:12796778, ECO:0000269\|PubMed:12911752, ECO:0000269\|PubMed:14507966, ECO:0000269\|PubMed:14578885, ECO:0000269\|PubMed:14691133, ECO:0000269\|PubMed:15173193, ECO:0000269\|PubMed:15473966, ECO:0000269\|PubMed:16107726, ECO:0000269\|PubMed:16203747, ECO:0000269\|PubMed:16369480, ECO:0000269\|PubMed:16481446, ECO:0000269\|PubMed:17330141}.


Subunit:		Component of the cytosolic PAF-AH (I) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity. Interacts with the catalytic dimer of PAF-AH (I) heterotetrameric enzyme: interacts with PAFAH1B2 homodimer (alpha2/alpha2 homodimer), PAFAH1B3 homodimer (alpha1/alpha1 homodimer) and PAFAH1B2-PAFAH1B3 heterodimer (alpha2/alpha1 heterodimer) (PubMed:11344260, PubMed:12885786, PubMed:16481446). Can self-associate (PubMed:11163259, PubMed:11344260, PubMed:12885786, PubMed:15572112). Interacts with DCX, dynein, dynactin, IQGAP1, KATNB1, NDE1, NDEL1, NUDC, and RSN (PubMed:11001923, PubMed:11056530, PubMed:11163258, PubMed:11163259, PubMed:11163260, PubMed:11231056, PubMed:11940666, PubMed:12885786, PubMed:15173193, PubMed:15473966, PubMed:15473967, PubMed:15572112, PubMed:16203747, PubMed:16291865, PubMed:16481446, PubMed:16369480). Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling (PubMed:14578885). Interacts with INTS13 (PubMed:23097494). Interacts with DCDC1 (By similarity). Interacts with DISC1, and this interaction is enhanced by NDEL1 (By similarity). {ECO:0000250\|UniProtKB:P43034, ECO:0000269\|PubMed:11001923, ECO:0000269\|PubMed:11056530, ECO:0000269\|PubMed:11163258, ECO:0000269\|PubMed:11163259, ECO:0000269\|PubMed:11163260, ECO:0000269\|PubMed:11231056, ECO:0000269\|PubMed:11344260, ECO:0000269\|PubMed:11940666, ECO:0000269\|PubMed:12885786, ECO:0000269\|PubMed:14578885, ECO:0000269\|PubMed:15173193, ECO:0000269\|PubMed:15473966, ECO:0000269\|PubMed:15473967, ECO:0000269\|PubMed:15572112, ECO:0000269\|PubMed:16203747, ECO:0000269\|PubMed:16291865, ECO:0000269\|PubMed:16369480, ECO:0000269\|PubMed:16481446, ECO:0000269\|PubMed:23097494}.
Subcellular location:		Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Nucleus membrane {ECO:0000255\|HAMAP-Rule:MF_03141}. Note=May localize to the nuclear membrane (By similarity). Localizes to the plus end of microtubules and to the centrosome. Redistributes to axons during neuronal development. Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes. {ECO:0000250}.
Tissue specificity:		Highly expressed in brain, particularly the hippocampus and the olfactory bulb. Also highly expressed in testis, including all seminiferous tubule cell types, all types of spermatogenic and Sertoli cells, and meiotically dividing and elongating spermatids. Expressed at lower levels in heart, kidney, large intestine, liver, lung, ovary, small intestine and spleen. {ECO:0000269\|PubMed:11163259, ECO:0000269\|PubMed:11163260, ECO:0000269\|PubMed:12551946}.
Developmental stage:		Embryonic expression begins prior to the blastocyst stage, when maternally expressed protein is depleted. By 10.5 dpc, expression is abundant in the developing central and peripheral nervous systems. Major sites of expression include the neuroepithelium of the fore-, mid-, and hindbrain, the spinal cord, the dorsal root and the cranial ganglia. By 13.5 dpc, highly expressed in neuroblasts as well as postmitotic neurons of the cortical plate. After completion of neuronal migration expression remains high in the cortex. Also expressed in the testis from P8. {ECO:0000269\|PubMed:11001923, ECO:0000269\|PubMed:11056530, ECO:0000269\|PubMed:11163259, ECO:0000269\|PubMed:11231056, ECO:0000269\|PubMed:11344260, ECO:0000269\|PubMed:12950100, ECO:0000269\|PubMed:15147871, ECO:0000269\|PubMed:15473966}.
Domain:		Dimerization mediated by the LisH domain may be required to activate dynein. {ECO:0000255\|HAMAP-Rule:MF_03141, ECO:0000269\|PubMed:15274919, ECO:0000269\|PubMed:16258276}.
Disruption phenotype:		Double heterozygous PAFAH1B1 and homozygous VLDLR knockout mice present no obvious cortical layering defects (PubMed:17330141). Double heterozygous PAFAH1B1 and homozygous LRP8 knockout mice display a reeler-like phenotype in the forebrain consisting of the inversion of cortical layers and hippocampal disorganization (PubMed:17330141). {ECO:0000269\|PubMed:17330141}.
Miscellaneous:		Originally the subunits of the type I platelet- activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1), beta (PAFAH1B2) and gamma (PAFAH1B3) (By similarity). Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and alpha1 (PAFAH1B3) respectively (By similarity). {ECO:0000250\|UniProtKB:P43034, ECO:0000250\|UniProtKB:P68402, ECO:0000250\|UniProtKB:Q15102, ECO:0000250\|UniProtKB:Q29460}.
Similarity:		Belongs to the WD repeat LIS1/nudF family. {ECO:0000255\|HAMAP-Rule:MF_03141}.