Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B1)

The protein contains 410 amino acids for an estimated molecular weight of 46638 Da.

 

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). 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 (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 microtubule (updated: Feb. 10, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 99

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VariantDescription
LIS1
LIS1
LIS1
SBH
SBH
LIS1
LIS1

Biological Process

Acrosome assembly GO Logo
Actin cytoskeleton organization GO Logo
Adult locomotory behavior GO Logo
Ameboidal-type cell migration GO Logo
Auditory receptor cell development GO Logo
Brain morphogenesis GO Logo
Cell division GO Logo
Cerebral cortex development GO Logo
Cerebral cortex neuron differentiation GO Logo
Chemical synaptic transmission GO Logo
Ciliary basal body-plasma membrane docking GO Logo
Cochlea development GO Logo
Corpus callosum morphogenesis GO Logo
Cortical microtubule organization GO Logo
Establishment of centrosome localization GO Logo
Establishment of mitotic spindle orientation GO Logo
Establishment of planar polarity of embryonic epithelium GO Logo
G2/M transition of mitotic cell cycle GO Logo
Germ cell development GO Logo
Hippocampus development GO Logo
Layer formation in cerebral cortex GO Logo
Learning or memory GO Logo
Lipid catabolic process GO Logo
Maintenance of centrosome location GO Logo
Microtubule cytoskeleton organization GO Logo
Microtubule cytoskeleton organization involved in establishment of planar polarity GO Logo
Microtubule organizing center organization GO Logo
Microtubule sliding GO Logo
Microtubule-based process GO Logo
Mitotic cell cycle GO Logo
Mitotic nuclear division GO Logo
Mitotic spindle organization GO Logo
Negative regulation of JNK cascade GO Logo
Negative regulation of neuron projection development GO Logo
Neuroblast proliferation GO Logo
Neuromuscular process controlling balance GO Logo
Neuron migration GO Logo
Nuclear membrane disassembly GO Logo
Nuclear migration GO Logo
Organelle organization GO Logo
Osteoclast development GO Logo
Platelet activating factor metabolic process GO Logo
Positive regulation of axon extension GO Logo
Positive regulation of cytokine-mediated signaling pathway GO Logo
Positive regulation of dendritic spine morphogenesis GO Logo
Positive regulation of embryonic development GO Logo
Positive regulation of mitotic cell cycle GO Logo
Protein secretion GO Logo
Reelin-mediated signaling pathway GO Logo
Regulation of G2/M transition of mitotic cell cycle GO Logo
Regulation of GTPase activity GO Logo
Regulation of microtubule cytoskeleton organization GO Logo
Regulation of microtubule motor activity GO Logo
Retrograde axonal transport GO Logo
Sister chromatid cohesion GO Logo
Stem cell division GO Logo
Transmission of nerve impulse GO Logo
Vesicle transport along microtubule GO Logo

The reference OMIM entry for this protein is 247200

Miller-dieker lissencephaly syndrome; mdls
Mds chromosome 17p13.3 deletion syndrome, included
Miller-dieker syndrome chromosome region, included; mdcr, included

A number sign (#) is used with this entry because Miller-Dieker lissencephaly syndrome is a contiguous gene deletion syndrome involving genes on chromosome 17p13.3. See also the 17p13.3 duplication syndrome (613215), which involves the same chromosomal region.

DESCRIPTION

Features of the Miller-Dieker syndrome include classic lissencephaly (pachygyria, incomplete or absent gyration of the cerebrum), microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, cardiac malformations, hypoplastic male extrenal genitalia, growth retardation, and mental deficiency with seizures and EEG abnormalities. Life expectancy is grossly reduced, with death most often occurring during early childhood (summary by Schinzel, 1988). Lissencephaly means 'smooth brain,' i.e., brain without convolutions or gyri. Deletion of or mutation in the LIS1 gene (PAFAH1B1; 601545) appears to cause the lissencephaly because point mutations have been identified in this gene in isolated lissencephaly sequence (ILS; see 607432). Facial dysmorphism and other anomalies in Miller-Dieker patients appear to be the consequence of deletion of additional genes distal to LIS1. Toyo-oka et al. (2003) presented evidence that the gene whose deletion is responsible for the greater severity of Miller-Dieker syndrome compared to isolated lissencephaly is the gene encoding 14-3-3-epsilon (YWHAE; 605066).

CLINICAL FEATURES

Miller (1963) described this condition in a brother and sister who were the fifth and sixth children of unrelated parents. The features were microcephaly, small mandible, bizarre facies, failure to thrive, retarded motor development, dysphagia, decorticate and decerebrate postures, and death at 3 and 4 months, respectively. Autopsy showed anomalies of the brain, kidney, heart, and gastrointestinal tract. The brains were smooth with large ventricles and a histologic architecture more like normal fetal brain of 3 to 4 months' gestation. Dieker et al. (1969) described 2 affected brothers and an affected female maternal first cousin. They also emphasized that this should be termed the lissencephaly syndrome because malformations of the heart, kidneys, and other organs, as well as polydactyly and unusual facial appearance, are associated. Reznik and Alberca-Serrano (1964) described 2 brothers with congenital hypertelorism, mental defect, intractable epilepsy, progressive spastic paraplegia, and death at ages 19 and 9 years. The mother showed hypertelorism and short-lived epileptiform attacks. Autopsy showed lissencephaly with massive neuronal heterotopia, and large ventricular cavities of embryonic type. (The findings in the mother made X-linked recessive inheritance a possibility.) The patients of Reznik and Alberca-Serrano (1964) may have suffered from a disorder distinct from that described by Miller (1963) and Dieker et al. (1969). All patients with the Miller-Dieker syndrome are severely retarded. None learned to speak. They may walk by 3 to 5 years but spastic diplegia with spastic gait is evident. As in other forms of stationary forebrain developmental anomalies, decerebrate posturing with head retraction emerges in the first year of life. Dobyns et al. (1983) stated that the most characteristic finding on computerized tomography is complete failure of opercularization of the frontal and temporal lobes, and that this most likely accounts for bitempo ... More on the omim web site

Subscribe to this protein entry history

Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 247200 was added.