P43034 · LIS1_HUMAN
- ProteinPlatelet-activating factor acetylhydrolase IB subunit beta
- GenePAFAH1B1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids410 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 in 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 microtubules. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (PubMed:22956769).
May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (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 microtubules. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (PubMed:22956769).
May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (By similarity).
Miscellaneous
Originally the subunits of the type I platelet-activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1), beta (PAFAH1B2) and gamma (PAFAH1B3) (By similarity) (Ref.4). Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and alpha1 (PAFAH1B3) respectively (By similarity).
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePlatelet-activating factor acetylhydrolase IB subunit beta
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP43034
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Redistributes to axons during neuronal development. Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes (By similarity).
Localizes to the plus end of microtubules and to the centrosome. May localize to the nuclear membrane
Localizes to the plus end of microtubules and to the centrosome. May localize to the nuclear membrane
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Lissencephaly 1 (LIS1)
- Note
- DescriptionA classical lissencephaly. It is characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. The cortex is abnormally thick and poorly organized with 4 primitive layers. Associated with enlarged and dysmorphic ventricles and often hypoplasia of the corpus callosum.
- See alsoMIM:607432
Natural variants in LIS1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_015398 | 31 | F>S | in LIS1; dbSNP:rs121434486 | |
VAR_007724 | 149 | H>R | in LIS1; abrogates interaction with NDE1 and reduces neuronal migration in vitro; dbSNP:rs121434482 | |
VAR_015399 | 162 | G>S | in LIS1; dbSNP:rs121434487 | |
VAR_037301 | 277 | H>P | in LIS1; dbSNP:rs121434490 | |
VAR_015400 | 317 | D>H | in LIS1; reduces neuronal migration in vitro; dbSNP:rs121434485 |
Subcortical band heterotopia (SBH)
- Note
- DescriptionSBH is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.
- See alsoMIM:607432
Natural variants in SBH
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_010203 | 169 | S>P | in SBH; abrogates interaction with NDE1 and reduces neuronal migration in vitro; dbSNP:rs121434484 | |
VAR_037300 | 241 | R>P | in SBH; somatic mosaicism in 18% of lymphocytes and 21% of hair root cells; dbSNP:rs121434488 |
Miller-Dieker lissencephaly syndrome (MDLS)
- Note
- DescriptionA contiguous gene deletion syndrome of chromosome 17p13.3, characterized by classical lissencephaly and distinct facial features. Additional congenital malformations can be part of the condition.
- See alsoMIM:247200
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_015398 | 31 | in LIS1; dbSNP:rs121434486 | |||
Sequence: F → S | ||||||
Natural variant | VAR_007724 | 149 | in LIS1; abrogates interaction with NDE1 and reduces neuronal migration in vitro; dbSNP:rs121434482 | |||
Sequence: H → R | ||||||
Natural variant | VAR_015399 | 162 | in LIS1; dbSNP:rs121434487 | |||
Sequence: G → S | ||||||
Natural variant | VAR_010203 | 169 | in SBH; abrogates interaction with NDE1 and reduces neuronal migration in vitro; dbSNP:rs121434484 | |||
Sequence: S → P | ||||||
Natural variant | VAR_037300 | 241 | in SBH; somatic mosaicism in 18% of lymphocytes and 21% of hair root cells; dbSNP:rs121434488 | |||
Sequence: R → P | ||||||
Natural variant | VAR_037301 | 277 | in LIS1; dbSNP:rs121434490 | |||
Sequence: H → P | ||||||
Natural variant | VAR_015400 | 317 | in LIS1; reduces neuronal migration in vitro; dbSNP:rs121434485 | |||
Sequence: D → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 373 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000051061 | 1-410 | UniProt | Platelet-activating factor acetylhydrolase IB subunit beta | |||
Sequence: MVLSQRQRDELNRAIADYLRSNGYEEAYSVFKKEAELDVNEELDKKYAGLLEKKWTSVIRLQKKVMELESKLNEAKEEFTSGGPLGQKRDPKEWIPRPPEKYALSGHRSPVTRVIFHPVFSVMVSASEDATIKVWDYETGDFERTLKGHTDSVQDISFDHSGKLLASCSADMTIKLWDFQGFECIRTMHGHDHNVSSVAIMPNGDHIVSASRDKTIKMWEVQTGYCVKTFTGHREWVRMVRPNQDGTLIASCSNDQTVRVWVVATKECKAELREHEHVVECISWAPESSYSSISEATGSETKKSGKPGPFLLSGSRDKTIKMWDVSTGMCLMTLVGHDNWVRGVLFHSGGKFILSCADDKTLRVWDYKNKRCMKTLNAHEHFVTSLDFHKTAPYVVTGSVDQTVKVWECR | |||||||
Modified residue (large scale data) | 28 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 53 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 81 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 105 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 109 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 109 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Fairly ubiquitous expression in both the frontal and occipital areas of the brain.
Gene expression databases
Organism-specific databases
Interaction
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) (By similarity).
Interacts with IQGAP1, KATNB1 and NUDC. Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling (By similarity).
Can self-associate. Interacts with DCX, dynein, dynactin, NDE1, NDEL1 and RSN. Interacts with DISC1, and this interaction is enhanced by NDEL1. Interacts with INTS13. Interacts with DCDC1 (PubMed:22159412).
Interacts with IQGAP1, KATNB1 and NUDC. Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling (By similarity).
Can self-associate. Interacts with DCX, dynein, dynactin, NDE1, NDEL1 and RSN. Interacts with DISC1, and this interaction is enhanced by NDEL1. Interacts with INTS13. Interacts with DCDC1 (PubMed:22159412).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P43034 | DISC1 Q9NRI5 | 2 | EBI-720620, EBI-529989 | |
BINARY | P43034 | HSP90AA1 P07900 | 5 | EBI-720620, EBI-296047 | |
XENO | P43034 | Nde1 Q9CZA6 | 6 | EBI-720620, EBI-309934 | |
BINARY | P43034 | NDEL1 Q9GZM8 | 6 | EBI-720620, EBI-928842 | |
BINARY | P43034 | NUDCD2 Q8WVJ2 | 8 | EBI-720620, EBI-1052153 | |
BINARY | P43034 | NUDCD3 Q8IVD9 | 2 | EBI-720620, EBI-744342 | |
BINARY | P43034 | PAFAH1B2 P68402 | 3 | EBI-720620, EBI-713724 | |
BINARY | P43034 | PAFAH1B3 Q15102 | 3 | EBI-720620, EBI-711522 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, coiled coil, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-38 | Required for self-association and interaction with PAFAH1B2 and PAFAH1B3 | ||||
Sequence: MVLSQRQRDELNRAIADYLRSNGYEEAYSVFKKEAELD | ||||||
Region | 1-66 | Interaction with NDE1 | ||||
Sequence: MVLSQRQRDELNRAIADYLRSNGYEEAYSVFKKEAELDVNEELDKKYAGLLEKKWTSVIRLQKKVM | ||||||
Region | 1-102 | Interaction with NDEL1 | ||||
Sequence: MVLSQRQRDELNRAIADYLRSNGYEEAYSVFKKEAELDVNEELDKKYAGLLEKKWTSVIRLQKKVMELESKLNEAKEEFTSGGPLGQKRDPKEWIPRPPEKY | ||||||
Domain | 7-39 | LisH | ||||
Sequence: QRDELNRAIADYLRSNGYEEAYSVFKKEAELDV | ||||||
Coiled coil | 56-82 | |||||
Sequence: TSVIRLQKKVMELESKLNEAKEEFTSG | ||||||
Region | 83-410 | Interaction with dynein and dynactin | ||||
Sequence: GPLGQKRDPKEWIPRPPEKYALSGHRSPVTRVIFHPVFSVMVSASEDATIKVWDYETGDFERTLKGHTDSVQDISFDHSGKLLASCSADMTIKLWDFQGFECIRTMHGHDHNVSSVAIMPNGDHIVSASRDKTIKMWEVQTGYCVKTFTGHREWVRMVRPNQDGTLIASCSNDQTVRVWVVATKECKAELREHEHVVECISWAPESSYSSISEATGSETKKSGKPGPFLLSGSRDKTIKMWDVSTGMCLMTLVGHDNWVRGVLFHSGGKFILSCADDKTLRVWDYKNKRCMKTLNAHEHFVTSLDFHKTAPYVVTGSVDQTVKVWECR | ||||||
Repeat | 106-147 | WD 1 | ||||
Sequence: GHRSPVTRVIFHPVFSVMVSASEDATIKVWDYETGDFERTLK | ||||||
Repeat | 148-187 | WD 2 | ||||
Sequence: GHTDSVQDISFDHSGKLLASCSADMTIKLWDFQGFECIRT | ||||||
Repeat | 190-229 | WD 3 | ||||
Sequence: GHDHNVSSVAIMPNGDHIVSASRDKTIKMWEVQTGYCVKT | ||||||
Repeat | 232-271 | WD 4 | ||||
Sequence: GHREWVRMVRPNQDGTLIASCSNDQTVRVWVVATKECKAE | ||||||
Repeat | 274-333 | WD 5 | ||||
Sequence: EHEHVVECISWAPESSYSSISEATGSETKKSGKPGPFLLSGSRDKTIKMWDVSTGMCLMT | ||||||
Repeat | 336-377 | WD 6 | ||||
Sequence: GHDNWVRGVLFHSGGKFILSCADDKTLRVWDYKNKRCMKTLN | ||||||
Region | 367-409 | Interaction with DCX | ||||
Sequence: YKNKRCMKTLNAHEHFVTSLDFHKTAPYVVTGSVDQTVKVWEC | ||||||
Repeat | 378-410 | WD 7 | ||||
Sequence: AHEHFVTSLDFHKTAPYVVTGSVDQTVKVWECR | ||||||
Region | 388-410 | Interaction with NDEL1 | ||||
Sequence: FHKTAPYVVTGSVDQTVKVWECR |
Domain
Dimerization mediated by the LisH domain may be required to activate dynein.
Sequence similarities
Belongs to the WD repeat LIS1/nudF family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P43034-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length410
- Mass (Da)46,638
- Last updated2007-01-23 v2
- Checksum3AB68D2641BA31C9
P43034-2
- Name2
Computationally mapped potential isoform sequences
There are 11 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0AAQ5BGP0 | A0AAQ5BGP0_HUMAN | PAFAH1B1 | 142 | ||
A0AAQ5BGP7 | A0AAQ5BGP7_HUMAN | PAFAH1B1 | 206 | ||
A0AAQ5BH67 | A0AAQ5BH67_HUMAN | PAFAH1B1 | 346 | ||
A0AAQ5BGM1 | A0AAQ5BGM1_HUMAN | PAFAH1B1 | 394 | ||
A0A6Q8PFT2 | A0A6Q8PFT2_HUMAN | PAFAH1B1 | 345 | ||
A0A6Q8PFU3 | A0A6Q8PFU3_HUMAN | PAFAH1B1 | 428 | ||
A0A6Q8PG63 | A0A6Q8PG63_HUMAN | PAFAH1B1 | 346 | ||
A0A6Q8PGF8 | A0A6Q8PGF8_HUMAN | PAFAH1B1 | 47 | ||
A0A6Q8PH33 | A0A6Q8PH33_HUMAN | PAFAH1B1 | 127 | ||
I3L495 | I3L495_HUMAN | PAFAH1B1 | 82 | ||
I3L3N5 | I3L3N5_HUMAN | PAFAH1B1 | 376 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_019376 | 12-64 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 21 | in Ref. 3; AAL34972/AAL34973 | ||||
Sequence: S → P | ||||||
Sequence conflict | 93 | in Ref. 3; AAL34973 | ||||
Sequence: E → G | ||||||
Alternative sequence | VSP_019377 | 134-170 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 177 | in Ref. 3; AAL34973 | ||||
Sequence: W → R | ||||||
Alternative sequence | VSP_019378 | 237 | in isoform 2 | |||
Sequence: V → I | ||||||
Alternative sequence | VSP_019379 | 238-410 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L13385 EMBL· GenBank· DDBJ | AAA02880.1 EMBL· GenBank· DDBJ | mRNA | ||
L13386 EMBL· GenBank· DDBJ | AAA02881.1 EMBL· GenBank· DDBJ | mRNA | ||
L13387 EMBL· GenBank· DDBJ | AAA02882.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
U72342 EMBL· GenBank· DDBJ | AAC51111.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U72334 EMBL· GenBank· DDBJ | AAC51111.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U72335 EMBL· GenBank· DDBJ | AAC51111.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U72336 EMBL· GenBank· DDBJ | AAC51111.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U72337 EMBL· GenBank· DDBJ | AAC51111.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U72338 EMBL· GenBank· DDBJ | AAC51111.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U72339 EMBL· GenBank· DDBJ | AAC51111.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U72340 EMBL· GenBank· DDBJ | AAC51111.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U72341 EMBL· GenBank· DDBJ | AAC51111.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF208837 EMBL· GenBank· DDBJ | AAL34972.1 EMBL· GenBank· DDBJ | mRNA | ||
AF208838 EMBL· GenBank· DDBJ | AAL34973.1 EMBL· GenBank· DDBJ | mRNA | ||
AF400434 EMBL· GenBank· DDBJ | AAK92483.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313078 EMBL· GenBank· DDBJ | BAG35904.1 EMBL· GenBank· DDBJ | mRNA | ||
BX538346 EMBL· GenBank· DDBJ | CAD98141.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471108 EMBL· GenBank· DDBJ | EAW90536.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC064638 EMBL· GenBank· DDBJ | AAH64638.1 EMBL· GenBank· DDBJ | mRNA |