General Information:

Id: 7,172
Diseases: Acrocallosal syndrome - [OMIM]
Joubert syndrome
Short-rib thoracic dysplasia 3 with or without polydactyly - [OMIM]
Mammalia
review
Reference: [PMID: 27765513]

Interaction Information:

Comment The mammalian Hedgehog (Hh) signaling pathway is required for development and for maintenance of adult stem cells, and overactivation of the pathway can cause tumorigenesis.
Formal Description
Interaction-ID: 70417
Comment The mammalian Hedgehog (Hh) signaling pathway is required for development and for maintenance of adult stem cells, and overactivation of the pathway can cause tumorigenesis.
Formal Description
Interaction-ID: 70596

affects_activity of

phenotype

neoplasm

Comment The mammalian Hedgehog (Hh) pathway depends on primary cilia and intraflagellar trafficking.
Formal Description
Interaction-ID: 70597

cellular component

cilium

increases_activity of

Comment The mammalian Hedgehog (Hh) pathway depends on primary cilia and intraflagellar trafficking.
Formal Description
Interaction-ID: 70598

increases_activity of

Comment The Hh signaling pathway (and therefore primary cilia) is responsible for many aspects of vertebrate embryonic development.
Formal Description
Interaction-ID: 70599
Comment Ciliary trafficking depends on the evolutionarily conserved process of intraflagellar transport (IFT). Large protein complexes organized into IFT trains – large structures that can be visualized under the light microscope – move between the plasma membrane and the axonemal microtubules and carry cargo between the base and the tip of the cilium. IFT trains are built from two large protein complexes: the IFT-B complex, which comprises 16 subunits and is essential for anterograde IFT, and the IFT-A complex, which comprises six subunits and is thought to have a particularly important role in retrograde IFT.
Formal Description
Interaction-ID: 70600

increases_activity of

Comment Ciliary trafficking depends on the evolutionarily conserved process of intraflagellar transport (IFT). Large protein complexes organized into IFT trains – large structures that can be visualized under the light microscope – move between the plasma membrane and the axonemal microtubules and carry cargo between the base and the tip of the cilium. IFT trains are built from two large protein complexes: the IFT-B complex, which comprises 16 subunits and is essential for anterograde IFT, and the IFT-A complex, which comprises six subunits and is thought to have a particularly important role in retrograde IFT.
Formal Description
Interaction-ID: 70601
Comment The anterograde motor kinesin-2 is required to move IFT trains from the ciliary base to the tip (i.e., towards the plus ends of axonemal microtubules) in organisms from Chlamydomonas to humans.
Formal Description
Interaction-ID: 70602

complex/PPI

Kinesin II complex

increases_activity of

Comment Cytoplasmic dynein-2 is the evolutionarily conserved motor that is dedicated to retrograde IFT from the ciliary tip to the base.
Formal Description
Interaction-ID: 70603

complex/PPI

Dynein-2 complex

increases_activity of

Comment The evolutionarily conserved kinesin responsible for anterograde trafficking of the IFT trains is the plus end-directed motor kinesin-2, a heterotrimeric complex that belongs to the kinesin-2 family. There are two distinct forms of the kinesin-2 motor complexes in vertebrates: KIF3A/KIF3B/KIFAP3 and KIF3A/KIF3C/KIFAP3. KIF3A and KIF3B/C form the motor heads responsible for the ATP-dependent power stroke. KIFAP3 (formerly KAP3) is thought to be a regulatory subunit that is important for motility and/or cargo recognition. Based on the similarity of the mouse phenotypes caused by the loss of KIF3A and KIF3B, it is likely that KIF3A/KIF3B/KIFAP3 is the major form of kinesin-2 in mammals.
Formal Description
Interaction-ID: 70604

complex/PPI

Kinesin II complex (KIF3A/KIF3B/KIFAP3)

increases_activity of

Comment The evolutionarily conserved kinesin responsible for anterograde trafficking of the IFT trains is the plus end-directed motor kinesin-2, a heterotrimeric complex that belongs to the kinesin-2 family. There are two distinct forms of the kinesin-2 motor complexes in vertebrates: KIF3A/KIF3B/KIFAP3 and KIF3A/KIF3C/KIFAP3. KIF3A and KIF3B/C form the motor heads responsible for the ATP-dependent power stroke. KIFAP3 (formerly KAP3) is thought to be a regulatory subunit that is important for motility and/or cargo recognition. Based on the similarity of the mouse phenotypes caused by the loss of KIF3A and KIF3B, it is likely that KIF3A/KIF3B/KIFAP3 is the major form of kinesin-2 in mammals.
Formal Description
Interaction-ID: 70605

complex/PPI

Kinesin II complex (KIF3A/KIF3C/KIFAP3)

increases_activity of

Comment KIF3A is required for ciliary formation and Hh signaling in every cell type tested in mice.
Formal Description
Interaction-ID: 70606

gene/protein

KIF3A

increases_activity of

process

cilium assembly

Comment KIF3A is required for ciliary formation and Hh signaling in every cell type tested in mice.
Formal Description
Interaction-ID: 70607

gene/protein

KIF3A

increases_activity of

Comment Four families of kinesins and one dynein are known to be associated with the structure and IFT of mammalian cilia. Heterotrimeric kinesin-2 and homodimeric KIF17 belong to the kinesin-2 family. Homodimeric KIF7 and KIF27 belong to the kinesin-4 family. Homodimeric kinesin KIF19 belongs to the kinesin-8 family. The motor domains of these kinesins are located at the N-terminus of the protein. KIF24 and KIF2A belong to the kinesin-13 family, with motor domains in the central region of the protein. Cytoplasmic dynein-2 is the only dynein required for intraflagellar transport. Both kinesin-2 and KIF17 are anterograde kinesins that move along the axoneme from the ciliary base (the minus end) to the ciliary tip (the plus end). KIF7 lacks motility along the microtubule lattice but can bind preferentially to GTP-bound tubulin at the growing ends of microtubules and promote microtubule catastrophe. Other members of the kinesin-4 family, including KIF4 and KIF21A, exhibit plus end-directed motility to reach microtubule ends, where these kinesins regulate microtubule dynamics. KIF19 is a motile kinesin, exhibits microtubule depolymerization activity towards the plus ends of microtubules, and appears to act specifically in motile cilia. KIF24 and KIF2A lack motility and show microtubule-depolymerizing activity towards both ends of microtubules. Although both kinesin-8 and kinesin-13 family members can shorten microtubules, their underlying actions differ. Cytoplasmic dynein-2 is required for microtubule-based cargo transport from plus ends to minus ends of microtubules within cilia. The motor activity resides in the heavy chain, which acts as a homodimer, and a large number of smaller chains mediate the cargo loading and specificity of the motor.
Formal Description
Interaction-ID: 70609

complex/PPI

KIF17 homodimer

increases_activity of

Comment Four families of kinesins and one dynein are known to be associated with the structure and IFT of mammalian cilia. Heterotrimeric kinesin-2 and homodimeric KIF17 belong to the kinesin-2 family. Homodimeric KIF7 and KIF27 belong to the kinesin-4 family. Homodimeric kinesin KIF19 belongs to the kinesin-8 family. The motor domains of these kinesins are located at the N-terminus of the protein. KIF24 and KIF2A belong to the kinesin-13 family, with motor domains in the central region of the protein. Cytoplasmic dynein-2 is the only dynein required for intraflagellar transport. Both kinesin-2 and KIF17 are anterograde kinesins that move along the axoneme from the ciliary base (the minus end) to the ciliary tip (the plus end). KIF7 lacks motility along the microtubule lattice but can bind preferentially to GTP-bound tubulin at the growing ends of microtubules and promote microtubule catastrophe. Other members of the kinesin-4 family, including KIF4 and KIF21A, exhibit plus end-directed motility to reach microtubule ends, where these kinesins regulate microtubule dynamics. KIF19 is a motile kinesin, exhibits microtubule depolymerization activity towards the plus ends of microtubules, and appears to act specifically in motile cilia. KIF24 and KIF2A lack motility and show microtubule-depolymerizing activity towards both ends of microtubules. Although both kinesin-8 and kinesin-13 family members can shorten microtubules, their underlying actions differ. Cytoplasmic dynein-2 is required for microtubule-based cargo transport from plus ends to minus ends of microtubules within cilia. The motor activity resides in the heavy chain, which acts as a homodimer, and a large number of smaller chains mediate the cargo loading and specificity of the motor.
Formal Description
Interaction-ID: 70610

complex/PPI

KIF7 homodimer

interacts (colocalizes) with

cellular component

microtubule plus-end

Comment Four families of kinesins and one dynein are known to be associated with the structure and IFT of mammalian cilia. Heterotrimeric kinesin-2 and homodimeric KIF17 belong to the kinesin-2 family. Homodimeric KIF7 and KIF27 belong to the kinesin-4 family. Homodimeric kinesin KIF19 belongs to the kinesin-8 family. The motor domains of these kinesins are located at the N-terminus of the protein. KIF24 and KIF2A belong to the kinesin-13 family, with motor domains in the central region of the protein. Cytoplasmic dynein-2 is the only dynein required for intraflagellar transport. Both kinesin-2 and KIF17 are anterograde kinesins that move along the axoneme from the ciliary base (the minus end) to the ciliary tip (the plus end). KIF7 lacks motility along the microtubule lattice but can bind preferentially to GTP-bound tubulin at the growing ends of microtubules and promote microtubule catastrophe. Other members of the kinesin-4 family, including KIF4 and KIF21A, exhibit plus end-directed motility to reach microtubule ends, where these kinesins regulate microtubule dynamics. KIF19 is a motile kinesin, exhibits microtubule depolymerization activity towards the plus ends of microtubules, and appears to act specifically in motile cilia. KIF24 and KIF2A lack motility and show microtubule-depolymerizing activity towards both ends of microtubules. Although both kinesin-8 and kinesin-13 family members can shorten microtubules, their underlying actions differ. Cytoplasmic dynein-2 is required for microtubule-based cargo transport from plus ends to minus ends of microtubules within cilia. The motor activity resides in the heavy chain, which acts as a homodimer, and a large number of smaller chains mediate the cargo loading and specificity of the motor.
Formal Description
Interaction-ID: 70611

gene/protein

KIF4A

interacts (colocalizes) with

cellular component

microtubule

Comment Four families of kinesins and one dynein are known to be associated with the structure and IFT of mammalian cilia. Heterotrimeric kinesin-2 and homodimeric KIF17 belong to the kinesin-2 family. Homodimeric KIF7 and KIF27 belong to the kinesin-4 family. Homodimeric kinesin KIF19 belongs to the kinesin-8 family. The motor domains of these kinesins are located at the N-terminus of the protein. KIF24 and KIF2A belong to the kinesin-13 family, with motor domains in the central region of the protein. Cytoplasmic dynein-2 is the only dynein required for intraflagellar transport. Both kinesin-2 and KIF17 are anterograde kinesins that move along the axoneme from the ciliary base (the minus end) to the ciliary tip (the plus end). KIF7 lacks motility along the microtubule lattice but can bind preferentially to GTP-bound tubulin at the growing ends of microtubules and promote microtubule catastrophe. Other members of the kinesin-4 family, including KIF4 and KIF21A, exhibit plus end-directed motility to reach microtubule ends, where these kinesins regulate microtubule dynamics. KIF19 is a motile kinesin, exhibits microtubule depolymerization activity towards the plus ends of microtubules, and appears to act specifically in motile cilia. KIF24 and KIF2A lack motility and show microtubule-depolymerizing activity towards both ends of microtubules. Although both kinesin-8 and kinesin-13 family members can shorten microtubules, their underlying actions differ. Cytoplasmic dynein-2 is required for microtubule-based cargo transport from plus ends to minus ends of microtubules within cilia. The motor activity resides in the heavy chain, which acts as a homodimer, and a large number of smaller chains mediate the cargo loading and specificity of the motor.
Formal Description
Interaction-ID: 70613

gene/protein

KIF21A

interacts (colocalizes) with

cellular component

microtubule

Comment Four families of kinesins and one dynein are known to be associated with the structure and IFT of mammalian cilia. Heterotrimeric kinesin-2 and homodimeric KIF17 belong to the kinesin-2 family. Homodimeric KIF7 and KIF27 belong to the kinesin-4 family. Homodimeric kinesin KIF19 belongs to the kinesin-8 family. The motor domains of these kinesins are located at the N-terminus of the protein. KIF24 and KIF2A belong to the kinesin-13 family, with motor domains in the central region of the protein. Cytoplasmic dynein-2 is the only dynein required for intraflagellar transport. Both kinesin-2 and KIF17 are anterograde kinesins that move along the axoneme from the ciliary base (the minus end) to the ciliary tip (the plus end). KIF7 lacks motility along the microtubule lattice but can bind preferentially to GTP-bound tubulin at the growing ends of microtubules and promote microtubule catastrophe. Other members of the kinesin-4 family, including KIF4 and KIF21A, exhibit plus end-directed motility to reach microtubule ends, where these kinesins regulate microtubule dynamics. KIF19 is a motile kinesin, exhibits microtubule depolymerization activity towards the plus ends of microtubules, and appears to act specifically in motile cilia. KIF24 and KIF2A lack motility and show microtubule-depolymerizing activity towards both ends of microtubules. Although both kinesin-8 and kinesin-13 family members can shorten microtubules, their underlying actions differ. Cytoplasmic dynein-2 is required for microtubule-based cargo transport from plus ends to minus ends of microtubules within cilia. The motor activity resides in the heavy chain, which acts as a homodimer, and a large number of smaller chains mediate the cargo loading and specificity of the motor.
Formal Description
Interaction-ID: 70614

complex/PPI

KIF19 homodimer

affects_activity of

Comment Four families of kinesins and one dynein are known to be associated with the structure and IFT of mammalian cilia. Heterotrimeric kinesin-2 and homodimeric KIF17 belong to the kinesin-2 family. Homodimeric KIF7 and KIF27 belong to the kinesin-4 family. Homodimeric kinesin KIF19 belongs to the kinesin-8 family. The motor domains of these kinesins are located at the N-terminus of the protein. KIF24 and KIF2A belong to the kinesin-13 family, with motor domains in the central region of the protein. Cytoplasmic dynein-2 is the only dynein required for intraflagellar transport. Both kinesin-2 and KIF17 are anterograde kinesins that move along the axoneme from the ciliary base (the minus end) to the ciliary tip (the plus end). KIF7 lacks motility along the microtubule lattice but can bind preferentially to GTP-bound tubulin at the growing ends of microtubules and promote microtubule catastrophe. Other members of the kinesin-4 family, including KIF4 and KIF21A, exhibit plus end-directed motility to reach microtubule ends, where these kinesins regulate microtubule dynamics. KIF19 is a motile kinesin, exhibits microtubule depolymerization activity towards the plus ends of microtubules, and appears to act specifically in motile cilia. KIF24 and KIF2A lack motility and show microtubule-depolymerizing activity towards both ends of microtubules. Although both kinesin-8 and kinesin-13 family members can shorten microtubules, their underlying actions differ. Cytoplasmic dynein-2 is required for microtubule-based cargo transport from plus ends to minus ends of microtubules within cilia. The motor activity resides in the heavy chain, which acts as a homodimer, and a large number of smaller chains mediate the cargo loading and specificity of the motor.
Formal Description
Interaction-ID: 70615

gene/protein

KIF24

affects_activity of

Comment Four families of kinesins and one dynein are known to be associated with the structure and IFT of mammalian cilia. Heterotrimeric kinesin-2 and homodimeric KIF17 belong to the kinesin-2 family. Homodimeric KIF7 and KIF27 belong to the kinesin-4 family. Homodimeric kinesin KIF19 belongs to the kinesin-8 family. The motor domains of these kinesins are located at the N-terminus of the protein. KIF24 and KIF2A belong to the kinesin-13 family, with motor domains in the central region of the protein. Cytoplasmic dynein-2 is the only dynein required for intraflagellar transport. Both kinesin-2 and KIF17 are anterograde kinesins that move along the axoneme from the ciliary base (the minus end) to the ciliary tip (the plus end). KIF7 lacks motility along the microtubule lattice but can bind preferentially to GTP-bound tubulin at the growing ends of microtubules and promote microtubule catastrophe. Other members of the kinesin-4 family, including KIF4 and KIF21A, exhibit plus end-directed motility to reach microtubule ends, where these kinesins regulate microtubule dynamics. KIF19 is a motile kinesin, exhibits microtubule depolymerization activity towards the plus ends of microtubules, and appears to act specifically in motile cilia. KIF24 and KIF2A lack motility and show microtubule-depolymerizing activity towards both ends of microtubules. Although both kinesin-8 and kinesin-13 family members can shorten microtubules, their underlying actions differ. Cytoplasmic dynein-2 is required for microtubule-based cargo transport from plus ends to minus ends of microtubules within cilia. The motor activity resides in the heavy chain, which acts as a homodimer, and a large number of smaller chains mediate the cargo loading and specificity of the motor.
Formal Description
Interaction-ID: 70616

gene/protein

KIF2A

affects_activity of

Comment No mutations in KIF3A, KIF3B, KIF3C, KIFAP3, or KIF17 have been identified in human ciliopathy patients, in contrast to the large number of ciliopathy-associated mutations in the subunits of the retrograde motor and in KIF7, which is associated with Joubert and acrocallosal syndrome.
Formal Description
Interaction-ID: 70617

gene/protein

KIF7

affects_activity of

Comment No mutations in KIF3A, KIF3B, KIF3C, KIFAP3, or KIF17 have been identified in human ciliopathy patients, in contrast to the large number of ciliopathy-associated mutations in the subunits of the retrograde motor and in KIF7, which is associated with Joubert and acrocallosal syndrome.
Formal Description
Interaction-ID: 70619

gene/protein

DYNC2H1

affects_activity of

Comment No mutations in KIF3A, KIF3B, KIF3C, KIFAP3, or KIF17 have been identified in human ciliopathy patients, in contrast to the large number of ciliopathy-associated mutations in the subunits of the retrograde motor and in KIF7, which is associated with Joubert and acrocallosal syndrome.
Formal Description
Interaction-ID: 70625

gene/protein

DYNC2LI1

affects_activity of

Comment No mutations in KIF3A, KIF3B, KIF3C, KIFAP3, or KIF17 have been identified in human ciliopathy patients, in contrast to the large number of ciliopathy-associated mutations in the subunits of the retrograde motor and in KIF7, which is associated with Joubert and acrocallosal syndrome.
Formal Description
Interaction-ID: 70626

gene/protein

WDR34

affects_activity of

Comment No mutations in KIF3A, KIF3B, KIF3C, KIFAP3, or KIF17 have been identified in human ciliopathy patients, in contrast to the large number of ciliopathy-associated mutations in the subunits of the retrograde motor and in KIF7, which is associated with Joubert and acrocallosal syndrome.
Formal Description
Interaction-ID: 70627

gene/protein

WDR60

affects_activity of

Comment In all mouse Dync2h1 alleles analyzed, Shh signaling is reduced in the neural tube and mutants lack the floor plate and V3 progenitors, which are specified by the highest level of Shh activity.
Formal Description
Interaction-ID: 70631

gene/protein

DYNC2H1

affects_activity of

Comment KIF7 localizes to the tip of the cilium throughout ciliogenesis and accumulates further at ciliary tips in response to Hh activation. Mammalian KIF7 is the homolog of Drosophila Cos2 and both are required to relay signals from the transmembrane protein SMO to the Ci/GLI transcription factors.
Formal Description
Interaction-ID: 70632

gene/protein

KIF7

is localized in

cellular component

ciliary tip

Comment Human KIF24, a kinesin-13 family member, preferentially localizes to the mother centriole in cultured cells.
Formal Description
Interaction-ID: 70633

gene/protein

KIF24

is localized in

cellular component

mother centriole

Comment Mammalian KIF2A, another member of the M-kinesin kinesin-13 family, is localized to the centrosome and can promote ciliary disassembly from the base in cell culture The microtubule-depolymerization activity of KIF2A depends on specific activation by Polo-like kinase 1 (PLK1) and is coupled to cell proliferation. Knockdown of KIF2A prevents ciliary disassembly when quiescent cells re-enter the proliferative phase.
Formal Description
Interaction-ID: 70635

gene/protein

KIF2A

is localized in

cellular component

centrosome

Comment Mammalian KIF2A, another member of the M-kinesin kinesin-13 family, is localized to the centrosome and can promote ciliary disassembly from the base in cell culture The microtubule-depolymerization activity of KIF2A depends on specific activation by Polo-like kinase 1 (PLK1) and is coupled to cell proliferation. Knockdown of KIF2A prevents ciliary disassembly when quiescent cells re-enter the proliferative phase.
Formal Description
Interaction-ID: 70636

gene/protein

KIF2A

affects_activity of

Comment Mammalian KIF2A, another member of the M-kinesin kinesin-13 family, is localized to the centrosome and can promote ciliary disassembly from the base in cell culture The microtubule-depolymerization activity of KIF2A depends on specific activation by Polo-like kinase 1 (PLK1) and is coupled to cell proliferation. Knockdown of KIF2A prevents ciliary disassembly when quiescent cells re-enter the proliferative phase.
Formal Description
Interaction-ID: 70637

gene/protein

PLK1

increases_activity of

gene/protein

KIF2A

Drugbank entries Show/Hide entries for PLK1
Comment KIF7 localizes to the tip of the cilium throughout ciliogenesis and accumulates further at ciliary tips in response to Hh activation. Mammalian KIF7 is the homolog of Drosophila Cos2 and both are required to relay signals from the transmembrane protein SMO to the Ci/GLI transcription factors.
Formal Description
Interaction-ID: 126693

gene/protein

KIF7

is localized in

cellular component

cilium