Recombinant Human Kinesin-like protein KIF21A (KIF21A), partial
Description
Overview of Recombinant Human Kinesin-like Protein KIF21A (KIF21A), Partial
Kinesin-like protein KIF21A (KIF21A) is a member of the kinesin superfamily proteins (KIFs) . KIFs are microtubule-dependent molecular motors that participate in various cellular processes, including intracellular transport, cell division, polarity, and migration . KIF21A plays a role in connecting the plus ends of microtubules with the cell cortex .
Structure and Interactions
KIF21A interacts with the KN motif and ankyrin repeat domain-containing protein 1 (KANK1), an adaptor protein that links the plus ends of microtubules to the cell cortex . The KANK1/KIF21A complex is crucial for the cross-talk between dynamic microtubules and the cell cortex, which is essential for cell division, polarity, and migration .
The interaction between KANK1 and KIF21A involves a conserved peptide fragment located in the middle of KIF21A and a folded domain structure immediately preceding the ankyrin (ANK) repeats of KANK1 . Structural analysis has revealed that a stretch of approximately 22 amino acids in KIF21A is sufficient for binding to KANK1 and its homolog KANK2 .
Functional Significance
KIF21A is involved in several key cellular functions:
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Microtubule Regulation: KIF21A, in conjunction with KANK1, regulates microtubule growth by recruiting KANK1 to the cell cortex .
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Intracellular Transport: As a kinesin superfamily protein, KIF21A facilitates intracellular transport along microtubules .
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Cellular Organization: KIF21A contributes to the maintenance of cell structure and organization .
Role in Disease
Genetic defects in KIF21A are associated with various diseases:
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Congenital Fibrosis of the Extraocular Muscles Type 1: Mutations in KIF21A have been linked to developmental diseases such as congenital fibrosis of the extraocular muscles type 1 . Increased KIF21A expression can result in changes in axon morphology, leading to axon guidance abnormalities .
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Cancers: Defects in the KANK1/KIF21A complex have been associated with various cancers . Missense mutations in cancer patients can destabilize the formation of the KANK1/KIF21A complex .
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Fetal Akinesia (FA) Sequence: Bi-allelic loss-of-function variants in KIF21A have been implicated in the pathogenesis of severe neurogenic FA sequence with arthrogryposis of multiple joints, pulmonary hypoplasia, and facial dysmorphisms .
KIF21A in Cancer Research
KIF21B, a related kinesin superfamily protein, has been investigated in the context of non-small cell lung cancer (NSCLC) . KIF21B is upregulated in NSCLC tissues and is associated with the pathological stage of the disease and poor prognosis . Studies have shown that silencing KIF21B inhibits the proliferation, migration, and invasion of NSCLC cells, suggesting its potential as a therapeutic target .
Regulation of KIF21A Autoinhibition
KIF21A activity is regulated through autoinhibition, where the stalk region of KIF21A interacts with the motor domain to prevent microtubule binding . The regulatory coiled coil (rCC1) in the KIF21A stalk forms an intramolecular antiparallel coiled coil that prevents the motor domain from binding to microtubules .
Tables
Table 1: KIF21A Interactions and Functions
| Interaction | Partner | Function | Reference |
|---|---|---|---|
| Protein Binding | KANK1 | Connects microtubules to the cell cortex, regulates microtubule growth | |
| Motor Activity | Microtubules | Intracellular transport |
Table 2: KIF21A and Disease Associations
Product Specs
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Target Background
- Key residues (Thr-1147, Leu-1152, Leu-1153, and Tyr-1154) in the KIF21A kinesin-binding domain (KBD) C-terminus interact with a hydrophobic patch (Tyr-1176, Met-1209, Leu-1210, Leu-1213, and Leu-1248) within KANK1. PMID: 29158259
- A recurrent missense KIF21A mutation (c.2860C>T) was identified in a Chinese family exhibiting congenital fibrosis of the extraocular muscles type 1 (CFEOM1) phenotypes. PMID: 28930843
- A heterozygous mutation (c.2860C>T, p.R954W) in KIF21A was identified in two families with CFEOM1 and CFEOM3, co-segregating with the disease and absent in 200 controls. PMID: 27513105
- Phenotypic findings associated with KIF21A mutations are discussed. PMID: 26190014
- Germline mosaicism of KIF21A c.2860C>T likely contributes to its high prevalence. PMID: 24426772
- The Kif21a-Map1b interaction plays a critical role in CFEOM1 pathogenesis, highlighting the oculomotor nerve's vulnerability to axon cytoskeleton disruptions. PMID: 24656932
- CFEOM1-associated mutations disinhibit KIF21A motor activity, leading to increased accumulation in axonal growth cones, aberrant axon morphology, and reduced responsiveness to inhibitory signals. PMID: 24120883
- KIF21A gene expression may influence axonal transport and nervous system development, impacting the Down syndrome phenotype. PMID: 22968744
- Congenital fibrosis of extraocular muscles associated with KIF21A mutations. PMID: 23535681
- KIF21A's widespread expression in the developing nervous system does not fully explain the restricted ocular phenotype in CFEOM1. PMID: 22465342
- Analysis of RRP1B, PCNT, KIF21A, and ADRB2 expression in Down syndrome leukocytes. PMID: 22552340
- KIF21A-mediated axonal transport and somatodendritic endocytosis regulate NCKX2's polarized surface expression. PMID: 22442075
- Novel deletion and recurrent KIF21A mutations in Chinese patients with CFEOM1. PMID: 21805025
- A c.2860C>T mutation in KIF21A identified in a Chinese family with CFEOM1. PMID: 21983718
- Absence of KIF21A mutations in Saudi Arabian patients with CFEOM1. PMID: 21264235
- The R954W KIF21A mutation is a common cause of CFEOM1 and CFEOM3 across ethnic groups. PMID: 21042561
- Parental germline mosaicism can mimic recessive inheritance in CFEOM and is potentially underdiagnosed. PMID: 19896199
- Surgery effectively improves ptosis in most classic CFEOM patients. PMID: 12702216
- Heterozygous KIF21A mutations are associated with CFEOM1. PMID: 14595441
- KIF21A mutations are a rare cause of CFEOM3. PMID: 15223798
- KIF21A mutations are associated with CFEOM. PMID: 15621876
- KIF21A CpG island mutations are associated with CFEOM. PMID: 15621877
- Orbital imaging in CFEOM1 reveals consistent abnormalities in motor and sensory innervation. PMID: 15671279
- CFEOM1 and CFEOM3 can result from the same KIF21A mutation in Chinese populations. PMID: 15827546
- A novel CFEOM1 KIF21A mutation is reported, along with the first reported genetic defect associated with Marcus Gunn jaw-winking. PMID: 16157808
- KIF21A mutations contribute to CFEOM1 development regardless of ethnicity. PMID: 16365788
- The p.Arg954Trp KIF21A mutation underlies CFEOM1. PMID: 16939002
- Three novel mutations affect amino acids within the third coiled-coil region of the KIF21A stalk, highlighting this domain's importance in CFEOM1 and CFEOM3 etiology. PMID: 17511870
- No KIF21A nucleotide changes were found in patients with congenital superior oblique muscle palsy. PMID: 18323871
- A novel KIF21A mutation (84C>G) in a CFEOM1 family affects the kinesin motor domain, indicating mutations can occur outside the commonly implicated coiled-coil domain. PMID: 18332320
- The R954W mutation in an Arabian Peninsula population confirms R954 as a KIF21A mutation hotspot. PMID: 18363169
- Co-immunoprecipitation studies suggest an interaction between the KIF21A C-terminal tail (containing seven WD-40 repeats) and the C-terminal region of BIG1. PMID: 19020088
- Patients exhibited bilateral movement restriction, near-complete loss of vertical ocular motility, reduced horizontal motility, ptosis, and compensatory chin elevation. PMID: 19551685
- KIF21A regulates Kank1 distribution; CFEOM1-associated KIF21A mutations enhance Kank1 accumulation in the membrane fraction. PMID: 19559006
- KIF21A and PHOX2A sequence variation does not appear to contribute to common congenital incomitant vertical strabismus. PMID: 19852579
- Mass spectrometry identified differential KIF21A expression in the dorsolateral prefrontal cortex of schizophrenia patients. PMID: 19165527
