Affinage

KIF13A

Kinesin-like protein KIF13A · UniProt Q9H1H9

Length
1805 aa
Mass
202.3 kDa
Annotated
2026-06-10
28 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF13A is a plus end-directed, microtubule-dependent kinesin motor that transports diverse membrane cargoes from the trans-Golgi network (TGN) and recycling endosomes to the plasma membrane (PMID:11106728). Its founding cargo route is established through a direct interaction with the AP-1 clathrin adaptor complex via β1-adaptin, which couples the motor to mannose-6-phosphate receptor (M6PR)-containing vesicles and controls cell-surface M6PR levels (PMID:11106728, PMID:29443872). Beyond M6PR, KIF13A carries a broad cargo repertoire to the cell surface—the serotonin 5HT1A receptor through its FHA domain (PMID:23438369), AMPA receptors during long-term potentiation (PMID:33999113), RhoB through Rab11 recycling endosomes (PMID:30049714), and MT1-MMP for collagen degradation and invasion (PMID:35122963)—and is hijacked by influenza A vRNPs and arenavirus Z matrix proteins for delivery to the plasma membrane (PMID:29061883, PMID:23279019). KIF13A is also required to generate and morphologically shape recycling endosome tubules, cooperating with RAB11, Rab10, and Rab22A (PMID:24462287, PMID:30700496, PMID:33536208), and Rab22A activates the motor by binding its NC-CC1 region to relieve a proline-mediated autoinhibition that otherwise holds KIF13A as an inactive monomer, thereby licensing dimerization and processive force generation (PMID:33536208). In polarized neurons, KIF13A is held at the TGN by AP-1 and functions as a dendrite-selective motor whose cargo specificity is gated by MARK2 phosphorylation at a 14-3-3 binding motif, which strips the motor from transferrin-receptor vesicles to confine their transport to dendrites (PMID:38446634, PMID:38709923). Independently, KIF13A is required for cytokinesis, translocating the FYVE-CENT (ZFYVE26)–TTC19 complex from the centrosome to the midbody in a PtdIns(3)P-dependent manner (PMID:20208530).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Established KIF13A as a motor that links the AP-1 adaptor to cargo, answering how M6PR vesicles are delivered from the TGN to the cell surface.

    Evidence Reciprocal Co-IP with β1-adaptin, dominant-negative blockade, and cell-surface M6PR assay

    PMID:11106728

    Open questions at the time
    • Did not resolve the motor's regulatory state (autoinhibition)
    • Cargo repertoire beyond M6PR unknown at this stage
  2. 2009 High

    Extended KIF13A–AP-1 cooperation to a tissue-specific role, showing it builds peripheral recycling endosomal subdomains required for melanosome cargo delivery.

    Evidence siRNA knockdown, immunocytochemistry, live imaging, and electron tomography in melanocytes

    PMID:19841138

    Open questions at the time
    • Molecular basis of subdomain positioning not defined
    • Did not identify the activating signal for the motor
  3. 2010 High

    Identified an unexpected cell-division role, showing KIF13A delivers FYVE-CENT–TTC19 to the midbody, linking the motor to cytokinesis completion.

    Evidence siRNA knockdown with multinucleation readout, live imaging, Co-IP, and PI(3)K-III epistasis

    PMID:20208530

    Open questions at the time
    • How PtdIns(3)P recruits the KIF13A cargo to microtubules is unresolved
    • Direct vs indirect FYVE-CENT binding not mapped
  4. 2013 High

    Defined a cargo-recognition module and an in vivo phenotype, showing the FHA domain directly binds 5HT1AR and that loss elevates anxiety in mice.

    Evidence In vitro reconstitution with motor+FHA minimotor, domain mapping, KO mouse behavior, knockdown surface-receptor assay

    PMID:23438369

    Open questions at the time
    • FHA-domain phospho-dependence of cargo binding not addressed
    • Behavioral phenotype not mechanistically tied to single neuronal circuit
  5. 2013 Medium

    Showed viral exploitation of KIF13A, with arenavirus Z matrix protein using the motor for plasma-membrane delivery and virion production.

    Evidence Co-IP, overexpression, dominant-negative and siRNA blockade, VLP and infectious-titer assays

    PMID:23279019

    Open questions at the time
    • Z-binding interface on KIF13A not mapped
    • Single lab
  6. 2014 High

    Reframed KIF13A as a tubule-morphogenesis factor, demonstrating it generates recycling-endosome tubules from vacuolar sorting endosomes together with RAB11.

    Evidence siRNA knockdown, dominant-negative expression, live imaging, RAB11 pulldown

    PMID:24462287

    Open questions at the time
    • Mechanical model for tubule pulling not yet established
    • RAB11 binding region not mapped here
  7. 2017 Medium

    Connected KIF13A to upstream signaling and immune function, placing its expression downstream of mTORC1/IL-2/IL-7 to set surface M6PR on T cells.

    Evidence Rapamycin inhibition, siRNA knockdown, flow cytometry, Treg cytotoxicity assay

    PMID:28496990

    Open questions at the time
    • Transcriptional vs post-transcriptional control by mTORC1 not distinguished
    • Single lab
  8. 2017 Medium

    Showed influenza A virus uses KIF13A on Rab11 vesicles to deliver vRNPs to the cell surface, generalizing the motor's viral-hijack role.

    Evidence siRNA knockdown, overexpression, immunofluorescence, viral titer assay

    PMID:29061883

    Open questions at the time
    • Direct vRNP-motor link vs Rab11-mediated coupling not separated
    • Single lab
  9. 2018 Medium

    Linked KIF13A to cell-shape and motility control by routing RhoB through Rab11 endosomes to drive amoeboid migration of leukemia cells.

    Evidence siRNA knockdown, live imaging, 3D migration assay, Rab5/Rab11 trafficking analysis

    PMID:30049714

    Open questions at the time
    • Whether RhoB is a direct cargo or indirect passenger unresolved
    • Single lab
  10. 2018 Medium

    Provided causal proof that the KIF13A–AP-1 interface is functionally essential, using a short β1-adaptin peptide to block pigmentation.

    Evidence Blocking-peptide treatment, pigmentation assay, 3D pigmented epidermis model

    PMID:29443872

    Open questions at the time
    • Peptide specificity for KIF13A vs KIF13B not fully resolved
    • Single lab
  11. 2019 Medium

    Identified Rab10 as a tubular-endosome partner requiring both the motor and Rab-binding homology domains of KIF13A for tubule formation.

    Evidence EGFP-Rab localization screen, Rab10 knockout, domain-deletion analysis, interaction assays

    PMID:30700496

    Open questions at the time
    • Functional distinction between Rab10, Rab11 and Rab22A inputs not integrated
    • Single lab
  12. 2021 High

    Resolved the activation mechanism, showing KIF13A is autoinhibited monomer relieved by Rab22A binding at NC-CC1 to permit dimerization and force generation.

    Evidence Single-molecule motility, dimerization assays, proline-substitution mutagenesis, Rab22A Co-IP, RE tubulation imaging

    PMID:33536208

    Open questions at the time
    • Whether other Rabs (RAB11, Rab10) activate via the same mechanism not tested
    • Structural model of the autoinhibited state not solved
  13. 2021 High

    Placed KIF13A in synaptic plasticity, showing it is required for AMPAR delivery and LTP and remodels dendritic Rab11-FIP2 endosomes via centaurin-α1.

    Evidence LTP electrophysiology, Co-IP with centaurin-α1/AMPARs, endosome imaging, knockdown in hippocampal slices

    PMID:33999113

    Open questions at the time
    • Direct AMPAR-motor contact not defined
    • Activity-dependent activation signal upstream unknown
  14. 2022 Medium

    Showed division of labor with KIF3A in two-step MT1-MMP delivery, tying KIF13A to invasive collagen degradation.

    Evidence siRNA knockdown, vesicle tracking, collagen degradation and invasion assays

    PMID:35122963

    Open questions at the time
    • Cargo handoff mechanism between KIF3A and KIF13A unresolved
    • Single lab
  15. 2024 Medium

    Established KIF13A as a dendrite-selective neuronal motor held at the TGN by AP-1, with AP-1 binding required for polarized trafficking.

    Evidence Live imaging in hippocampal neurons, AP-1 interference, polarized transport assays

    PMID:38446634

    Open questions at the time
    • How AP-1 retention is released for transport not defined
    • Single lab
  16. 2024 Medium

    Defined the polarity-determining switch, showing MARK2 phosphorylation creates a 14-3-3 motif that strips KIF13A from TfR vesicles to confine transport to dendrites.

    Evidence Live imaging, KIF13A and MARK2 knockouts, BioID proximity labeling, overexpression

    PMID:38709923

    Open questions at the time
    • Structural basis of the 14-3-3-driven cargo release not solved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple Rab inputs (RAB11, Rab10, Rab22A), AP-1 retention, and MARK2/14-3-3 phosphoregulation are integrated to select among the diverse cargoes in a given cell type remains unresolved.
  • No unified model linking activation, cargo selection, and polarity
  • Structure of full-length autoinhibited and cargo-bound motor not solved
  • Direct vs Rab-bridged cargo binding undefined for most cargoes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 3 GO:0005215 transporter activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005768 endosome 4 GO:0005794 Golgi apparatus 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-112316 Neuronal System 3 R-HSA-1643685 Disease 3 R-HSA-9609507 Protein localization 3 R-HSA-1640170 Cell Cycle 1
Partners
AP1B1KIF3AMARK2RAB10RAB11RAB22AYWHAZFYVE26

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 KIF13A is a plus end-directed microtubule-dependent motor protein that directly interacts with β1-adaptin (a subunit of the AP-1 adaptor complex) to transport mannose-6-phosphate receptor (M6PR)-containing vesicles from the TGN to the plasma membrane; overexpression mislocalizes AP-1 and M6PR, while functional blockade reduces cell-surface M6PR expression. Co-immunoprecipitation, overexpression/dominant-negative functional blockade, cell-surface expression assay Cell High 11106728
2010 KIF13A is required for translocation of FYVE-CENT (ZFYVE26) and its binding partner TTC19 from the centrosome to the midbody during cytokinesis; this translocation is dependent on PtdIns(3)P produced by PI(3)K-III, and KIF13A depletion causes cytokinesis arrest and multinucleation similar to depletion of FYVE-CENT or VPS34. siRNA knockdown with cytokinesis phenotype readout (binucleate/multinucleate cell counting), live-cell imaging, Co-IP Nature cell biology High 20208530
2009 KIF13A cooperates with the clathrin adaptor AP-1 to create peripheral recycling endosomal subdomains in melanocytes required for delivery of melanosomal cargo (e.g., Tyrp1) to maturing melanosomes; depletion of either AP-1 or KIF13A redistributes recycling endosomes to pericentriolar clusters and inhibits melanin synthesis. siRNA knockdown, immunocytochemistry, live-cell imaging, electron tomography The Journal of cell biology High 19841138
2014 KIF13A associates with recycling endosome tubules and is required for their morphogenesis from vacuolar sorting endosomes (SEs); loss of KIF13A function impairs endosomal tubule formation, causing defects in endosome homeostasis and cargo recycling. KIF13A also interacts and cooperates with RAB11 to generate endosomal tubules. siRNA knockdown, dominant-negative expression, live-cell imaging, Co-IP/pulldown with RAB11 Cell reports High 24462287
2019 Rab10 localizes to tubular endosomes and interacts with KIF13A (and KIF13B); knockout of Rab10 abolishes tubular endosomal structures. Both the Rab10-binding homology domain and the motor domain of KIF13A are required for Rab10-positive tubular endosome formation. EGFP-Rab GTPase localization screen, Rab10 knockout, domain deletion analysis, in silico screening confirmed by interaction assays Journal of cell science Medium 30700496
2013 KIF13A transports serotonin type 1A receptor (5HT1AR) to the cell surface via direct interaction between its forkhead-associated (FHA) domain and an intracellular loop of 5HT1AR; a minimotor comprising the motor and FHA domains reconstitutes transport of 5HT1AR-carrying organelles in vitro. KIF13A-deficient mice exhibit elevated anxiety-related behavior coinciding with reduced 5HT1AR surface expression. Kif13a knockout mice (behavioral phenotype), KIF13A knockdown in neuroblastoma cells (surface receptor assay), biochemical domain-mapping, in vitro reconstitution assay Cell reports High 23438369
2018 KIF13A controls RhoB plasma membrane localization by mediating trafficking of RhoB through Rab11-positive recycling endosomes; KIF13A depletion inhibits RhoB plasma membrane localization, membrane blebbing, and 3D amoeboid migration of ALL cells. siRNA knockdown, live-cell imaging, 3D migration assay, endosomal trafficking analysis with Rab5/Rab11 markers The EMBO journal Medium 30049714
2017 KIF13A mediates transport of influenza A virus ribonucleoproteins (vRNPs) on Rab11-positive vesicles to the cell surface; KIF13A depletion reduces viral titers and vRNP accumulation at the cell surface without affecting other viral proteins at assembly sites. siRNA knockdown, overexpression, immunofluorescence, viral titer assay Journal of cell science Medium 29061883
2013 KIF13A interacts with the Lassa virus (LASV) matrix protein Z and mediates its microtubule-dependent transport to the plasma membrane; KIF13A overexpression relocalizes Z to the cell periphery, while dominant-negative or siRNA knockdown causes perinuclear accumulation and decreased production of Z-induced VLPs and infectious LASV. This interaction extends to Z proteins from both Old and New World arenaviruses. Co-immunoprecipitation, overexpression, dominant-negative expression, siRNA knockdown, VLP production assay, infectious virus titer Cellular microbiology Medium 23279019
2017 mTORC1 regulates KIF13A expression downstream of IL-2 and IL-7 signaling to control cell-surface M6PR levels on T cells; rapamycin-mediated mTORC1 inhibition or siRNA knockdown of KIF13A reduces surface M6PR expression and renders T cells resistant to Treg granzyme-B-mediated killing. Signaling inhibitors (rapamycin), siRNA knockdown of KIF13A, flow cytometry for surface M6PR, functional cytotoxicity assay Cell discovery Medium 28496990
2021 KIF13A exists as inactive monomers in cells due to a conserved proline residue between the neck coil and coiled-coil 1 (NC-CC1) domains that creates steric hindrance. Rab22A binds to the NC-CC1 domains of KIF13A, relieves proline-mediated inhibition, and facilitates motor dimerization, enabling balanced motility and force generation against dyneins for recycling endosome tubulation. Single-molecule assays, biochemical dimerization assays, domain mutagenesis (proline substitution), Co-IP with Rab22A, live-cell imaging of RE tubulation Science advances High 33536208
2018 A 5-amino-acid β1-adaptin AP-1 subunit-derived peptide blocks the KIF13A–AP-1 interaction in melanocytes and decreases pigmentation by impacting melanosome maturation, confirming that the KIF13A–β1-adaptin interaction is functionally required for melanosome biogenesis. Blocking peptide treatment, pigmentation assay, 3D-reconstructed pigmented epidermis model International journal of molecular sciences Medium 29443872
2021 KIF13A is specifically required for delivery of AMPA receptors (AMPARs) to the spine surface during LTP induction; KIF13A depletion abolishes LTP expression. KIF13A interacts with centaurin-α1 as part of the transport machinery engaged with AMPARs upon LTP induction, and is responsible for remodeling Rab11-FIP2 endosomal structures in the dendritic shaft during LTP. Electrophysiology (LTP recording), biochemistry (Co-IP with centaurin-α1/AMPARs), imaging of Rab11-FIP2 endosomes, KIF13A depletion from hippocampal slices The Journal of cell biology High 33999113
2022 KIF13A and KIF3A coordinate to transport MT1-MMP-containing vesicles from the trans-Golgi to endosomes, while KIF13A alone transports vesicles from the endosome to the plasma membrane; KIF13A knockdown inhibits MT1-MMP-dependent collagen degradation and cancer cell invasion. siRNA knockdown, live-cell imaging (vesicle tracking), collagen degradation assay, invasion assay Matrix biology Medium 35122963
2024 KIF13A is a dedicated dendrite-selective kinesin in neurons; both KIF13A and KIF13B are maintained at the trans-Golgi network by interactions with the AP-1 adaptor complex, and interference with KIF13 binding to AP-1 disrupts dendrite- and axon-selective trafficking. Live-cell imaging in cultured hippocampal neurons, AP-1 interaction interference assay, polarized transport assays Molecular biology of the cell Medium 38446634
2024 MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening KIF13A interaction with 14-3-3 proteins and causing KIF13A to dissociate from transferrin receptor (TfR)-containing vesicles at the proximal axon, thereby restricting TfR vesicle transport exclusively to dendrites. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. Live-cell imaging, KIF13A knockout, BioID proximity labeling assay, MARK2 knockout, overexpression studies Proceedings of the National Academy of Sciences of the United States of America Medium 38709923
2023 MARK2 phosphorylates KIF13A at a 14-3-3 binding site to dissociate KIF13A from TfR-containing vesicles, preventing their axonal transport (preprint version of the published PNAS study). Live-cell imaging, KIF13A knockout, BioID assay bioRxivpreprint Low 38105964

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex. Cell 229 11106728
2010 PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody. Nature cell biology 185 20208530
2009 AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome biogenesis. The Journal of cell biology 145 19841138
2014 Recycling endosome tubule morphogenesis from sorting endosomes requires the kinesin motor KIF13A. Cell reports 123 24462287
2019 Rab10 regulates tubular endosome formation through KIF13A and KIF13B motors. Journal of cell science 90 30700496
2002 Genomic amplification in retinoblastoma narrowed to 0.6 megabase on chromosome 6p containing a kinesin-like gene, RBKIN. Cancer research 34 11861365
2013 A molecular motor, KIF13A, controls anxiety by transporting the serotonin type 1A receptor. Cell reports 33 23438369
2018 KIF13A-regulated RhoB plasma membrane localization governs membrane blebbing and blebby amoeboid cell migration. The EMBO journal 29 30049714
2017 KIF13A mediates trafficking of influenza A virus ribonucleoproteins. Journal of cell science 22 29061883
2017 mTORC1 regulates mannose-6-phosphate receptor transport and T-cell vulnerability to regulatory T cells by controlling kinesin KIF13A. Cell discovery 19 28496990
2022 KIF13A-A Key Regulator of Recycling Endosome Dynamics. Frontiers in cell and developmental biology 18 35547822
2017 Identification of a novel KIF13A-RET fusion in lung adenocarcinoma by next-generation sequencing. Lung cancer (Amsterdam, Netherlands) 17 29571998
2021 KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell. Science advances 16 33536208
2013 The microtubule motor protein KIF13A is involved in intracellular trafficking of the Lassa virus matrix protein Z. Cellular microbiology 16 23279019
2022 Coordination of two kinesin superfamily motor proteins, KIF3A and KIF13A, is essential for pericellular matrix degradation by membrane-type 1 matrix metalloproteinase (MT1-MMP) in cancer cells. Matrix biology : journal of the International Society for Matrix Biology 15 35122963
2001 Identification of the human KIF13A gene homologous to Drosophila kinesin-73 and candidate for schizophrenia. Genomics 15 11374900
2018 AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis. International journal of molecular sciences 14 29443872
2021 KIF13A drives AMPA receptor synaptic delivery for long-term potentiation via endosomal remodeling. The Journal of cell biology 12 33999113
2024 Polarized transport requires AP-1-mediated recruitment of KIF13A and KIF13B at the trans-Golgi. Molecular biology of the cell 5 38446634
2020 Characterization of 5-HT1A receptor and transport protein KIF13A expression in the hippocampus of stress-adaptive and -maladaptive mice. Neuroscience letters 4 32461107
2023 Case Report: A case of ultra-late recurrence of KIF13A-RET fusion non-small cell lung cancer response to selpercatinib. Frontiers in oncology 3 37182165
2021 Postzygotic inactivating mutation of KIF13A located at chromosome 6p22.3 in a patient with a novel mosaic neuroectodermal syndrome. Journal of human genetics 3 33526817
2023 First case report of a novel KIF13A-ALK fusion in a lung adenocarcinoma patient and response to alectinib with a 4-year follow-up. Frontiers in genetics 2 38155713
2024 MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites. Proceedings of the National Academy of Sciences of the United States of America 1 38709923
2023 MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites. bioRxiv : the preprint server for biology 1 38105964
2026 Intracellular Vesicle Transport Impairment as a Candidate Systems-Level Bottleneck in Chronic Diabetic Foot Ulcers: Network Medicine Identifies KIF13A as a Potential Therapeutic Vulnerability. Biomedicines 0 42193464
2025 A pan-cancer analysis of the oncogenic role of KIF13A in human tumors. Discover oncology 0 41436683
2024 A Locally Advanced NSCLC Patient Harboring a Rare KIF13A-RET Fusion Benefited from Pralsetinib: A Case Report. Current oncology (Toronto, Ont.) 0 39057153

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