SPAST | ENSG00000021574 | NCBI 6683

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

Description
Proteins

## Summary [SPAST](/details-gene/6683), also known as spastin, is a protein-coding gene located on chromosome 2p22.3 that encodes a microtubule-severing ATPase. As a member of the AAA (ATPases Associated with diverse cellular Activities) protein family, spastin plays a fundamental role in regulating microtubule dynamics, which is critical for a wide range of cellular processes. Its functions include axonogenesis, axonal transport, cell division (cytokinesis and mitotic spindle disassembly), and membrane trafficking ([Link](https://doi.org/10.1093/hmg/11.2.153), [Link](https://doi.org/10.1093/hmg/ddh223)). Mutations in [SPAST](/details-gene/6683) are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP), a neurodegenerative disorder characterized by progressive lower limb spasticity and weakness ([OMIM:182601](https://omim.org/entry/182601), [Link](https://doi.org/10.1038/15472)). **Overall**, expression data reveals its high significance not only in specific neuronal subtypes, such as [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) and [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041), but also unexpectedly in highly proliferative cells like [erythroblast](/details-cell/CL0000765)s and [progenitor cell](/details-cell/CL0011026)s, highlighting its broad importance in both terminally differentiated and developing cell types. ## Cellular Roles and Expression Landscape The expression profile of [SPAST](/details-gene/6683) underscores its central role in processes requiring dynamic cytoskeletal remodeling. The **Overall** analysis identifies several key cell types where [SPAST](/details-gene/6683) shows high significance, which can be grouped into distinct functional contexts. First, the gene is a prominent marker in highly proliferative and differentiating hematopoietic cells, with [erythroblast](/details-cell/CL0000765)s showing the highest significance (CSI: 8.93). This suggests a critical function during erythropoiesis, a process involving extensive cellular reorganization and enucleation. Its importance in dividing cells is further supported by its high significance in undifferentiated [progenitor cell](/details-cell/CL0011026)s. Second, consistent with its known role in neurobiology, [SPAST](/details-gene/6683) is highly significant in specific neuronal populations, including [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) and long-projection [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041). This expression pattern is consistent with its function in maintaining axonal integrity, facilitating axonal transport, and supporting the complex architecture of mature neurons. Third, the gene shows moderate to high significance across a diverse array of other cell types, including [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695)s, [pulmonary alveolar type 1 cell](/details-cell/CL0002062)s, [cardiac endothelial cell](/details-cell/CL0010008)s, and [epithelial cell of proximal tubule](/details-cell/CL0002306). This broad but variable expression suggests that while [SPAST](/details-gene/6683) is a core component of cellular machinery, its activity level is tailored to the specific cytoskeletal demands of different cell types, from immune surveillance to barrier function and transport. ## Pathways and Molecular Function The functions of [SPAST](/details-gene/6683) are intrinsically linked to its molecular role as a microtubule-severing enzyme. Functional annotations reveal its core molecular function is [microtubule severing atpase activity](/details-gene/GO:0008568), which involves binding to microtubules ([microtubule binding](/details-gene/GO:0008017)) and using energy from ATP hydrolysis ([atp hydrolysis activity](/details-gene/GO:0016887)) to break them into smaller filaments. This primary activity enables its participation in numerous biological processes. Its involvement in [anterograde axonal transport](/details-gene/GO:0008089) and [axonogenesis](/details-gene/GO:0007409) is crucial for neuronal development and maintenance, and defects in these processes are thought to underlie the pathogenesis of hereditary spastic paraplegia ([Link](https://doi.org/10.1083/jcb.200409058)). This is consistent with its high expression in various neuronal subtypes. Furthermore, [SPAST](/details-gene/6683) is deeply integrated into the mechanics of cell division. It is annotated in pathways such as [cell cycle, mitotic](/details-gene/R-HSA-69278), where it contributes to [mitotic spindle disassembly](/details-gene/GO:0051228) and [cytokinetic process](/details-gene/GO:0032506). Its localization to the spindle pole and midbody further supports this role ([Link](https://doi.org/10.1093/hmg/ddh223)). This function aligns perfectly with its high significance in rapidly dividing [progenitor cell](/details-cell/CL0011026)s and [erythroblast](/details-cell/CL0000765)s. The gene also plays a role in organelle biogenesis and trafficking, including [endoplasmic reticulum to golgi vesicle-mediated transport](/details-gene/GO:0006888) and [nuclear membrane reassembly](/details-gene/GO:0031468), indicating its importance in maintaining subcellular architecture. ## Research Directions The available data highlights both established and novel aspects of [SPAST](/details-gene/6683) biology, prompting several new research avenues. The gene's well-documented role in neuronal function contrasts with its newly revealed high significance in non-neuronal cells, suggesting its functions are more diverse than previously appreciated. **Testable Hypotheses:** 1. Given its top significance score in [erythroblast](/details-cell/CL0000765)s, [SPAST](/details-gene/6683)-mediated microtubule severing is likely essential for the extensive cytoskeletal remodeling required for enucleation during terminal erythroid differentiation. Its dysfunction could lead to novel forms of anemia or erythropoietic defects. 2. The high significance of [SPAST](/details-gene/6683) in specific long-projection neurons ([L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041)) suggests that its expression level is a critical factor for maintaining the integrity of exceptionally long axons. This may explain the selective vulnerability of corticospinal tracts in hereditary spastic paraplegia, where minor reductions in spastin function could disproportionately affect the most structurally demanding neurons. **Proposed Experiment:** To test the first hypothesis regarding the role of [SPAST](/details-gene/6683) in erythropoiesis, a robust experimental approach would involve an *in vitro* differentiation system. Specifically, CRISPR-Cas9 could be used to knock down or knock out [SPAST](/details-gene/6683) in primary human hematopoietic stem and progenitor cells (CD34+). These modified cells would then be cultured under conditions that promote erythroid differentiation. The efficiency of terminal differentiation and enucleation would be quantified using flow cytometry (staining for erythroid markers like CD235a and a nuclear dye). Furthermore, immunofluorescence microscopy of differentiating erythroblasts could be used to directly visualize the microtubule cytoskeleton and nuclear positioning, revealing any defects in the formation of the contractile actin ring or the process of nuclear extrusion. **Therapeutic Potential:** As mutations in [SPAST](/details-gene/6683) leading to hereditary spastic paraplegia are typically loss-of-function, therapeutic strategies should focus on **functional restoration or activation**. Gene therapy, using adeno-associated virus (AAV) vectors with neuron-specific promoters to deliver a correct copy of the [SPAST](/details-gene/6683) gene to the affected corticospinal motor neurons, represents a promising long-term strategy. An alternative approach could involve the development of small-molecule chaperones or activators that enhance the microtubule-severing activity of the remaining wild-type or partially functional mutant spastin protein. However, the broad expression of [SPAST](/details-gene/6683) presents a significant challenge, as systemic therapies could have unintended consequences on highly proliferative tissues. Therefore, targeted delivery to the central nervous system would be essential for any viable therapeutic intervention.

Disclaimer: This in-silico analysis is generated by an AI language model and may contain inaccuracies or hallucinations. However, it is cross-referenced with curated gene expression data from major biological sources. Please verify the information before use.

Spastic paraplegia 4 protein
E5KRP6_HUMAN

Genular Protein ID: 840893059

Symbol: SPAST_HUMAN

Name: Spastic paraplegia 4 protein

UniProtKB Accession Codes:

Q9UBP0 A7E2A7 Q9UPR9

Database IDs:

Citations:

PubMed ID: 10610178

Title: Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia.

PubMed ID: 10610178

DOI: 10.1038/15472

PubMed ID: 10470851

Title: Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 10470851

DOI: 10.1093/dnares/6.3.197

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11809724

Title: Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics.

PubMed ID: 11809724

DOI: 10.1093/hmg/11.2.153

PubMed ID: 12676568

Title: The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia.

PubMed ID: 12676568

DOI: 10.1016/s0888-7543(03)00011-9

PubMed ID: 15147984

Title: Identification of nuclear localisation sequences in spastin (SPG4) using a novel Tetra-GFP reporter system.

PubMed ID: 15147984

DOI: 10.1016/j.bbrc.2004.03.195

PubMed ID: 15269182

Title: Spastin interacts with the centrosomal protein NA14, and is enriched in the spindle pole, the midbody and the distal axon.

PubMed ID: 15269182

DOI: 10.1093/hmg/ddh223

PubMed ID: 16026783

Title: Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus.

PubMed ID: 16026783

DOI: 10.1016/j.yexcr.2005.06.009

PubMed ID: 15537668

Title: The hereditary spastic paraplegia protein spastin interacts with the ESCRT-III complex-associated endosomal protein CHMP1B.

PubMed ID: 15537668

DOI: 10.1093/hmg/ddi003

PubMed ID: 15716377

Title: Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing.

PubMed ID: 15716377

DOI: 10.1083/jcb.200409058

PubMed ID: 16219033

Title: Human spastin has multiple microtubule-related functions.

PubMed ID: 16219033

DOI: 10.1111/j.1471-4159.2005.03472.x

PubMed ID: 15891913

Title: Subcellular localization of spastin: implications for the pathogenesis of hereditary spastic paraplegia.

PubMed ID: 15891913

DOI: 10.1007/s10048-005-0219-2

PubMed ID: 16826525

Title: ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary spastic paraplegia.

PubMed ID: 16826525

DOI: 10.1086/504927

PubMed ID: 16339213

Title: Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners.

PubMed ID: 16339213

DOI: 10.1093/hmg/ddi447

PubMed ID: 16602018

Title: Spastin, the most commonly mutated protein in hereditary spastic paraplegia interacts with Reticulon 1 an endoplasmic reticulum protein.

PubMed ID: 16602018

DOI: 10.1007/s10048-006-0034-4

PubMed ID: 16815977

Title: Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance.

PubMed ID: 16815977

DOI: 10.1073/pnas.0510863103

PubMed ID: 17389232

Title: Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing.

PubMed ID: 17389232

DOI: 10.1083/jcb.200610072

PubMed ID: 18613979

Title: A cryptic promoter in the first exon of the SPG4 gene directs the synthesis of the 60-kDa spastin isoform.

PubMed ID: 18613979

DOI: 10.1186/1741-7007-6-31

PubMed ID: 18410514

Title: Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule.

PubMed ID: 18410514

DOI: 10.1111/j.1471-4159.2008.05414.x

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 19000169

Title: Spastin couples microtubule severing to membrane traffic in completion of cytokinesis and secretion.

PubMed ID: 19000169

DOI: 10.1111/j.1600-0854.2008.00847.x

PubMed ID: 20200447

Title: Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network.

PubMed ID: 20200447

DOI: 10.1172/jci40979

PubMed ID: 20530212

Title: Tubulin polyglutamylation stimulates spastin-mediated microtubule severing.

PubMed ID: 20530212

DOI: 10.1083/jcb.201001024

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 21310966

Title: Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments.

PubMed ID: 21310966

DOI: 10.1126/science.1201847

PubMed ID: 22637577

Title: Subunit Interactions and cooperativity in the microtubule-severing AAA ATPase spastin.

PubMed ID: 22637577

DOI: 10.1074/jbc.m111.291898

PubMed ID: 22232211

Title: Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12.

PubMed ID: 22232211

DOI: 10.1172/jci60560

PubMed ID: 23272056

Title: Spastin's microtubule-binding properties and comparison to katanin.

PubMed ID: 23272056

DOI: 10.1371/journal.pone.0050161

PubMed ID: 23745751

Title: The nucleotide cycle of spastin correlates with its microtubule-binding properties.

PubMed ID: 23745751

DOI: 10.1111/febs.12385

PubMed ID: 23897888

Title: An ESCRT-spastin interaction promotes fission of recycling tubules from the endosome.

PubMed ID: 23897888

DOI: 10.1083/jcb.201211045

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 23969831

Title: Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation.

PubMed ID: 23969831

DOI: 10.1073/pnas.1307391110

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25390646

Title: Spastin-interacting protein NA14/SSNA1 functions in cytokinesis and axon development.

PubMed ID: 25390646

DOI: 10.1371/journal.pone.0112428

PubMed ID: 26040712

Title: Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.

PubMed ID: 26040712

DOI: 10.1038/nature14408

PubMed ID: 25875445

Title: Spastin binds to lipid droplets and affects lipid metabolism.

PubMed ID: 25875445

DOI: 10.1371/journal.pgen.1005149

PubMed ID: 26875866

Title: Graded control of microtubule severing by tubulin glutamylation.

PubMed ID: 26875866

DOI: 10.1016/j.cell.2016.01.019

PubMed ID: 18997780

Title: Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B.

PubMed ID: 18997780

DOI: 10.1038/nsmb.1512

PubMed ID: 22446388

Title: Crystal structure of the human spastin AAA domain.

PubMed ID: 22446388

DOI: 10.1016/j.jsb.2012.03.002

PubMed ID: 11039577

Title: Hereditary spastic paraplegia caused by mutations in the SPG4 gene.

PubMed ID: 11039577

DOI: 10.1038/sj.ejhg.5200528

PubMed ID: 10699187

Title: Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia.

PubMed ID: 10699187

DOI: 10.1093/hmg/9.4.637

PubMed ID: 11015453

Title: Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis.

PubMed ID: 11015453

DOI: 10.1136/jmg.37.10.759

PubMed ID: 11087788

Title: Novel mutations in spastin gene and absence of correlation with age at onset of symptoms.

PubMed ID: 11087788

DOI: 10.1212/wnl.55.9.1388

PubMed ID: 11309678

Title: Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia.

PubMed ID: 11309678

DOI: 10.1086/320111

PubMed ID: 12460147

Title: A Japanese SPG4 family with a novel missense mutation of the SPG4 gene: intrafamilial variability in age at onset and clinical severity.

PubMed ID: 12460147

DOI: 10.1034/j.1600-0404.2002.01254.x

PubMed ID: 11843700

Title: Spectrum of SPG4 mutations in a large collection of North American families with hereditary spastic paraplegia.

PubMed ID: 11843700

DOI: 10.1001/archneur.59.2.281

PubMed ID: 12124993

Title: Mutation analysis of the spastin gene (SPG4) in patients in Germany with autosomal dominant hereditary spastic paraplegia.

PubMed ID: 12124993

DOI: 10.1002/humu.10105

PubMed ID: 12161613

Title: Spastin gene mutation in Japanese with hereditary spastic paraplegia.

PubMed ID: 12161613

DOI: 10.1136/jmg.39.8.e46

PubMed ID: 11985387

Title: Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia.

PubMed ID: 11985387

DOI: 10.1007/pl00007865

PubMed ID: 12163196

Title: Three novel spastin (SPG4) mutations in families with autosomal dominant hereditary spastic paraplegia.

PubMed ID: 12163196

DOI: 10.1016/s0022-510x(02)00192-2

PubMed ID: 12202986

Title: A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia.

PubMed ID: 12202986

DOI: 10.1007/s100380200068

PubMed ID: 12552568

Title: Screening of patients with hereditary spastic paraplegia reveals seven novel mutations in the SPG4 (Spastin) gene.

PubMed ID: 12552568

DOI: 10.1002/humu.9108

PubMed ID: 12939659

Title: Novel spastin mutations and their expression analysis in two Italian families.

PubMed ID: 12939659

DOI: 10.1038/sj.ejhg.5201027

PubMed ID: 14732620

Title: Three novel mutations of the spastin gene in Chinese patients with hereditary spastic paraplegia.

PubMed ID: 14732620

DOI: 10.1001/archneur.61.1.49

PubMed ID: 15210521

Title: Hereditary spastic paraplegia: clinical genetic study of 15 families.

PubMed ID: 15210521

DOI: 10.1001/archneur.61.6.849

PubMed ID: 15667412

Title: Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation.

PubMed ID: 15667412

DOI: 10.1111/j.1468-1331.2004.00888.x

PubMed ID: 15248095

Title: Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations.

PubMed ID: 15248095

DOI: 10.1007/s10048-004-0186-z

PubMed ID: 15482961

Title: Two novel mutations in the spastin gene (SPG4) found by DHPLC mutation analysis.

PubMed ID: 15482961

DOI: 10.1016/j.nmd.2004.05.017

PubMed ID: 15159500

Title: A new SPG4 mutation in a variant form of spastic paraplegia with congenital arachnoid cysts.

PubMed ID: 15159500

DOI: 10.1212/01.wnl.0000125324.32082.d9

PubMed ID: 15326248

Title: Infantile hereditary spastic paraparesis due to codominant mutations in the spastin gene.

PubMed ID: 15326248

DOI: 10.1212/01.wnl.0000135346.63675.3e

PubMed ID: 16682546

Title: Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia.

PubMed ID: 16682546

DOI: 10.1001/archneur.63.5.750

PubMed ID: 16684598

Title: Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia.

PubMed ID: 16684598

DOI: 10.1016/j.nmd.2006.03.009

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 17594340

Title: Seven novel mutations and four exon deletions in a collection of Norwegian patients with SPG4 hereditary spastic paraplegia.

PubMed ID: 17594340

DOI: 10.1111/j.1468-1331.2007.01861.x

PubMed ID: 20214791

Title: Unique spectrum of SPAST variants in Estonian HSP patients: presence of benign missense changes but lack of exonic rearrangements.

PubMed ID: 20214791

DOI: 10.1186/1471-2377-10-17

PubMed ID: 20932283

Title: Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia.

PubMed ID: 20932283

DOI: 10.1186/1471-2377-10-89

PubMed ID: 20562464

Title: Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations.

PubMed ID: 20562464

DOI: 10.1136/jnnp.2009.201103

PubMed ID: 20718791

Title: Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia.

PubMed ID: 20718791

DOI: 10.1111/j.1399-0004.2010.01501.x

PubMed ID: 20550563

Title: Clinical and genetic findings in a series of Italian children with pure hereditary spastic paraplegia.

PubMed ID: 20550563

DOI: 10.1111/j.1468-1331.2010.03102.x

PubMed ID: 21546041

Title: Detection of novel mutations and review of published data suggests that hereditary spastic paraplegia caused by spastin (SPAST) mutations is found more often in males.

PubMed ID: 21546041

DOI: 10.1016/j.jns.2011.03.043

PubMed ID: 22960362

Title: Novel and recurrent spastin mutations in a large series of SPG4 Italian families.

PubMed ID: 22960362

DOI: 10.1016/j.neulet.2012.08.036

PubMed ID: 23279441

Title: First mutation in the nuclear localization signal sequence of spastin protein identified in a patient with hereditary spastic paraplegia.

PubMed ID: 23279441

DOI: 10.1111/ene.12000

PubMed ID: 25421405

Title: High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia.

PubMed ID: 25421405

DOI: 10.1186/s12883-014-0216-x

PubMed ID: 25045380

Title: Mutation analysis of SPAST, ATL1, and REEP1 in Korean Patients with Hereditary Spastic Paraplegia.

PubMed ID: 25045380

DOI: 10.3988/jcn.2014.10.3.257

PubMed ID: 24824479

Title: Spastin mutation screening in Chinese patients with pure hereditary spastic paraplegia.

PubMed ID: 24824479

DOI: 10.1016/j.parkreldis.2014.04.021

PubMed ID: 28572275

Title: Truncating mutations in SPAST patients are associated with a high rate of psychiatric comorbidities in hereditary spastic paraplegia.

PubMed ID: 28572275

DOI: 10.1136/jnnp-2017-315796

Sequence Information:

Length: 616
Mass: 67197
Checksum: 75E5FC5787132B4C
Sequence:

MNSPGGRGKK KGSGGASNPV PPRPPPPCLA PAPPAAGPAP PPESPHKRNL YYFSYPLFVG 
FALLRLVAFH LGLLFVWLCQ RFSRALMAAK RSSGAAPAPA SASAPAPVPG GEAERVRVFH 
KQAFEYISIA LRIDEDEKAG QKEQAVEWYK KGIEELEKGI AVIVTGQGEQ CERARRLQAK 
MMTNLVMAKD RLQLLEKMQP VLPFSKSQTD VYNDSTNLAC RNGHLQSESG AVPKRKDPLT 
HTSNSLPRSK TVMKTGSAGL SGHHRAPSYS GLSMVSGVKQ GSGPAPTTHK GTPKTNRTNK 
PSTPTTATRK KKDLKNFRNV DSNLANLIMN EIVDNGTAVK FDDIAGQDLA KQALQEIVIL 
PSLRPELFTG LRAPARGLLL FGPPGNGKTM LAKAVAAESN ATFFNISAAS LTSKYVGEGE 
KLVRALFAVA RELQPSIIFI DEVDSLLCER REGEHDASRR LKTEFLIEFD GVQSAGDDRV 
LVMGATNRPQ ELDEAVLRRF IKRVYVSLPN EETRLLLLKN LLCKQGSPLT QKELAQLARM 
TDGYSGSDLT ALAKDAALGP IRELKPEQVK NMSASEMRNI RLSDFTESLK KIKRSVSPQT 
LEAYIRWNKD FGDTTV

Genular Protein ID: 2143725779

Symbol: E5KRP6_HUMAN

Name: N/A

UniProtKB Accession Codes:

E5KRP6

Database IDs:

Citations:

PubMed ID: 20843780

Title: Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.

PubMed ID: 20843780

DOI: 10.1093/nar/gkq750

Sequence Information:

Length: 584
Mass: 63606
Checksum: 502F0FCB78ECED14
Sequence:

MNSPGGRGKK KGSGGASNPV PPRPPPPCLA PAPPAAGPAP PPESPHKRNL YYFSYPLFVG 
FALLRLVAFH LGLLFVWLCQ RFSRALMAAK RSSGAAPAPA SASAPAPVPG GEAERVRVFH 
KQAFEYISIA LRIDEDEKAG QKEQAVEWYK KGIEELEKGI AVIVTGQGEQ CERARRLQAK 
MMTNLVMAKD RLQLLESGAV PKRKDPLTHT SNSLPRSKTV MKTGSAGLSG HHRAPSYSGL 
SMVSGVKQGS GPAPTTHKGT PKTNRTNKPS TPTTATRKKK DLKNFRNVDS NLANLIMNEI 
VDNGTAVKFD DIAGQDLAKQ ALQEIVILPS LRPELFTGLR APARGLLLFG PPGNGKTMLA 
KAVAAESNAT FFNISAASLT SKYVGEGEKL VRALFAVARE LQPSIIFIDE VDSLLCERRE 
GEHDASRRLK TEFLIEFDGV QSAGDDRVLV MGATNRPQEL DEAVLRRFIK RVYVSLPNEE 
TRLLLLKNLL CKQGSPLTQK ELAQLARMTD GYSGSDLTAL AKDAALGPIR ELKPEQVKNM 
SASEMRNIRL SDFTESLKKI KRSVSPQTLE AYIRWNKDFG DTTV

	Overall overall
	Acute kidney failure MONDO0002492
	Alzheimer disease MONDO0004975
	Amyotrophic lateral sclerosis MONDO0004976
	Basal cell carcinoma MONDO0020804
	Bipolar disorder MONDO0004985
	Bipolar I disorder MONDO0001866
	Blood UBERON0000178
	\|— Blood Cytomegalovirus infection UBERON0000178_MONDO0005132
	\|— Blood Healthy UBERON0000178_PATO0000461
	Brain UBERON0000955
	\|— Brain Healthy UBERON0000955_PATO0000461
	Breast cancer MONDO0007254
	Cerebellum UBERON0002037
	\|— Cerebellum Healthy UBERON0002037_PATO0000461
	Cerebral cortex UBERON0000956
	\|— Cerebral cortex Healthy UBERON0000956_PATO0000461
	Choroid plexus UBERON0001886
	Cortex of kidney UBERON0001225
	\|— Cortex of kidney Healthy UBERON0001225_PATO0000461
	COVID-19 MONDO0100096
	Cytomegalovirus infection MONDO0005132
	Dementia MONDO0001627
	Dorsolateral prefrontal cortex UBERON0009834
	\|— Dorsolateral prefrontal cortex Bipolar disorder UBERON0009834_MONDO0004985
	\|— Dorsolateral prefrontal cortex Bipolar I disorder UBERON0009834_MONDO0001866
	\|— Dorsolateral prefrontal cortex Dementia UBERON0009834_MONDO0001627
	\|— Dorsolateral prefrontal cortex Healthy UBERON0009834_PATO0000461
	\|— Dorsolateral prefrontal cortex Schizophrenia UBERON0009834_MONDO0005090
	\|— Dorsolateral prefrontal cortex Vascular dementia UBERON0009834_MONDO0004648
	Frontal cortex UBERON0001870
	Glioblastoma MONDO0018177
	Healthy PATO0000461
	Heart left ventricle UBERON0002084
	\|— Heart left ventricle Healthy UBERON0002084_PATO0000461
	Heart right ventricle UBERON0002080
	\|— Heart right ventricle Healthy UBERON0002080_PATO0000461
	Hippocampal formation UBERON0002421
	\|— Hippocampal formation Healthy UBERON0002421_PATO0000461
	Hypothalamus UBERON0001898
	\|— Hypothalamus Healthy UBERON0001898_PATO0000461
	Interventricular septum UBERON0002094
	Isolated focal cortical dysplasia type II MONDO0011818
	Kidney UBERON0002113
	Leukoencephalopathy, diffuse hereditary, with spheroids 1 MONDO0800027
	Liver UBERON0002107
	Lung UBERON0002048
	\|— Lung Healthy UBERON0002048_PATO0000461
	Medial orbital frontal cortex UBERON0022352
	Midbrain UBERON0001891
	\|— Midbrain Healthy UBERON0001891_PATO0000461
	Neocortex UBERON0001950
	\|— Neocortex Healthy UBERON0001950_PATO0000461
	Neuroblastoma MONDO0005072
	Occipital cortex UBERON0016540
	Parkinson disease MONDO0005180
	Peripheral region of retina UBERON0013682
	\|— Peripheral region of retina Healthy UBERON0013682_PATO0000461
	Pons UBERON0000988
	\|— Pons Healthy UBERON0000988_PATO0000461
	Prefrontal cortex UBERON0000451
	Primary motor cortex UBERON0001384
	Respiratory airway UBERON0001005
	\|— Respiratory airway COVID-19 UBERON0001005_MONDO0100096
	Retina UBERON0000966
	\|— Retina Healthy UBERON0000966_PATO0000461
	Right atrium auricular region UBERON0006631
	Schizophrenia MONDO0005090
	Substantia nigra pars compacta UBERON0001965
	Telencephalon UBERON0001893
	\|— Telencephalon Healthy UBERON0001893_PATO0000461
	Thalamic complex UBERON0010225
	\|— Thalamic complex Healthy UBERON0010225_PATO0000461
	UBERON0005290 UBERON0005290
	\|— UBERON0005290 Healthy UBERON0005290_PATO0000461
	UBERON8440012 UBERON8440012
	\|— UBERON8440012 Healthy UBERON8440012_PATO0000461
	Vascular dementia MONDO0004648

Details for: SPAST

Cell Significance Landscape

Associated with

Significant Cells

Network Configuration

Legend:

Other Information

Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. PubMed ID: 10610178

Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. PubMed ID: 10470851

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). PubMed ID: 15489334

Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics. PubMed ID: 11809724

The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia. PubMed ID: 12676568

Identification of nuclear localisation sequences in spastin (SPG4) using a novel Tetra-GFP reporter system. PubMed ID: 15147984

Spastin interacts with the centrosomal protein NA14, and is enriched in the spindle pole, the midbody and the distal axon. PubMed ID: 15269182

Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus. PubMed ID: 16026783

The hereditary spastic paraplegia protein spastin interacts with the ESCRT-III complex-associated endosomal protein CHMP1B. PubMed ID: 15537668

Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing. PubMed ID: 15716377

Human spastin has multiple microtubule-related functions. PubMed ID: 16219033

Subcellular localization of spastin: implications for the pathogenesis of hereditary spastic paraplegia. PubMed ID: 15891913

ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary spastic paraplegia. PubMed ID: 16826525

Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners. PubMed ID: 16339213

Spastin, the most commonly mutated protein in hereditary spastic paraplegia interacts with Reticulon 1 an endoplasmic reticulum protein. PubMed ID: 16602018

Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance. PubMed ID: 16815977

Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing. PubMed ID: 17389232

A cryptic promoter in the first exon of the SPG4 gene directs the synthesis of the 60-kDa spastin isoform. PubMed ID: 18613979

Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule. PubMed ID: 18410514

A quantitative atlas of mitotic phosphorylation. PubMed ID: 18669648

Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. PubMed ID: 19690332

Spastin couples microtubule severing to membrane traffic in completion of cytokinesis and secretion. PubMed ID: 19000169

Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network. PubMed ID: 20200447

Tubulin polyglutamylation stimulates spastin-mediated microtubule severing. PubMed ID: 20530212

Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. PubMed ID: 20068231

System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. PubMed ID: 21406692

Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. PubMed ID: 21310966

Subunit Interactions and cooperativity in the microtubule-severing AAA ATPase spastin. PubMed ID: 22637577

Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. PubMed ID: 22232211

Spastin's microtubule-binding properties and comparison to katanin. PubMed ID: 23272056

The nucleotide cycle of spastin correlates with its microtubule-binding properties. PubMed ID: 23745751

An ESCRT-spastin interaction promotes fission of recycling tubules from the endosome. PubMed ID: 23897888

Toward a comprehensive characterization of a human cancer cell phosphoproteome. PubMed ID: 23186163

Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation. PubMed ID: 23969831

An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. PubMed ID: 24275569

Spastin-interacting protein NA14/SSNA1 functions in cytokinesis and axon development. PubMed ID: 25390646

Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. PubMed ID: 26040712

Spastin binds to lipid droplets and affects lipid metabolism. PubMed ID: 25875445

Graded control of microtubule severing by tubulin glutamylation. PubMed ID: 26875866

Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B. PubMed ID: 18997780

Crystal structure of the human spastin AAA domain. PubMed ID: 22446388

Hereditary spastic paraplegia caused by mutations in the SPG4 gene. PubMed ID: 11039577

Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. PubMed ID: 10699187

Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis. PubMed ID: 11015453

Novel mutations in spastin gene and absence of correlation with age at onset of symptoms. PubMed ID: 11087788

Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia. PubMed ID: 11309678

A Japanese SPG4 family with a novel missense mutation of the SPG4 gene: intrafamilial variability in age at onset and clinical severity. PubMed ID: 12460147

Spectrum of SPG4 mutations in a large collection of North American families with hereditary spastic paraplegia. PubMed ID: 11843700

Mutation analysis of the spastin gene (SPG4) in patients in Germany with autosomal dominant hereditary spastic paraplegia. PubMed ID: 12124993

Spastin gene mutation in Japanese with hereditary spastic paraplegia. PubMed ID: 12161613

Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia. PubMed ID: 11985387

Three novel spastin (SPG4) mutations in families with autosomal dominant hereditary spastic paraplegia. PubMed ID: 12163196

A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia. PubMed ID: 12202986

Screening of patients with hereditary spastic paraplegia reveals seven novel mutations in the SPG4 (Spastin) gene. PubMed ID: 12552568

Novel spastin mutations and their expression analysis in two Italian families. PubMed ID: 12939659

Three novel mutations of the spastin gene in Chinese patients with hereditary spastic paraplegia. PubMed ID: 14732620

Hereditary spastic paraplegia: clinical genetic study of 15 families. PubMed ID: 15210521

Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation. PubMed ID: 15667412

Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations. PubMed ID: 15248095

Two novel mutations in the spastin gene (SPG4) found by DHPLC mutation analysis. PubMed ID: 15482961

A new SPG4 mutation in a variant form of spastic paraplegia with congenital arachnoid cysts. PubMed ID: 15159500

Infantile hereditary spastic paraparesis due to codominant mutations in the spastin gene. PubMed ID: 15326248

Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia. PubMed ID: 16682546

Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia. PubMed ID: 16684598

The consensus coding sequences of human breast and colorectal cancers. PubMed ID: 16959974

Seven novel mutations and four exon deletions in a collection of Norwegian patients with SPG4 hereditary spastic paraplegia. PubMed ID: 17594340

Unique spectrum of SPAST variants in Estonian HSP patients: presence of benign missense changes but lack of exonic rearrangements. PubMed ID: 20214791

Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia. PubMed ID: 20932283

Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations. PubMed ID: 20562464

Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia. PubMed ID: 20718791

Clinical and genetic findings in a series of Italian children with pure hereditary spastic paraplegia. PubMed ID: 20550563

Detection of novel mutations and review of published data suggests that hereditary spastic paraplegia caused by spastin (SPAST) mutations is found more often in males. PubMed ID: 21546041

Novel and recurrent spastin mutations in a large series of SPG4 Italian families. PubMed ID: 22960362