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Q9UBP0

- SPAST_HUMAN

UniProt

Q9UBP0 - SPAST_HUMAN

Protein

Spastin

Gene

SPAST

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    Functioni

    ATP-dependent microtubule severing protein. Microtubule severing may promote reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and for completion of the abscission stage of cytokinesis. May also play a role in axon growth and the formation of axonal branches.6 Publications

    Catalytic activityi

    ATP + H2O = ADP + phosphate.6 PublicationsUniRule annotation

    Enzyme regulationi

    Allosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers. Microtubule binding promotes cooperative interactions among spastin subunits.1 Publication

    Kineticsi

    Kinetic parameters shown are for full length enzyme. N-terminally truncated spastin (residues 228-616), which has been shown to exhibit full severing activity, shows a basal ATP turnover rate of 0.78 sec(-1) in the absence of microtubules, a KM of 0.16 mM for ATP, and the ATP turnover rate is extrapolated to 3.83 sec(-1) in the presence of microtubules. ATPase activity shows non-Michaelis-Menten kinetics in the presence of microtubules, but is close to non-cooperative behavior in their absence (PubMed:22637577).1 Publication

    1. KM=0.45 mM for ATP3 Publications

    Vmax=1.2 nmol/min/µg enzyme3 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi382 – 3898ATPCurated

    GO - Molecular functioni

    1. alpha-tubulin binding Source: UniProtKB
    2. ATP binding Source: UniProtKB-HAMAP
    3. beta-tubulin binding Source: UniProtKB
    4. microtubule binding Source: UniProtKB
    5. microtubule-severing ATPase activity Source: UniProtKB
    6. protein binding Source: UniProtKB

    GO - Biological processi

    1. ATP catabolic process Source: GOC
    2. axonogenesis Source: UniProtKB-HAMAP
    3. cell death Source: UniProtKB-KW
    4. cytokinesis, completion of separation Source: UniProtKB
    5. ER to Golgi vesicle-mediated transport Source: UniProtKB
    6. microtubule bundle formation Source: UniProtKB
    7. microtubule severing Source: UniProtKB
    8. positive regulation of microtubule depolymerization Source: UniProtKB-HAMAP
    9. protein hexamerization Source: UniProtKB
    10. protein homooligomerization Source: UniProtKB

    Keywords - Molecular functioni

    Developmental protein, Hydrolase

    Keywords - Biological processi

    Cell cycle, Cell division, Differentiation, Neurogenesis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    SpastinUniRule annotation (EC:3.6.4.3UniRule annotation)
    Alternative name(s):
    Spastic paraplegia 4 protein
    Gene namesi
    Name:SPASTUniRule annotation
    Synonyms:ADPSP, FSP2, KIAA1083, SPG4UniRule annotation
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:11233. SPAST.

    Subcellular locationi

    Membrane UniRule annotation; Single-pass membrane protein UniRule annotation. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmcytoskeleton. Cytoplasmperinuclear region. Endoplasmic reticulum. Endosome. Nucleus. Cytoplasmcytoskeletonspindle
    Note: Localization to the centrosome is independent of microtubules. Localizes to the midbody of dividing cells, and this requires CHMP1B. Enriched in the distal axons and branches of postmitotic neurons. Isoform 3 is the main endosomal form.

    GO - Cellular componenti

    1. centrosome Source: UniProtKB-HAMAP
    2. cytoplasm Source: UniProtKB
    3. cytoplasmic vesicle Source: MGI
    4. endoplasmic reticulum Source: UniProtKB-SubCell
    5. endosome Source: UniProtKB-SubCell
    6. extracellular vesicular exosome Source: UniProt
    7. integral component of membrane Source: UniProtKB-KW
    8. microtubule Source: UniProtKB-HAMAP
    9. midbody Source: UniProtKB-HAMAP
    10. nucleus Source: UniProtKB
    11. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    12. spindle Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Endoplasmic reticulum, Endosome, Membrane, Microtubule, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Spastic paraplegia 4, autosomal dominant (SPG4) [MIM:182601]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.29 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti44 – 441S → L Rare polymorphism which modifies the phenotype of SPG4 disease; may decrease the activity of the alternative promoter which directs the synthesis of isoform 3 and isoform 4. 6 Publications
    Corresponds to variant rs121908515 [ dbSNP | Ensembl ].
    VAR_010194
    Natural varianti45 – 451P → Q Rare polymorphism which modifies the phenotype of SPG4 disease. 1 Publication
    VAR_027205
    Natural varianti195 – 1951L → V in SPG4. 1 Publication
    VAR_026758
    Natural varianti287 – 2871Missing in SPG4. 1 Publication
    VAR_067631
    Natural varianti293 – 2931P → L in SPG4. 1 Publication
    VAR_067632
    Natural varianti344 – 3441I → K in SPG4; abrogates ATPase activity and promotes microtubule binding. 1 Publication
    VAR_019448
    Natural varianti347 – 3471Q → K in SPG4; promotes microtubule binding. 1 Publication
    VAR_027206
    Natural varianti361 – 3611P → L in SPG4. 1 Publication
    VAR_027207
    Natural varianti362 – 3621S → C in SPG4. 2 Publications
    VAR_010195
    Natural varianti364 – 3641R → T in SPG4. 1 Publication
    VAR_067636
    Natural varianti370 – 3701G → R in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027208
    Natural varianti378 – 3781L → Q in SPG4. 1 Publication
    VAR_019439
    Natural varianti378 – 3781L → R in SPG4. 1 Publication
    VAR_067637
    Natural varianti380 – 3801L → H in SPG4. 2 Publications
    VAR_067638
    Natural varianti381 – 3811F → C in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027209
    Natural varianti386 – 3861N → K in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027210
    Natural varianti386 – 3861N → S in SPG4. 1 Publication
    VAR_019440
    Natural varianti388 – 3881K → R in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles and impairs traffic from the ER to Golgi. 2 Publications
    VAR_027211
    Natural varianti390 – 3901M → V in SPG4. 1 Publication
    VAR_019441
    Natural varianti391 – 3911L → P in SPG4. 1 Publication
    VAR_067639
    Natural varianti393 – 3964Missing in SPG4.
    VAR_067640
    Natural varianti399 – 3991S → L in SPG4. 1 Publication
    VAR_027212
    Natural varianti404 – 4041Missing in SPG4. 1 Publication
    VAR_019449
    Natural varianti406 – 4061I → V in SPG4. 1 Publication
    VAR_026759
    Natural varianti407 – 4071S → R in SPG4. 1 Publication
    VAR_019450
    Natural varianti409 – 4091A → T in SPG4. 1 Publication
    VAR_067641
    Natural varianti410 – 4101S → R in SPG4. 1 Publication
    VAR_067642
    Natural varianti413 – 4131S → L in SPG4. 1 Publication
    VAR_067568
    Natural varianti424 – 4241R → G in SPG4. 1 Publication
    VAR_010196
    Natural varianti426 – 4261L → F in SPG4. 1 Publication
    VAR_067643
    Natural varianti426 – 4261L → V in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications
    VAR_027213
    Natural varianti435 – 4351P → L in SPG4. 1 Publication
    VAR_027214
    Natural varianti436 – 4361S → F in SPG4. 1 Publication
    VAR_027215
    Natural varianti436 – 4361S → P in SPG4. 1 Publication
    VAR_067644
    Natural varianti441 – 4411D → G in SPG4. 1 Publication
    VAR_027216
    Natural varianti441 – 4411D → N in SPG4. 1 Publication
    VAR_067645
    Natural varianti448 – 4481C → Y in SPG4; abrogates binding to the tail of beta-3-tubulin, abolishes microtubule severing and promotes the formation of thick microtubule bundles. 2 Publications
    VAR_010197
    Natural varianti454 – 4541E → K in SPG4. 1 Publication
    VAR_067571
    Natural varianti459 – 4591R → G in SPG4. 1 Publication
    VAR_027217
    Natural varianti460 – 4601R → C in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027218
    Natural varianti460 – 4601R → L in SPG4. 1 Publication
    VAR_027219
    Natural varianti460 – 4601R → S in SPG4. 3 Publications
    VAR_067572
    Natural varianti463 – 4631T → A in SPG4. 1 Publication
    VAR_067646
    Natural varianti470 – 4701D → V in SPG4. 1 Publication
    Corresponds to variant rs28939368 [ dbSNP | Ensembl ].
    VAR_027220
    Natural varianti485 – 4851A → V in SPG4. 1 Publication
    VAR_027221
    Natural varianti489 – 4891P → L in SPG4. 1 Publication
    VAR_027222
    Natural varianti492 – 4921L → F in SPG4. 1 Publication
    VAR_067648
    Natural varianti493 – 4931D → G in SPG4. 1 Publication
    VAR_026760
    Natural varianti498 – 4981R → G in SPG4. 2 Publications
    VAR_067649
    Natural varianti499 – 4991R → C in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles. 4 Publications
    VAR_010198
    Natural varianti499 – 4991R → H in SPG4. 1 Publication
    VAR_026761
    Natural varianti503 – 5031R → L in SPG4. 1 Publication
    VAR_019442
    Natural varianti503 – 5031R → RR in SPG4. 1 Publication
    VAR_067650
    Natural varianti503 – 5031R → W in SPG4. 1 Publication
    VAR_026762
    Natural varianti512 – 5121E → D in SPG4. 1 Publication
    VAR_027223
    Natural varianti514 – 5141R → G in SPG4. 1 Publication
    VAR_067651
    Natural varianti515 – 5151Missing in SPG4. 1 Publication
    VAR_019443
    Natural varianti534 – 5341L → P in SPG4. 1 Publication
    VAR_019444
    Natural varianti551 – 5511A → Y in SPG4; requires 2 nucleotide substitutions. 1 Publication
    VAR_019451
    Natural varianti555 – 5551D → N in SPG4. 1 Publication
    VAR_027224
    Natural varianti556 – 5561A → V in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027225
    Natural varianti559 – 5591G → D in SPG4. 2 Publications
    VAR_027226
    Natural varianti562 – 5621R → G in SPG4. 2 Publications
    VAR_027227
    Natural varianti562 – 5621R → Q in SPG4. 1 Publication
    VAR_027228
    Natural varianti580 – 5801I → T in SPG4. 1 Publication
    VAR_067654
    Natural varianti584 – 5841D → H in SPG4. 1 Publication
    VAR_010199
    Natural varianti607 – 6071W → C in SPG4. 1 Publication
    VAR_026763
    Natural varianti614 – 6141T → I in SPG4; variant form with congenital arachnoid cysts. 1 Publication
    VAR_019445
    Natural varianti615 – 6151T → I in SPG4. 1 Publication
    VAR_019452

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1 – 11M → V: Cytoplasmic and nuclear. 1 Publication
    Mutagenesisi87 – 871M → V: Exclusively cytoplasmic. 1 Publication
    Mutagenesisi120 – 1201H → D: Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-124. 1 Publication
    Mutagenesisi124 – 1241F → A: Impairs binding to CHMP1B. 1 Publication
    Mutagenesisi124 – 1241F → D: Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-120. 1 Publication
    Mutagenesisi310 – 3123KKK → QQQ: Loss of microtubule-binding.
    Mutagenesisi388 – 3881K → A: Abrogates ATPase activity and abolishes microtubule severing. 1 Publication
    Mutagenesisi415 – 4151Y → A: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing. 1 Publication
    Mutagenesisi442 – 4421E → Q: Abrogates ATP hydrolysis, abolishes microtubule severing, stabilizes the homohexameric form, and promotes microtubule binding and redistribution from the endosome to microtubules. 6 Publications
    Mutagenesisi451 – 4511R → G: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing. 1 Publication
    Mutagenesisi457 – 4571A → E: Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin and abolishes microtubule severing. 1 Publication

    Keywords - Diseasei

    Hereditary spastic paraplegia, Neurodegeneration

    Organism-specific databases

    MIMi182601. phenotype.
    Orphaneti100985. Autosomal dominant spastic paraplegia type 4.
    PharmGKBiPA36063.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 616616SpastinPRO_0000084763Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei245 – 2451Phosphoserine1 Publication
    Modified residuei268 – 2681Phosphoserine3 Publications
    Modified residuei306 – 3061Phosphothreonine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9UBP0.
    PaxDbiQ9UBP0.
    PeptideAtlasiQ9UBP0.
    PRIDEiQ9UBP0.

    PTM databases

    PhosphoSiteiQ9UBP0.

    Expressioni

    Tissue specificityi

    Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. The short isoforms may predominate in brain and spinal cord.1 Publication

    Developmental stagei

    Expressed in fetal brain, heart, kidney, liver, lung, skeletal muscle, spleen and thymus.1 Publication

    Gene expression databases

    ArrayExpressiQ9UBP0.
    BgeeiQ9UBP0.
    CleanExiHS_SPAST.
    GenevestigatoriQ9UBP0.

    Organism-specific databases

    HPAiHPA017311.

    Interactioni

    Subunit structurei

    Homohexamer. Mostly monomeric, but assembles into hexameric structure for short periods of time. Oligomerization seems to be a prerequisite for catalytic activity. Binding to ATP in a cleft between two adjacent subunits stabilizes the homohexameric form. Binds to microtubules at least in part via the alpha-tubulin and beta-tubulin tails. The hexamer adopts a ring conformation through which microtubules pass prior to being severed. Does not interact strongly with tubulin heterodimers. Interacts (via MIT domain) with CHMP1B; the interaction is direct. Interacts with ATL1, RTN1, SSNA1 and ZFYVE27. Isoform 1 but not isoform 3 interacts with RTN2. Interacts with REEP1.13 Publications

    Protein-protein interaction databases

    BioGridi112562. 7 interactions.
    IntActiQ9UBP0. 4 interactions.
    STRINGi9606.ENSP00000320885.

    Structurei

    Secondary structure

    1
    616
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi112 – 13625
    Beta strandi139 – 1413
    Helixi142 – 1443
    Helixi146 – 16116
    Helixi169 – 19527
    Helixi328 – 3303
    Helixi341 – 3433
    Helixi348 – 35710
    Helixi359 – 3635
    Turni365 – 3673
    Helixi370 – 3723
    Beta strandi376 – 3838
    Helixi388 – 39811
    Beta strandi402 – 4065
    Helixi420 – 43213
    Beta strandi433 – 4419
    Helixi443 – 4464
    Helixi458 – 47215
    Beta strandi480 – 4878
    Helixi489 – 4913
    Helixi494 – 4974
    Beta strandi502 – 5054
    Helixi511 – 52212
    Helixi531 – 54010
    Turni541 – 5433
    Helixi546 – 55611
    Helixi559 – 5624
    Beta strandi573 – 5753
    Helixi582 – 59110
    Helixi598 – 61013

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3EABX-ray2.50A/B/C/D/E/F112-196[»]
    3VFDX-ray3.30A228-616[»]
    ProteinModelPortaliQ9UBP0.
    SMRiQ9UBP0. Positions 112-196, 324-612.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UBP0.

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei57 – 7721HelicalUniRule annotationAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini120 – 19576MITUniRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 300300Required for interaction with RTN1Add
    BLAST
    Regioni1 – 194194Required for midbody localizationAdd
    BLAST
    Regioni1 – 8080Required for interaction with ATL1Add
    BLAST
    Regioni1 – 5050Required for nuclear localizationAdd
    BLAST
    Regioni50 – 8738Required for interaction with SSNA1 and microtubulesAdd
    BLAST
    Regioni112 – 19685Sufficient for interaction with CHMP1BAdd
    BLAST
    Regioni114 – 20087Required for interaction with microtubulesAdd
    BLAST
    Regioni226 – 328103Sufficient for interaction with microtubulesBy similarityAdd
    BLAST
    Regioni228 – 616389Sufficient for microtubule severingAdd
    BLAST
    Regioni270 – 32859Required for interaction with microtubules and microtubule severingAdd
    BLAST
    Regioni310 – 3123Required for interaction with microtubules

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi4 – 118Nuclear localization signal1 PublicationUniRule annotation
    Motifi59 – 679Nuclear export signal
    Motifi309 – 3124Nuclear localization signal1 PublicationUniRule annotation

    Sequence similaritiesi

    Belongs to the AAA ATPase family. Spastin subfamily.UniRule annotation
    Contains 1 MIT domain.UniRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0464.
    HOGENOMiHOG000225146.
    HOVERGENiHBG108502.
    InParanoidiQ9UBP0.
    KOiK13254.
    OMAiSEMRNIK.
    OrthoDBiEOG7GXPCR.
    PhylomeDBiQ9UBP0.
    TreeFamiTF105014.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    HAMAPiMF_03021. Spastin.
    InterProiIPR003593. AAA+_ATPase.
    IPR003959. ATPase_AAA_core.
    IPR003960. ATPase_AAA_CS.
    IPR007330. MIT.
    IPR027417. P-loop_NTPase.
    IPR017179. Spastin.
    [Graphical view]
    PfamiPF00004. AAA. 1 hit.
    PF04212. MIT. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037338. Spastin. 1 hit.
    SMARTiSM00382. AAA. 1 hit.
    SM00745. MIT. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    PROSITEiPS00674. AAA. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative promoter usage, alternative splicing and alternative initiation. Align

    Note: Alternative promoter usage of a cryptic promoter in exon 1 can direct the synthesis of N-terminally truncated isoforms, which may also arise from alternative initiation.2 Publications

    Isoform 1 (identifier: Q9UBP0-1) [UniParc]FASTAAdd to Basket

    Also known as: Long, Long variant 1

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MNSPGGRGKK KGSGGASNPV PPRPPPPCLA PAPPAAGPAP PPESPHKRNL    50
    YYFSYPLFVG FALLRLVAFH LGLLFVWLCQ RFSRALMAAK RSSGAAPAPA 100
    SASAPAPVPG GEAERVRVFH KQAFEYISIA LRIDEDEKAG QKEQAVEWYK 150
    KGIEELEKGI AVIVTGQGEQ CERARRLQAK MMTNLVMAKD RLQLLEKMQP 200
    VLPFSKSQTD VYNDSTNLAC RNGHLQSESG AVPKRKDPLT HTSNSLPRSK 250
    TVMKTGSAGL SGHHRAPSYS GLSMVSGVKQ GSGPAPTTHK GTPKTNRTNK 300
    PSTPTTATRK KKDLKNFRNV DSNLANLIMN EIVDNGTAVK FDDIAGQDLA 350
    KQALQEIVIL PSLRPELFTG LRAPARGLLL FGPPGNGKTM LAKAVAAESN 400
    ATFFNISAAS LTSKYVGEGE KLVRALFAVA RELQPSIIFI DEVDSLLCER 450
    REGEHDASRR LKTEFLIEFD GVQSAGDDRV LVMGATNRPQ ELDEAVLRRF 500
    IKRVYVSLPN EETRLLLLKN LLCKQGSPLT QKELAQLARM TDGYSGSDLT 550
    ALAKDAALGP IRELKPEQVK NMSASEMRNI RLSDFTESLK KIKRSVSPQT 600
    LEAYIRWNKD FGDTTV 616
    Length:616
    Mass (Da):67,197
    Last modified:May 1, 2000 - v1
    Checksum:i75E5FC5787132B4C
    GO
    Isoform 2 (identifier: Q9UBP0-2) [UniParc]FASTAAdd to Basket

    Also known as: Long variant 2

    The sequence of this isoform differs from the canonical sequence as follows:
         197-228: Missing.

    Show »
    Length:584
    Mass (Da):63,606
    Checksum:i502F0FCB78ECED14
    GO
    Isoform 3 (identifier: Q9UBP0-3) [UniParc]FASTAAdd to Basket

    Also known as: Short, Short variant 1

    The sequence of this isoform differs from the canonical sequence as follows:
         1-86: Missing.

    Note: Produced by alternative promoter usage. May also be produced by alternative initiation at Met-87 of isoform 1. Major isoform.

    Show »
    Length:530
    Mass (Da):58,009
    Checksum:i0A4DB33B07801675
    GO
    Isoform 4 (identifier: Q9UBP0-4) [UniParc]FASTAAdd to Basket

    Also known as: Short variant 2

    The sequence of this isoform differs from the canonical sequence as follows:
         1-86: Missing.
         197-228: Missing.

    Note: Produced by alternative promoter usage and alternative splicing. May also be produced by alternative initiation at Met-87 of isoform 2.

    Show »
    Length:498
    Mass (Da):54,418
    Checksum:iF8BB32A6C8CB1D73
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti44 – 441S → L Rare polymorphism which modifies the phenotype of SPG4 disease; may decrease the activity of the alternative promoter which directs the synthesis of isoform 3 and isoform 4. 6 Publications
    Corresponds to variant rs121908515 [ dbSNP | Ensembl ].
    VAR_010194
    Natural varianti45 – 451P → Q Rare polymorphism which modifies the phenotype of SPG4 disease. 1 Publication
    VAR_027205
    Natural varianti97 – 971P → T in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067628
    Natural varianti162 – 1621V → I in a patient with hereditary spastic paraplegia; unknown pathological significance. 2 Publications
    Corresponds to variant rs141944844 [ dbSNP | Ensembl ].
    VAR_067563
    Natural varianti195 – 1951L → V in SPG4. 1 Publication
    VAR_026758
    Natural varianti201 – 2011V → D in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067629
    Natural varianti229 – 2291S → G.1 Publication
    VAR_067630
    Natural varianti287 – 2871Missing in SPG4. 1 Publication
    VAR_067631
    Natural varianti293 – 2931P → L in SPG4. 1 Publication
    VAR_067632
    Natural varianti314 – 3141L → S in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067633
    Natural varianti328 – 3281I → L in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067634
    Natural varianti344 – 3441I → K in SPG4; abrogates ATPase activity and promotes microtubule binding. 1 Publication
    VAR_019448
    Natural varianti347 – 3471Q → K in SPG4; promotes microtubule binding. 1 Publication
    VAR_027206
    Natural varianti356 – 3561E → K in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067564
    Natural varianti360 – 3601L → V in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067635
    Natural varianti361 – 3611P → L in SPG4. 1 Publication
    VAR_027207
    Natural varianti362 – 3621S → C in SPG4. 2 Publications
    VAR_010195
    Natural varianti364 – 3641R → T in SPG4. 1 Publication
    VAR_067636
    Natural varianti365 – 3651P → S in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067565
    Natural varianti370 – 3701G → R in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027208
    Natural varianti378 – 3781L → Q in SPG4. 1 Publication
    VAR_019439
    Natural varianti378 – 3781L → R in SPG4. 1 Publication
    VAR_067637
    Natural varianti380 – 3801L → H in SPG4. 2 Publications
    VAR_067638
    Natural varianti381 – 3811F → C in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027209
    Natural varianti382 – 3821G → R in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067566
    Natural varianti386 – 3861N → K in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027210
    Natural varianti386 – 3861N → S in SPG4. 1 Publication
    VAR_019440
    Natural varianti388 – 3881K → R in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles and impairs traffic from the ER to Golgi. 2 Publications
    VAR_027211
    Natural varianti390 – 3901M → V in SPG4. 1 Publication
    VAR_019441
    Natural varianti391 – 3911L → P in SPG4. 1 Publication
    VAR_067639
    Natural varianti393 – 3964Missing in SPG4.
    VAR_067640
    Natural varianti399 – 3991S → L in SPG4. 1 Publication
    VAR_027212
    Natural varianti404 – 4041Missing in SPG4. 1 Publication
    VAR_019449
    Natural varianti406 – 4061I → V in SPG4. 1 Publication
    VAR_026759
    Natural varianti407 – 4071S → I in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067567
    Natural varianti407 – 4071S → R in SPG4. 1 Publication
    VAR_019450
    Natural varianti409 – 4091A → T in SPG4. 1 Publication
    VAR_067641
    Natural varianti410 – 4101S → R in SPG4. 1 Publication
    VAR_067642
    Natural varianti413 – 4131S → L in SPG4. 1 Publication
    VAR_067568
    Natural varianti422 – 4221L → F in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067569
    Natural varianti423 – 4231V → L in a breast cancer sample; somatic mutation. 1 Publication
    VAR_035902
    Natural varianti424 – 4241R → G in SPG4. 1 Publication
    VAR_010196
    Natural varianti426 – 4261L → F in SPG4. 1 Publication
    VAR_067643
    Natural varianti426 – 4261L → V in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 2 Publications
    VAR_027213
    Natural varianti435 – 4351P → L in SPG4. 1 Publication
    VAR_027214
    Natural varianti436 – 4361S → F in SPG4. 1 Publication
    VAR_027215
    Natural varianti436 – 4361S → P in SPG4. 1 Publication
    VAR_067644
    Natural varianti441 – 4411D → G in SPG4. 1 Publication
    VAR_027216
    Natural varianti441 – 4411D → N in SPG4. 1 Publication
    VAR_067645
    Natural varianti445 – 4451S → N in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067570
    Natural varianti448 – 4481C → Y in SPG4; abrogates binding to the tail of beta-3-tubulin, abolishes microtubule severing and promotes the formation of thick microtubule bundles. 2 Publications
    VAR_010197
    Natural varianti454 – 4541E → K in SPG4. 1 Publication
    VAR_067571
    Natural varianti459 – 4591R → G in SPG4. 1 Publication
    VAR_027217
    Natural varianti460 – 4601R → C in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027218
    Natural varianti460 – 4601R → L in SPG4. 1 Publication
    VAR_027219
    Natural varianti460 – 4601R → S in SPG4. 3 Publications
    VAR_067572
    Natural varianti463 – 4631T → A in SPG4. 1 Publication
    VAR_067646
    Natural varianti464 – 4641E → A in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067647
    Natural varianti470 – 4701D → V in SPG4. 1 Publication
    Corresponds to variant rs28939368 [ dbSNP | Ensembl ].
    VAR_027220
    Natural varianti482 – 4821V → L in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067573
    Natural varianti485 – 4851A → V in SPG4. 1 Publication
    VAR_027221
    Natural varianti489 – 4891P → L in SPG4. 1 Publication
    VAR_027222
    Natural varianti492 – 4921L → F in SPG4. 1 Publication
    VAR_067648
    Natural varianti493 – 4931D → G in SPG4. 1 Publication
    VAR_026760
    Natural varianti498 – 4981R → G in SPG4. 2 Publications
    VAR_067649
    Natural varianti499 – 4991R → C in SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles. 4 Publications
    VAR_010198
    Natural varianti499 – 4991R → H in SPG4. 1 Publication
    VAR_026761
    Natural varianti503 – 5031R → L in SPG4. 1 Publication
    VAR_019442
    Natural varianti503 – 5031R → RR in SPG4. 1 Publication
    VAR_067650
    Natural varianti503 – 5031R → W in SPG4. 1 Publication
    VAR_026762
    Natural varianti512 – 5121E → D in SPG4. 1 Publication
    VAR_027223
    Natural varianti512 – 5121Missing in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067574
    Natural varianti514 – 5141R → G in SPG4. 1 Publication
    VAR_067651
    Natural varianti515 – 5151Missing in SPG4. 1 Publication
    VAR_019443
    Natural varianti534 – 5341L → P in SPG4. 1 Publication
    VAR_019444
    Natural varianti534 – 5341L → V Found at homozygosity in two children with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067575
    Natural varianti550 – 5501T → I in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067652
    Natural varianti551 – 5511A → Y in SPG4; requires 2 nucleotide substitutions. 1 Publication
    VAR_019451
    Natural varianti555 – 5551D → N in SPG4. 1 Publication
    VAR_027224
    Natural varianti556 – 5561A → V in SPG4; promotes microtubule binding and the formation of thick microtubule bundles. 1 Publication
    VAR_027225
    Natural varianti559 – 5591G → D in SPG4. 2 Publications
    VAR_027226
    Natural varianti562 – 5621R → G in SPG4. 2 Publications
    VAR_027227
    Natural varianti562 – 5621R → P in a patient with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    VAR_067576
    Natural varianti562 – 5621R → Q in SPG4. 1 Publication
    VAR_027228
    Natural varianti579 – 5791N → H Found in patients with hereditary spastic paraplegia; unknown pathological significance. 1 Publication
    Corresponds to variant rs144594804 [ dbSNP | Ensembl ].
    VAR_067653
    Natural varianti580 – 5801I → T in SPG4. 1 Publication
    VAR_067654
    Natural varianti584 – 5841D → H in SPG4. 1 Publication
    VAR_010199
    Natural varianti607 – 6071W → C in SPG4. 1 Publication
    VAR_026763
    Natural varianti614 – 6141T → I in SPG4; variant form with congenital arachnoid cysts. 1 Publication
    VAR_019445
    Natural varianti615 – 6151T → I in SPG4. 1 Publication
    VAR_019452

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 8686Missing in isoform 3 and isoform 4. CuratedVSP_036650Add
    BLAST
    Alternative sequencei197 – 22832Missing in isoform 2 and isoform 4. 2 PublicationsVSP_000024Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ246001 mRNA. Translation: CAB60141.1.
    AJ246003 Genomic DNA. Translation: CAB60208.1.
    AB029006 mRNA. Translation: BAA83035.1.
    CH471053 Genomic DNA. Translation: EAX00462.1.
    BC150260 mRNA. Translation: AAI50261.1.
    CCDSiCCDS1778.1. [Q9UBP0-1]
    CCDS1779.1. [Q9UBP0-2]
    RefSeqiNP_055761.2. NM_014946.3. [Q9UBP0-1]
    NP_955468.1. NM_199436.1. [Q9UBP0-2]
    UniGeneiHs.468091.

    Genome annotation databases

    EnsembliENST00000315285; ENSP00000320885; ENSG00000021574. [Q9UBP0-1]
    ENST00000345662; ENSP00000340817; ENSG00000021574. [Q9UBP0-2]
    GeneIDi6683.
    KEGGihsa:6683.
    UCSCiuc002roc.3. human. [Q9UBP0-1]

    Polymorphism databases

    DMDMi12230611.

    Keywords - Coding sequence diversityi

    Alternative initiation, Alternative promoter usage, Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Protein Spotlight

    The making of crooked - Issue 104 of April 2009

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ246001 mRNA. Translation: CAB60141.1 .
    AJ246003 Genomic DNA. Translation: CAB60208.1 .
    AB029006 mRNA. Translation: BAA83035.1 .
    CH471053 Genomic DNA. Translation: EAX00462.1 .
    BC150260 mRNA. Translation: AAI50261.1 .
    CCDSi CCDS1778.1. [Q9UBP0-1 ]
    CCDS1779.1. [Q9UBP0-2 ]
    RefSeqi NP_055761.2. NM_014946.3. [Q9UBP0-1 ]
    NP_955468.1. NM_199436.1. [Q9UBP0-2 ]
    UniGenei Hs.468091.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3EAB X-ray 2.50 A/B/C/D/E/F 112-196 [» ]
    3VFD X-ray 3.30 A 228-616 [» ]
    ProteinModelPortali Q9UBP0.