SPAST_HUMAN » Spastin

SPAST_HUMAN » Spastin
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Topology in Endosome membrane
Topologyendosome lumenal side
cytoplasmic side
SPAST_HUMAN » Spastin » Spastic paraplegia 4 protein;
Hydrophobic Thickness 28.0 ± 2.8 Å
Tilt Angle 44 ± 0°
ΔGtransfer -20.5 kcal/mol
ΔGfold -13.2 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 55-80 (54-90)
Pathways none
PDB 3vfd (228-616), 3eab (A/B...=112-196)
OPM none
Complexes none
Interactions none
Domains

AA: 378-508, PDBID: 3VFD, Subunit A, Seq Identity:100%, ATPase family associated with various cellular activities (AAA)

AA: 563-612, PDBID: 3VFD, Subunit A, Seq Identity:100%, Vps4 C terminal oligomerisation domain

UniProt annotation for SPAST_HUMAN » Spastin
FUNCTION: 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.

CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.

ENZYME REGULATION: 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.

SUBUNIT: 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.

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

DEVELOPMENTAL STAGE: Expressed in fetal brain, heart, kidney, liver, lung, skeletal muscle, spleen and thymus.

DISEASE: Spastic paraplegia 4, autosomal dominant (SPG4) OMIM: 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. mutations affecting the gene represented in this entry.

UniProt features for SPAST_HUMAN » Spastin
CHAIN 1 616 Spastin.
DOMAIN 120 195 MIT.
REGION 1 300 Required for interaction with RTN1.
REGION 1 194 Required for midbody localization.
REGION 1 80 Required for interaction with ATL1.
REGION 1 50 Required for nuclear localization.
REGION 50 87 Required for interaction with SSNA1 and microtubules.
REGION 112 196 Sufficient for interaction with CHMP1B.
REGION 114 200 Required for interaction with microtubules.
REGION 226 328 Sufficient for interaction with microtubules (By similarity).
REGION 228 616 Sufficient for microtubule severing.
REGION 270 328 Required for interaction with microtubules and microtubule severing.
MOTIF 4 11 Nuclear localization signal.
MOTIF 59 67 Nuclear export signal.
MOTIF 309 312 Nuclear localization signal.
Amino Acid Sequence for SPAST_HUMAN » Spastin
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