SHOT1_RAT
ID SHOT1_RAT Reviewed; 633 AA.
AC A0MZ67; A0MZ64;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Shootin-1 {ECO:0000312|RGD:1311558};
DE AltName: Full=Shootin1 {ECO:0000303|PubMed:17030985};
GN Name=Shtn1 {ECO:0000312|RGD:1311558};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), IDENTIFICATION BY MASS
RP SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RUFY3,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=Sprague-Dawley;
RX PubMed=17030985; DOI=10.1083/jcb.200604160;
RA Toriyama M., Shimada T., Kim K.B., Mitsuba M., Nomura E., Katsuta K.,
RA Sakumura Y., Roepstorff P., Inagaki N.;
RT "Shootin1: a protein involved in the organization of an asymmetric signal
RT for neuronal polarization.";
RL J. Cell Biol. 175:147-157(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Wistar;
RA Katsuta K., Toriyama M., Shimada T., Inagaki N.;
RT "Shootin2: a splicing variant of shootin1.";
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=17439943; DOI=10.1074/jbc.m700770200;
RA Mori T., Wada T., Suzuki T., Kubota Y., Inagaki N.;
RT "Singar1, a novel RUN domain-containing protein, suppresses formation of
RT surplus axons for neuronal polarity.";
RL J. Biol. Chem. 282:19884-19893(2007).
RN [4]
RP FUNCTION, INTERACTION WITH L1CAM, INTERACTION WITH F-ACTIN, DOMAIN,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18519736; DOI=10.1083/jcb.200712138;
RA Shimada T., Toriyama M., Uemura K., Kamiguchi H., Sugiura T., Watanabe N.,
RA Inagaki N.;
RT "Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon
RT outgrowth.";
RL J. Cell Biol. 181:817-829(2008).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=20664640; DOI=10.1038/msb.2010.51;
RA Toriyama M., Sakumura Y., Shimada T., Ishii S., Inagaki N.;
RT "A diffusion-based neurite length-sensing mechanism involved in neuronal
RT symmetry breaking.";
RL Mol. Syst. Biol. 6:394-394(2010).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-506, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [7]
RP FUNCTION, INTERACTION WITH F-ACTIN, PHOSPHORYLATION AT SER-101 AND SER-249,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-101 AND SER-249.
RX PubMed=23453953; DOI=10.1016/j.cub.2013.02.017;
RA Toriyama M., Kozawa S., Sakumura Y., Inagaki N.;
RT "Conversion of a signal into forces for axon outgrowth through Pak1-
RT mediated shootin1 phosphorylation.";
RL Curr. Biol. 23:529-534(2013).
RN [8]
RP DEVELOPMENTAL STAGE.
RX PubMed=23408951; DOI=10.1371/journal.pone.0054905;
RA Wissner-Gross Z.D., Scott M.A., Steinmeyer J.D., Yanik M.F.;
RT "Synchronous symmetry breaking in neurons with different neurite counts.";
RL PLoS ONE 8:E54905-E54905(2013).
CC -!- FUNCTION: Involved in the generation of internal asymmetric signals
CC required for neuronal polarization and neurite outgrowth
CC (PubMed:17030985, PubMed:17439943, PubMed:18519736, PubMed:20664640).
CC Mediates netrin-1-induced F-actin-substrate coupling or 'clutch
CC engagement' within the axon growth cone through activation of CDC42,
CC RAC1 and PAK1-dependent signaling pathway, thereby converting the F-
CC actin retrograde flow into traction forces, concomitantly with
CC filopodium extension and axon outgrowth (PubMed:18519736,
CC PubMed:23453953). Plays a role in cytoskeletal organization by
CC regulating the subcellular localization of phosphoinositide 3-kinase
CC (PI3K) activity at the axonal growth cone (PubMed:17030985). Also plays
CC a role in regenerative neurite outgrowth (PubMed:20664640). In the
CC developing cortex, cooperates with KIF20B to promote both the
CC transition from the multipolar to the bipolar stage and the radial
CC migration of cortical neurons from the ventricular zone toward the
CC superficial layer of the neocortex. Involved in the accumulation of
CC phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of
CC primary hippocampal neurons (By similarity).
CC {ECO:0000250|UniProtKB:Q8K2Q9, ECO:0000269|PubMed:17030985,
CC ECO:0000269|PubMed:17439943, ECO:0000269|PubMed:18519736,
CC ECO:0000269|PubMed:20664640, ECO:0000269|PubMed:23453953}.
CC -!- SUBUNIT: Interacts with PFN2. Interacts (via N-terminus) with KIF20B;
CC this interaction is direct and promotes the association of SHTN1 to
CC microtubules in primary neurons. Associates with microtubule (By
CC similarity). Interacts with L1CAM; this interaction occurs in axonal
CC growth cones (PubMed:18519736). Interacts with actin filament
CC retrograde flow; this interaction is enhanced in a netrin-1- and PAK1-
CC dependent manner and promotes F-actin-substrate coupling and
CC concomitant formation of traction forces at axonal growth cones
CC (PubMed:18519736, PubMed:23453953). Interacts with RUFY3
CC (PubMed:17030985). {ECO:0000250|UniProtKB:Q8K2Q9,
CC ECO:0000269|PubMed:17030985, ECO:0000269|PubMed:18519736,
CC ECO:0000269|PubMed:23453953}.
CC -!- INTERACTION:
CC A0MZ67; Q63787: Pik3r1; NbExp=2; IntAct=EBI-1392040, EBI-518443;
CC -!- SUBCELLULAR LOCATION: Perikaryon {ECO:0000269|PubMed:17030985,
CC ECO:0000269|PubMed:20664640}. Cell projection, axon
CC {ECO:0000269|PubMed:17030985, ECO:0000269|PubMed:20664640}. Cell
CC projection, growth cone {ECO:0000269|PubMed:17030985,
CC ECO:0000269|PubMed:18519736, ECO:0000269|PubMed:20664640,
CC ECO:0000269|PubMed:23453953}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q8K2Q9}. Cell projection, filopodium
CC {ECO:0000269|PubMed:18519736, ECO:0000269|PubMed:23453953}. Cell
CC projection, lamellipodium {ECO:0000269|PubMed:18519736,
CC ECO:0000269|PubMed:23453953}. Note=Localizes in multiple growth cones
CC at neurite tips before the neuronal symmetry-breaking step
CC (PubMed:23453953). Accumulates in growth cones of a single nascent axon
CC in a neurite length-dependent manner during the neuronal symmetry-
CC breaking step; when absent from the nascent axon's siblings, probably
CC due to competitive transport, prevents the formation of surplus axons
CC (PubMed:17030985, PubMed:23453953). Transported anterogradely from the
CC soma to the axon growth cone in an actin and myosin-dependent manner
CC and passively diffuses back to the cell bodies (PubMed:23453953).
CC Colocalized with L1CAM in close apposition with actin filaments in
CC filopodia and lamellipodia of axonal growth cones in hippocampal
CC neurons (PubMed:18519736). Exhibits retrograde movements in filopodia
CC and lamellopodia of axonal growth cones (PubMed:18519736). Colocalized
CC with KIF20B along microtubules to the tip of the growing cone in
CC primary hippocampal neurons. Recruited to the growth cone of developing
CC axon in a KIF20B- and microtubule-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:Q8K2Q9, ECO:0000269|PubMed:17030985,
CC ECO:0000269|PubMed:18519736, ECO:0000269|PubMed:23453953}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Shootin2;
CC IsoId=A0MZ67-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0MZ67-2; Sequence=VSP_027056, VSP_027057;
CC -!- TISSUE SPECIFICITY: Brain-specific (at protein level)
CC (PubMed:17030985). Expressed in hippocampal neurons (PubMed:18519736).
CC {ECO:0000269|PubMed:17030985, ECO:0000269|PubMed:18519736}.
CC -!- DEVELOPMENTAL STAGE: Expressed in hippocampal neurons at 18 dpc
CC (PubMed:23408951). Expressed at high level both in hippocampal neurons
CC and in brain, during the period of axon formation and elongation.
CC Accumulates in axonal growth cones during the stage 2/3 transition.
CC Accumulates asymmetrically in a single neurite before polarization,
CC while it is depleted in its sibling neurites, through competitive
CC transport to multiple neurites. Transported anterogradely to the growth
CC cones and diffused back to the soma (at protein level)
CC (PubMed:17030985). {ECO:0000269|PubMed:17030985,
CC ECO:0000269|PubMed:23408951}.
CC -!- INDUCTION: Up-regulated by axonal regeneration (PubMed:20664640).
CC {ECO:0000269|PubMed:20664640}.
CC -!- DOMAIN: The N-terminus region is necessary for interaction with actin
CC retrograde filament flow and accumulation in neuronal growth cones
CC (PubMed:18519736). {ECO:0000269|PubMed:18519736}.
CC -!- PTM: Phosphorylated on Ser-101 and Ser-249 by PAK1 through a CDC42- and
CC RAC1-dependent signaling pathway, which enhances its association with
CC F-actin retrograde flow in filopodia and lamellipodia of axonal growth
CC cones (PubMed:23453953). Phosphorylation on Ser-101 and Ser-249 is
CC increased by netrin-1 (PubMed:23453953). {ECO:0000269|PubMed:23453953}.
CC -!- SIMILARITY: Belongs to the shootin family. {ECO:0000305}.
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DR EMBL; EF055485; ABK56020.1; -; mRNA.
DR EMBL; EF055488; ABK56023.1; -; mRNA.
DR RefSeq; NP_001073173.2; NM_001079705.4. [A0MZ67-1]
DR RefSeq; NP_001290466.1; NM_001303537.1. [A0MZ67-2]
DR AlphaFoldDB; A0MZ67; -.
DR SMR; A0MZ67; -.
DR IntAct; A0MZ67; 1.
DR STRING; 10116.ENSRNOP00000061843; -.
DR iPTMnet; A0MZ67; -.
DR PhosphoSitePlus; A0MZ67; -.
DR jPOST; A0MZ67; -.
DR PaxDb; A0MZ67; -.
DR PeptideAtlas; A0MZ67; -.
DR PRIDE; A0MZ67; -.
DR Ensembl; ENSRNOT00000085778; ENSRNOP00000074944; ENSRNOG00000018350. [A0MZ67-2]
DR GeneID; 292139; -.
DR KEGG; rno:292139; -.
DR CTD; 57698; -.
DR RGD; 1311558; Shtn1.
DR eggNOG; ENOG502QVVT; Eukaryota.
DR GeneTree; ENSGT00510000048167; -.
DR InParanoid; A0MZ67; -.
DR OrthoDB; 744654at2759; -.
DR PhylomeDB; A0MZ67; -.
DR PRO; PR:A0MZ67; -.
DR Proteomes; UP000002494; Chromosome 1.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0044295; C:axonal growth cone; IDA:UniProtKB.
DR GO; GO:0031252; C:cell leading edge; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005875; C:microtubule associated complex; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:UniProtKB.
DR GO; GO:0019894; F:kinesin binding; ISO:RGD.
DR GO; GO:0061573; P:actin filament bundle retrograde transport; IMP:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; IDA:MGI.
DR GO; GO:0032488; P:Cdc42 protein signal transduction; IDA:UniProtKB.
DR GO; GO:0060327; P:cytoplasmic actin-based contraction involved in cell motility; IDA:UniProtKB.
DR GO; GO:0061163; P:endoplasmic reticulum polarization; ISS:UniProtKB.
DR GO; GO:0038007; P:netrin-activated signaling pathway; IDA:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:RGD.
DR GO; GO:0045773; P:positive regulation of axon extension; IDA:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IDA:UniProtKB.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:2001222; P:regulation of neuron migration; ISO:RGD.
DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; IDA:UniProtKB.
DR InterPro; IPR024849; Shootin-1.
DR PANTHER; PTHR46606; PTHR46606; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell projection; Coiled coil; Cytoplasm;
KW Cytoskeleton; Developmental protein; Phosphoprotein; Reference proteome.
FT CHAIN 1..633
FT /note="Shootin-1"
FT /id="PRO_0000295743"
FT REGION 343..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 525..633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 7..353
FT /evidence="ECO:0000255"
FT COMPBIAS 350..371
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 393..422
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 454..471
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 472..489
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 490..508
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 592..624
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q8K2Q9"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K2Q9"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0MZ66"
FT MOD_RES 101
FT /note="Phosphoserine; by PAK1"
FT /evidence="ECO:0000269|PubMed:23453953"
FT MOD_RES 249
FT /note="Phosphoserine; by PAK1"
FT /evidence="ECO:0000269|PubMed:23453953"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0MZ66"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0MZ66"
FT MOD_RES 487
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A0MZ66"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0MZ66"
FT MOD_RES 496
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A0MZ66"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 515
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0MZ66"
FT MOD_RES 537
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A0MZ66"
FT VAR_SEQ 454..456
FT /note="GTL -> ASQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17030985"
FT /id="VSP_027056"
FT VAR_SEQ 457..633
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17030985"
FT /id="VSP_027057"
FT MUTAGEN 101
FT /note="S->A: Inhibits F-actin retrograde flow at the
FT peripheral region of growth cones; when associated with A-
FT 249."
FT /evidence="ECO:0000269|PubMed:23453953"
FT MUTAGEN 101
FT /note="S->D: Does not inhibit F-actin retrograde flow at
FT the peripheral region of growth cones; when associated with
FT D-249."
FT /evidence="ECO:0000269|PubMed:23453953"
FT MUTAGEN 249
FT /note="S->A: Inhibits F-actin retrograde flow at the
FT peripheral region of growth cones; when associated with A-
FT 101."
FT /evidence="ECO:0000269|PubMed:23453953"
FT MUTAGEN 249
FT /note="S->D: Does not inhibit F-actin retrograde flow at
FT the peripheral region of growth cones; when associated with
FT D-101."
FT /evidence="ECO:0000269|PubMed:23453953"
SQ SEQUENCE 633 AA; 71446 MW; 7E982A943E7E98C5 CRC64;
MNSSDEEKQL QLITSLKEQA IGEYEDLRAE NQKTKETCDK IRQERDEAVK KLEEFQKISH
MVIEEVNFMQ NHLEIEKTCR ESAEALATKL NKENKTLKRI SMLYMAKLGP DVITEEINID
DDDPGTDTDA AAETCVSVQC QKQIKELRDQ IVSVQEEKKV LAIELESLKS KLGEVMEEVN
KVKQEKAVLN SEVLEQRKVL EKCNRVSVLA VEEYEELQVN LELEKDLRKK AESFAQEMFI
EQNKLKRQSH LLLQSSLPDQ QLLKALDENA KLIQQLEEER IQHQQKVKEL EERLENEALH
KEIHNLRQQL ELLEDDKREL EQKYQSSEEK ARNLKHSVDE LQKRVNQSEN SVPPPPPPPP
PLPPPPPNPI RSLMSMIRKR SHPSGGSTKK EKATQPETAE EVTDLKRQAV EEMMDRIKKG
VHLRPVNQTA RPKAKPDSLK GSESAVDELK GILGTLNKST SSRSLKSLGP ENSETELERI
LRRRKLTAEA DSSSPTGILA TSESKSMPVL GSVSSVTKSA LNKKTLEAEF NNPCPLTPEP
GEGPRKLEGC TNSKVTFQPP SKGGYRRKCV GSENQSEPVV VLDPVSTHEP QTKDQAAEKD
PTQCKEEERG ETQPEFKEDS SGGKTGETDS SNC
