SEPT4_MOUSE
ID SEPT4_MOUSE Reviewed; 478 AA.
AC P28661; B2KGM3; B2KGM6; Q3UVH1; Q3UZC3; Q5ND10; Q5ND15; Q5ND16; Q5ND19;
AC Q7TPM7; Q80VX1;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Septin-4 {ECO:0000312|MGI:MGI:1270156};
DE AltName: Full=Bradeion beta {ECO:0000250|UniProtKB:O43236};
DE AltName: Full=Brain protein H5 {ECO:0000303|PubMed:12581152};
DE AltName: Full=CE5B3 beta {ECO:0000250|UniProtKB:O43236};
DE AltName: Full=Cell division control-related protein 2 {ECO:0000250|UniProtKB:O43236};
DE Short=hCDCREL-2 {ECO:0000250|UniProtKB:O43236};
DE AltName: Full=Peanut-like protein 2 {ECO:0000250|UniProtKB:O43236};
GN Name=Septin4 {ECO:0000312|MGI:MGI:1270156};
GN Synonyms=Bh5 {ECO:0000312|MGI:MGI:1270156},
GN Gm11492 {ECO:0000312|MGI:MGI:1270156},
GN Pnutl2 {ECO:0000312|MGI:MGI:1270156}, Sep4 {ECO:0000250|UniProtKB:O43236},
GN Sept4 {ECO:0000312|MGI:MGI:1270156};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY
RP (ISOFORM 1).
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=12106288; DOI=10.1111/j.1460-9568.1990.tb00460.x;
RA Kato K.;
RT "A collection of cDNA clones with specific expression patterns in mouse
RT brain.";
RL Eur. J. Neurosci. 2:704-711(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), INTERACTION WITH DPYSL5 (ISOFORM
RP 4), SUBCELLULAR LOCATION (ISOFORMS 1 AND 4), TISSUE SPECIFICITY (ISOFORMS 1
RP AND 4), PHOSPHORYLATION (ISOFORM 4), AND DEVELOPMENTAL STAGE (ISOFORMS 1
RP AND 4).
RC TISSUE=Brain;
RX PubMed=12581152; DOI=10.1046/j.1365-2443.2003.00617.x;
RA Takahashi S., Inatome R., Yamamura H., Yanagi S.;
RT "Isolation and expression of a novel mitochondrial septin that interacts
RT with CRMP/CRAM in the developing neurones.";
RL Genes Cells 8:81-93(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 5 AND 6).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 282-290, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=15737930; DOI=10.1016/j.devcel.2004.12.005;
RA Ihara M., Kinoshita A., Yamada S., Tanaka H., Tanigaki A., Kitano A.,
RA Goto M., Okubo K., Nishiyama H., Ogawa O., Takahashi C., Itohara S.,
RA Nishimune Y., Noda M., Kinoshita M.;
RT "Cortical organization by the septin cytoskeleton is essential for
RT structural and mechanical integrity of mammalian spermatozoa.";
RL Dev. Cell 8:343-352(2005).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY (ISOFORMS 1 AND 5),
RP ALTERNATIVE SPLICING, AND SUBCELLULAR LOCATION.
RX PubMed=15737931; DOI=10.1016/j.devcel.2005.01.021;
RA Kissel H., Georgescu M.M., Larisch S., Manova K., Hunnicutt G.R.,
RA Steller H.;
RT "The Sept4 septin locus is required for sperm terminal differentiation in
RT mice.";
RL Dev. Cell 8:353-364(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-68, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=17546647; DOI=10.1002/humu.20554;
RA Sudo K., Ito H., Iwamoto I., Morishita R., Asano T., Nagata K.;
RT "SEPT9 sequence alternations causing hereditary neuralgic amyotrophy are
RT associated with altered interactions with SEPT4/SEPT11 and resistance to
RT Rho/Rhotekin-signaling.";
RL Hum. Mutat. 28:1005-1013(2007).
RN [12]
RP FUNCTION, INTERACTION WITH SLC6A3; SNCA AND STX1A, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17296554; DOI=10.1016/j.neuron.2007.01.019;
RA Ihara M., Yamasaki N., Hagiwara A., Tanigaki A., Kitano A., Hikawa R.,
RA Tomimoto H., Noda M., Takanashi M., Mori H., Hattori N., Miyakawa T.,
RA Kinoshita M.;
RT "Sept4, a component of presynaptic scaffold and Lewy bodies, is required
RT for the suppression of alpha-synuclein neurotoxicity.";
RL Neuron 53:519-533(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [14]
RP INTERACTION WITH DYRK1A, TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=18938227; DOI=10.1016/j.neuroscience.2008.09.034;
RA Sitz J.H., Baumgaertel K., Haemmerle B., Papadopoulos C., Hekerman P.,
RA Tejedor F.J., Becker W., Lutz B.;
RT "The Down syndrome candidate dual-specificity tyrosine phosphorylation-
RT regulated kinase 1A phosphorylates the neurodegeneration-related septin
RT 4.";
RL Neuroscience 157:596-605(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; SER-29; SER-68; SER-117;
RP SER-118; SER-325; SER-432 AND THR-434, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20952537; DOI=10.1101/gad.1970110;
RA Garcia-Fernandez M., Kissel H., Brown S., Gorenc T., Schile A.J., Rafii S.,
RA Larisch S., Steller H.;
RT "Sept4/ARTS is required for stem cell apoptosis and tumor suppression.";
RL Genes Dev. 24:2282-2293(2010).
RN [17]
RP FUNCTION, INTERACTION WITH SEPTIN14, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=20181826; DOI=10.1091/mbc.e09-10-0869;
RA Shinoda T., Ito H., Sudo K., Iwamoto I., Morishita R., Nagata K.;
RT "Septin 14 is involved in cortical neuronal migration via interaction with
RT Septin 4.";
RL Mol. Biol. Cell 21:1324-1334(2010).
RN [18]
RP TISSUE SPECIFICITY, AND INDUCTION BY S.JAPONICUM INFECTION.
RX PubMed=21679490; DOI=10.1017/s0031182011000667;
RA Duan Y.N., Qian H.Y., Qin Y.W., Zhu D.D., He X.X., Zhou Q., Yang Y.N.,
RA Bao J., Feng J.R., Sun W., Chen J.L.;
RT "Dynamics of Sept4 expression in fibrotic livers of mice infected with
RT Schistosoma japonicum.";
RL Parasitology 138:1003-1010(2011).
RN [19]
RP INTERACTION WITH AREL1.
RX PubMed=23479728; DOI=10.1074/jbc.m112.436113;
RA Kim J.B., Kim S.Y., Kim B.M., Lee H., Kim I., Yun J., Jo Y., Oh T., Jo Y.,
RA Chae H.D., Shin D.Y.;
RT "Identification of a novel anti-apoptotic E3 ubiquitin ligase that
RT ubiquitinates antagonists of inhibitor of apoptosis proteins SMAC, HtrA2,
RT and ARTS.";
RL J. Biol. Chem. 288:12014-12021(2013).
RN [20]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23788729; DOI=10.1126/science.1233029;
RA Fuchs Y., Brown S., Gorenc T., Rodriguez J., Fuchs E., Steller H.;
RT "Sept4/ARTS regulates stem cell apoptosis and skin regeneration.";
RL Science 341:286-289(2013).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=27811987; DOI=10.1038/srep36468;
RA Maruyama S.Y., Ito M., Ikami Y., Okitsu Y., Ito C., Toshimori K., Fujii W.,
RA Yogo K.;
RT "A critical role of solute carrier 22a14 in sperm motility and male
RT fertility in mice.";
RL Sci. Rep. 6:36468-36468(2016).
RN [22]
RP FUNCTION, INTERACTION WITH XIAP, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=30389919; DOI=10.1038/s41467-018-06941-4;
RA Koren E., Yosefzon Y., Ankawa R., Soteriou D., Jacob A., Nevelsky A.,
RA Ben-Yosef R., Bar-Sela G., Fuchs Y.;
RT "ARTS mediates apoptosis and regeneration of the intestinal stem cell
RT niche.";
RL Nat. Commun. 9:4582-4582(2018).
CC -!- FUNCTION: Filament-forming cytoskeletal GTPase (Probable). Pro-
CC apoptotic protein involved in LGR5-positive intestinal stem cell and
CC Paneth cell expansion in the intestines, via its interaction with XIAP
CC (PubMed:30389919). May also play a role in the regulation of cell fate
CC in the intestine (PubMed:30389919). Positive regulator of apoptosis
CC involved in hematopoietic stem cell homeostasis; via its interaction
CC with XIAP (PubMed:20952537). Negative regulator of repair and hair
CC follicle regeneration in response to injury, due to inhibition of hair
CC follicle stem cell proliferation, potentially via its interaction with
CC XIAP (PubMed:23788729). Plays an important role in male fertility and
CC sperm motility (PubMed:15737930, PubMed:15737931). During
CC spermiogenesis, essential for the establishment of the annulus (a
CC fibrous ring structure connecting the midpiece and the principal piece
CC of the sperm flagellum) which is a requisite for the structural and
CC mechanical integrity of the sperm (PubMed:15737930, PubMed:15737931).
CC Involved in the migration of cortical neurons and the formation of
CC neuron leading processes during embryonic development
CC (PubMed:20181826). Required for dopaminergic metabolism in presynaptic
CC autoreceptors; potentially via activity as a presynaptic scaffold
CC protein (PubMed:17296554). {ECO:0000269|PubMed:15737930,
CC ECO:0000269|PubMed:15737931, ECO:0000269|PubMed:17296554,
CC ECO:0000269|PubMed:20181826, ECO:0000269|PubMed:20952537,
CC ECO:0000269|PubMed:23788729, ECO:0000269|PubMed:30389919, ECO:0000305}.
CC -!- SUBUNIT: Septins polymerize into heterooligomeric protein complexes
CC that form filaments, and can associate with cellular membranes, actin
CC filaments and microtubules. GTPase activity is required for filament
CC formation. Interacts with SEPTIN8 (By similarity). Component of a
CC septin core octomeric complex consisting of SEPTIN12, SEPTIN7, SEPTIN6
CC and SEPTIN2 or SEPTIN4 in the order 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-
CC 7-12 (By similarity). Interacts with SEPTIN14 (via C-terminus)
CC (PubMed:20181826). Interacts with DYRK1A (PubMed:18938227). Interacts
CC with SLC6A3/DAT and SNCA/alpha-synuclein (PubMed:17296554). Interacts
CC with STX1A; in the striatum (PubMed:17296554). Interacts with XIAP (via
CC BIR3 domain) following the induction of apoptosis (PubMed:30389919).
CC Interacts with AREL1 (via HECT domain); in the cytoplasm following
CC induction of apoptosis (PubMed:23479728).
CC {ECO:0000250|UniProtKB:O43236, ECO:0000269|PubMed:17296554,
CC ECO:0000269|PubMed:18938227, ECO:0000269|PubMed:20181826,
CC ECO:0000269|PubMed:23479728, ECO:0000269|PubMed:30389919}.
CC -!- SUBUNIT: [Isoform 4]: Interacts with DPYSL5.
CC {ECO:0000269|PubMed:12581152}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17546647,
CC ECO:0000269|PubMed:20181826}. Cell projection, cilium, flagellum
CC {ECO:0000269|PubMed:15737930, ECO:0000269|PubMed:15737931,
CC ECO:0000269|PubMed:27811987}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:O43236}. Cell projection, axon
CC {ECO:0000269|PubMed:17296554, ECO:0000269|PubMed:20181826}. Cell
CC projection, dendrite {ECO:0000269|PubMed:20181826}. Perikaryon
CC {ECO:0000269|PubMed:20181826}. Synapse {ECO:0000250|UniProtKB:O43236}.
CC Note=Found in the sperm annulus, a fibrous ring structure connecting
CC the midpiece and the principal piece of the sperm flagellum
CC (PubMed:15737930, PubMed:15737931, PubMed:27811987). In platelets,
CC found in areas surrounding alpha-granules (By similarity). Expressed
CC and colocalized with SLC6A3 and SNCA in axon terminals, especially at
CC the varicosities (PubMed:17296554). {ECO:0000250|UniProtKB:O43236,
CC ECO:0000269|PubMed:15737930, ECO:0000269|PubMed:15737931,
CC ECO:0000269|PubMed:17296554, ECO:0000269|PubMed:27811987}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:12581152}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Mitochondrion
CC {ECO:0000269|PubMed:12581152}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:12581152}. Note=In retinoic acid-treated P19 cells,
CC found first in the mitochondria and at later times, as neuronal
CC differentiation proceeds, in the cytosol.
CC {ECO:0000269|PubMed:12581152}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=H5 {ECO:0000303|PubMed:12581152,
CC ECO:0000303|PubMed:15737931};
CC IsoId=P28661-1; Sequence=Displayed;
CC Name=2; Synonyms=Cdcrel-2b {ECO:0000303|PubMed:15737931};
CC IsoId=P28661-2; Sequence=VSP_038308;
CC Name=3;
CC IsoId=P28661-3; Sequence=VSP_038313, VSP_038314;
CC Name=4; Synonyms=Mitochondrial septin, M-septin
CC {ECO:0000303|PubMed:15737931};
CC IsoId=P28661-4; Sequence=VSP_038309;
CC Name=5; Synonyms=ARTS {ECO:0000303|PubMed:15737931,
CC ECO:0000303|PubMed:16141072};
CC IsoId=P28661-5; Sequence=VSP_038307, VSP_038310, VSP_038313,
CC VSP_038314;
CC Name=6;
CC IsoId=P28661-6; Sequence=VSP_038308, VSP_038311, VSP_038312;
CC Name=7;
CC IsoId=P28661-7; Sequence=VSP_061408;
CC -!- TISSUE SPECIFICITY: Expressed in the cerebral cortex, striatum,
CC midbrain, cerebellum and spinal cord (at protein level). Expressed in
CC the substantia nigra pars compacta, ventral tegmental area, projection
CC fiber bundles and in axon terminals surrounding striatal neurons (at
CC protein level) (PubMed:17296554). Expressed in hair follicle stem cells
CC (at protein level) (PubMed:23788729). Expressed in small intestinal
CC crypts; abundantly expressed at the crypt base (at protein level)
CC (PubMed:30389919). Widely expressed in the brain and to a lesser extent
CC in the testis, lung and liver (PubMed:21679490, PubMed:17296554).
CC {ECO:0000269|PubMed:17296554, ECO:0000269|PubMed:21679490,
CC ECO:0000269|PubMed:23788729, ECO:0000269|PubMed:30389919}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Highly expressed in the brain and
CC testis and, to a lesser extent in the heart, lung and kidney
CC (PubMed:12106288, PubMed:12581152, PubMed:15737931). In the brain,
CC abundant in areas of high cell density, particularly in the stria
CC terminalis (PubMed:12106288). Expressed in the entorhinal, temporal and
CC visual cortices and the hippocampus of the brain where is colocalizes
CC with DYRK1A in postnatal day 1 and adult mice. Expressed and
CC extensively colocalizes with DYRK1A in apical dendrites of pyramidal
CC cells (PubMed:18938227). {ECO:0000269|PubMed:12106288,
CC ECO:0000269|PubMed:12581152, ECO:0000269|PubMed:15737931,
CC ECO:0000269|PubMed:18938227}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Predominantly expressed in embryonic
CC brain and dorsal root ganglion neurons. {ECO:0000269|PubMed:12581152}.
CC -!- TISSUE SPECIFICITY: [Isoform 5]: Expressed in LGR5-positive intestinal
CC stem cells and lysozyme-positive Paneth cells (at protein level)
CC (PubMed:30389919). Expressed in the brain and testis (PubMed:15737931).
CC {ECO:0000269|PubMed:15737931, ECO:0000269|PubMed:30389919}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the intermediate zone and cortical
CC plate of the cortex at 15.5 dpc. {ECO:0000269|PubMed:20181826}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 1]: Widely expressed in embryos at 7 dpc.
CC {ECO:0000269|PubMed:12581152}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 4]: Predominantly expressed in the brain
CC at 14 dpc and on postnatal day 1. {ECO:0000269|PubMed:12581152}.
CC -!- INDUCTION: Induced by S.japonicum egg-mediated liver fibrosis at the
CC site of egg granulomas; expression peaks at 12 weeks post infection
CC with expression decreasing thereafter. {ECO:0000269|PubMed:21679490}.
CC -!- PTM: Phosphorylated by DYRK1A. {ECO:0000269|PubMed:18938227}.
CC -!- PTM: Ubiquitinated by AREL1. {ECO:0000250|UniProtKB:O43236}.
CC -!- PTM: [Isoform 4]: May be phosphorylated. {ECO:0000269|PubMed:12581152}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice have a decreased basal prepulse
CC startle response and an enhanced acoustic startle response
CC (PubMed:17296554). Decreased concentration of TH and SLC6A3/DAT in
CC dopaminergic axons and axon terminals, does not affect axon morphology
CC (PubMed:17296554). Male mice are sterile due to immotile and
CC structurally defective sperm (PubMed:15737930, PubMed:15737931). Sperms
CC exhibit defective mitochondrial architecture, bent and nonmotile tails,
CC absence of the annulus (a fibrous ring structure connecting the
CC midpiece and the principal piece of the sperm flagellum), lower ATP
CC consumption, impaired capacitation and defects in the removal of
CC residual cytoplasm (PubMed:15737930, PubMed:15737931). Increased in
CC intestinal crypt diameter, length and cell number (PubMed:30389919).
CC Decreased apoptosis and increased maintenance of colon crypt
CC architecture in response to intestinal barrier damage, as a result of
CC improved Lgr5-positive intestinal stem cell-mediated regeneration
CC (PubMed:30389919). Decrease in differentiated intestinal goblet cells
CC (PubMed:30389919). Increase proliferation of Lgr5-positive intestinal
CC stem cells and lysozyme-positive granular Paneth cells in the crypt
CC base of both the small and large intestines (PubMed:30389919). Increase
CC in Reg4-positive cells in colon epithelium and nuclear localization of
CC CTNNB1 in cells of the intestinal crypt base (PubMed:30389919).
CC Increased incidence of spontaneous hematopoietic malignancies,
CC splenomegaly and a third of mice developed spontaneous neoplasia at 11
CC to 15 months old (PubMed:20952537). Increased number of B-linage
CC progenitors, immature B cells and increased functional hematopoietic
CC progenitor cells in the bone marrow of 6 to 13 week old mice, increased
CC hematopoietic progenitor cell levels persisted in 11 to 15 month old
CC mice (PubMed:20952537). Normal hair follicle bulge morphology but twice
CC as many epithelial progenitor cells and an elongated tail epithelial
CC strand (PubMed:23788729). Significantly improved dorsal skin wound
CC repair which included an increased amount of proliferating hair
CC follicle stem cells in the wound bed (PubMed:23788729). Decrease in
CC apoptosis of hematopoietic progenitors in response to irradiation
CC (PubMed:20952537). SEPTIN4 and XIAP double knockout mice show no
CC differences in apoptosis or lymphoproliferation in hematopoietic stem
CC and progenitor cells (PubMed:20952537). Delayed dermal wound repair and
CC hair follicle regeneration, via increased apoptosis of hair follicle
CC stem cells (PubMed:23788729). {ECO:0000269|PubMed:15737930,
CC ECO:0000269|PubMed:15737931, ECO:0000269|PubMed:17296554,
CC ECO:0000269|PubMed:20952537, ECO:0000269|PubMed:23788729,
CC ECO:0000269|PubMed:30389919}.
CC -!- MISCELLANEOUS: May act as a tumor suppressor in both hematopoietic and
CC neoplastic malignancies. {ECO:0000269|PubMed:20952537}.
CC -!- SIMILARITY: Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like
CC GTPase superfamily. Septin GTPase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01056}.
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DR EMBL; X61452; CAA43692.1; -; mRNA.
DR EMBL; AB078010; BAC55241.1; -; mRNA.
DR EMBL; AK133933; BAE21934.1; -; mRNA.
DR EMBL; AK135143; BAE22437.1; -; mRNA.
DR EMBL; AK137299; BAE23298.1; -; mRNA.
DR EMBL; AL596086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU406988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466556; EDL15822.1; -; Genomic_DNA.
DR EMBL; BC055101; AAH55101.1; -; mRNA.
DR CCDS; CCDS25213.1; -. [P28661-1]
DR CCDS; CCDS70275.1; -. [P28661-5]
DR CCDS; CCDS70276.1; -. [P28661-3]
DR CCDS; CCDS70277.1; -. [P28661-4]
DR CCDS; CCDS88214.1; -. [P28661-2]
DR PIR; S16867; S16867.
DR RefSeq; NP_001271321.1; NM_001284392.1. [P28661-4]
DR RefSeq; NP_001271323.1; NM_001284394.1. [P28661-3]
DR RefSeq; NP_001271327.1; NM_001284398.1. [P28661-5]
DR RefSeq; NP_035259.1; NM_011129.2. [P28661-1]
DR RefSeq; XP_006532561.1; XM_006532498.3.
DR AlphaFoldDB; P28661; -.
DR SMR; P28661; -.
DR BioGRID; 202286; 16.
DR IntAct; P28661; 1.
DR STRING; 10090.ENSMUSP00000018544; -.
DR iPTMnet; P28661; -.
DR PhosphoSitePlus; P28661; -.
DR SwissPalm; P28661; -.
DR EPD; P28661; -.
DR jPOST; P28661; -.
DR MaxQB; P28661; -.
DR PaxDb; P28661; -.
DR PeptideAtlas; P28661; -.
DR PRIDE; P28661; -.
DR ProteomicsDB; 255382; -. [P28661-1]
DR ProteomicsDB; 255383; -. [P28661-2]
DR ProteomicsDB; 255384; -. [P28661-3]
DR ProteomicsDB; 255385; -. [P28661-4]
DR ProteomicsDB; 255386; -. [P28661-5]
DR ProteomicsDB; 255387; -. [P28661-6]
DR ProteomicsDB; 284159; -.
DR DNASU; 18952; -.
DR Ensembl; ENSMUST00000018544; ENSMUSP00000018544; ENSMUSG00000020486. [P28661-1]
DR Ensembl; ENSMUST00000060360; ENSMUSP00000053087; ENSMUSG00000020486. [P28661-7]
DR Ensembl; ENSMUST00000063156; ENSMUSP00000060127; ENSMUSG00000020486. [P28661-4]
DR Ensembl; ENSMUST00000107960; ENSMUSP00000103594; ENSMUSG00000020486. [P28661-3]
DR Ensembl; ENSMUST00000107962; ENSMUSP00000103596; ENSMUSG00000020486. [P28661-2]
DR Ensembl; ENSMUST00000122067; ENSMUSP00000112960; ENSMUSG00000020486. [P28661-5]
DR GeneID; 18952; -.
DR KEGG; mmu:18952; -.
DR UCSC; uc007kts.2; mouse. [P28661-6]
DR UCSC; uc007ktu.2; mouse. [P28661-5]
DR UCSC; uc007ktw.2; mouse. [P28661-1]
DR UCSC; uc007ktx.2; mouse. [P28661-3]
DR UCSC; uc007kty.2; mouse. [P28661-4]
DR CTD; 5414; -.
DR MGI; MGI:1270156; Septin4.
DR VEuPathDB; HostDB:ENSMUSG00000020486; -.
DR eggNOG; ENOG502SETZ; Eukaryota.
DR eggNOG; KOG2655; Eukaryota.
DR GeneTree; ENSGT00940000157152; -.
DR HOGENOM; CLU_575631_0_0_1; -.
DR InParanoid; P28661; -.
DR OrthoDB; 845354at2759; -.
DR PhylomeDB; P28661; -.
DR TreeFam; TF101079; -.
DR TreeFam; TF338016; -.
DR Reactome; R-MMU-111457; Release of apoptotic factors from the mitochondria.
DR Reactome; R-MMU-111469; SMAC, XIAP-regulated apoptotic response.
DR BioGRID-ORCS; 18952; 0 hits in 46 CRISPR screens.
DR ChiTaRS; Sept4; mouse.
DR PRO; PR:Q5ND19; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P28661; protein.
DR Bgee; ENSMUSG00000020486; Expressed in cerebellum lobe and 253 other tissues.
DR ExpressionAtlas; P28661; baseline and differential.
DR Genevisible; P28661; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0043679; C:axon terminus; IDA:UniProtKB.
DR GO; GO:0032153; C:cell division site; IBA:GO_Central.
DR GO; GO:0042995; C:cell projection; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0031514; C:motile cilium; IMP:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0031105; C:septin complex; IDA:UniProtKB.
DR GO; GO:0005940; C:septin ring; IBA:GO_Central.
DR GO; GO:0097227; C:sperm annulus; IDA:UniProtKB.
DR GO; GO:0036126; C:sperm flagellum; IDA:MGI.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0061640; P:cytoskeleton-dependent cytokinesis; IBA:GO_Central.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:UniProtKB.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IMP:UniProtKB.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IMP:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0008104; P:protein localization; IBA:GO_Central.
DR GO; GO:0017157; P:regulation of exocytosis; IBA:GO_Central.
DR GO; GO:0048240; P:sperm capacitation; IMP:MGI.
DR GO; GO:0030382; P:sperm mitochondrion organization; IMP:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:MGI.
DR GO; GO:0048515; P:spermatid differentiation; IMP:UniProtKB.
DR GO; GO:0048729; P:tissue morphogenesis; IMP:UniProtKB.
DR CDD; cd01850; CDC_Septin; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR030379; G_SEPTIN_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR016491; Septin.
DR Pfam; PF00735; Septin; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51719; G_SEPTIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Cell projection; Cilium;
KW Coiled coil; Cytoplasm; Cytoplasmic vesicle; Differentiation;
KW Direct protein sequencing; Flagellum; GTP-binding; Mitochondrion;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Spermatogenesis;
KW Synapse; Ubl conjugation.
FT CHAIN 1..478
FT /note="Septin-4"
FT /id="PRO_0000173520"
FT DOMAIN 141..414
FT /note="Septin-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01056"
FT REGION 1..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 151..158
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01056"
FT REGION 208..211
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01056"
FT REGION 289..292
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01056"
FT REGION 428..449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 447..478
FT /evidence="ECO:0000255"
FT COMPBIAS 19..38
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 83..100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 151..158
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9UH03"
FT BINDING 185
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9UH03"
FT BINDING 290..298
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9UH03"
FT BINDING 348
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9UH03"
FT BINDING 363
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9UH03"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 434
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..478
FT /note="MDHSLGWQGNSVPEDGTEAGIKHFLEDSSDDAELSKFVKDFPGSEPYHSAES
FT KTRVARPQILEPRPQSPDLCDDDVEFRGSLWPQPSDSQQYFSAPAPLSPSSRPRSPWGK
FT LDPYDSSEDDKEYVGFATLPNQVHRKSVKKGFDFTLMVAGESGLGKSTLVNSLFLTDLY
FT RDRKLLGAEERIMQTVEITKHAVDIEEKGVRLRLTIVDTPGFGDAVNNTECWKPVAEYI
FT DQQFEQYFRDESGLNRKNIQDNRVHCCLYFISPFGHGLRPLDVEFMKALHQRVNIVPIL
FT AKADTLTPPEVDRKKCKIREEIEHFGIKIYQFPDCDSDEDEDFKLQDQALKESIPFAVI
FT GSNTVVEARGRRVRGRLYPWGIVEVENPGHCDFVKLRTMLVRTHMQDLKDVTRETHYEN
FT YRAQCIQSMTRLVVKERNRNKLTRESGTDFPIPAVPPGTDPETEKLIREKDEELRRMQE
FT MLHKIQRQMKETH -> MASTQKATVYQVYKTNKNGSKVAVSSHRGAEVTTSTPQRGHG
FT YYSSSQRATAAVSLSPPPLPSQRRAEATSTTHHSTSDYLHPVSPQPGPGLSAVSTSRGT
FT ETRTRIEVPCHHSPHHSPHHSPHHSPHRKNQSIQTMSSHLAGVHRNVSPVREESTRRTE
FT TRPGREVAHHSSTTSDAKCRHLYFTGEKEEDPPSKVQNPQGVKVPRRISAYPKDEAIQT
FT EPTRRTTAEVRSSRNISVQEHGIRMANNPQIVIRKVPPQEPEVGHSSIYSEPKTSQKST
FT KLSSGLKLSVLRDLDGAPRAAPPRPERSVCIGTKPSPKILISEAENTMRSPTREREVTR
FT KVTISPGKQSTQPPHRVTCRTVSEGSYKSPLYPELSTKPSTHVPSAFELTPRPLPPRSL
FT PRYGPDCSWWALLNPKVETPPNHSSFDLEPKSPPPLDPLESFYEMDSTPFCEDLLFQRD
FT KASLPPSPKDSLYRVPLTEVQKTPKYTSKQPTQGFNAFFLDVSEEMYNRILWWLKGLCF
FT PFLGGGGGVGGREGLGKGFGEG (in isoform 7)"
FT /id="VSP_061408"
FT VAR_SEQ 1..118
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038307"
FT VAR_SEQ 1..20
FT /note="MDHSLGWQGNSVPEDGTEAG -> M (in isoform 2 and isoform
FT 6)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038308"
FT VAR_SEQ 21..119
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12581152"
FT /id="VSP_038309"
FT VAR_SEQ 119
FT /note="E -> M (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038310"
FT VAR_SEQ 221..223
FT /note="CWK -> WYV (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038311"
FT VAR_SEQ 224..478
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038312"
FT VAR_SEQ 426..431
FT /note="NKLTRE -> KDRSRN (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_038313"
FT VAR_SEQ 432..478
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_038314"
FT CONFLICT 394
FT /note="D -> N (in Ref. 3; BAE21934)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 478 AA; 54936 MW; 36655DE54A6C4908 CRC64;
MDHSLGWQGN SVPEDGTEAG IKHFLEDSSD DAELSKFVKD FPGSEPYHSA ESKTRVARPQ
ILEPRPQSPD LCDDDVEFRG SLWPQPSDSQ QYFSAPAPLS PSSRPRSPWG KLDPYDSSED
DKEYVGFATL PNQVHRKSVK KGFDFTLMVA GESGLGKSTL VNSLFLTDLY RDRKLLGAEE
RIMQTVEITK HAVDIEEKGV RLRLTIVDTP GFGDAVNNTE CWKPVAEYID QQFEQYFRDE
SGLNRKNIQD NRVHCCLYFI SPFGHGLRPL DVEFMKALHQ RVNIVPILAK ADTLTPPEVD
RKKCKIREEI EHFGIKIYQF PDCDSDEDED FKLQDQALKE SIPFAVIGSN TVVEARGRRV
RGRLYPWGIV EVENPGHCDF VKLRTMLVRT HMQDLKDVTR ETHYENYRAQ CIQSMTRLVV
KERNRNKLTR ESGTDFPIPA VPPGTDPETE KLIREKDEEL RRMQEMLHKI QRQMKETH
