ID SEPT4_HUMAN Reviewed; 996 AA. AC O43236; A0A5F9ZHH3; B2RD42; B3KSX9; B4DXC6; B4DXV5; Q6IAP3; Q8N821; Q8NEP4; AC Q9H315; Q9UM58; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 28-JAN-2026, sequence version 2. DT 28-JAN-2026, entry version 207. DE RecName: Full=Septin-4 {ECO:0000312|HGNC:HGNC:9165}; DE AltName: Full=Bradeion beta {ECO:0000303|PubMed:11511094}; DE AltName: Full=Brain protein H5 {ECO:0000250|UniProtKB:P28661}; DE AltName: Full=CE5B3 beta {ECO:0000312|HGNC:HGNC:9165}; DE AltName: Full=Cell division control-related protein 2 {ECO:0000312|HGNC:HGNC:9165}; DE Short=hCDCREL-2 {ECO:0000312|HGNC:HGNC:9165}; DE AltName: Full=Peanut-like protein 2 {ECO:0000303|PubMed:9889007}; GN Name=SEPTIN4 {ECO:0000312|HGNC:HGNC:9165}; GN Synonyms=C17orf47 {ECO:0000312|HGNC:HGNC:9165}, GN PNUTL2 {ECO:0000303|PubMed:9889007}, SEP4 {ECO:0000312|HGNC:HGNC:9165}, GN SEPT4 {ECO:0000312|HGNC:HGNC:9165}; ORFNames=hucep-7; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=9889007; DOI=10.1006/geno.1998.5612; RA Paavola P., Horelli-Kuitunen N., Palotie A., Peltonen L.; RT "Characterization of a novel gene, PNUTL2, on human chromosome 17q22-q23 RT and its exclusion as the Meckel syndrome gene."; RL Genomics 55:122-125(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RC TISSUE=Brain, and Fetal brain; RX PubMed=11167005; DOI=10.1016/s0378-1119(00)00527-8; RA Zieger B., Tran H., Hainmann I., Wunderle D., Zgaga-Griesz A., Blaeser S., RA Ware J.; RT "Characterization and expression analysis of two human septin genes, PNUTL1 RT and PNUTL2."; RL Gene 261:197-203(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ARTS), FUNCTION (ISOFORM ARTS), TISSUE RP SPECIFICITY (ISOFORM ARTS), SUBCELLULAR LOCATION (ISOFORM ARTS), AND RP MUTAGENESIS OF 137-GLY--SER-139 (ISOFORM ARTS). RC TISSUE=Fetal brain; RX PubMed=11146656; DOI=10.1038/35046566; RA Larisch S., Yi Y., Lotan R., Kerner H., Eimerl S., Parks W.T., Yossi G., RA Reffey S.B., de Caestecker M.P., Danielpour D., Book-Melamed N., RA Timberg R., Duckett C., Lechleider R.J., Steller H., Orly J., Kim S.-J., RA Roberts A.B.; RT "A novel mitochondrial septin-like protein, ARTS, mediates apoptosis RT dependent on its P-loop motif."; RL Nat. Cell Biol. 2:915-921(2000). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=11511094; DOI=10.1006/bbrc.2001.5413; RA Tanaka M., Tanaka T., Kijima H., Itoh J., Matsuda T., Hori S., Yamamoto M.; RT "Characterization of tissue- and cell-type-specific expression of a novel RT human septin family gene, Bradeion."; RL Biochem. Biophys. Res. Commun. 286:547-553(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Yoshimoto M., Yazaki M., Matsumoto K., Takayama K.; RT "Molecular cloning of a new GTP binding protein from human brain."; RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Zha D., Hu G.; RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4; 5 AND 8). RC TISSUE=Amygdala, Brain cortex, Subthalamic nucleus, and Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 8). RC TISSUE=Hippocampus, and Testis; 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 [12] RP INTERACTION WITH SEPTIN8, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=15116257; DOI=10.1160/th03-09-0578; RA Blaeser S., Horn J., Wuermell P., Bauer H., Struempell S., Nurden P., RA Pagenstecher A., Busse A., Wunderle D., Hainmann I., Zieger B.; RT "The novel human platelet septin SEPT8 is an interaction partner of RT SEPT4."; RL Thromb. Haemost. 91:959-966(2004). RN [13] RP PROTEIN SEQUENCE OF 659-675 AND 800-808, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Fetal brain; RA Lubec G., Chen W.-Q.; RL Submitted (JAN-2009) to UniProtKB. RN [14] RP FUNCTION (ISOFORM ARTS). RX PubMed=15837787; DOI=10.1074/jbc.m501955200; RA Lotan R., Rotem A., Gonen H., Finberg J.P.M., Kemeny S., Steller H., RA Ciechanover A., Larisch S.; RT "Regulation of the proapoptotic ARTS protein by ubiquitin-mediated RT degradation."; RL J. Biol. Chem. 280:25802-25810(2005). RN [15] RP TISSUE SPECIFICITY. RX PubMed=15915442; DOI=10.1002/path.1789; RA Hall P.A., Jung K., Hillan K.J., Russell S.E.H.; RT "Expression profiling the human septin gene family."; RL J. Pathol. 206:269-278(2005). RN [16] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-843, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [18] RP INTERACTION WITH XIAP, AND SUBCELLULAR LOCATION. RX PubMed=21695558; DOI=10.1007/s10495-011-0622-0; RA Bornstein B., Gottfried Y., Edison N., Shekhtman A., Lev T., Glaser F., RA Larisch S.; RT "ARTS binds to a distinct domain in XIAP-BIR3 and promotes apoptosis by a RT mechanism that is different from other IAP-antagonists."; RL Apoptosis 16:869-881(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635; SER-636 AND SER-843, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP INTERACTION WITH SEPTIN9 HNA VARIANTS. 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 [21] RP FUNCTION (ISOFORM ARTS), SUBCELLULAR LOCATION (ISOFORM ARTS), INTERACTION RP WITH XIAP (ISOFORM ARTS), AND MUTAGENESIS OF 137-GLY--SER-139 (ISOFORM RP ARTS). RX PubMed=15029247; DOI=10.1038/sj.emboj.7600155; RA Gottfried Y., Rotem A., Lotan R., Steller H., Larisch S.; RT "The mitochondrial ARTS protein promotes apoptosis through targeting RT XIAP."; RL EMBO J. 23:1627-1635(2004). RN [22] RP INTERACTION WITH AREL1, AND UBIQUITINATION. 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 [23] RP SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=25588830; DOI=10.1242/jcs.158998; RA Kuo Y.C., Shen Y.R., Chen H.I., Lin Y.H., Wang Y.Y., Chen Y.R., Wang C.Y., RA Kuo P.L.; RT "SEPT12 orchestrates the formation of mammalian sperm annulus by organizing RT core octameric complexes with other SEPT proteins."; RL J. Cell Sci. 128:923-934(2015). RN [24] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH BCL2 AND XIAP, AND INTERACTION RP WITH BCL2 AND XIAP. RX PubMed=29020630; DOI=10.1016/j.celrep.2017.09.052; RA Edison N., Curtz Y., Paland N., Mamriev D., Chorubczyk N., RA Haviv-Reingewertz T., Kfir N., Morgenstern D., Kupervaser M., Kagan J., RA Kim H.T., Larisch S.; RT "Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis."; RL Cell Rep. 21:442-454(2017). RN [25] RP TISSUE SPECIFICITY. 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). RN [26] RP INVOLVEMENT IN SPGF99, VARIANTS SPGF99 69-ARG--TYR-996 DEL AND RP 241-ARG--TYR-996 DEL, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=36135717; DOI=10.1002/humu.24475; RA Wang G., Zhu X., Gao Y., Lv M., Li K., Tang D., Wu H., Xu C., Geng H., RA Shen Q., Zha X., Duan Z., Zhang J., Hua R., Tao F., Zhou P., Wei Z., RA Cao Y., Guo R., He X.; RT "Biallelic loss-of-function mutations in SEPTIN4 (C17ORF47), encoding a RT conserved annulus protein, cause thin midpiece spermatozoa and male RT infertility in humans."; RL Hum. Mutat. 43:2079-2090(2022). 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 (By similarity). May also play a role in the regulation of cell fate in CC the intestine (By similarity). Positive regulator of apoptosis involved CC in hematopoietic stem cell homeostasis; via its interaction with XIAP CC (By similarity). Negative regulator of repair and hair follicle CC regeneration in response to injury, due to inhibition of hair follicle CC stem cell proliferation, potentially via its interaction with XIAP (By CC similarity). Plays an important role in male fertility and sperm CC motility (PubMed:36135717). During spermiogenesis, essential for the CC establishment of the annulus (a fibrous ring structure connecting the CC midpiece and the principal piece of the sperm flagellum) which is a CC requisite for the structural and mechanical integrity of the sperm CC (PubMed:36135717). Involved in the migration of cortical neurons and CC the formation of neuron leading processes during embryonic development CC (By similarity). Required for dopaminergic metabolism in presynaptic CC autoreceptors; potentially via activity as a presynaptic scaffold CC protein (By similarity). {ECO:0000250|UniProtKB:P28661, CC ECO:0000269|PubMed:36135717, ECO:0000305}. CC -!- FUNCTION: [Isoform ARTS]: Required for the induction of cell death CC mediated by TGF-beta and possibly by other apoptotic stimuli CC (PubMed:11146656, PubMed:15837787). Induces apoptosis through binding CC and inhibition of XIAP resulting in significant reduction in XIAP CC levels, leading to caspase activation and cell death (PubMed:15029247). CC Mediates the interaction between BCL2 and XIAP, thereby positively CC regulating the ubiquitination and degradation of BCL2 and promoting CC apoptosis (PubMed:29020630). {ECO:0000269|PubMed:11146656, CC ECO:0000269|PubMed:15029247, ECO:0000269|PubMed:15837787, CC ECO:0000269|PubMed:29020630}. 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 (PubMed:15116257). In a mesenchymal CC cell line, interacts with SEPTIN9 isoform 2 variants HNA Trp-106 and CC Phe-111, but not the wild type SEPTIN9 (PubMed:17546647). Component of CC a septin core octameric complex consisting of SEPTIN12, SEPTIN7, CC SEPTIN6 and SEPTIN2 or SEPTIN4 in the order 12-7-6-2-2-6-7-12 or 12-7- CC 6-4-4-6-7-12 (PubMed:25588830). Interacts with SEPTIN14 (via C- CC terminus) (By similarity). Interacts with DYRK1A (By similarity). CC Interacts with SLC6A3/DAT and SNCA/alpha-synuclein (By similarity). CC Interacts with STX1A; in the striatum (By similarity). Interacts with CC XIAP (via BIR3 domain) following the induction of apoptosis (By CC similarity). Interacts with AREL1 (via HECT domain); in the cytoplasm CC following induction of apoptosis (PubMed:23479728). CC {ECO:0000250|UniProtKB:P28661, ECO:0000269|PubMed:15116257, CC ECO:0000269|PubMed:17546647, ECO:0000269|PubMed:23479728, CC ECO:0000269|PubMed:25588830}. CC -!- SUBUNIT: [Isoform ARTS]: Part of a complex composed of SEPTIN4 isoform CC ARTS, XIAP and BCL2, within the complex interacts with both BCL2 (via CC BH3 domain) and XIAP, ARTS acts as a scaffold protein and stabilizes CC the complex (PubMed:29020630). Interacts with XIAP (via BIR3 domain) CC following the induction of apoptosis (PubMed:15029247, CC PubMed:21695558). {ECO:0000269|PubMed:15029247, CC ECO:0000269|PubMed:21695558, ECO:0000269|PubMed:29020630}. CC -!- INTERACTION: CC O43236; P05067: APP; NbExp=3; IntAct=EBI-1047513, EBI-77613; CC O43236; P63167: DYNLL1; NbExp=5; IntAct=EBI-1047513, EBI-349105; CC O43236; Q96FJ2: DYNLL2; NbExp=3; IntAct=EBI-1047513, EBI-742371; CC O43236; P42858: HTT; NbExp=3; IntAct=EBI-1047513, EBI-466029; CC O43236; Q8IYM1: SEPTIN12; NbExp=6; IntAct=EBI-1047513, EBI-2585067; CC O43236; P37840: SNCA; NbExp=3; IntAct=EBI-1047513, EBI-985879; CC O43236-6; Q8IUQ4: SIAH1; NbExp=2; IntAct=EBI-4372019, EBI-747107; CC O43236-6; P98170: XIAP; NbExp=4; IntAct=EBI-4372019, EBI-517127; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P28661}. Cell CC projection, cilium, flagellum {ECO:0000269|PubMed:25588830, CC ECO:0000269|PubMed:36135717}. Cytoplasmic vesicle, secretory vesicle CC {ECO:0000269|PubMed:15116257}. Cell projection, axon CC {ECO:0000250|UniProtKB:P28661}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:P28661}. Perikaryon CC {ECO:0000250|UniProtKB:P28661}. Synapse {ECO:0000269|PubMed:17296554}. CC Note=In platelets, found in areas surrounding alpha-granules CC (PubMed:15116257). Found in the sperm annulus, a fibrous ring structure CC connecting the midpiece and the principal piece of the sperm flagellum CC (PubMed:25588830, PubMed:36135717). Expressed and colocalized with CC SLC6A3 and SNCA in axon terminals, especially at the varicosities (By CC similarity). {ECO:0000250|UniProtKB:P28661, CC ECO:0000269|PubMed:15116257, ECO:0000269|PubMed:25588830, CC ECO:0000269|PubMed:36135717}. CC -!- SUBCELLULAR LOCATION: [Isoform ARTS]: Mitochondrion CC {ECO:0000269|PubMed:11146656, ECO:0000269|PubMed:15029247, CC ECO:0000269|PubMed:21695558}. Nucleus {ECO:0000269|PubMed:11146656, CC ECO:0000269|PubMed:15029247}. Note=While predominantly localized in the CC mitochondria under resting conditions, translocates into the nucleus CC after TGF-beta treatment and apoptosis induction. CC {ECO:0000269|PubMed:11146656}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=7; CC IsoId=O43236-7; Sequence=Displayed; CC Name=1; Synonyms=PNUTL2, PNUTL2a, H5/CDCrel-2 CC {ECO:0000303|PubMed:11167005}, SEPT4_i1; CC IsoId=O43236-1; Sequence=VSP_062618; CC Name=2; Synonyms=PNUTL2b, CDCrel-1 {ECO:0000303|PubMed:11167005}; CC IsoId=O43236-2; Sequence=VSP_062619; CC Name=3; CC IsoId=O43236-3; Sequence=VSP_062621; CC Name=4; CC IsoId=O43236-4; Sequence=VSP_062620; CC Name=5; CC IsoId=O43236-5; Sequence=VSP_062617; CC Name=ARTS {ECO:0000303|PubMed:11146656}; Synonyms=SEPT4_i2; CC IsoId=O43236-6; Sequence=VSP_062619, VSP_062624, VSP_062625; CC Name=8; CC IsoId=O43236-8; Sequence=VSP_062622, VSP_062623; CC -!- TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues with CC highest expression in adult brain (at protein level), heart, liver and CC adrenal gland and fetal heart, kidney, liver and lung. Expressed in CC presynaptic terminals of dopaminergic neurons projecting from the CC substantia nigra pars compacta to the striatum (at protein level) CC (PubMed:17296554). Expressed in axonal varicosities in dopaminergic CC nerve terminals (at protein level) (PubMed:17296554). Expressed in the CC putamen and in the adjacent cerebral cortex (at protein level) CC (PubMed:17296554). Expressed in colonic crypts (at protein level) CC (PubMed:30389919). Expressed in platelets. Expressed in spermatozoa (at CC protein level) (PubMed:36135717). {ECO:0000269|PubMed:11146656, CC ECO:0000269|PubMed:11167005, ECO:0000269|PubMed:11511094, CC ECO:0000269|PubMed:15116257, ECO:0000269|PubMed:15915442, CC ECO:0000269|PubMed:17296554, ECO:0000269|PubMed:30389919, CC ECO:0000269|PubMed:36135717, ECO:0000269|PubMed:9889007}. CC -!- TISSUE SPECIFICITY: [Isoform ARTS]: Highly expressed in the brain and CC heart. {ECO:0000269|PubMed:11146656}. CC -!- PTM: Phosphorylated by DYRK1A. {ECO:0000250|UniProtKB:P28661}. CC -!- PTM: Ubiquitinated by AREL1. {ECO:0000269|PubMed:23479728}. CC -!- DISEASE: Spermatogenic failure 99 (SPGF99) [MIM:621194]: An autosomal CC recessive, male infertility disorder characterized by CC asthenoteratozoospermia with markedly reduced sperm progressive CC motility, and abnormal sperm morphology. Patient sperm exhibit a thin CC midpiece, absence of the annulus, and disorganization of the CC mitochondrial sheath. {ECO:0000269|PubMed:36135717}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Colocalizes with alpha-synuclein in Lewy bodies in the CC substantia nigra pars compacta of Parkinson disease patients CC (PubMed:17296554). Shows reduced expression in dopaminergic nerve CC terminals of the striatum in sporadic Parkinson disease CC (PubMed:17296554). {ECO:0000269|PubMed:17296554}. CC -!- MISCELLANEOUS: [Isoform ARTS]: May be defective in GTP-binding. CC {ECO:0000305}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF073312; AAC25673.1; -; mRNA. DR EMBL; U88829; AAD00653.1; -; mRNA. DR EMBL; U88870; AAD00657.1; -; mRNA. DR EMBL; AF176379; AAG45673.1; -; mRNA. DR EMBL; AB008753; BAB70695.1; -; mRNA. DR EMBL; D89278; BAB46922.1; -; mRNA. DR EMBL; AF035811; AAB88512.1; -; mRNA. DR EMBL; CR457111; CAG33392.1; -; mRNA. DR EMBL; AK315396; BAG37789.1; -; mRNA. DR EMBL; AK094579; BAG52891.1; -; mRNA. DR EMBL; AK294094; BAG57432.1; -; mRNA. DR EMBL; AK301914; BAG63338.1; -; mRNA. DR EMBL; AK302146; BAG63517.1; -; mRNA. DR EMBL; AK097440; BAC05054.1; -; mRNA. DR EMBL; AC005666; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471109; EAW94440.1; -; Genomic_DNA. DR EMBL; CH471109; EAW94442.1; -; Genomic_DNA. DR EMBL; BC018056; AAH18056.3; -; mRNA. DR EMBL; BC022189; AAH22189.2; -; mRNA. DR CCDS; CCDS11609.1; -. [O43236-2] DR CCDS; CCDS11610.1; -. [O43236-1] DR CCDS; CCDS32691.1; -. [O43236-8] DR CCDS; CCDS45743.1; -. [O43236-6] DR CCDS; CCDS56041.1; -. [O43236-3] DR CCDS; CCDS58581.1; -. [O43236-5] DR CCDS; CCDS58582.1; -. [O43236-4] DR CCDS; CCDS92368.1; -. [O43236-7] DR RefSeq; NP_001033793.3; NM_001038704.4. [O43236-8] DR RefSeq; NP_001185642.1; NM_001198713.2. [O43236-3] DR RefSeq; NP_001243711.1; NM_001256782.2. [O43236-4] DR RefSeq; NP_001243751.1; NM_001256822.2. [O43236-5] DR RefSeq; NP_001355700.1; NM_001368771.2. [O43236-7] DR RefSeq; NP_004565.1; NM_004574.5. [O43236-1] DR RefSeq; NP_536340.1; NM_080415.4. [O43236-6] DR RefSeq; NP_536341.1; NM_080416.4. [O43236-2] DR RefSeq; XP_006722018.1; XM_006721955.4. [O43236-5] DR RefSeq; XP_011523214.1; XM_011524912.3. [O43236-5] DR RefSeq; XP_024306576.1; XM_024450808.2. [O43236-5] DR RefSeq; XP_047292265.1; XM_047436309.1. [O43236-4] DR RefSeq; XP_054172497.1; XM_054316522.1. [O43236-4] DR RefSeq; XP_054172501.1; XM_054316526.1. [O43236-5] DR RefSeq; XP_054172502.1; XM_054316527.1. [O43236-5] DR RefSeq; XP_054172503.1; XM_054316528.1. [O43236-5] DR PDB; 6WB3; X-ray; 1.35 A; A/B=966-995. DR PDBsum; 6WB3; -. DR AlphaFoldDB; O43236; -. DR SMR; O43236; -. DR BioGRID; 111415; 28. DR BioGRID; 129753; 3. DR FunCoup; O43236; 359. DR IntAct; O43236; 27. DR MINT; O43236; -. DR STRING; 9606.ENSP00000354874; -. DR iPTMnet; O43236; -. DR PhosphoSitePlus; O43236; -. DR SwissPalm; O43236; -. DR BioMuta; C17orf47; -. DR BioMuta; SEPT4; -. DR DMDM; 300669697; -. DR jPOST; O43236; -. DR MassIVE; O43236; -. DR PaxDb; 9606-ENSP00000402000; -. DR PeptideAtlas; O43236; -. DR ProteomicsDB; 48814; -. [O43236-1] DR ProteomicsDB; 48815; -. [O43236-2] DR ProteomicsDB; 48816; -. [O43236-3] DR ProteomicsDB; 48817; -. [O43236-4] DR ProteomicsDB; 48818; -. [O43236-5] DR ProteomicsDB; 48819; -. [O43236-6] DR ProteomicsDB; 73193; -. DR Antibodypedia; 3484; 276 antibodies from 37 providers. DR DNASU; 284083; -. DR DNASU; 5414; -. DR Ensembl; ENST00000317256.10; ENSP00000321071.6; ENSG00000108387.16. [O43236-2] DR Ensembl; ENST00000317268.7; ENSP00000321674.3; ENSG00000108387.16. [O43236-1] DR Ensembl; ENST00000321691.3; ENSP00000354874.2; ENSG00000108387.16. [O43236-8] DR Ensembl; ENST00000393086.5; ENSP00000376801.1; ENSG00000108387.16. [O43236-2] DR Ensembl; ENST00000412945.7; ENSP00000414779.3; ENSG00000108387.16. [O43236-3] DR Ensembl; ENST00000426861.5; ENSP00000402348.1; ENSG00000108387.16. [O43236-6] DR Ensembl; ENST00000457347.6; ENSP00000402000.2; ENSG00000108387.16. [O43236-4] DR Ensembl; ENST00000583114.5; ENSP00000463768.1; ENSG00000108387.16. [O43236-5] DR Ensembl; ENST00000672673.2; ENSP00000500383.1; ENSG00000108387.16. [O43236-7] DR Ensembl; ENST00000672699.1; ENSP00000500355.1; ENSG00000108387.16. [O43236-4] DR GeneID; 5414; -. DR KEGG; hsa:5414; -. DR MANE-Select; ENST00000672673.2; ENSP00000500383.1; NM_001368771.2; NP_001355700.1. [O43236-7] DR UCSC; uc002iwm.4; human. [O43236-1] DR AGR; HGNC:9165; -. DR ClinPGx; PA33487; -. DR CTD; 5414; -. DR DisGeNET; 5414; -. DR GeneCards; SEPTIN4; -. DR HGNC; HGNC:9165; SEPTIN4. DR HPA; ENSG00000108387; Group enriched (brain, retina). DR MalaCards; SEPTIN4; -. DR MIM; 603696; gene. DR MIM; 621194; phenotype. DR OpenTargets; ENSG00000108387; -. DR Orphanet; 171709; Male infertility due to globozoospermia. DR VEuPathDB; HostDB:ENSG00000108387; -. DR eggNOG; ENOG502SETZ; Eukaryota. DR eggNOG; KOG2655; Eukaryota. DR GeneTree; ENSGT00390000018146; -. DR HOGENOM; CLU_575631_0_0_1; -. DR InParanoid; O43236; -. DR OMA; SSICTEP; -. DR OrthoDB; 416553at2759; -. DR PAN-GO; O43236; 11 GO annotations based on evolutionary models. DR PhylomeDB; O43236; -. DR PathwayCommons; O43236; -. DR Reactome; R-HSA-111457; Release of apoptotic factors from the mitochondria. [O43236-6] DR Reactome; R-HSA-111469; SMAC, XIAP-regulated apoptotic response. [O43236-6] DR SignaLink; O43236; -. DR SIGNOR; O43236; -. DR Agora; ENSG00000108387; -. DR BioGRID-ORCS; 284083; 14 hits in 1105 CRISPR screens. DR BioGRID-ORCS; 5414; 9 hits in 1084 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; SEPT4; human. DR GeneWiki; SEPT4; -. DR GenomeRNAi; 5414; -. DR Pharos; O43236; Tbio. DR PRO; PR:Q8NEP4; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; O43236; protein. DR Bgee; ENSG00000108387; Expressed in C1 segment of cervical spinal cord and 149 other cell types or tissues. DR ExpressionAtlas; O43236; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0032153; C:cell division site; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0098691; C:dopaminergic synapse; IDA:SynGO. DR GO; GO:0015630; C:microtubule cytoskeleton; IBA:GO_Central. DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; NAS:UniProtKB. DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB. DR GO; GO:0098793; C:presynapse; IDA:SynGO. 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:0008021; C:synaptic vesicle; IBA:GO_Central. DR GO; GO:0005525; F:GTP binding; IMP:CAFA. DR GO; GO:0003924; F:GTPase activity; IMP:CAFA. DR GO; GO:0042802; F:identical protein binding; IPI:CAFA. DR GO; GO:0000287; F:magnesium ion binding; IMP:CAFA. DR GO; GO:0060090; F:molecular adaptor activity; IBA:GO_Central. DR GO; GO:0005198; F:structural molecule activity; TAS:ProtInc. DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB. DR GO; GO:0061640; P:cytoskeleton-dependent cytokinesis; IBA:GO_Central. DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB. DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; ISS:UniProtKB. DR GO; GO:0008104; P:intracellular protein localization; IBA:GO_Central. DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB. DR GO; GO:0017157; P:regulation of exocytosis; IBA:GO_Central. DR GO; GO:0048515; P:spermatid differentiation; ISS:UniProtKB. DR CDD; cd01850; CDC_Septin; 1. DR DisProt; DP00537; -. DR DisProt; DP01325; -. [O43236-6] DR FunFam; 3.40.50.300:FF:000064; Septin 4; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR030379; G_SEPTIN_dom. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR016491; Septin. DR PANTHER; PTHR18884; SEPTIN; 1. DR Pfam; PF00735; Septin; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51719; G_SEPTIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Cell division; KW Cell projection; Cilium; Coiled coil; Cytoplasm; Cytoplasmic vesicle; KW Differentiation; Direct protein sequencing; Disease variant; Flagellum; KW GTP-binding; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; Spermatogenesis; Synapse; KW Ubl conjugation. FT CHAIN 1..996 FT /note="Septin-4" FT /id="PRO_0000173519" FT DOMAIN 659..932 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 428..448 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 669..676 FT /note="G1 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01056" FT REGION 726..729 FT /note="G3 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01056" FT REGION 807..810 FT /note="G4 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01056" FT COILED 965..996 FT /evidence="ECO:0000255" FT COMPBIAS 13..26 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 95..108 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 669..676 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q9UH03" FT BINDING 703 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q9UH03" FT BINDING 808..816 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q9UH03" FT BINDING 866 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q9UH03" FT BINDING 881 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q9UH03" FT MOD_RES 635 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 636 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 843 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18318008, FT ECO:0007744|PubMed:24275569" FT MOD_RES 950 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28661" FT MOD_RES 952 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P28661" FT VAR_SEQ 1..665 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_062617" FT VAR_SEQ 1..538 FT /note="MVKTNKPGAKVAVSAQRGSEVTTNTSPQQGHGYVLASSHRSAAVSLNPSHRR FT SEAAHPTTPHSASDYPRSVSLQSGPGHYAVPTPRGPETGPRTESSRHSSPHLKSQKTQT FT LASHASSRQWKVSPPREEAARRGSESKSGREVGHHASSIPDAKSTHQLSFQDQKNNLQS FT QILEDDPPSKVQNPQGVRVPRRILSYPKDEAVQTEPIQRITTTSEIRSPRSPSLLEHGS FT SCVSADYQTAQRRVPVEESETGPYGPIPSKPKALYRNMNLDSLLKLSVLKDSDGVHRVS FT ARVDPESLHKYSAYPETKPSAKVLVSSQVESNVRTPIRGNSEVGRRVTISPGVQSVEPT FT HHVTVPSVSEGSHKSSMFVTPEPIYKQQTQKPPEITYMSQGPTPRYPELSQKPSIHAEL FT ELTPRPLPPRSLPRYGPDSSWWPLLNPEVETPQSQLTTPDFEPKCSPSLDLLLSGFKID FT SSPFCEDLKFQREKASLSPPSPPKEFPSWAPLSEVPQTPKHTCKQPIQRFTAFFLDVSE FT EMYNRVIWWLKDEE -> MDRSLGWQGNSVPEDRTEAG (in isoform 1)" FT /id="VSP_062618" FT VAR_SEQ 1..538 FT /note="MVKTNKPGAKVAVSAQRGSEVTTNTSPQQGHGYVLASSHRSAAVSLNPSHRR FT SEAAHPTTPHSASDYPRSVSLQSGPGHYAVPTPRGPETGPRTESSRHSSPHLKSQKTQT FT LASHASSRQWKVSPPREEAARRGSESKSGREVGHHASSIPDAKSTHQLSFQDQKNNLQS FT QILEDDPPSKVQNPQGVRVPRRILSYPKDEAVQTEPIQRITTTSEIRSPRSPSLLEHGS FT SCVSADYQTAQRRVPVEESETGPYGPIPSKPKALYRNMNLDSLLKLSVLKDSDGVHRVS FT ARVDPESLHKYSAYPETKPSAKVLVSSQVESNVRTPIRGNSEVGRRVTISPGVQSVEPT FT HHVTVPSVSEGSHKSSMFVTPEPIYKQQTQKPPEITYMSQGPTPRYPELSQKPSIHAEL FT ELTPRPLPPRSLPRYGPDSSWWPLLNPEVETPQSQLTTPDFEPKCSPSLDLLLSGFKID FT SSPFCEDLKFQREKASLSPPSPPKEFPSWAPLSEVPQTPKHTCKQPIQRFTAFFLDVSE FT EMYNRVIWWLKDEE -> M (in isoform 2 and isoform ARTS)" FT /evidence="ECO:0000303|PubMed:11146656, FT ECO:0000303|PubMed:11167005, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_062619" FT VAR_SEQ 1..537 FT /note="MVKTNKPGAKVAVSAQRGSEVTTNTSPQQGHGYVLASSHRSAAVSLNPSHRR FT SEAAHPTTPHSASDYPRSVSLQSGPGHYAVPTPRGPETGPRTESSRHSSPHLKSQKTQT FT LASHASSRQWKVSPPREEAARRGSESKSGREVGHHASSIPDAKSTHQLSFQDQKNNLQS FT QILEDDPPSKVQNPQGVRVPRRILSYPKDEAVQTEPIQRITTTSEIRSPRSPSLLEHGS FT SCVSADYQTAQRRVPVEESETGPYGPIPSKPKALYRNMNLDSLLKLSVLKDSDGVHRVS FT ARVDPESLHKYSAYPETKPSAKVLVSSQVESNVRTPIRGNSEVGRRVTISPGVQSVEPT FT HHVTVPSVSEGSHKSSMFVTPEPIYKQQTQKPPEITYMSQGPTPRYPELSQKPSIHAEL FT ELTPRPLPPRSLPRYGPDSSWWPLLNPEVETPQSQLTTPDFEPKCSPSLDLLLSGFKID FT SSPFCEDLKFQREKASLSPPSPPKEFPSWAPLSEVPQTPKHTCKQPIQRFTAFFLDVSE FT EMYNRVIWWLKDE -> MRSSPALFSSRAAPQKPRKEGSQAAGLLVFSDSL (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_062620" FT VAR_SEQ 1..535 FT /note="MVKTNKPGAKVAVSAQRGSEVTTNTSPQQGHGYVLASSHRSAAVSLNPSHRR FT SEAAHPTTPHSASDYPRSVSLQSGPGHYAVPTPRGPETGPRTESSRHSSPHLKSQKTQT FT LASHASSRQWKVSPPREEAARRGSESKSGREVGHHASSIPDAKSTHQLSFQDQKNNLQS FT QILEDDPPSKVQNPQGVRVPRRILSYPKDEAVQTEPIQRITTTSEIRSPRSPSLLEHGS FT SCVSADYQTAQRRVPVEESETGPYGPIPSKPKALYRNMNLDSLLKLSVLKDSDGVHRVS FT ARVDPESLHKYSAYPETKPSAKVLVSSQVESNVRTPIRGNSEVGRRVTISPGVQSVEPT FT HHVTVPSVSEGSHKSSMFVTPEPIYKQQTQKPPEITYMSQGPTPRYPELSQKPSIHAEL FT ELTPRPLPPRSLPRYGPDSSWWPLLNPEVETPQSQLTTPDFEPKCSPSLDLLLSGFKID FT SSPFCEDLKFQREKASLSPPSPPKEFPSWAPLSEVPQTPKHTCKQPIQRFTAFFLDVSE FT EMYNRVIWWLK -> MPGFYSVMT (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_062621" FT VAR_SEQ 536..570 FT /note="DEEIKRFLEDTTDDGELSKFVKDFSGNASCHPPEA -> GLCFSLLWAHCGS FT LGDGRTGEEWHLCIYRAGSFRR (in isoform 8)" FT /id="VSP_062622" FT VAR_SEQ 571..996 FT /note="Missing (in isoform 8)" FT /id="VSP_062623" FT VAR_SEQ 785..811 FT /note="LRPLDVEFMKALHQRVNIVPILAKADT -> YGPSLRLLAPPGAVKGTGQEH FT QGQGCH (in isoform ARTS)" FT /evidence="ECO:0000303|PubMed:11146656" FT /id="VSP_062624" FT VAR_SEQ 812..996 FT /note="Missing (in isoform ARTS)" FT /evidence="ECO:0000303|PubMed:11146656" FT /id="VSP_062625" FT VARIANT 69..996 FT /note="Missing (in SPGF99; likely pathogenic; loss of FT protein expression)" FT /evidence="ECO:0000269|PubMed:36135717" FT /id="VAR_090727" FT VARIANT 88 FT /note="P -> T (in dbSNP:rs8071623)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_090728" FT VARIANT 241..996 FT /note="Missing (in SPGF99; likely pathogenic; loss of FT protein expression)" FT /evidence="ECO:0000269|PubMed:36135717" FT /id="VAR_090729" FT VARIANT 829 FT /note="E -> V (in dbSNP:rs17741424)" FT /id="VAR_051935" FT CONFLICT 187 FT /note="V -> A (in Ref. 8; BAC05054)" FT /evidence="ECO:0000305" FT CONFLICT 674 FT /note="G -> D (in Ref. 7; BAG37789)" FT /evidence="ECO:0000305" FT CONFLICT 900 FT /note="K -> E (in Ref. 7; BAG63517)" FT /evidence="ECO:0000305" FT HELIX 967..994 FT /evidence="ECO:0007829|PDB:6WB3" FT MUTAGEN O43236-6:137..139 FT /note="GKS->ENP: Loss of TGF-beta-induced apoptosis. No FT translocation to the nucleus following TGF-beta treatment. FT Loss of XIAP-binding." FT /evidence="ECO:0000269|PubMed:11146656, FT ECO:0000269|PubMed:15029247" SQ SEQUENCE 996 AA; 112439 MW; 8306167C9EF5CFF0 CRC64; MVKTNKPGAK VAVSAQRGSE VTTNTSPQQG HGYVLASSHR SAAVSLNPSH RRSEAAHPTT PHSASDYPRS VSLQSGPGHY AVPTPRGPET GPRTESSRHS SPHLKSQKTQ TLASHASSRQ WKVSPPREEA ARRGSESKSG REVGHHASSI PDAKSTHQLS FQDQKNNLQS QILEDDPPSK VQNPQGVRVP RRILSYPKDE AVQTEPIQRI TTTSEIRSPR SPSLLEHGSS CVSADYQTAQ RRVPVEESET GPYGPIPSKP KALYRNMNLD SLLKLSVLKD SDGVHRVSAR VDPESLHKYS AYPETKPSAK VLVSSQVESN VRTPIRGNSE VGRRVTISPG VQSVEPTHHV TVPSVSEGSH KSSMFVTPEP IYKQQTQKPP EITYMSQGPT PRYPELSQKP SIHAELELTP RPLPPRSLPR YGPDSSWWPL LNPEVETPQS QLTTPDFEPK CSPSLDLLLS GFKIDSSPFC EDLKFQREKA SLSPPSPPKE FPSWAPLSEV PQTPKHTCKQ PIQRFTAFFL DVSEEMYNRV IWWLKDEEIK RFLEDTTDDG ELSKFVKDFS GNASCHPPEA KTWASRPQVP EPRPQAPDLY DDDLEFRPPS RPQSSDNQQY FCAPAPLSPS ARPRSPWGKL DPYDSSEDDK EYVGFATLPN QVHRKSVKKG FDFTLMVAGE SGLGKSTLVN SLFLTDLYRD RKLLGAEERI MQTVEITKHA VDIEEKGVRL RLTIVDTPGF GDAVNNTECW KPVAEYIDQQ FEQYFRDESG LNRKNIQDNR VHCCLYFISP FGHGLRPLDV EFMKALHQRV NIVPILAKAD TLTPPEVDHK KRKIREEIEH FGIKIYQFPD CDSDEDEDFK LQDQALKESI PFAVIGSNTV VEARGRRVRG RLYPWGIVEV ENPGHCDFVK LRTMLVRTHM QDLKDVTRET HYENYRAQCI QSMTRLVVKE RNRNKLTRES GTDFPIPAVP PGTDPETEKL IREKDEELRR MQEMLHKIQK QMKENY //