ID SEPT4_HUMAN Reviewed; 478 AA. AC O43236; A0A5F9ZHH3; B2RD42; B3KSX9; B4DXC6; B4DXV5; Q6IAP3; Q8N821; Q8NEP4; AC Q9H315; Q9UM58; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 27-MAR-2024, entry version 199. 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}, PNUTL2 GN {ECO:0000303|PubMed:9889007}, SEP4 {ECO:0000312|HGNC:HGNC:9165}, SEPT4 GN {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 156-GLY--SER-158 (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 141-157 AND 282-290, 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-325, 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-117; SER-118 AND SER-325, 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 156-GLY--SER-158 (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 octomeric 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). 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 (By similarity). 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 (By CC similarity). Involved in the migration of cortical neurons and the CC formation of neuron leading processes during embryonic development (By CC similarity). Required for dopaminergic metabolism in presynaptic CC autoreceptors; potentially via activity as a presynaptic scaffold CC protein (By similarity). {ECO:0000250|UniProtKB:P28661, 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=5; 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 Cytoplasmic vesicle, secretory vesicle {ECO:0000269|PubMed:15116257}. CC Cell projection, axon {ECO:0000250|UniProtKB:P28661}. Cell projection, CC dendrite {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). Expressed and colocalized with SLC6A3 and SNCA in CC axon terminals, especially at the varicosities (By similarity). CC {ECO:0000250|UniProtKB:P28661, ECO:0000269|PubMed:15116257, CC ECO:0000269|PubMed:25588830}. 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=1; Synonyms=PNUTL2, PNUTL2a, H5/CDCrel-2 CC {ECO:0000303|PubMed:11167005}, SEPT4_i1; CC IsoId=O43236-1; Sequence=Displayed; CC Name=2; Synonyms=PNUTL2b, CDCrel-1 {ECO:0000303|PubMed:11167005}; CC IsoId=O43236-2; Sequence=VSP_006050; CC Name=3; CC IsoId=O43236-3; Sequence=VSP_038303; CC Name=4; CC IsoId=O43236-4; Sequence=VSP_038304; CC Name=5; CC IsoId=O43236-5; Sequence=VSP_038302; CC Name=ARTS {ECO:0000303|PubMed:11146656}; Synonyms=SEPT4_i2; CC IsoId=O43236-6; Sequence=VSP_006050, VSP_038305, VSP_038306; CC Name=7; CC IsoId=O43236-7; Sequence=VSP_060789; CC Name=8; CC IsoId=O43236-8; Sequence=VSP_060788; 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). Also expressed in colorectal cancers and malignant CC melanomas. Expressed in platelets. {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: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 -!- 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_001033793.2; NM_001038704.2. [O43236-8] DR RefSeq; NP_001185642.1; NM_001198713.1. [O43236-3] DR RefSeq; NP_001243711.1; NM_001256782.1. [O43236-4] DR RefSeq; NP_001243751.1; NM_001256822.1. [O43236-5] DR RefSeq; NP_004565.1; NM_004574.4. [O43236-1] DR RefSeq; NP_536340.1; NM_080415.3. [O43236-6] DR RefSeq; NP_536341.1; NM_080416.3. [O43236-2] DR RefSeq; XP_006722017.1; XM_006721954.2. DR RefSeq; XP_006722018.1; XM_006721955.2. [O43236-5] DR RefSeq; XP_011523213.1; XM_011524911.1. DR RefSeq; XP_011523214.1; XM_011524912.1. [O43236-5] DR PDB; 6WB3; X-ray; 1.35 A; A/B=448-477. DR PDBsum; 6WB3; -. DR AlphaFoldDB; O43236; -. DR SMR; O43236; -. DR BioGRID; 111415; 27. DR BioGRID; 129753; 3. DR IntAct; O43236; 24. DR MINT; O43236; -. DR STRING; 9606.ENSP00000354874; -. DR iPTMnet; O43236; -. DR PhosphoSitePlus; O43236; -. DR BioMuta; C17orf47; -. DR BioMuta; SEPT4; -. DR DMDM; 300669697; -. DR EPD; O43236; -. DR jPOST; O43236; -. DR MassIVE; O43236; -. DR MaxQB; 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; 305 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 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 neXtProt; NX_O43236; -. DR OpenTargets; ENSG00000108387; -. DR Orphanet; 171709; Male infertility due to globozoospermia. DR PharmGKB; PA33487; -. 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; 5396944at2759; -. DR PhylomeDB; O43236; -. DR TreeFam; TF101079; -. DR TreeFam; TF338016; -. 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 BioGRID-ORCS; 284083; 14 hits in 1105 CRISPR screens. DR BioGRID-ORCS; 5414; 9 hits in 1084 CRISPR screens. 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: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:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; NAS:UniProtKB. DR GO; GO:0043204; C:perikaryon; ISS: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: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: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 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 PANTHER; PTHR18884:SF71; SEPTIN-4; 1. DR Pfam; PF00735; Septin; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51719; G_SEPTIN; 1. DR Genevisible; O43236; HS. 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; Flagellum; GTP-binding; KW Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Spermatogenesis; Synapse; Ubl conjugation. FT CHAIN 1..478 FT /note="Septin-4" FT /id="PRO_0000173519" 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..448 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 447..478 FT /evidence="ECO:0000255" FT COMPBIAS 16..37 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 82..96 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 117 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 118 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 325 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18318008, FT ECO:0007744|PubMed:24275569" FT MOD_RES 432 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28661" FT MOD_RES 434 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P28661" FT VAR_SEQ 1..478 FT /note="MDRSLGWQGNSVPEDRTEAGIKRFLEDTTDDGELSKFVKDFSGNASCHPPEA FT KTWASRPQVPEPRPQAPDLYDDDLEFRPPSRPQSSDNQQYFCAPAPLSPSARPRSPWGK FT LDPYDSSEDDKEYVGFATLPNQVHRKSVKKGFDFTLMVAGESGLGKSTLVNSLFLTDLY FT RDRKLLGAEERIMQTVEITKHAVDIEEKGVRLRLTIVDTPGFGDAVNNTECWKPVAEYI FT DQQFEQYFRDESGLNRKNIQDNRVHCCLYFISPFGHGLRPLDVEFMKALHQRVNIVPIL FT AKADTLTPPEVDHKKRKIREEIEHFGIKIYQFPDCDSDEDEDFKLQDQALKESIPFAVI FT GSNTVVEARGRRVRGRLYPWGIVEVENPGHCDFVKLRTMLVRTHMQDLKDVTRETHYEN FT YRAQCIQSMTRLVVKERNRNKLTRESGTDFPIPAVPPGTDPETEKLIREKDEELRRMQE FT MLHKIQKQMKENY -> MVKTNKPGAKVAVSAQRGSEVTTNTSPQQGHGYVLASSHRSA FT AVSLNPSHRRSEAAHPTTPHSASDYPRSVSLQSGPGHYAVPTPRGPETGPRTESSRHSS FT PHLKSQKTQTLASHASSRQWKVSPPREEAARRGSESKSGREVGHHASSIPDAKSTHQLS FT FQDQKNNLQSQILEDDPPSKVQNPQGVRVPRRILSYPKDEAVQTEPIQRITTTSEIRSP FT RSPSLLEHGSSCVSADYQTAQRRVPVEESETGPYGPIPSKPKALYRNMNLDSLLKLSVL FT KDSDGVHRVSARVDPESLHKYSAYPETKPSAKVLVSSQVESNVRTPIRGNSEVGRRVTI FT SPGVQSVEPTHHVTVPSVSEGSHKSSMFVTPEPIYKQQTQKPPEITYMSQGPTPRYPEL FT SQKPSIHAELELTPRPLPPRSLPRYGPDSSWWPLLNPEVETPQSQLTTPDFEPKCSPSL FT DLLLSGFKIDSSPFCEDLKFQREKASLSPPSPPKEFPSWAPLSEVPQTPKHTCKQPIQR FT FTAFFLDVSEEMYNRVIWWLKGLCFSLLWAHCGSLGDGRTGEEWHLCIYRAGSFRR FT (in isoform 8)" FT /id="VSP_060788" FT VAR_SEQ 1..147 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038302" FT VAR_SEQ 1..20 FT /note="MDRSLGWQGNSVPEDRTEAG -> M (in isoform 2 and isoform FT ARTS)" FT /evidence="ECO:0000303|PubMed:11146656, FT ECO:0000303|PubMed:11167005, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_006050" FT VAR_SEQ 1..20 FT /note="MDRSLGWQGNSVPEDRTEAG -> MPGFYSVMTDEE (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038303" FT VAR_SEQ 1..20 FT /note="MDRSLGWQGNSVPEDRTEAG -> MRSSPALFSSRAAPQKPRKEGSQAAGLL FT VFSDSLE (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038304" FT VAR_SEQ 1..20 FT /note="MDRSLGWQGNSVPEDRTEAG -> MVKTNKPGAKVAVSAQRGSEVTTNTSPQ FT QGHGYVLASSHRSAAVSLNPSHRRSEAAHPTTPHSASDYPRSVSLQSGPGHYAVPTPRG FT PETGPRTESSRHSSPHLKSQKTQTLASHASSRQWKVSPPREEAARRGSESKSGREVGHH FT ASSIPDAKSTHQLSFQDQKNNLQSQILEDDPPSKVQNPQGVRVPRRILSYPKDEAVQTE FT PIQRITTTSEIRSPRSPSLLEHGSSCVSADYQTAQRRVPVEESETGPYGPIPSKPKALY FT RNMNLDSLLKLSVLKDSDGVHRVSARVDPESLHKYSAYPETKPSAKVLVSSQVESNVRT FT PIRGNSEVGRRVTISPGVQSVEPTHHVTVPSVSEGSHKSSMFVTPEPIYKQQTQKPPEI FT TYMSQGPTPRYPELSQKPSIHAELELTPRPLPPRSLPRYGPDSSWWPLLNPEVETPQSQ FT LTTPDFEPKCSPSLDLLLSGFKIDSSPFCEDLKFQREKASLSPPSPPKEFPSWAPLSEV FT PQTPKHTCKQPIQRFTAFFLDVSEEMYNRVIWWLKDEE (in isoform 7)" FT /id="VSP_060789" FT VAR_SEQ 267..293 FT /note="LRPLDVEFMKALHQRVNIVPILAKADT -> YGPSLRLLAPPGAVKGTGQEH FT QGQGCH (in isoform ARTS)" FT /evidence="ECO:0000303|PubMed:11146656" FT /id="VSP_038305" FT VAR_SEQ 294..478 FT /note="Missing (in isoform ARTS)" FT /evidence="ECO:0000303|PubMed:11146656" FT /id="VSP_038306" FT VARIANT 311 FT /note="E -> V (in dbSNP:rs17741424)" FT /id="VAR_051935" FT CONFLICT 156 FT /note="G -> D (in Ref. 7; BAG37789)" FT /evidence="ECO:0000305" FT CONFLICT 382 FT /note="K -> E (in Ref. 7; BAG63517)" FT /evidence="ECO:0000305" FT HELIX 449..476 FT /evidence="ECO:0007829|PDB:6WB3" FT MUTAGEN O43236-6:156..158 FT /note="LLG->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" FT VARIANT O43236-8:88 FT /note="P -> T (in dbSNP:rs8071623)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_083877" FT CONFLICT O43236-8:187 FT /note="V -> A (in Ref. 8)" FT /evidence="ECO:0000305" SQ SEQUENCE 478 AA; 55098 MW; 2F08D3611EF6523D CRC64; MDRSLGWQGN SVPEDRTEAG IKRFLEDTTD DGELSKFVKD FSGNASCHPP EAKTWASRPQ VPEPRPQAPD LYDDDLEFRP PSRPQSSDNQ QYFCAPAPLS PSARPRSPWG KLDPYDSSED DKEYVGFATL PNQVHRKSVK KGFDFTLMVA GESGLGKSTL VNSLFLTDLY RDRKLLGAEE RIMQTVEITK HAVDIEEKGV RLRLTIVDTP GFGDAVNNTE CWKPVAEYID QQFEQYFRDE SGLNRKNIQD NRVHCCLYFI SPFGHGLRPL DVEFMKALHQ RVNIVPILAK ADTLTPPEVD HKKRKIREEI EHFGIKIYQF PDCDSDEDED FKLQDQALKE SIPFAVIGSN TVVEARGRRV RGRLYPWGIV EVENPGHCDF VKLRTMLVRT HMQDLKDVTR ETHYENYRAQ CIQSMTRLVV KERNRNKLTR ESGTDFPIPA VPPGTDPETE KLIREKDEEL RRMQEMLHKI QKQMKENY //