ID ZFY27_HUMAN Reviewed; 411 AA. AC Q5T4F4; B7Z3S0; B7Z404; B7Z626; G8JLC3; G8JLF0; J3KP98; Q5T4F1; Q5T4F2; AC Q5T4F3; Q8N1K0; Q8N6D6; Q8NCA0; Q8NDE4; Q96M08; DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 27-MAR-2024, entry version 173. DE RecName: Full=Protrudin; DE AltName: Full=Spastic paraplegia 33 protein {ECO:0000303|PubMed:24668814}; DE AltName: Full=Zinc finger FYVE domain-containing protein 27; GN Name=ZFYVE27; Synonyms=SPG33 {ECO:0000303|PubMed:24668814}; 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 [LARGE SCALE MRNA] (ISOFORMS 2; 4; 5; 6; 7 AND 8), AND RP VARIANT VAL-138. RC TISSUE=Brain, Testis, Thalamus, and Thymus; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-138. 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 23-411 (ISOFORM 3), AND VARIANT RP VAL-138. RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP FUNCTION, INTERACTION WITH FKBP8 AND RAB11A, PHOSPHORYLATION, AND RP MUTAGENESIS OF LEU-13 AND ILE-49. RX PubMed=17082457; DOI=10.1126/science.1134027; RA Shirane M., Nakayama K.I.; RT "Protrudin induces neurite formation by directional membrane trafficking."; RL Science 314:818-821(2006). RN [6] RP INTERACTION WITH FKBP8. RX PubMed=18459960; DOI=10.1111/j.1365-2443.2008.01194.x; RA Shirane M., Ogawa M., Motoyama J., Nakayama K.I.; RT "Regulation of apoptosis and neurite extension by FKBP38 is required for RT neural tube formation in the mouse."; RL Genes Cells 13:635-651(2008). RN [7] RP FUNCTION, INTERACTION WITH VAPA AND VAPB, MUTAGENESIS OF ASP-289, AND RP SUBCELLULAR LOCATION. RX PubMed=19289470; DOI=10.1074/jbc.m807938200; RA Saita S., Shirane M., Natume T., Iemura S., Nakayama K.I.; RT "Promotion of neurite extension by protrudin requires its interaction with RT vesicle-associated membrane protein-associated protein."; RL J. Biol. Chem. 284:13766-13777(2009). RN [8] RP FUNCTION, AND INTERACTION WITH KIF5A; VAPA; VAPB AND RTN3. RX PubMed=21976701; DOI=10.1091/mbc.e11-01-0068; RA Matsuzaki F., Shirane M., Matsumoto M., Nakayama K.I.; RT "Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes RT in vesicular transport during process formation."; RL Mol. Biol. Cell 22:4602-4620(2011). RN [9] RP STRUCTURE BY NMR OF 341-411. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the FYVE domain from human FYVE domain containing 27 RT isoform B protein."; RL Submitted (NOV-2005) to the PDB data bank. RN [10] RP VARIANT SPG33 VAL-191, CHARACTERIZATION OF VARIANT SPG33 VAL-191, RP SUBCELLULAR LOCATION, AND INTERACTION WITH SPAST. RX PubMed=16826525; DOI=10.1086/504927; RA Mannan A.U., Krawen P., Sauter S.M., Boehm J., Chronowska A., Paulus W., RA Neesen J., Engel W.; RT "ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary RT spastic paraplegia."; RL Am. J. Hum. Genet. 79:351-357(2006). RN [11] RP CHARACTERIZATION OF VARIANT SPG33 VAL-191. RX PubMed=18606302; DOI=10.1016/j.ajhg.2008.05.014; RA Martignoni M., Riano E., Rugarli E.I.; RT "The role of ZFYVE27/protrudin in hereditary spastic paraplegia."; RL Am. J. Hum. Genet. 83:127-130(2008). RN [12] RP CHARACTERIZATION OF VARIANT SPG33 VAL-191, FUNCTION, SUBUNIT, SUBCELLULAR RP LOCATION, TOPOLOGY, AND INTERACTION WITH REEP1; REEP5; ATL1; ATL2; ATL3 AND RP SPAST. RX PubMed=23969831; DOI=10.1073/pnas.1307391110; RA Chang J., Lee S., Blackstone C.; RT "Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and RT regulates network formation."; RL Proc. Natl. Acad. Sci. U.S.A. 110:14954-14959(2013). RN [13] RP CHARACTERIZATION OF VARIANT SPG33 VAL-191, FUNCTION, SUBCELLULAR LOCATION, RP AND INTERACTION WITH REEP1; REEP5 AND ATL1. RX PubMed=24668814; DOI=10.1074/jbc.m113.528687; RA Hashimoto Y., Shirane M., Matsuzaki F., Saita S., Ohnishi T., RA Nakayama K.I.; RT "Protrudin regulates endoplasmic reticulum morphology and function RT associated with the pathogenesis of hereditary spastic paraplegia."; RL J. Biol. Chem. 289:12946-12961(2014). CC -!- FUNCTION: Key regulator of RAB11-dependent vesicular trafficking during CC neurite extension through polarized membrane transport CC (PubMed:17082457). Promotes axonal elongation and contributes to the CC establishment of neuronal cell polarity (By similarity). Involved in CC nerve growth factor-induced neurite formation in VAPA-dependent manner CC (PubMed:19289470). Contributes to both the formation and stabilization CC of the tubular ER network (PubMed:24668814). Involved in ER CC morphogenesis by regulating the sheet-to-tubule balance and possibly CC the density of tubule interconnections (PubMed:23969831). Acts as an CC adapter protein and facilitates the interaction of KIF5A with VAPA, CC VAPB, SURF4, RAB11A, RAB11B and RTN3 and the ZFYVE27-KIF5A complex CC contributes to the transport of these proteins in neurons. Can induce CC formation of neurite-like membrane protrusions in non-neuronal cells in CC a KIF5A/B-dependent manner (PubMed:21976701). CC {ECO:0000250|UniProtKB:Q3TXX3, ECO:0000269|PubMed:17082457, CC ECO:0000269|PubMed:19289470, ECO:0000269|PubMed:21976701, CC ECO:0000269|PubMed:23969831, ECO:0000269|PubMed:24668814}. CC -!- SUBUNIT: Can form homooligomers (monomers, dimers and tetramers) CC (PubMed:23969831). Interacts with RAB11A (GDP-bound form); regulates CC RAB11A (PubMed:17082457). Interacts with FKBP8; may negatively regulate CC ZFYVE27 phosphorylation (PubMed:17082457, PubMed:18459960). Interacts CC with VAPA (via MSP domain); may regulate ZFYVE27 retention in the CC endoplasmic reticulum and its function in cell projections formation CC (PubMed:19289470, PubMed:21976701). Interacts with VAPB (via MSP CC domain) (PubMed:19289470, PubMed:21976701). Interacts with REEP1, REEP5 CC and ATL1 (PubMed:24668814, PubMed:23969831). Interacts with ATL2, ATL3 CC and SPAST (PubMed:23969831). Interacts with KIF5A and RTN3 CC (PubMed:21976701). Interacts with RAB11B (GDP-bound form), SURF4, KIF5B CC and KIF5C (By similarity). {ECO:0000250|UniProtKB:Q3TXX3, CC ECO:0000269|PubMed:16826525, ECO:0000269|PubMed:17082457, CC ECO:0000269|PubMed:18459960, ECO:0000269|PubMed:19289470, CC ECO:0000269|PubMed:21976701, ECO:0000269|PubMed:23969831, CC ECO:0000269|PubMed:24668814}. CC -!- INTERACTION: CC Q5T4F4; Q8WXF7: ATL1; NbExp=6; IntAct=EBI-3892947, EBI-2410266; CC Q5T4F4; Q8NHH9: ATL2; NbExp=2; IntAct=EBI-3892947, EBI-2410430; CC Q5T4F4; Q6DD88: ATL3; NbExp=3; IntAct=EBI-3892947, EBI-6165882; CC Q5T4F4; Q14318: FKBP8; NbExp=4; IntAct=EBI-3892947, EBI-724839; CC Q5T4F4; Q8WWP7: GIMAP1; NbExp=3; IntAct=EBI-3892947, EBI-11991950; CC Q5T4F4; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-3892947, EBI-6166686; CC Q5T4F4; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-3892947, EBI-725665; CC Q5T4F4; Q9P0S3: ORMDL1; NbExp=3; IntAct=EBI-3892947, EBI-1054848; CC Q5T4F4; Q7RTS5: OTOP3; NbExp=3; IntAct=EBI-3892947, EBI-12853910; CC Q5T4F4; Q8N4L2: PIP4P2; NbExp=3; IntAct=EBI-3892947, EBI-2820617; CC Q5T4F4; P62491: RAB11A; NbExp=4; IntAct=EBI-3892947, EBI-745098; CC Q5T4F4; Q9H902: REEP1; NbExp=2; IntAct=EBI-3892947, EBI-1644241; CC Q5T4F4; Q00765: REEP5; NbExp=4; IntAct=EBI-3892947, EBI-1549827; CC Q5T4F4; Q9NTJ5: SACM1L; NbExp=3; IntAct=EBI-3892947, EBI-3917235; CC Q5T4F4; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-3892947, EBI-8652744; CC Q5T4F4; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-3892947, EBI-10262251; CC Q5T4F4; Q8N2U9: SLC66A2; NbExp=3; IntAct=EBI-3892947, EBI-3907610; CC Q5T4F4; Q9UBP0: SPAST; NbExp=3; IntAct=EBI-3892947, EBI-1222832; CC Q5T4F4; O15400: STX7; NbExp=3; IntAct=EBI-3892947, EBI-3221827; CC Q5T4F4; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-3892947, EBI-10694905; CC Q5T4F4; Q9P0S9: TMEM14C; NbExp=3; IntAct=EBI-3892947, EBI-2339195; CC Q5T4F4; Q9BU79: TMEM243; NbExp=3; IntAct=EBI-3892947, EBI-12887458; CC Q5T4F4; Q6PI78: TMEM65; NbExp=3; IntAct=EBI-3892947, EBI-6656213; CC Q5T4F4; O60636: TSPAN2; NbExp=3; IntAct=EBI-3892947, EBI-3914288; CC Q5T4F4; Q9P0L0: VAPA; NbExp=5; IntAct=EBI-3892947, EBI-1059156; CC Q5T4F4; O95292: VAPB; NbExp=2; IntAct=EBI-3892947, EBI-1188298; CC Q5T4F4; O95070: YIF1A; NbExp=3; IntAct=EBI-3892947, EBI-2799703; CC Q5T4F4; Q5T4F4: ZFYVE27; NbExp=2; IntAct=EBI-3892947, EBI-3892947; CC Q5T4F4-1; P18067: RAB7A; Xeno; NbExp=2; IntAct=EBI-16152863, EBI-7991906; CC -!- SUBCELLULAR LOCATION: Recycling endosome membrane CC {ECO:0000250|UniProtKB:Q6P7B7}; Multi-pass membrane protein CC {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:19289470, ECO:0000269|PubMed:23969831, CC ECO:0000269|PubMed:24668814}; Multi-pass membrane protein CC {ECO:0000269|PubMed:23969831}. Cell projection, growth cone membrane CC {ECO:0000250|UniProtKB:Q3TXX3}; Multi-pass membrane protein CC {ECO:0000255}. Note=Localizes at both dendrites and axons (By CC similarity). Localizes to endoplasmic reticulum tubular network. CC {ECO:0000250|UniProtKB:Q3TXX3, ECO:0000269|PubMed:23969831, CC ECO:0000269|PubMed:24668814}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=1; CC IsoId=Q5T4F4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5T4F4-2; Sequence=VSP_019754; CC Name=3; CC IsoId=Q5T4F4-3; Sequence=VSP_019753; CC Name=4; CC IsoId=Q5T4F4-4; Sequence=VSP_019751, VSP_019753, VSP_019754, CC VSP_019755, VSP_019756; CC Name=5; CC IsoId=Q5T4F4-5; Sequence=VSP_019752, VSP_019754; CC Name=6; CC IsoId=Q5T4F4-6; Sequence=VSP_045266, VSP_019754; CC Name=7; CC IsoId=Q5T4F4-7; Sequence=VSP_045265, VSP_019753, VSP_019754; CC Name=8; CC IsoId=Q5T4F4-8; Sequence=VSP_046051, VSP_019754; CC -!- PTM: Phosphorylated. Phosphorylation is induced by NGF through the CC MAPK/ERK pathway and modulates interaction with RAB11A. CC {ECO:0000269|PubMed:17082457}. CC -!- DISEASE: Spastic paraplegia 33, autosomal dominant (SPG33) CC [MIM:610244]: A form of spastic paraplegia, a neurodegenerative CC disorder characterized by a slow, gradual, progressive weakness and CC spasticity of the lower limbs. Rate of progression and the severity of CC symptoms are quite variable. Initial symptoms may include difficulty CC with balance, weakness and stiffness in the legs, muscle spasms, and CC dragging the toes when walking. In some forms of the disorder, bladder CC symptoms (such as incontinence) may appear, or the weakness and CC stiffness may spread to other parts of the body. CC {ECO:0000269|PubMed:16826525, ECO:0000269|PubMed:18606302, CC ECO:0000269|PubMed:23969831, ECO:0000269|PubMed:24668814}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. According to PubMed:18606302, the properties of the variant Val- CC 191 and its frequency in some populations raise doubts on the CC implication of that gene in the disease. CC -!- SEQUENCE CAUTION: CC Sequence=CAD38913.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; 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; AK057481; BAB71506.1; -; mRNA. DR EMBL; AK097945; BAC05200.1; -; mRNA. DR EMBL; AK074876; BAC11260.1; -; mRNA. DR EMBL; AK296295; BAH12306.1; -; mRNA. DR EMBL; AK296588; BAH12390.1; -; mRNA. DR EMBL; AK299735; BAH13112.1; -; mRNA. DR EMBL; AL358938; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC030621; AAH30621.2; -; mRNA. DR EMBL; AL834235; CAD38913.2; ALT_INIT; mRNA. DR CCDS; CCDS31262.1; -. [Q5T4F4-3] DR CCDS; CCDS31263.1; -. [Q5T4F4-1] DR CCDS; CCDS31264.1; -. [Q5T4F4-2] DR CCDS; CCDS53562.1; -. [Q5T4F4-8] DR CCDS; CCDS53563.1; -. [Q5T4F4-5] DR CCDS; CCDS53564.1; -. [Q5T4F4-6] DR CCDS; CCDS53565.1; -. [Q5T4F4-7] DR RefSeq; NP_001002261.1; NM_001002261.3. [Q5T4F4-3] DR RefSeq; NP_001002262.1; NM_001002262.3. [Q5T4F4-2] DR RefSeq; NP_001167590.1; NM_001174119.1. [Q5T4F4-8] DR RefSeq; NP_001167591.1; NM_001174120.1. [Q5T4F4-5] DR RefSeq; NP_001167592.1; NM_001174121.1. [Q5T4F4-7] DR RefSeq; NP_001167593.1; NM_001174122.1. [Q5T4F4-6] DR RefSeq; NP_653189.3; NM_144588.6. [Q5T4F4-1] DR RefSeq; XP_005269559.1; XM_005269502.3. DR RefSeq; XP_005269560.1; XM_005269503.3. DR RefSeq; XP_005269561.1; XM_005269504.3. DR RefSeq; XP_005269563.1; XM_005269506.3. DR PDB; 1X4U; NMR; -; A=341-411. DR PDBsum; 1X4U; -. DR AlphaFoldDB; Q5T4F4; -. DR BMRB; Q5T4F4; -. DR SMR; Q5T4F4; -. DR BioGRID; 125623; 70. DR CORUM; Q5T4F4; -. DR DIP; DIP-61530N; -. DR ELM; Q5T4F4; -. DR IntAct; Q5T4F4; 53. DR STRING; 9606.ENSP00000409594; -. DR TCDB; 1.R.1.1.1; the membrane contact site (mcs) family. DR iPTMnet; Q5T4F4; -. DR PhosphoSitePlus; Q5T4F4; -. DR BioMuta; ZFYVE27; -. DR DMDM; 74744927; -. DR EPD; Q5T4F4; -. DR jPOST; Q5T4F4; -. DR MassIVE; Q5T4F4; -. DR MaxQB; Q5T4F4; -. DR PaxDb; 9606-ENSP00000377282; -. DR PeptideAtlas; Q5T4F4; -. DR ProteomicsDB; 34183; -. DR ProteomicsDB; 34208; -. DR ProteomicsDB; 64452; -. [Q5T4F4-1] DR ProteomicsDB; 64453; -. [Q5T4F4-2] DR ProteomicsDB; 64454; -. [Q5T4F4-3] DR ProteomicsDB; 64455; -. [Q5T4F4-4] DR ProteomicsDB; 64456; -. [Q5T4F4-5] DR Pumba; Q5T4F4; -. DR Antibodypedia; 17359; 213 antibodies from 25 providers. DR DNASU; 118813; -. DR Ensembl; ENST00000337540.11; ENSP00000337993.7; ENSG00000155256.18. [Q5T4F4-8] DR Ensembl; ENST00000357540.8; ENSP00000350148.4; ENSG00000155256.18. [Q5T4F4-5] DR Ensembl; ENST00000359980.5; ENSP00000353069.3; ENSG00000155256.18. [Q5T4F4-2] DR Ensembl; ENST00000370610.7; ENSP00000359642.3; ENSG00000155256.18. [Q5T4F4-7] DR Ensembl; ENST00000370613.7; ENSP00000359646.3; ENSG00000155256.18. [Q5T4F4-6] DR Ensembl; ENST00000393677.8; ENSP00000377282.3; ENSG00000155256.18. [Q5T4F4-1] DR Ensembl; ENST00000423811.3; ENSP00000409594.2; ENSG00000155256.18. [Q5T4F4-3] DR Ensembl; ENST00000684270.1; ENSP00000506975.1; ENSG00000155256.18. [Q5T4F4-1] DR GeneID; 118813; -. DR KEGG; hsa:118813; -. DR MANE-Select; ENST00000684270.1; ENSP00000506975.1; NM_001385875.1; NP_001372804.1. DR UCSC; uc001kol.3; human. [Q5T4F4-1] DR AGR; HGNC:26559; -. DR CTD; 118813; -. DR DisGeNET; 118813; -. DR GeneCards; ZFYVE27; -. DR HGNC; HGNC:26559; ZFYVE27. DR HPA; ENSG00000155256; Low tissue specificity. DR MalaCards; ZFYVE27; -. DR MIM; 610243; gene. DR MIM; 610244; phenotype. DR neXtProt; NX_Q5T4F4; -. DR OpenTargets; ENSG00000155256; -. DR PharmGKB; PA134863310; -. DR VEuPathDB; HostDB:ENSG00000155256; -. DR eggNOG; ENOG502QVKC; Eukaryota. DR GeneTree; ENSGT00390000013298; -. DR HOGENOM; CLU_060341_0_0_1; -. DR InParanoid; Q5T4F4; -. DR OMA; FLLRWKM; -. DR OrthoDB; 38671at2759; -. DR PhylomeDB; Q5T4F4; -. DR TreeFam; TF331044; -. DR PathwayCommons; Q5T4F4; -. DR SignaLink; Q5T4F4; -. DR BioGRID-ORCS; 118813; 18 hits in 1157 CRISPR screens. DR ChiTaRS; ZFYVE27; human. DR EvolutionaryTrace; Q5T4F4; -. DR GenomeRNAi; 118813; -. DR Pharos; Q5T4F4; Tbio. DR PRO; PR:Q5T4F4; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q5T4F4; Protein. DR Bgee; ENSG00000155256; Expressed in pancreatic ductal cell and 143 other cell types or tissues. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0071782; C:endoplasmic reticulum tubular network; IDA:UniProtKB. DR GO; GO:0032584; C:growth cone membrane; ISS:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB. DR GO; GO:0071787; P:endoplasmic reticulum tubular network formation; IMP:UniProtKB. DR GO; GO:0031175; P:neuron projection development; IDA:UniProtKB. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0045773; P:positive regulation of axon extension; ISS:UniProtKB. DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB. DR GO; GO:0016192; P:vesicle-mediated transport; IDA:UniProtKB. DR CDD; cd15723; FYVE_protrudin; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR042405; Protrudin. DR InterPro; IPR000306; Znf_FYVE. DR InterPro; IPR017455; Znf_FYVE-rel. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR14543; PROTRUDIN; 1. DR PANTHER; PTHR14543:SF1; PROTRUDIN; 1. DR Pfam; PF01363; FYVE; 1. DR SMART; SM00064; FYVE; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1. DR PROSITE; PS50178; ZF_FYVE; 1. DR Genevisible; Q5T4F4; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cell projection; KW Disease variant; Endoplasmic reticulum; Endosome; KW Hereditary spastic paraplegia; Membrane; Metal-binding; Neurodegeneration; KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix; KW Zinc; Zinc-finger. FT CHAIN 1..411 FT /note="Protrudin" FT /id="PRO_0000245601" FT TOPO_DOM 1..66 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23969831" FT TRANSMEM 67..87 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 88 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:23969831" FT TRANSMEM 89..109 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 110..187 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23969831" FT INTRAMEM 188..208 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 209..411 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23969831" FT ZN_FING 344..410 FT /note="FYVE-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT REGION 1..205 FT /note="Sufficient for localization to endoplasmic reticulum FT tubular network and for interactions with REEP1, REEP5, FT ATL1, ATL2, ATL3 and SPAST" FT /evidence="ECO:0000269|PubMed:23969831, FT ECO:0000269|PubMed:24668814" FT REGION 1..92 FT /note="Sufficient for homooligomerization" FT /evidence="ECO:0000269|PubMed:23969831" FT REGION 1..27 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 51..64 FT /note="Necessary for interaction with RAB11A and function FT in neurite outgrowth" FT /evidence="ECO:0000269|PubMed:17082457" FT REGION 234..286 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 271..361 FT /note="Necessary for interaction with KIF5A" FT /evidence="ECO:0000269|PubMed:21976701" FT REGION 286..292 FT /note="Necessary for interaction with VAPA and function in FT cell projections formation" FT BINDING 350 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 353 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 366 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 369 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 374 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 377 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 402 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 405 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT VAR_SEQ 1..98 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045265" FT VAR_SEQ 1..68 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019751" FT VAR_SEQ 58..89 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046051" FT VAR_SEQ 66..152 FT /note="RWQMPLCSLLTCLGLNVLFLTLNEGAWYSVGALMISVPALLGYLQEVCRARL FT PDSELMRRKYHSVRQEDLQRGRLSRPEAVAEVKSF -> S (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019752" FT VAR_SEQ 67..184 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045266" FT VAR_SEQ 268 FT /note="E -> ESLSSQ (in isoform 3, isoform 4 and isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17974005" FT /id="VSP_019753" FT VAR_SEQ 294..300 FT /note="Missing (in isoform 2, isoform 4, isoform 5, isoform FT 6, isoform 7 and isoform 8)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019754" FT VAR_SEQ 349..356 FT /note="NCTGCSAT -> VTGAGSS (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019755" FT VAR_SEQ 357..411 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019756" FT VARIANT 82 FT /note="V -> I (in dbSNP:rs17108378)" FT /id="VAR_027002" FT VARIANT 138 FT /note="G -> V (in dbSNP:rs10882993)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005" FT /id="VAR_027003" FT VARIANT 191 FT /note="G -> V (in SPG33; no effect on its function in the FT regulation of ER morphology and stability, no effect on its FT localization to ER but according to PubMed:16826525 an FT aberrant subcellular localization to cell membrane seen, FT altered interaction with SPAST, increased susceptibility to FT ER stress, no effect on its interaction with REEP1, REEP5 FT and ATL1 and increased protein stability; FT dbSNP:rs35077384)" FT /evidence="ECO:0000269|PubMed:16826525, FT ECO:0000269|PubMed:18606302, ECO:0000269|PubMed:23969831, FT ECO:0000269|PubMed:24668814" FT /id="VAR_027269" FT MUTAGEN 13 FT /note="L->A: Alters interaction with RAB11A; when FT associated with A-49." FT /evidence="ECO:0000269|PubMed:17082457" FT MUTAGEN 49 FT /note="I->A: Alters interaction with RAB11A; when FT associated with A-13." FT /evidence="ECO:0000269|PubMed:17082457" FT MUTAGEN 289 FT /note="D->A: Loss of interaction with VAPA and loss of FT function in cell projections formation." FT /evidence="ECO:0000269|PubMed:19289470" FT CONFLICT 50 FT /note="Y -> N (in Ref. 3; AAH30621)" FT /evidence="ECO:0000305" FT CONFLICT 218 FT /note="E -> G (in Ref. 1; BAC11260)" FT /evidence="ECO:0000305" FT CONFLICT 222 FT /note="V -> F (in Ref. 1; BAH13112)" FT /evidence="ECO:0000305" FT CONFLICT 340 FT /note="K -> R (in Ref. 1; BAH13112)" FT /evidence="ECO:0000305" FT CONFLICT 387 FT /note="M -> A (in Ref. 1; BAH13112)" FT /evidence="ECO:0000305" FT STRAND 351..353 FT /evidence="ECO:0007829|PDB:1X4U" FT STRAND 359..361 FT /evidence="ECO:0007829|PDB:1X4U" FT STRAND 367..369 FT /evidence="ECO:0007829|PDB:1X4U" FT TURN 375..377 FT /evidence="ECO:0007829|PDB:1X4U" FT STRAND 380..382 FT /evidence="ECO:0007829|PDB:1X4U" FT TURN 385..387 FT /evidence="ECO:0007829|PDB:1X4U" FT STRAND 399..401 FT /evidence="ECO:0007829|PDB:1X4U" FT HELIX 403..410 FT /evidence="ECO:0007829|PDB:1X4U" SQ SEQUENCE 411 AA; 45843 MW; 5B86C64A398033D2 CRC64; MQTSEREGSG PELSPSVMPE APLESPPFPT KSPAFDLFNL VLSYKRLEIY LEPLKDAGDG VRYLLRWQMP LCSLLTCLGL NVLFLTLNEG AWYSVGALMI SVPALLGYLQ EVCRARLPDS ELMRRKYHSV RQEDLQRGRL SRPEAVAEVK SFLIQLEAFL SRLCCTCEAA YRVLHWENPV VSSQFYGALL GTVCMLYLLP LCWVLTLLNS TLFLGNVEFF RVVSEYRASL QQRMNPKQEE HAFESPPPPD VGGKDGLMDS TPALTPTEDL TPGSVEEAEE AEPDEEFKDA IEETHLVVLE DDEGAPCPAE DELALQDNGF LSKNEVLRSK VSRLTERLRK RYPTNNFGNC TGCSATFSVL KKRRSCSNCG NSFCSRCCSF KVPKSSMGAT APEAQRETVF VCASCNQTLS K //