ZFY27_HUMAN
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 03-AUG-2022, entry version 164.
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};
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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. [Q5T4F4-3]
DR RefSeq; XP_005269560.1; XM_005269503.3. [Q5T4F4-3]
DR RefSeq; XP_005269561.1; XM_005269504.3. [Q5T4F4-1]
DR RefSeq; XP_005269563.1; XM_005269506.3. [Q5T4F4-2]
DR PDB; 1X4U; NMR; -; A=341-411.
DR PDBsum; 1X4U; -.
DR AlphaFoldDB; Q5T4F4; -.
DR BMRB; Q5T4F4; -.
DR SMR; Q5T4F4; -.
DR BioGRID; 125623; 64.
DR CORUM; Q5T4F4; -.
DR DIP; DIP-61530N; -.
DR ELM; Q5T4F4; -.
DR IntAct; Q5T4F4; 52.
DR STRING; 9606.ENSP00000377282; -.
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; Q5T4F4; -.
DR PeptideAtlas; Q5T4F4; -.
DR PRIDE; 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 Antibodypedia; 17359; 182 antibodies from 24 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 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; NEVAWFS; -.
DR OrthoDB; 1136113at2759; -.
DR PhylomeDB; Q5T4F4; -.
DR TreeFam; TF331044; -.
DR PathwayCommons; Q5T4F4; -.
DR SignaLink; Q5T4F4; -.
DR BioGRID-ORCS; 118813; 17 hits in 1080 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 141 other tissues.
DR Genevisible; Q5T4F4; HS.
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:0071782; C:endoplasmic reticulum tubular network; IDA:UniProtKB.
DR GO; GO:0032584; C:growth cone membrane; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA: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 Gene3D; 3.30.40.10; -; 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; PTHR14543; 1.
DR Pfam; PF01363; FYVE; 1.
DR SMART; SM00064; FYVE; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
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
