ZFY27_MOUSE
ID ZFY27_MOUSE Reviewed; 415 AA.
AC Q3TXX3; Q8CFP8;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Protrudin;
DE AltName: Full=Zinc finger FYVE domain-containing protein 27;
GN Name=Zfyve27;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Visual cortex;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH
RP VAPA; VAPB AND KIF5A, AND TISSUE SPECIFICITY.
RX PubMed=24251978; DOI=10.1111/gtc.12109;
RA Ohnishi T., Shirane M., Hashimoto Y., Saita S., Nakayama K.I.;
RT "Identification and characterization of a neuron-specific isoform of
RT protrudin.";
RL Genes Cells 19:97-111(2014).
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [5]
RP PHOSPHORYLATION.
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 [6]
RP FUNCTION, AND INTERACTION WITH RAB11A; RAB11B; SURF4; KIF5A; KIF5B AND
RP KIF5C.
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 [7]
RP SUBCELLULAR LOCATION, TOPOLOGY, 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 (By similarity).
CC Promotes axonal elongation and contributes to the establishment of
CC neuronal cell polarity (PubMed:24251978). Involved in nerve growth
CC factor-induced neurite formation in VAPA-dependent manner. Contributes
CC to both the formation and stabilization of the tubular ER network.
CC Involved in ER morphogenesis by regulating the sheet-to-tubule balance
CC and possibly the density of tubule interconnections (By similarity).
CC Acts as an adapter protein that facilitates the interaction of KIF5A
CC with VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 and the ZFYVE27-KIF5A
CC complex contributes to the transport of these proteins in neurons. Can
CC induce formation of neurite-like membrane protrusions in non-neuronal
CC cells in a KIF5A/B-dependent manner (PubMed:21976701).
CC {ECO:0000250|UniProtKB:Q5T4F4, ECO:0000269|PubMed:21976701,
CC ECO:0000269|PubMed:24251978}.
CC -!- SUBUNIT: Can form homooligomers (monomers, dimers and tetramers) (By
CC similarity). Interacts with RAB11A (GDP-bound form); regulates RAB11A
CC (PubMed:21976701). Interacts with FKBP8; may negatively regulate
CC ZFYVE27 phosphorylation (By similarity). Isoform 1 interacts to a
CC greater extent than isoform 2 with VAPB (via MSP domain). Isoform 1
CC interacts to a greater extent than isoform 2 with VAPA (via MSP domain)
CC (PubMed:24251978). Interaction with VAPA may regulate ZFYVE27 retention
CC in the endoplasmic reticulum and its function in cell projections
CC formation. Interacts with ATL2, ATL3, SPAST and RTN3 (By similarity).
CC Interacts with REEP1, REEP5 and ATL1 (PubMed:24668814). Interacts with
CC RAB11B (GDP-bound form), SURF4, KIF5B and KIF5C (PubMed:21976701).
CC Isoform 1 and 2 interact with KIFA (PubMed:21976701, PubMed:24251978).
CC {ECO:0000250|UniProtKB:Q5T4F4, ECO:0000269|PubMed:21976701,
CC ECO:0000269|PubMed:24251978, ECO:0000269|PubMed:24668814}.
CC -!- SUBCELLULAR LOCATION: Recycling endosome membrane
CC {ECO:0000305|PubMed:17082457}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:17082457}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:24668814}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:24668814}. Cell projection, growth cone membrane
CC {ECO:0000269|PubMed:17082457}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localizes at both dendrites and axons
CC (PubMed:17082457). Localizes to endoplasmic reticulum tubular network.
CC {ECO:0000269|PubMed:17082457, ECO:0000269|PubMed:24668814}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Protrudin-L {ECO:0000303|PubMed:24251978};
CC IsoId=Q3TXX3-1; Sequence=Displayed;
CC Name=2; Synonyms=Protrudin-S {ECO:0000303|PubMed:24251978};
CC IsoId=Q3TXX3-2; Sequence=VSP_019757;
CC -!- TISSUE SPECIFICITY: Astrocytes express both isoform 1 and isoform 2 and
CC oligodendrocytes express only isoform 2 (at protein level). Isoform 1
CC is expressed specifically in the central nervous system and selectively
CC in neuronal cells. Isoform 2 is expressed in cerebrum, cerebellum,
CC spinal cord, heart, thymus, spleen, intestine and lung.
CC {ECO:0000269|PubMed:17082457, ECO:0000269|PubMed:24251978}.
CC -!- PTM: Phosphorylated. Phosphorylation is induced by NGF through the
CC MAPK/ERK pathway and modulates interaction with RAB11A (Probable).
CC {ECO:0000305|PubMed:18459960}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH42595.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK159065; BAE34791.1; -; mRNA.
DR EMBL; BC042595; AAH42595.1; ALT_INIT; mRNA.
DR CCDS; CCDS29825.2; -. [Q3TXX3-1]
DR CCDS; CCDS50440.1; -. [Q3TXX3-2]
DR RefSeq; NP_001158003.1; NM_001164531.1. [Q3TXX3-2]
DR RefSeq; NP_796293.2; NM_177319.3. [Q3TXX3-1]
DR AlphaFoldDB; Q3TXX3; -.
DR SMR; Q3TXX3; -.
DR CORUM; Q3TXX3; -.
DR IntAct; Q3TXX3; 1.
DR STRING; 10090.ENSMUSP00000130684; -.
DR iPTMnet; Q3TXX3; -.
DR PhosphoSitePlus; Q3TXX3; -.
DR EPD; Q3TXX3; -.
DR MaxQB; Q3TXX3; -.
DR PaxDb; Q3TXX3; -.
DR PeptideAtlas; Q3TXX3; -.
DR PRIDE; Q3TXX3; -.
DR ProteomicsDB; 299557; -. [Q3TXX3-1]
DR ProteomicsDB; 299558; -. [Q3TXX3-2]
DR Antibodypedia; 17359; 182 antibodies from 24 providers.
DR DNASU; 319740; -.
DR Ensembl; ENSMUST00000099443; ENSMUSP00000097042; ENSMUSG00000018820. [Q3TXX3-2]
DR Ensembl; ENSMUST00000169536; ENSMUSP00000130684; ENSMUSG00000018820. [Q3TXX3-1]
DR GeneID; 319740; -.
DR KEGG; mmu:319740; -.
DR UCSC; uc008hnj.2; mouse. [Q3TXX3-2]
DR UCSC; uc012blu.1; mouse. [Q3TXX3-1]
DR CTD; 118813; -.
DR MGI; MGI:1919602; Zfyve27.
DR VEuPathDB; HostDB:ENSMUSG00000018820; -.
DR eggNOG; ENOG502QVKC; Eukaryota.
DR GeneTree; ENSGT00390000013298; -.
DR HOGENOM; CLU_060341_0_0_1; -.
DR InParanoid; Q3TXX3; -.
DR OMA; NEVAWFS; -.
DR OrthoDB; 1136113at2759; -.
DR PhylomeDB; Q3TXX3; -.
DR TreeFam; TF331044; -.
DR BioGRID-ORCS; 319740; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Zfyve27; mouse.
DR PRO; PR:Q3TXX3; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q3TXX3; protein.
DR Bgee; ENSMUSG00000018820; Expressed in granulocyte and 253 other tissues.
DR ExpressionAtlas; Q3TXX3; baseline and differential.
DR Genevisible; Q3TXX3; MM.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0071782; C:endoplasmic reticulum tubular network; IDA:UniProtKB.
DR GO; GO:0032584; C:growth cone membrane; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
DR GO; GO:0071787; P:endoplasmic reticulum tubular network formation; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045773; P:positive regulation of axon extension; IMP: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 Alternative splicing; Cell membrane; Cell projection;
KW Endoplasmic reticulum; Endosome; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Zinc; Zinc-finger.
FT CHAIN 1..415
FT /note="Protrudin"
FT /id="PRO_0000245602"
FT TOPO_DOM 1..66
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24668814"
FT TRANSMEM 67..87
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 88
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:24668814"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 110..192
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24668814"
FT INTRAMEM 193..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..415
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24668814"
FT ZN_FING 348..414
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 1..210
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:0000250|UniProtKB:Q5T4F4"
FT REGION 1..92
FT /note="Sufficient for homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:Q5T4F4"
FT REGION 1..24
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:0000250"
FT REGION 254..290
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..365
FT /note="Necessary for interaction with KIF5A"
FT /evidence="ECO:0000250|UniProtKB:Q5T4F4"
FT REGION 290..296
FT /note="Necessary for interaction with VAPA"
FT /evidence="ECO:0000250"
FT BINDING 354
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 357
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 370
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 373
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 409
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT VAR_SEQ 297..303
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:24251978"
FT /id="VSP_019757"
FT CONFLICT 41
FT /note="V -> A (in Ref. 1; BAE34791)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 415 AA; 46202 MW; EC11945BFEDC76D5 CRC64;
MQTSDRDLSG PEASPSGMPE VLSECPPAPT KSAAFDLFNL VLSYKRLEIY LEPLKDAGDG
VRYLLRWQMP LCSLLTCLGL NILFLTLNEG AWYSMGALMI SVPALLGYLQ EVCRGQLPES
ELMRRKYHSI RQEDLQRVRL SRVHLSRPEA VAEVKSFLIQ LEAFLARLCY TCESAYRVLH
WENPVVSSQF YGALLGMVCM LYLLPLCWVL ALLNSTLFLG NGDFFRVVCE YRACLQRRMN
PRQEECACES SALQGAGGRG LLDSSPAPTP TEDLTPGSVE EAEEAEPDEE FKDAIEETHL
VVLEDEEGTP CPAEDELTLQ DNGFLSKNEV LRSKVSRLTE RLRKRYPTNN FGNCAGCAAT
FSVLKKRRSC SNCGNSFCSR CCSFKVPRSS MGATAPEAQR ETVCVCASCN QTLSK
