CL16A_DROME
ID CL16A_DROME Reviewed; 1067 AA.
AC Q9VEV4; Q5BIH5; Q8MRD4;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Protein CLEC16A homolog {ECO:0000305};
DE AltName: Full=Endosomal maturation defective protein {ECO:0000303|PubMed:22493244};
GN Name=ema {ECO:0000312|FlyBase:FBgn0038427};
GN ORFNames=CG12753 {ECO:0000312|FlyBase:FBgn0038427};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAM51979.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM51979.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAM51979.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000312|EMBL:AAX33397.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAX33397.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAX33397.1};
RA Stapleton M., Carlson J., Chavez C., Frise E., George R., Pacleb J.,
RA Park S., Wan K., Yu C., Rubin G.M., Celniker S.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH CAR; DOR AND VPS16A, SUBCELLULAR LOCATION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=20194640; DOI=10.1083/jcb.200911126;
RA Kim S., Wairkar Y.P., Daniels R.W., DiAntonio A.;
RT "The novel endosomal membrane protein Ema interacts with the class C Vps-
RT HOPS complex to promote endosomal maturation.";
RL J. Cell Biol. 188:717-734(2010).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=22493244; DOI=10.1073/pnas.1120320109;
RA Kim S., Naylor S.A., DiAntonio A.;
RT "Drosophila Golgi membrane protein Ema promotes autophagosomal growth and
RT function.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E1072-E1081(2012).
CC -!- FUNCTION: Required for mitophagy, autophagy and endosome maturation,
CC possibly by acting in multiple membrane trafficking pathways
CC (PubMed:20194640, PubMed:22493244). Required for endosome trafficking
CC and maturation (PubMed:20194640). Functions with the class C Vps-HOPS
CC complex member Vps16a to promote endosomal maturation into degradative
CC late endosomes and lysosomes (PubMed:20194640). In response to
CC starvation, functions at an early stage of autophagy to promote
CC autophagosome growth and efficient autophagy (PubMed:22493244).
CC Essential for the recruitment of lva-positive Golgi elements to
CC autophagosomes (PubMed:22493244). Likely to function by promoting
CC membrane traffic from the Golgi complex to the developing
CC autophagosomes (PubMed:22493244). Also regulates synaptic growth at the
CC neuromuscular junctions (NMJ) by down-regulating BMP signaling
CC (PubMed:20194640). {ECO:0000269|PubMed:20194640,
CC ECO:0000269|PubMed:22493244}.
CC -!- SUBUNIT: Interacts with the class C Vps-HOPS complex components; Car,
CC Dor and Vps16a. {ECO:0000269|PubMed:20194640}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome membrane
CC {ECO:0000269|PubMed:22493244}; Single-pass membrane protein
CC {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:20194640};
CC Single-pass membrane protein {ECO:0000269|PubMed:20194640}. Golgi
CC apparatus membrane {ECO:0000269|PubMed:22493244}; Single-pass membrane
CC protein {ECO:0000255}. Note=Under normal conditions detected in small
CC punctate structures throughout the cytosol of fat body cells, upon
CC induction of autophagy by starvation becomes localized to the outer
CC membrane surface of autophagosomes. Not detected in the Golgi of
CC Garland cells. {ECO:0000269|PubMed:22493244}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A {ECO:0000312|FlyBase:FBgn0038427};
CC IsoId=Q9VEV4-1; Sequence=Displayed;
CC Name=B {ECO:0000312|FlyBase:FBgn0038427};
CC IsoId=Q9VEV4-2; Sequence=VSP_059009;
CC -!- DISRUPTION PHENOTYPE: Pupal lethal (PubMed:20194640). Larval
CC neuromuscular junctions (NMJ) display an increase in synaptic bouton
CC number and synaptic area (PubMed:20194640). In Garland cells endosome
CC trafficking is impaired (PubMed:20194640). Early and late endosomes are
CC unable to progress into mature degradative endosomes and lysosomes
CC resulting in enlarged endosomal compartments (PubMed:20194640). In
CC larvae, starvation-induced autophagosomes are significantly decreased
CC in size (PubMed:22493244). However, autophagosomes are able to form and
CC can mature via fusion with endosomes and lysosomes (PubMed:22493244).
CC {ECO:0000269|PubMed:20194640, ECO:0000269|PubMed:22493244}.
CC -!- SIMILARITY: Belongs to the CLEC16A/gop-1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM51979.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AE014297; AAF55313.2; -; Genomic_DNA.
DR EMBL; AE014297; ABC66179.1; -; Genomic_DNA.
DR EMBL; AY121652; AAM51979.1; ALT_FRAME; mRNA.
DR EMBL; BT021249; AAX33397.1; -; mRNA.
DR RefSeq; NP_001034058.1; NM_001038969.2. [Q9VEV4-2]
DR RefSeq; NP_650542.1; NM_142285.2. [Q9VEV4-1]
DR AlphaFoldDB; Q9VEV4; -.
DR IntAct; Q9VEV4; 1.
DR STRING; 7227.FBpp0082766; -.
DR PaxDb; Q9VEV4; -.
DR PRIDE; Q9VEV4; -.
DR EnsemblMetazoa; FBtr0083315; FBpp0082766; FBgn0038427. [Q9VEV4-1]
DR EnsemblMetazoa; FBtr0100643; FBpp0100104; FBgn0038427. [Q9VEV4-2]
DR GeneID; 41992; -.
DR KEGG; dme:Dmel_CG12753; -.
DR UCSC; CG12753-RA; d. melanogaster. [Q9VEV4-1]
DR UCSC; CG12753-RB; d. melanogaster.
DR CTD; 107924; -.
DR FlyBase; FBgn0038427; ema.
DR VEuPathDB; VectorBase:FBgn0038427; -.
DR eggNOG; KOG2219; Eukaryota.
DR GeneTree; ENSGT00390000013826; -.
DR InParanoid; Q9VEV4; -.
DR OMA; FMFDDHI; -.
DR PhylomeDB; Q9VEV4; -.
DR BioGRID-ORCS; 41992; 0 hits in 1 CRISPR screen.
DR ChiTaRS; heph; fly.
DR GenomeRNAi; 41992; -.
DR PRO; PR:Q9VEV4; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0038427; Expressed in oviduct (Drosophila) and 25 other tissues.
DR ExpressionAtlas; Q9VEV4; baseline and differential.
DR Genevisible; Q9VEV4; DM.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0036020; C:endolysosome membrane; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:FlyBase.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:FlyBase.
DR GO; GO:0005770; C:late endosome; IDA:FlyBase.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031267; F:small GTPase binding; IPI:FlyBase.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0016197; P:endosomal transport; IGI:FlyBase.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:FlyBase.
DR GO; GO:1901096; P:regulation of autophagosome maturation; IBA:GO_Central.
DR InterPro; IPR039272; CLEC16A/TT9.
DR InterPro; IPR019155; CLEC16A/TT9_N.
DR InterPro; IPR045820; CLEC16A_C.
DR PANTHER; PTHR21481; PTHR21481; 1.
DR Pfam; PF19439; CLEC16A_C; 2.
DR Pfam; PF09758; FPL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasmic vesicle; Endosome;
KW Golgi apparatus; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1067
FT /note="Protein CLEC16A homolog"
FT /id="PRO_0000440899"
FT TRANSMEM 333..353
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 50..199
FT /note="FPL"
FT /evidence="ECO:0000255"
FT REGION 409..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 837..861
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 876..993
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1037..1067
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..432
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 837..860
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 877..892
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 928..955
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 956..972
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 973..992
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 895..963
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_059009"
FT CONFLICT 541
FT /note="S -> P (in Ref. 3; AAM51979)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1067 AA; 119367 MW; E325AA430AA57394 CRC64;
MFRSRSWFGG PWGGRPKNRL SLEHLKYLYS ILEKNTTVSE SNRGLLVESL RCIAEILIWG
DQHDSLVFDF FLEKNMLSYF LHIMRQKSGG SSFVCVQLLQ TLNILFENIR NETSLYYLLS
NNHVNSIMVH KFDFSDEDVM GYYILFLKTL SLKLNTHTIH FFYNEHTNDF PLYTEAIKFF
NHPESMVRIA VRTISLNVYK VQNPSMLRFI RDKTAAPYFS NLVWFIGKHI LELDTCVRTD
IDHQSNQKLS NLVAEHLDHL HYLSDILLLE IKDLNAVLTE HLLHKLFVPL YIFSLTPAPP
PPSLAVVTQN LAAVLNRNVD IDIQEMHNPR VSSIVALFLL SLVFLVVSHA PLVHALAWVI
LNGDHSVFKE GAAEILNSYV EHREVVVPGF GEPDESLEQA LDTVTGQSSS SSYALSEDSG
VESSSPATTE LDSQADAVEA EQIKLRNITD EEKQLLQKSS SSTKADFAEM AKPFLDTVLH
ALDCTENDYL ALLSLCLIYA MSHNRGIKNE WFEQVLAKST RGAFSYKTAL IEHLLNIITQ
SSQPSSRIRL ITVEIALELL VTFTRPSSDD SRCITAAQQD LLFSARNQSM VVIRNFYKSE
DIFLDLFEDE YNEMRKAQLN VEFLCMDSTI LLPPTGTPLT GINFTRRLPC GEVEKARRAI
RVYFLLRRTC QKFLNEKESL LPLTNVVNLV QVENVLDLNN SDLIACTVVA KDSSKQRRFL
VIDALQLILV EPDAKLLGWG VAKFVGFLQD VEVQGDKDDS RCLHITVHRG GVTHNRTPLL
SAKFLFDDHI RCMAAKQRLT KGRSKARQKK MYQIAQLIEI PGQMDSPVYA VGGTMVASSS
GGSGNSSGSS SRSSHHRPMF STANRVPGFA AVLRGSNSAG VSRTQMAPNR SIEGIRNESA
GRSRRRSPSS TSGSNLRADH SDRERSPSVS MGSHSSSQSR ENSQPRSTGN RSRESSPRMP
RPRSEEIPLE DFQHSRNNSP HSRGNPSPAS RSHTPIRVLH YDQLSGHSGS PREASLGGTN
ALLSQLNGLN REVLPTQSSE ETSFIGSDGN EATGGSEGRR RGAIETV
