COMM_DROME
ID COMM_DROME Reviewed; 370 AA.
AC Q24139; Q9VUT9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Protein commissureless 1 {ECO:0000305};
DE AltName: Full=Protein commissureless {ECO:0000305};
GN Name=comm {ECO:0000312|FlyBase:FBgn0010105};
GN ORFNames=CG17943 {ECO:0000312|FlyBase:FBgn0010105};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8785048; DOI=10.1016/s0896-6273(00)80070-7;
RA Tear G., Harris R., Sutaria S., Kilomanski K., Goodman C.S., Seeger M.A.;
RT "Commissureless controls growth cone guidance across the CNS midline in
RT Drosophila and encodes a novel membrane protein.";
RL Neuron 16:501-514(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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 [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
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 [4]
RP FUNCTION, INTERACTION WITH NEDD4 AND ROBO, DOMAIN, UBIQUITINATION,
RP MUTAGENESIS OF PRO-221; TYR-223; PRO-230 AND TYR-232, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12165468; DOI=10.1016/s0896-6273(02)00795-x;
RA Myat A., Henry P., McCabe V., Flintoft L., Rotin D., Tear G.;
RT "Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to
RT control cell surface levels of the roundabout receptor.";
RL Neuron 35:447-459(2002).
RN [5]
RP FUNCTION, LACK OF UBIQUITINATION, AND SUBCELLULAR LOCATION.
RX PubMed=15657595; DOI=10.1038/nn1388;
RA Keleman K., Ribeiro C., Dickson B.J.;
RT "Comm function in commissural axon guidance: cell-autonomous sorting of
RT Robo in vivo.";
RL Nat. Neurosci. 8:156-163(2005).
RN [6]
RP STRUCTURE BY NMR OF 227-237 IN COMPLEX WITH NEDD4 WW2 DOMAIN.
RX PubMed=16531238; DOI=10.1016/j.str.2005.11.018;
RA Kanelis V., Bruce M.C., Skrynnikov N.R., Rotin D., Forman-Kay J.D.;
RT "Structural determinants for high-affinity binding in a Nedd4 WW3* domain-
RT Comm PY motif complex.";
RL Structure 14:543-553(2006).
CC -!- FUNCTION: Controls axon guidance across the CNS midline by preventing
CC the delivery of Robo to the growth cone. {ECO:0000269|PubMed:12165468,
CC ECO:0000269|PubMed:15657595}.
CC -!- SUBUNIT: Interacts (probably via PY-motifs) with Nedd4 (via WW2 domain)
CC (PubMed:12165468, PubMed:16531238). Interacts with Robo
CC (PubMed:12165468). {ECO:0000269|PubMed:12165468,
CC ECO:0000269|PubMed:16531238}.
CC -!- INTERACTION:
CC Q24139; Q9VVI3: Nedd4; NbExp=3; IntAct=EBI-118294, EBI-498113;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000305}. Cell membrane
CC {ECO:0000305}; Single-pass membrane protein {ECO:0000305}.
CC -!- DOMAIN: The cytoplasmic domain is required for function in axon
CC guidance. {ECO:0000269|PubMed:12165468}.
CC -!- PTM: Ubiquitinated by Nedd4; which promotes endocytosis of the
CC comm/robo complex and comm proteasomal degradation (PubMed:12165468).
CC Not ubiquitinated by Nedd4 (PubMed:15657595).
CC {ECO:0000269|PubMed:12165468, ECO:0000269|PubMed:15657595}.
CC -!- SIMILARITY: Belongs to the commissureless family. {ECO:0000305}.
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DR EMBL; U35854; AAC47019.1; -; mRNA.
DR EMBL; AE014296; AAF49584.1; -; Genomic_DNA.
DR RefSeq; NP_001261891.1; NM_001274962.1.
DR RefSeq; NP_524095.1; NM_079371.4.
DR PDB; 2EZ5; NMR; -; P=227-237.
DR PDBsum; 2EZ5; -.
DR AlphaFoldDB; Q24139; -.
DR SMR; Q24139; -.
DR BioGRID; 65032; 16.
DR DIP; DIP-22799N; -.
DR IntAct; Q24139; 2.
DR STRING; 7227.FBpp0305237; -.
DR PaxDb; Q24139; -.
DR PRIDE; Q24139; -.
DR DNASU; 39717; -.
DR EnsemblMetazoa; FBtr0075579; FBpp0075332; FBgn0010105.
DR EnsemblMetazoa; FBtr0333023; FBpp0305237; FBgn0010105.
DR GeneID; 39717; -.
DR KEGG; dme:Dmel_CG17943; -.
DR UCSC; CG17943-RA; d. melanogaster.
DR CTD; 39717; -.
DR FlyBase; FBgn0010105; comm.
DR VEuPathDB; VectorBase:FBgn0010105; -.
DR eggNOG; ENOG502TFH7; Eukaryota.
DR HOGENOM; CLU_732109_0_0_1; -.
DR InParanoid; Q24139; -.
DR OMA; TPAICIN; -.
DR OrthoDB; 1082370at2759; -.
DR PhylomeDB; Q24139; -.
DR SignaLink; Q24139; -.
DR BioGRID-ORCS; 39717; 0 hits in 1 CRISPR screen.
DR EvolutionaryTrace; Q24139; -.
DR GenomeRNAi; 39717; -.
DR PRO; PR:Q24139; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0010105; Expressed in crop (Drosophila) and 66 other tissues.
DR ExpressionAtlas; Q24139; baseline and differential.
DR Genevisible; Q24139; DM.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0030139; C:endocytic vesicle; IDA:FlyBase.
DR GO; GO:0005794; C:Golgi apparatus; IDA:FlyBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; IDA:FlyBase.
DR GO; GO:0031902; C:late endosome membrane; IDA:FlyBase.
DR GO; GO:0005765; C:lysosomal membrane; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:FlyBase.
DR GO; GO:0048495; F:Roundabout binding; IPI:FlyBase.
DR GO; GO:0050699; F:WW domain binding; IDA:FlyBase.
DR GO; GO:0007411; P:axon guidance; IMP:FlyBase.
DR GO; GO:0016199; P:axon midline choice point recognition; IMP:UniProtKB.
DR GO; GO:0070983; P:dendrite guidance; IMP:FlyBase.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase.
DR GO; GO:0006897; P:endocytosis; TAS:FlyBase.
DR GO; GO:0090160; P:Golgi to lysosome transport; IDA:FlyBase.
DR GO; GO:0007399; P:nervous system development; TAS:FlyBase.
DR GO; GO:0008038; P:neuron recognition; IMP:FlyBase.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IMP:FlyBase.
DR GO; GO:0031623; P:receptor internalization; IDA:UniProtKB.
DR GO; GO:0050773; P:regulation of dendrite development; IMP:FlyBase.
DR GO; GO:0007416; P:synapse assembly; IMP:FlyBase.
DR DisProt; DP01366; -.
DR InterPro; IPR031878; Commissureless.
DR Pfam; PF15957; Comm; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasmic vesicle; Developmental protein;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..370
FT /note="Protein commissureless 1"
FT /id="PRO_0000090013"
FT TOPO_DOM 1..136
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 158..370
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 108..131
FT /note="Required for vesicular localization"
FT REGION 227..237
FT /note="Interaction with Nedd4"
FT /evidence="ECO:0000269|PubMed:16531238"
FT REGION 287..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 220..223
FT /note="PY-motif 1"
FT /evidence="ECO:0000269|PubMed:12165468"
FT MOTIF 229..232
FT /note="PY-motif 2"
FT /evidence="ECO:0000269|PubMed:12165468"
FT COMPBIAS 291..312
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 221
FT /note="P->A: Abolishes interaction with Nedd4,
FT ubiquitination and internalization; when associated with A-
FT 230."
FT /evidence="ECO:0000269|PubMed:12165468"
FT MUTAGEN 223
FT /note="Y->A: No effect on interaction with Nedd4."
FT /evidence="ECO:0000269|PubMed:12165468"
FT MUTAGEN 230
FT /note="P->A: Abolishes interaction with Nedd4,
FT ubiquitination and internalization; when associated with A-
FT 221."
FT /evidence="ECO:0000269|PubMed:12165468"
FT MUTAGEN 232
FT /note="Y->A: No effect on interaction with Nedd4."
FT /evidence="ECO:0000269|PubMed:12165468"
SQ SEQUENCE 370 AA; 40311 MW; EB298EA415D4FBDA CRC64;
MISTTDYPTV ETTTTAEELY AEYISAPASS MSPAAIAEHL QQNQITFEIP SAHDLRHIDA
LNSFNALLQR IGNAAVSYDP APPSGWSPDG SISTEQLSKS VVLDLADLRD RSEESGESSW
WSQIFGDADM HVIINYLWIG VVSSLVILSL VFILFSCYFY RKFRTWKKCN KDIRAQIHAA
SDSYSSHLVG CDASRLLLHQ QMQHPHHRSS EAGFYQIESP PCYTIATGLP SYDEALHHQP
RHFAYGMKFV YPSLAAVHHH HHCISNWEKQ EPLNKLQKCK LSAAAAVEED KADSSSSTSA
SASPSSSESS NLATATPAIC INMPSGRQDE EVDNSDSDSA IAVAVAVAQS LQPAAPADDD
CASLVVVVAA
