NIJA_DROME
ID NIJA_DROME Reviewed; 245 AA.
AC Q8MPP0; M9PHZ8; Q8MPN9; Q8SYI2; Q9VTB5;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Ninjurin-A {ECO:0000303|PubMed:16815999, ECO:0000303|Ref.1};
DE Short=dNINJ-A {ECO:0000303|PubMed:33472215};
DE Contains:
DE RecName: Full=Secreted ninjurin-A {ECO:0000305};
GN Name=NijA {ECO:0000303|PubMed:16815999, ECO:0000312|FlyBase:FBgn0036101};
GN Synonyms=ninA {ECO:0000303|Ref.1};
GN ORFNames=CG6449 {ECO:0000312|FlyBase:FBgn0036101};
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] (ISOFORMS A; B AND C).
RC STRAIN=Oregon-R; TISSUE=Epithelium, and Nervous system;
RA Garcia-Alonso L.A.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
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, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND INDUCTION.
RX PubMed=16815999; DOI=10.1101/gad.1426906;
RA Zhang S., Dailey G.M., Kwan E., Glasheen B.M., Sroga G.E., Page-McCaw A.;
RT "An MMP liberates the Ninjurin A ectodomain to signal a loss of cell
RT adhesion.";
RL Genes Dev. 20:1899-1910(2006).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=23028562; DOI=10.1371/journal.pone.0044567;
RA Broderick S., Wang X., Simms N., Page-McCaw A.;
RT "Drosophila Ninjurin A induces nonapoptotic cell death.";
RL PLoS ONE 7:e44567-e44567(2012).
RN [6]
RP FUNCTION.
RX PubMed=33472215; DOI=10.1038/s41586-021-03218-7;
RA Kayagaki N., Kornfeld O.S., Lee B.L., Stowe I.B., O'Rourke K., Li Q.,
RA Sandoval W., Yan D., Kang J., Xu M., Zhang J., Lee W.P., McKenzie B.S.,
RA Ulas G., Payandeh J., Roose-Girma M., Modrusan Z., Reja R., Sagolla M.,
RA Webster J.D., Cho V., Andrews T.D., Morris L.X., Miosge L.A., Goodnow C.C.,
RA Bertram E.M., Dixit V.M.;
RT "NINJ1 mediates plasma membrane rupture during lytic cell death.";
RL Nature 591:131-136(2021).
CC -!- FUNCTION: [Ninjurin-A]: Homophilic transmembrane adhesion molecule
CC involved in non-apoptotic necrotic cell death (PubMed:23028562).
CC Promotes cell adhesion by mediating homophilic interactions via its
CC extracellular region (By similarity). Probably involved in non-
CC apoptotic necrotic cell death by mediating plasma membrane rupture
CC (cytolysis), leading to release intracellular molecules that propagate
CC the inflammatory response (PubMed:33472215).
CC {ECO:0000250|UniProtKB:O70131, ECO:0000269|PubMed:23028562,
CC ECO:0000269|PubMed:33472215}.
CC -!- FUNCTION: [Secreted ninjurin-A]: Secreted form generated by cleavage,
CC which acts as a negative regulator of cell adhesion (PubMed:16815999).
CC Promotes the loss of cell adhesion in a cell non-autonomous manner
CC (PubMed:16815999). {ECO:0000269|PubMed:16815999}.
CC -!- SUBUNIT: [Ninjurin-A]: Homooligomer. {ECO:0000250|UniProtKB:Q92982}.
CC -!- SUBCELLULAR LOCATION: [Ninjurin-A]: Cell membrane
CC {ECO:0000269|PubMed:23028562, ECO:0000305|PubMed:16815999}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Secreted ninjurin-A]: Secreted
CC {ECO:0000269|PubMed:16815999}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=B; Synonyms=Alpha {ECO:0000303|Ref.1};
CC IsoId=Q8MPP0-1; Sequence=Displayed;
CC Name=D;
CC IsoId=Q8MPP0-2; Sequence=VSP_061060, VSP_061061;
CC Name=C; Synonyms=Beta {ECO:0000303|Ref.1};
CC IsoId=Q8MPP0-3; Sequence=VSP_061061;
CC Name=A; Synonyms=Gamma {ECO:0000303|Ref.1};
CC IsoId=Q8MPP0-4; Sequence=VSP_061060;
CC -!- INDUCTION: Up-regulated upon injury. {ECO:0000269|PubMed:16815999}.
CC -!- PTM: [Ninjurin-A]: Cleaved by Mmp1 protease to generate the Secreted
CC ninjurin-A form. {ECO:0000269|PubMed:16815999}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype; flies are viable and
CC fertile with no obvious developmental abnormalities.
CC {ECO:0000269|PubMed:23028562}.
CC -!- SIMILARITY: Belongs to the ninjurin family. {ECO:0000305}.
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DR EMBL; AJ428205; CAD21015.1; -; mRNA.
DR EMBL; AJ428206; CAD21016.1; -; mRNA.
DR EMBL; AJ428207; CAD21017.1; -; mRNA.
DR EMBL; AE014296; AAS65042.1; -; Genomic_DNA.
DR EMBL; AE014296; AAS65043.1; -; Genomic_DNA.
DR EMBL; AE014296; AGB94381.1; -; Genomic_DNA.
DR EMBL; AE014296; AAF50137.2; -; Genomic_DNA.
DR EMBL; AY071530; AAL49152.1; -; mRNA.
DR RefSeq; NP_001261687.1; NM_001274758.2. [Q8MPP0-2]
DR RefSeq; NP_648410.1; NM_140153.5. [Q8MPP0-4]
DR RefSeq; NP_996039.1; NM_206317.2. [Q8MPP0-3]
DR RefSeq; NP_996040.1; NM_206318.2. [Q8MPP0-1]
DR AlphaFoldDB; Q8MPP0; -.
DR IntAct; Q8MPP0; 1.
DR STRING; 7227.FBpp0089001; -.
DR GlyGen; Q8MPP0; 2 sites.
DR PaxDb; Q8MPP0; -.
DR PRIDE; Q8MPP0; -.
DR DNASU; 39215; -.
DR EnsemblMetazoa; FBtr0089569; FBpp0088536; FBgn0036101. [Q8MPP0-4]
DR EnsemblMetazoa; FBtr0089570; FBpp0089001; FBgn0036101. [Q8MPP0-1]
DR EnsemblMetazoa; FBtr0089571; FBpp0089002; FBgn0036101. [Q8MPP0-3]
DR EnsemblMetazoa; FBtr0331575; FBpp0303965; FBgn0036101. [Q8MPP0-2]
DR GeneID; 39215; -.
DR KEGG; dme:Dmel_CG6449; -.
DR UCSC; CG6449-RA; d. melanogaster.
DR UCSC; CG6449-RB; d. melanogaster. [Q8MPP0-1]
DR UCSC; CG6449-RC; d. melanogaster.
DR CTD; 39215; -.
DR FlyBase; FBgn0036101; NijA.
DR VEuPathDB; VectorBase:FBgn0036101; -.
DR eggNOG; ENOG502S12Z; Eukaryota.
DR HOGENOM; CLU_074201_1_0_1; -.
DR InParanoid; Q8MPP0; -.
DR OMA; QENINNH; -.
DR OrthoDB; 1560683at2759; -.
DR PhylomeDB; Q8MPP0; -.
DR BioGRID-ORCS; 39215; 0 hits in 3 CRISPR screens.
DR ChiTaRS; NijA; fly.
DR GenomeRNAi; 39215; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0036101; Expressed in eye disc (Drosophila) and 19 other tissues.
DR ExpressionAtlas; Q8MPP0; baseline and differential.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IDA:FlyBase.
DR GO; GO:0019835; P:cytolysis; IDA:UniProtKB.
DR GO; GO:0070265; P:necrotic cell death; IDA:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB.
DR GO; GO:0042246; P:tissue regeneration; IEA:InterPro.
DR InterPro; IPR007007; Ninjurin.
DR PANTHER; PTHR12316; PTHR12316; 1.
DR Pfam; PF04923; Ninjurin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell membrane; Cytolysis;
KW Glycoprotein; Membrane; Reference proteome; Secreted; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..245
FT /note="Ninjurin-A"
FT /id="PRO_0000452828"
FT CHAIN 1..?
FT /note="Secreted ninjurin-A"
FT /evidence="ECO:0000305|PubMed:33472215"
FT /id="PRO_0000452829"
FT TOPO_DOM 1..170
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 171..191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 192..211
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..245
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT REGION 32..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..70
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..101
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 28
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 23..26
FT /note="Missing (in isoform D and isoform A)"
FT /id="VSP_061060"
FT VAR_SEQ 52..67
FT /note="Missing (in isoform D and isoform C)"
FT /id="VSP_061061"
SQ SEQUENCE 245 AA; 26491 MW; BC6D5E81294E64AD CRC64;
MSNLEHITLE MDKVPLGDNK TLVRNTENIS KHSYGGAIDG RTRNTLRVPR AVPETDDDDN
DDRPFVKDGN DNPGVDDGLF STVGGNGGNG GNVNVNVPNG GRRPSFSFPG YNGPGFVTIN
GVETPIPDVN AYQHKKTLAQ GMMDLALLSA NANQLRYVLE TSSQHPYFYP SLLFISLSII
FQIAVGVGLI LNGQYNIKNG HDICRANRIN NYTVSGIFIV TVVNVLISAF TVDRDTVPAL
PANTT
