NNAD_DROME
ID NNAD_DROME Reviewed; 1201 AA.
AC Q9VY99; A8JUW0; C7LAD7; Q86B56; Q8T9D7;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Cytosolic carboxypeptidase Nna1 {ECO:0000305};
DE EC=3.4.17.-;
DE AltName: Full=Nervous system nuclear protein induced by axotomy protein 1 homolog;
GN Name=Nna1 {ECO:0000312|FlyBase:FBgn0265726};
GN Synonyms=NnaD {ECO:0000303|PubMed:20620870};
GN ORFNames=CG44533 {ECO:0000312|FlyBase:FBgn0265726};
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 [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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=20620870; DOI=10.1016/j.neuron.2010.05.024;
RA Chakrabarti L., Zahra R., Jackson S.M., Kazemi-Esfarjani P., Sopher B.L.,
RA Mason A.G., Toneff T., Ryu S., Shaffer S., Kansy J.W., Eng J., Merrihew G.,
RA MacCoss M.J., Murphy A., Goodlett D.R., Hook V., Bennett C.L.,
RA Pallanck L.J., La Spada A.R.;
RT "Mitochondrial dysfunction in NnaD mutant flies and Purkinje cell
RT degeneration mice reveals a role for Nna proteins in neuronal
RT bioenergetics.";
RL Neuron 66:835-847(2010).
CC -!- FUNCTION: Metallocarboxypeptidase. {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:20620870}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=A;
CC IsoId=Q9VY99-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9VY99-2; Sequence=VSP_040442;
CC Name=C;
CC IsoId=Q9VY99-3; Sequence=VSP_040439;
CC Name=D;
CC IsoId=Q9VY99-4; Sequence=VSP_040440;
CC Name=E;
CC IsoId=Q9VY99-5; Sequence=VSP_040441, VSP_040443;
CC -!- TISSUE SPECIFICITY: In larvae, highly expressed in the brain, optic
CC lobes, and ventral ganglia. {ECO:0000269|PubMed:20620870}.
CC -!- DEVELOPMENTAL STAGE: Expressed in larvae and adults.
CC {ECO:0000269|PubMed:20620870}.
CC -!- DISRUPTION PHENOTYPE: Semilethal phenotype: females survive, while
CC males die. Most male flies die between the late second instar larval
CC stage and early pupal stage. Mutant males that survive to produce pupal
CC cases initiate morphogenesis but die before head eversion. Almost all
CC male flies that survive past head eversion do complete morphogenesis,
CC and then eclose as 'escaper' males. Escapers display a range of
CC phenotypes that mirror the disease pathology observed in pcd mice,
CC including retinal degeneration. {ECO:0000269|PubMed:20620870}.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR EMBL; AE014298; AAF48304.2; -; Genomic_DNA.
DR EMBL; AE014298; AAN09334.1; -; Genomic_DNA.
DR EMBL; AE014298; AAO41651.1; -; Genomic_DNA.
DR EMBL; AE014298; ABW09409.1; -; Genomic_DNA.
DR EMBL; AY069812; AAL39957.1; -; mRNA.
DR EMBL; BT099687; ACV44473.1; -; mRNA.
DR RefSeq; NP_001096975.1; NM_001103505.3. [Q9VY99-4]
DR RefSeq; NP_001245656.1; NM_001258727.1. [Q9VY99-3]
DR RefSeq; NP_572914.2; NM_132686.3. [Q9VY99-1]
DR RefSeq; NP_727728.1; NM_167379.2. [Q9VY99-2]
DR RefSeq; NP_788899.1; NM_176726.2. [Q9VY99-3]
DR AlphaFoldDB; Q9VY99; -.
DR SMR; Q9VY99; -.
DR BioGRID; 58706; 2.
DR IntAct; Q9VY99; 1.
DR STRING; 7227.FBpp0073644; -.
DR MEROPS; M14.A21; -.
DR PaxDb; Q9VY99; -.
DR PRIDE; Q9VY99; -.
DR DNASU; 32329; -.
DR EnsemblMetazoa; FBtr0340671; FBpp0309513; FBgn0265726. [Q9VY99-1]
DR EnsemblMetazoa; FBtr0340672; FBpp0309514; FBgn0265726. [Q9VY99-2]
DR EnsemblMetazoa; FBtr0340673; FBpp0309515; FBgn0265726. [Q9VY99-3]
DR EnsemblMetazoa; FBtr0340674; FBpp0309516; FBgn0265726. [Q9VY99-4]
DR EnsemblMetazoa; FBtr0340676; FBpp0309518; FBgn0265726. [Q9VY99-3]
DR GeneID; 32329; -.
DR KEGG; dme:Dmel_CG44533; -.
DR UCSC; CG32627-RA; d. melanogaster. [Q9VY99-1]
DR UCSC; CG32627-RB; d. melanogaster.
DR UCSC; CG32627-RC; d. melanogaster.
DR UCSC; CG32627-RD; d. melanogaster.
DR CTD; 32329; -.
DR FlyBase; FBgn0265726; Nna1.
DR VEuPathDB; VectorBase:FBgn0265726; -.
DR eggNOG; KOG3641; Eukaryota.
DR InParanoid; Q9VY99; -.
DR PhylomeDB; Q9VY99; -.
DR BioGRID-ORCS; 32329; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 32329; -.
DR PRO; PR:Q9VY99; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0265726; Expressed in testis and 17 other tissues.
DR ExpressionAtlas; Q9VY99; baseline and differential.
DR Genevisible; Q9VY99; DM.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002164; P:larval development; IMP:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0035610; P:protein side chain deglutamylation; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR040626; Pepdidase_M14_N.
DR InterPro; IPR000834; Peptidase_M14.
DR Pfam; PF18027; Pepdidase_M14_N; 1.
DR Pfam; PF00246; Peptidase_M14; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Carboxypeptidase; Hydrolase; Metal-binding;
KW Metalloprotease; Mitochondrion; Protease; Reference proteome; Zinc.
FT CHAIN 1..1201
FT /note="Cytosolic carboxypeptidase Nna1"
FT /id="PRO_0000403765"
FT REGION 63..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 255..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 362..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 474..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 544..574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 623..651
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 70..97
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..275
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 383..400
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 502..518
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 635..651
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 988
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 938
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 941
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1034
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..288
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_040439"
FT VAR_SEQ 1..143
FT /note="MAEREREAMSASLSRLLRTLSSASMSRRHCPLALLQPIPLHQSEIALGSASS
FT GGSAERCCSSCSDDSNNNERCKSAERGTAADEVGEEGREEVELESKEDAVEGEQDELEL
FT KRDSSTVNVNVVRANFKCNDMECSLVLGDYVN -> MDFGGGRVQFLQAQLFPVCTLTT
FT SSG (in isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_040440"
FT VAR_SEQ 1..143
FT /note="MAEREREAMSASLSRLLRTLSSASMSRRHCPLALLQPIPLHQSEIALGSASS
FT GGSAERCCSSCSDDSNNNERCKSAERGTAADEVGEEGREEVELESKEDAVEGEQDELEL
FT KRDSSTVNVNVVRANFKCNDMECSLVLGDYVN -> MQKGVKDKENRNSAMGPEICEVQ
FT QHPSKQND (in isoform E)"
FT /evidence="ECO:0000305"
FT /id="VSP_040441"
FT VAR_SEQ 444..707
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_040442"
FT VAR_SEQ 1183..1201
FT /note="GCIMNDKLKVKRSVEKSVS -> ILNLLKQQDRLRSKIIERLMREGSSADEP
FT LNIPLSDYSSDEGNCSSSSDNEGKHSITTSDLEGPCCAPTRAPPSSPEVIHEIRKFRMR
FT RMRKVMHELDRIYFTPLFQRKFKTLTTLKRRRQKMGVKAAPSGKRLRGGGGPAVSAATP
FT TPAPAVQAAAPVVETNDVQKLHTPRQLARSLPSNSDQPTGGQSSDSSESMDSSQSESLL
FT EPDGSSGSTAASKEVTKKVKTSGAGTKKTAKKKKFMPTEKKKPVVNQKLHVDRNFRLWL
FT ANRRIYIYRRKKSTQARRTKVRNKPSKKRGEVVRTTLDLPTTDPGSDLHFSTDDEEHSP
FT TSGHNGYGAVPPLRHTLLQSDLQRRYIEEIGDTVVQKPKASHMPPELIVTTPSKSGTPG
FT GGKKLDVYKLTPRTAPELDTGIGMMQRQAGGTGTSARRTYSWHNLDQQEIPNGNGGGQG
FT KANFYIGDTKPGIKTMAKPLPRRSVPSNFIPQRHGNVQTADDLQLKLSLKKKVWTGANG
FT DADGRPLAWYKGHSITASQMANTTTTIRSAGGGAAGGGGAGAGAGAGGGGGGQNRNMFP
FT SNGREQTAASGGIAMGVPPAFVGAPRRFRKLEQVDLFNACSQKLMMWQQQEEQRRSHPQ
FT QAQRLLKVEDHPQHSRDREQQPFKPMHVVRKSTGTTSQAKVIQALVAAESGGKVKRKSS
FT SMMKIAETTQLVTRFARNRNSAGGSAAQQQQQQQPPQHMHHQHKRLLFKGQGGVGAMGS
FT RMHSAGVMGNMQGNGGGRAPNKFKTGGLVITAVQQPTNMTGGGSRRMRNAAGLQAKGSN
FT GALGSSTGQMQYQRSNASVQANKSATEISMDAVSLVRKVKTKLKKRKSRTLSTGAPK
FT (in isoform E)"
FT /evidence="ECO:0000305"
FT /id="VSP_040443"
SQ SEQUENCE 1201 AA; 133999 MW; AC52F081324B879B CRC64;
MAEREREAMS ASLSRLLRTL SSASMSRRHC PLALLQPIPL HQSEIALGSA SSGGSAERCC
SSCSDDSNNN ERCKSAERGT AADEVGEEGR EEVELESKED AVEGEQDELE LKRDSSTVNV
NVVRANFKCN DMECSLVLGD YVNGFLGSFL SKGLKTNQLV VNTDEKTLRP VARLKEPRDL
FALPKDKDND CSQQAPRWPV ECQVIEERII HIPYVPAVPE PLNAPTGNEL KPRPVGEENG
IVVFSYSPIS AVNYEKPKAK KEDDESSDES DYSSDSRQDS TPPSRSTPMR LAGGGECAPG
KLNSVSKMIN NVDNRSTSAS LDDNDDYYDD EYDTSGGYCG GSGEAKEKAI IKDLIEAKKK
RYQEEAEVTP VGGGTARNSR AASRSEASKD ASDIDDIWKN NTSEYKPASP RYVLSQFGKN
VTKAVIDRIV DHEDLVPPSG SQKVSNQFAV GPVKLPKTNI ARLEVAFERS ACQDRSKSRL
KKKMSSSRRR RESTSDEDSS SSSLGNEEDE EVDDSDSDAE NTGSGIGLRR ILGSYSARLA
GGAEKCPCPG SGSVSDTETL VGDESRSRLA GSNGLHQQDV VCSRNRQAQS RSPLRSVPHT
HAATVAAAAA ALARGRNRDK DGCLGGKDEK NMGMGVGTTG TSSMGTRTSS PVRNNVFRLS
KDQHILLNSM TSQETTGTLI SSTSTNQTTT TTNSSQSFLC SDLPQAQFSR SAVGGARFMT
NCHPMNPEEY DGLEFESRFE SGNLAKAVQI TPTYYELYLR PDLYTSRSKQ WFYFRVRRTR
RKMLYRFSIV NLVKSDSLYN DGMQPVMYST LGAKEKSEGW RRCGDNICYY RNDDESASSS
ANEDDEDNST YTLTFTIEFE HDDDTVFFAH SYPYTYSDLQ DYLMEIQRHP VKSKFCKLRL
LCRTLAGNNV YYLTVTAPSS NEENMRRKKS IVVSARVHPS ETPASWMMKG LMDFITGDTT
VAKRLRHKFI FKLVPMLNPD GVIVGNTRNS LTGKDLNRQY RTVIRETYPS IWYTKAMIRR
LIEECGVAMY CDMHAHSRKH NIFIYGCENK RNPEKKLTEQ VFPLMLHKNS ADRFSFESCK
FKIQRSKEGT GRIVVWMLGI TNSYTIEASF GGSSLGSRKG THFNTQDYEH MGRAFCETLL
DYCDENPNKV KRHAKLFKQI KKIRKREKRE QKALKLQKMA DQGCIMNDKL KVKRSVEKSV
S
