SEMP1_DROME
ID SEMP1_DROME Reviewed; 251 AA.
AC Q9VJN9; Q8MZE8; S0ASJ3;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Seminal metalloprotease 1 {ECO:0000303|PubMed:24514904};
DE EC=3.4.24.- {ECO:0000255|RuleBase:RU361183};
DE Flags: Precursor;
GN Name=Semp1 {ECO:0000312|FlyBase:FBgn0028944};
GN ORFNames=CG11864 {ECO:0000312|FlyBase:FBgn0028944};
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:AAM29219.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM29219.1};
RC TISSUE=Testis {ECO:0000312|EMBL:AAM29219.1};
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:AGO63477.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AGO63477.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (JUN-2013) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND CLEAVAGE.
RX PubMed=15979005; DOI=10.1016/j.ibmb.2005.05.001;
RA Ravi Ram K., Ji S., Wolfner M.F.;
RT "Fates and targets of male accessory gland proteins in mated female
RT Drosophila melanogaster.";
RL Insect Biochem. Mol. Biol. 35:1059-1071(2005).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, CLEAVAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=17116868; DOI=10.1073/pnas.0606228103;
RA Ravi Ram K., Sirot L.K., Wolfner M.F.;
RT "Predicted seminal astacin-like protease is required for processing of
RT reproductive proteins in Drosophila melanogaster.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:18674-18679(2006).
RN [7] {ECO:0000305}
RP FUNCTION, CLEAVAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-41; ARG-43
RP AND 45-GLY-ILE-46.
RX PubMed=24514904; DOI=10.1534/genetics.113.160101;
RA Laflamme B.A., Avila F.W., Michalski K., Wolfner M.F.;
RT "A Drosophila protease cascade member, seminal metalloprotease-1, is
RT activated stepwise by male factors and requires female factors for full
RT activity.";
RL Genetics 196:1117-1129(2014).
CC -!- FUNCTION: Seminal fluid metalloprotease which is transferred to females
CC during mating and is required for processing of two other seminal fluid
CC proteins Acp26Aa and Acp36DE in mated females.
CC {ECO:0000269|PubMed:15979005, ECO:0000269|PubMed:17116868,
CC ECO:0000269|PubMed:24514904}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01211};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU01211};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15979005,
CC ECO:0000269|PubMed:17116868}. Note=Secreted into seminal fluid.
CC {ECO:0000269|PubMed:15979005, ECO:0000269|PubMed:17116868}.
CC -!- TISSUE SPECIFICITY: Produced in the male accessory glands and secreted
CC into seminal fluid. In mated females, confined to the reproductive
CC tract and also detected in eggs laid by mated females (at protein
CC level). {ECO:0000269|PubMed:15979005}.
CC -!- PTM: Undergoes cleavage in the male during mating with a cleaved
CC product detected in the ejaculatory duct and/or bulb of males by 8-10
CC minutes after the start of mating (PubMed:17116868). Further cleavage
CC occurs in the mated female (PubMed:15979005). May undergo cleavage in a
CC two-step process where it is first cleaved by Sems, making it
CC susceptible to activational cleavage which may be carried out by
CC another protease or by autocleavage (PubMed:24514904).
CC {ECO:0000269|PubMed:15979005, ECO:0000269|PubMed:17116868,
CC ECO:0000269|PubMed:24514904}.
CC -!- DISRUPTION PHENOTYPE: Loss of cleavage of accessory gland proteins
CC Acp26Aa and Acp36DE in females mated with mutant males
CC (PubMed:24514904). RNAi-mediated knockdown in males results in
CC incomplete and delayed processing of Acp26Aa and Acp36DE in females
CC mated with these males. {ECO:0000269|PubMed:17116868,
CC ECO:0000269|PubMed:24514904}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AGO63477.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE014134; AAF53469.1; -; Genomic_DNA.
DR EMBL; AY113214; AAM29219.1; -; mRNA.
DR EMBL; BT150134; AGO63477.1; ALT_INIT; mRNA.
DR RefSeq; NP_609756.1; NM_135912.3.
DR AlphaFoldDB; Q9VJN9; -.
DR SMR; Q9VJN9; -.
DR STRING; 7227.FBpp0080342; -.
DR MEROPS; M12.330; -.
DR GlyGen; Q9VJN9; 3 sites.
DR PaxDb; Q9VJN9; -.
DR PRIDE; Q9VJN9; -.
DR EnsemblMetazoa; FBtr0080784; FBpp0080342; FBgn0028944.
DR GeneID; 34914; -.
DR KEGG; dme:Dmel_CG11864; -.
DR UCSC; CG11864-RA; d. melanogaster.
DR CTD; 34914; -.
DR FlyBase; FBgn0028944; Semp1.
DR VEuPathDB; VectorBase:FBgn0028944; -.
DR eggNOG; KOG3714; Eukaryota.
DR GeneTree; ENSGT00940000171076; -.
DR HOGENOM; CLU_017286_2_3_1; -.
DR InParanoid; Q9VJN9; -.
DR OMA; HWPNRTV; -.
DR OrthoDB; 681837at2759; -.
DR PhylomeDB; Q9VJN9; -.
DR BioGRID-ORCS; 34914; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 34914; -.
DR PRO; PR:Q9VJN9; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0028944; Expressed in male reproductive gland and 5 other tissues.
DR ExpressionAtlas; Q9VJN9; baseline and differential.
DR Genevisible; Q9VJN9; DM.
DR GO; GO:0005615; C:extracellular space; HDA:FlyBase.
DR GO; GO:0004175; F:endopeptidase activity; IMP:FlyBase.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0016477; P:cell migration; IMP:FlyBase.
DR GO; GO:0016485; P:protein processing; IMP:FlyBase.
DR GO; GO:0006508; P:proteolysis; IMP:FlyBase.
DR GO; GO:0019953; P:sexual reproduction; HEP:FlyBase.
DR CDD; cd04280; ZnMc_astacin_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR034035; Astacin-like_dom.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001506; Peptidase_M12A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR Pfam; PF01400; Astacin; 1.
DR PRINTS; PR00480; ASTACIN.
DR SMART; SM00235; ZnMc; 1.
DR PROSITE; PS51864; ASTACIN; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Hydrolase; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..?
FT /note="Activation peptide"
FT /evidence="ECO:0000305"
FT /id="PRO_0000436915"
FT CHAIN ?..251
FT /note="Seminal metalloprotease 1"
FT /evidence="ECO:0000305"
FT /id="PRO_5005144955"
FT DOMAIN 44..248
FT /note="Peptidase M12A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT ACT_SITE 145
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 87..247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 111..136
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT MUTAGEN 41
FT /note="R->A: Incomplete processing of Acp26Aa and Semp1 in
FT mated females."
FT /evidence="ECO:0000269|PubMed:24514904"
FT MUTAGEN 43
FT /note="R->A: No processing of Acp26Aa in mated females and
FT incomplete processing of Semp1."
FT /evidence="ECO:0000269|PubMed:24514904"
FT MUTAGEN 45..46
FT /note="GI->AA: Loss of cleavage of Acp26Aa and Acp36DE."
FT /evidence="ECO:0000269|PubMed:24514904"
FT CONFLICT 7
FT /note="G -> A (in Ref. 3; AAM29219)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="Y -> H (in Ref. 3; AAM29219)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="K -> E (in Ref. 3; AAM29219)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 251 AA; 29282 MW; 247390E1C49CBAB1 CRC64;
MFPQIWGVIF LFTPTVFSEL FKDPELLAGF YQGDIKAHPI RTRNGIVNQI YHWPNRTVPY
MIEDDAFADS HYREILRAIS IIEENSCVIF KPATEMDFPM ALVITSKGLG CNTVHLGYRN
KTQVVNLEIY PLGEGCFRIG SIIHELLHVL GFEHQHVSQN RDQYVSIQWK NINPQYNINF
VNNDNSTAWH DFDEGYDYES VMHYVPRAFS RNGQPTIVPL REGAENMGQR FYMSEKDIRK
LNKMYRCPDH V
