NEP4_DROME
ID NEP4_DROME Reviewed; 1040 AA.
AC Q8T062; Q9I7I4;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Neprilysin-4 {ECO:0000303|PubMed:19880729};
DE EC=3.4.24.11 {ECO:0000269|PubMed:19880729};
GN Name=Nep4 {ECO:0000303|PubMed:19880729, ECO:0000312|FlyBase:FBgn0038818};
GN ORFNames=CG4058 {ECO:0000312|FlyBase:FBgn0038818};
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:AAL39680.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL39680.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAL39680.1};
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:ACV53077.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley {ECO:0000312|EMBL:ACV53077.1};
RC TISSUE=Head {ECO:0000312|EMBL:ACV53077.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION (ISOFORM A), CATALYTIC ACTIVITY (ISOFORM A), BIOPHYSICOCHEMICAL
RP PROPERTIES (ISOFORM A), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=19880729; DOI=10.1242/jeb.034272;
RA Meyer H., Panz M., Zmojdzian M., Jagla K., Paululat A.;
RT "Neprilysin 4, a novel endopeptidase from Drosophila melanogaster, displays
RT distinct substrate specificities and exceptional solubility states.";
RL J. Exp. Biol. 212:3673-3683(2009).
RN [6] {ECO:0000305}
RP FUNCTION (ISOFORM A), INTERACTION WITH CG3534 (ISOFORM A), SUBCELLULAR
RP LOCATION (ISOFORM A), TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF GLU-873.
RX PubMed=22583317; DOI=10.1111/boc.201100069;
RA Panz M., Vitos-Faleato J., Jendretzki A., Heinisch J.J., Paululat A.,
RA Meyer H.;
RT "A novel role for the non-catalytic intracellular domain of Neprilysins in
RT muscle physiology.";
RL Biol. Cell 104:553-568(2012).
RN [7] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=24395329; DOI=10.1534/genetics.113.160945;
RA Sitnik J.L., Francis C., Hens K., Huybrechts R., Wolfner M.F.,
RA Callaerts P.;
RT "Neprilysins: an evolutionarily conserved family of metalloproteases that
RT play important roles in reproduction in Drosophila.";
RL Genetics 196:781-797(2014).
RN [8] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION (ISOFORM A), AND
RP DISRUPTION PHENOTYPE.
RX PubMed=27919317; DOI=10.7554/elife.19430;
RA Hallier B., Schiemann R., Cordes E., Vitos-Faleato J., Walter S.,
RA Heinisch J.J., Malmendal A., Paululat A., Meyer H.;
RT "Drosophila neprilysins control insulin signaling and food intake via
RT cleavage of regulatory peptides.";
RL Elife 5:E19430-E19430(2016).
RN [9] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27629706; DOI=10.1523/jneurosci.3730-15.2016;
RA Turrel O., Lampin-Saint-Amaux A., Preat T., Goguel V.;
RT "Drosophila neprilysins are involved in middle-term and long-term memory.";
RL J. Neurosci. 36:9535-9546(2016).
CC -!- FUNCTION: Metalloendoprotease which cleaves peptides at the amino side
CC of hydrophobic residues - such as the hormones Akh and Dh31, and the
CC neuropeptides Allatostatins (AST1, AST2, AST3 and AST4), Crz,
CC Drosulfakinins (DSK-I and DSK-II), Lk, sNPF and the tachykinin peptides
CC TK-1, TK-2, TK-4 and TK-5 (PubMed:27919317). Functions in female
CC fertility, memory formation and may also act in regulating insulin
CC signaling and food intake (PubMed:24395329, PubMed:27629706). Likely to
CC be involved in controlling feeding behavior and the expression of
CC insulin-like peptides by cleaving various regulatory peptides that
CC include certain Drosulfakinins, Allatostatins and tachykinin peptides
CC (PubMed:27919317). Required in females for normal patterns of egg
CC laying and hatching (PubMed:24395329). Required in the dorsal paired
CC medial neurons for the proper formation of long-term (LTM) and middle-
CC term memories (MTM) (PubMed:27629706). Also required in the mushroom
CC body neurons where it functions redundantly with neprilysins Nep2 and
CC Nep3, in normal LTM formation (PubMed:27629706).
CC {ECO:0000269|PubMed:24395329, ECO:0000269|PubMed:27629706,
CC ECO:0000269|PubMed:27919317}.
CC -!- FUNCTION: [Isoform A]: Cleaves angiotensin-1 and tachykinin
CC neuropeptide substance P (PubMed:19880729). Functions in maintaining
CC muscle integrity, possibly independently of its endopeptidase activity
CC (PubMed:22583317). {ECO:0000269|PubMed:19880729,
CC ECO:0000269|PubMed:22583317}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage of polypeptides between hydrophobic
CC residues, particularly with Phe or Tyr at P1'.; EC=3.4.24.11;
CC Evidence={ECO:0000269|PubMed:19880729, ECO:0000269|PubMed:27919317};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P08473};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P08473};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:19880729};
CC -!- SUBUNIT: [Isoform A]: Interacts (via intracellular domain) with the
CC putative carbohydrate kinase CG3534. {ECO:0000269|PubMed:22583317}.
CC -!- SUBCELLULAR LOCATION: [Isoform A]: Cell membrane
CC {ECO:0000269|PubMed:19880729, ECO:0000269|PubMed:27919317}; Single-pass
CC type II membrane protein {ECO:0000305}. Sarcoplasmic reticulum
CC {ECO:0000269|PubMed:22583317}. Note=In larval muscles, localizes to
CC both the cell surface and sarcoplasmic reticulum membranes that are
CC continuous with the nuclear membrane. {ECO:0000269|PubMed:22583317,
CC ECO:0000269|PubMed:27919317}.
CC -!- SUBCELLULAR LOCATION: [Isoform B]: Cytoplasm
CC {ECO:0000269|PubMed:19880729}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=A {ECO:0000303|PubMed:19880729};
CC IsoId=Q8T062-1; Sequence=Displayed;
CC Name=B {ECO:0000303|PubMed:19880729}; Synonyms=C
CC {ECO:0000312|FlyBase:FBgn0038818};
CC IsoId=Q8T062-2; Sequence=VSP_059156;
CC -!- TISSUE SPECIFICITY: Expressed in the gonads and testes of adults, and
CC the adult and larval brain (at protein level) (PubMed:19880729). In
CC embryos, expressed in the pericardial, muscle founder and glia cells
CC (at protein level) (PubMed:19880729). In stage 12 embryos, expressed in
CC specific dorsal muscle founder cells such as DA1 and DO2, and also in
CC the certain pericardial progenitor cells where expression persists
CC throughout embryogenesis (PubMed:19880729, PubMed:24395329). Expressed
CC in the glia cells of the embryonic, larval and adult central nervous
CC system (PubMed:19880729, PubMed:24395329). Expressed in the somatic
CC muscles of larvae, pupae and adults (PubMed:22583317). Isoform A:
CC Detected in the male abdomen (at protein level) (PubMed:19880729).
CC Isoform B: Not detected in the male or female abdomen (at protein
CC level) (PubMed:19880729). {ECO:0000269|PubMed:19880729,
CC ECO:0000269|PubMed:22583317, ECO:0000269|PubMed:24395329}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development and in adults (at
CC protein level). Isoform A: Highly expressed in adults and low levels of
CC expression in larvae and pupae (at protein level). Isoform B: High
CC levels of expression in larvae (at protein level), and low levels of
CC expression in embryos (4-24 hr after oviposition), pupae and adults (at
CC protein level). {ECO:0000269|PubMed:19880729}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown females lay fewer eggs
CC and display a reduced hatch rate when mated to wild-type males
CC (PubMed:24395329). Wild-type females mated to males that undergo RNAi-
CC mediated knockdown, lay the same number of eggs and have a similar
CC hatch rate to those mated to wild-type males (PubMed:24395329). RNAi-
CC mediated knockdown in the dorsal paired medial neurons impairs middle-
CC term (MTM) and long-term memory (LTM), but has no effect on normal
CC aversion learning and anesthesia-resistant memory (ARM)
CC (PubMed:27629706). RNAi-mediated knockdown in all mushroom body neurons
CC has no effect on learning, ARM and LTM (PubMed:27629706). However,
CC simultaneous knockdown with Nep3 does impair LTM, and simultaneous
CC knockdown with both Nep2 and Nep3 results in a further reduction in LTM
CC formation (PubMed:27629706). However, simultaneous knockdown with only
CC Nep2 has no effect on LTM formation (PubMed:27629706). RNAi-mediated
CC knockdown in somatic muscles is pupal lethal (PubMed:22583317,
CC PubMed:27919317). Muscles of second instar larvae display signs of
CC necrotic degeneration, and undergo fewer and weaker contractions
CC leading to a reduction in their crawling speed (PubMed:22583317). Also
CC displays reduced food intake after 10 minutes (47% of control intake)
CC and 20 minutes of feeding (72% of control intake), but not after 40
CC minutes (PubMed:27919317). Displays an 82% reduction in expression of
CC insulin-like peptide 4 (PubMed:27919317). {ECO:0000269|PubMed:22583317,
CC ECO:0000269|PubMed:24395329, ECO:0000269|PubMed:27629706,
CC ECO:0000269|PubMed:27919317}.
CC -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01233, ECO:0000305}.
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DR EMBL; AE014297; AAG22165.3; -; Genomic_DNA.
DR EMBL; AE014297; AAN14361.2; -; Genomic_DNA.
DR EMBL; AE014297; AGB96153.1; -; Genomic_DNA.
DR EMBL; AY069535; AAL39680.1; -; mRNA.
DR EMBL; BT099713; ACV53077.1; -; mRNA.
DR RefSeq; NP_001262773.1; NM_001275844.1. [Q8T062-2]
DR RefSeq; NP_650904.3; NM_142647.3. [Q8T062-1]
DR RefSeq; NP_732540.2; NM_169912.1. [Q8T062-2]
DR AlphaFoldDB; Q8T062; -.
DR SMR; Q8T062; -.
DR STRING; 7227.FBpp0083345; -.
DR MEROPS; M13.014; -.
DR GlyGen; Q8T062; 6 sites.
DR PaxDb; Q8T062; -.
DR PRIDE; Q8T062; -.
DR DNASU; 42449; -.
DR EnsemblMetazoa; FBtr0083936; FBpp0083344; FBgn0038818. [Q8T062-2]
DR EnsemblMetazoa; FBtr0083937; FBpp0083345; FBgn0038818. [Q8T062-1]
DR EnsemblMetazoa; FBtr0334642; FBpp0306704; FBgn0038818. [Q8T062-2]
DR GeneID; 42449; -.
DR KEGG; dme:Dmel_CG4058; -.
DR UCSC; CG4058-RA; d. melanogaster. [Q8T062-1]
DR UCSC; CG4058-RB; d. melanogaster.
DR CTD; 42449; -.
DR FlyBase; FBgn0038818; Nep4.
DR VEuPathDB; VectorBase:FBgn0038818; -.
DR eggNOG; KOG3624; Eukaryota.
DR GeneTree; ENSGT00940000171376; -.
DR InParanoid; Q8T062; -.
DR OMA; EIHPEKY; -.
DR PhylomeDB; Q8T062; -.
DR BRENDA; 3.4.24.11; 1994.
DR Reactome; R-DME-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 42449; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 42449; -.
DR PRO; PR:Q8T062; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0038818; Expressed in excretory cell and 46 other tissues.
DR ExpressionAtlas; Q8T062; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0016021; C:integral component of membrane; ISM:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:FlyBase.
DR GO; GO:0004175; F:endopeptidase activity; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; ISM:FlyBase.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IDA:FlyBase.
DR CDD; cd08662; M13; 1.
DR Gene3D; 1.10.1380.10; -; 1.
DR Gene3D; 3.40.390.10; -; 2.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR000718; Peptidase_M13.
DR InterPro; IPR018497; Peptidase_M13_C.
DR InterPro; IPR042089; Peptidase_M13_dom_2.
DR InterPro; IPR008753; Peptidase_M13_N.
DR PANTHER; PTHR11733; PTHR11733; 1.
DR Pfam; PF01431; Peptidase_M13; 1.
DR Pfam; PF05649; Peptidase_M13_N; 1.
DR PRINTS; PR00786; NEPRILYSIN.
DR PROSITE; PS51885; NEPRILYSIN; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Cell membrane; Cytoplasm; Disulfide bond;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Sarcoplasmic reticulum; Signal-anchor;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..1040
FT /note="Neprilysin-4"
FT /id="PRO_0000441993"
FT TOPO_DOM 1..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 56..76
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..1040
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT DOMAIN 251..1040
FT /note="Peptidase M13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT REGION 1..45
FT /note="Required for maintaining muscle integrity"
FT /evidence="ECO:0000269|PubMed:22583317"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 873
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 938
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 872
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 876
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 934
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 593
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 723
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 819
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 916
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 969
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 277..1025
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 285..985
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 452..700
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 909..1037
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT VAR_SEQ 1..63
FT /note="MSRHSQLKLAMPSVHGAPATAPGSPMNAKARSVKLGLGVNQRTGRVQWCPGL
FT TCCKMLLLLPV -> M (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_059156"
FT MUTAGEN 873
FT /note="E->Q: No effect on its function in maintaining
FT muscle integrity."
FT /evidence="ECO:0000269|PubMed:22583317"
SQ SEQUENCE 1040 AA; 119577 MW; 48BE8CD06433AE57 CRC64;
MSRHSQLKLA MPSVHGAPAT APGSPMNAKA RSVKLGLGVN QRTGRVQWCP GLTCCKMLLL
LPVVMLPLTL VLILIMRLDG MLAALQLNEQ RMRDLRNSHS EVPVYMEDYE ALLPEGSTYN
DLINEEFILP ASKRTQLQIL AAERARRCQP YRYGNGESME LEERNTLMKD SRTSFLPLGI
PRECLGSGIE LDIKPIDEEA YQRQKKRYQD IAPYWLEKIR IRERREAERH AEEASAEISE
ATAALQSFWN EEGTREGIRM TQAKTMKRYM DNKVDPCVDF YKYACGNWER LHPIPKDKAG
FDTFEMLRES LDLVLRNLLE KNTPVHSAAE LRKSPVRNTL FKLNEQGEGE GEADQAAELT
AERLRRHIVS KRQLLNRVLV RYKRYTNGTK RKRLIETPRE RTKEEEAAPP VVLPKDKTKD
KSDNEEQLHV PTDFLKPHQD AQLKAKNLYR SCVNSAVLAK RGLEPLHTLI RELGGWPVLE
SQWSESNFNW QVLAATLRRY NNDILIVQWV GADIKNSEEN IVQFDQTGLG LPTREYFLQP
SNAKYLQAYQ RYMAEVMHKM GASKADAQRV ASELVAFETQ LAGITAPAEQ RLNVTKLYKR
MTLDQLQAVV PEIKWRAYLQ SLQDREVLGT EEVVIYAVEY MSKLVTLLDE TDPRTVSNYM
MWRFVRHRIN NVDDRFDDIK QSFYHALFGR EESPQRWKVC IAQVNTNMGM AVGSMFVSRY
FDNNSKRDTL RMTHDLQQAF RDILKTTDWL DDTTKQLAEE KVNAMSLKIG YPDFILNPSE
LNSKYAGIEI YPEKYFENTL NVLLHTAKTE QAKLHERVNK TNWQTAPAIV NAYYSRNKNQ
IMFPAGILQP PFYHRHFPKS LNFGGIGVVI GHELTHGFDD KGRLFDRNGN IHKWWTDSSI
RGFDERARCI IAQYSNYTVE EVGIVLNGES TQGENIADNG GLRQAFHAYQ RWLKEHPSEV
SDEILPGLNM TGPQLFFLNF GQVWCGAMRP EAIRNKLNTA IHSPGRFRVI GTLSNSVDFA
REFNCPLGSP MNPQKKCSVW
