APH4_DROME
ID APH4_DROME Reviewed; 596 AA.
AC Q24238; B9EQR2; Q3KN28; Q8IMH0; Q8SXW6; Q9VA19;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2003, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Alkaline phosphatase 4 {ECO:0000303|PubMed:10628988};
DE EC=3.1.3.1;
DE Flags: Precursor;
GN Name=Alp4 {ECO:0000312|FlyBase:FBgn0016123};
GN Synonyms=aph-4 {ECO:0000303|PubMed:10628988};
GN ORFNames=CG1462 {ECO:0000312|FlyBase:FBgn0016123};
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|EMBL:AAN14265.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Head;
RX PubMed=10628988; DOI=10.1093/genetics/154.1.285;
RA Yang M.Y., Wang Z., MacPherson M., Dow J.A.T., Kaiser K.;
RT "A novel Drosophila alkaline phosphatase specific to the ellipsoid body of
RT the adult brain and the lower Malpighian (renal) tubule.";
RL Genetics 154:285-297(2000).
RN [2] {ECO:0000305}
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] {ECO:0000305}
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Head;
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 [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
RC STRAIN=Berkeley; TISSUE=Testis;
RA Stapleton M., Carlson J.W., Booth B., Chavez C., Frise E., George R.A.,
RA Pacleb J.M., Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Important role in neural and renal epithelial function.
CC {ECO:0000269|PubMed:10628988}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a phosphate monoester + H2O = an alcohol + phosphate;
CC Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10042};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 1 Mg(2+) ion. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions. {ECO:0000250};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P05187}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC anchor {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A {ECO:0000303|PubMed:10731132};
CC IsoId=Q24238-1; Sequence=Displayed;
CC Name=B {ECO:0000303|PubMed:10731132};
CC IsoId=Q24238-2; Sequence=VSP_007002;
CC -!- TISSUE SPECIFICITY: Ellipsoid body ring neurons in the adult brain and
CC in the lower Malpighian tubule and ureter.
CC {ECO:0000269|PubMed:10628988}.
CC -!- DEVELOPMENTAL STAGE: Highest abundance during larval stage (prior to
CC the secretion of pupal cuticle) and adult stage.
CC {ECO:0000269|PubMed:10628988}.
CC -!- SIMILARITY: Belongs to the alkaline phosphatase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA67052.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X98402; CAA67052.1; ALT_FRAME; mRNA.
DR EMBL; AE014297; AAF57106.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN14265.1; -; Genomic_DNA.
DR EMBL; AY075544; AAL68351.1; -; mRNA.
DR EMBL; BT023911; ABA81845.1; -; mRNA.
DR EMBL; BT057987; ACM16697.1; -; mRNA.
DR RefSeq; NP_524601.2; NM_079862.3. [Q24238-1]
DR RefSeq; NP_733413.1; NM_170534.2. [Q24238-2]
DR AlphaFoldDB; Q24238; -.
DR SMR; Q24238; -.
DR IntAct; Q24238; 2.
DR STRING; 7227.FBpp0085095; -.
DR GlyGen; Q24238; 5 sites.
DR PaxDb; Q24238; -.
DR PRIDE; Q24238; -.
DR DNASU; 43671; -.
DR EnsemblMetazoa; FBtr0085733; FBpp0085095; FBgn0016123. [Q24238-1]
DR EnsemblMetazoa; FBtr0085734; FBpp0085096; FBgn0016123. [Q24238-2]
DR GeneID; 43671; -.
DR KEGG; dme:Dmel_CG1462; -.
DR CTD; 43671; -.
DR FlyBase; FBgn0016123; Alp4.
DR VEuPathDB; VectorBase:FBgn0016123; -.
DR eggNOG; KOG4126; Eukaryota.
DR GeneTree; ENSGT00950000183063; -.
DR InParanoid; Q24238; -.
DR OMA; ITYANGP; -.
DR PhylomeDB; Q24238; -.
DR BioGRID-ORCS; 43671; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 43671; -.
DR PRO; PR:Q24238; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0016123; Expressed in oviduct (Drosophila) and 17 other tissues.
DR Genevisible; Q24238; DM.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; ISS:FlyBase.
DR GO; GO:0005576; C:extracellular region; ISM:FlyBase.
DR GO; GO:0005615; C:extracellular space; ISM:FlyBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004035; F:alkaline phosphatase activity; ISS:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016311; P:dephosphorylation; ISS:FlyBase.
DR GO; GO:0042045; P:epithelial fluid transport; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEP:UniProtKB.
DR GO; GO:0019953; P:sexual reproduction; IEP:FlyBase.
DR CDD; cd16012; ALP; 1.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR001952; Alkaline_phosphatase.
DR InterPro; IPR018299; Alkaline_phosphatase_AS.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR PANTHER; PTHR11596; PTHR11596; 1.
DR Pfam; PF00245; Alk_phosphatase; 1.
DR PRINTS; PR00113; ALKPHPHTASE.
DR SMART; SM00098; alkPPc; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
DR PROSITE; PS00123; ALKALINE_PHOSPHATASE; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW GPI-anchor; Hydrolase; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..570
FT /note="Alkaline phosphatase 4"
FT /id="PRO_0000024049"
FT PROPEP 571..596
FT /note="Removed in mature form"
FT /id="PRO_0000024050"
FT TRANSMEM 571..591
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 548..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..566
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 144
FT /note="Phosphoserine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10042"
FT BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 202
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 204
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 369
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 374
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 415
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 416
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 504
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT LIPID 570
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 539..550
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..94
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:10731132, ECO:0000303|Ref.5"
FT /id="VSP_007002"
FT CONFLICT 200
FT /note="I -> N (in Ref. 4; AAL68351)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="T -> S (in Ref. 5; ABA81845)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="G -> D (in Ref. 1; CAA67052)"
FT /evidence="ECO:0000305"
FT CONFLICT 375
FT /note="Q -> H (in Ref. 1; CAA67052)"
FT /evidence="ECO:0000305"
FT CONFLICT 495..496
FT /note="AT -> EP (in Ref. 1; CAA67052)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="N -> S (in Ref. 1; CAA67052)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="T -> S (in Ref. 1; CAA67052)"
FT /evidence="ECO:0000305"
FT CONFLICT 593..594
FT /note="GR -> CH (in Ref. 1; CAA67052 and 5; ABA81845)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 596 AA; 65262 MW; 333F3345BEFBAEFB CRC64;
MHCLVILGFL LGSLVAFSWA GVTTQPPPLI RTLSAGGDIG PQFDVGKTKE PEDAEFWHNV
GLRQLEKTIK QAQRVKEDSY QKKARNIIIF IGDGMGISTI SAGRIYKGQY LKHGYGEEET
LVFDDFPNTG MAKTYNVDKQ VPDSAGTATA IFSGSKTHYG AIGMDATRSK KNGQQGRVQS
VMEWAQKEGK RTGVVTTTRI THATPAATYA HIYDRDWECD TEVPAESVGF HVDIARQLVE
NAPGNRFNVI LGGGMSPMGI LNASEVKTTI FEGPTETICT RGDNRNLPAE WLAHHANDTV
PPALVHNRKD LLNVNVKKVD HLMGLFRNNH ITYSIAREAG EPSLQEMTET ALGILERGDE
SNGFVLLVEG GRIDQGHHMN YARAALHELY EFDLAIQAAV NNTDPDETLI LVTADHSHAV
TFNGYALRGA DILGTANSHE KNDPMFYETI SYANGPGYWD HLANDSRPQN SSNMWMPLKH
FTAEERAAPT YRHLATVPRK DETHGGEDVA VFAYGPGSSL IRGVFEQNYL AYVMSYAGCL
GPAKDFDDSC EDHKDGQKDR PLDKPNPKRN GATVVGASLI PILTAATAAI LRGRGL
