PGAP6_MOUSE
ID PGAP6_MOUSE Reviewed; 769 AA.
AC Q9ESN3; Q543X8; Q99JS5;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Post-GPI attachment to proteins factor 6;
DE EC=3.1.1.4;
DE AltName: Full=GPI processing phospholipase A2;
DE Short=GPI-PLA2;
DE AltName: Full=M83 protein;
DE AltName: Full=Transmembrane protein 8;
DE AltName: Full=Transmembrane protein 8A;
DE Flags: Precursor;
GN Name=Pgap6 {ECO:0000303|PubMed:27881714}; Synonyms=Tmem8, Tmem8a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RC TISSUE=Thymus;
RX PubMed=11006113; DOI=10.1006/bbrc.2000.3409;
RA Motohashi T., Miyoshi S., Osawa M., Eyre H.J., Sutherland G.R., Matsuda Y.,
RA Nakamura Y., Shibuya A., Iwama A., Nakauchi H.;
RT "Molecular cloning and chromosomal mapping of a novel five-span
RT transmembrane protein gene, M83.";
RL Biochem. Biophys. Res. Commun. 276:244-250(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
RC TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=27881714; DOI=10.1083/jcb.201605121;
RA Lee G.H., Fujita M., Takaoka K., Murakami Y., Fujihara Y., Kanzawa N.,
RA Murakami K.I., Kajikawa E., Takada Y., Saito K., Ikawa M., Hamada H.,
RA Maeda Y., Kinoshita T.;
RT "A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in
RT embryos by shedding CRIPTO.";
RL J. Cell Biol. 215:705-718(2016).
CC -!- FUNCTION: Involved in the lipid remodeling steps of GPI-anchor
CC maturation. Lipid remodeling steps consist in the generation of 2
CC saturated fatty chains at the sn-2 position of GPI-anchor proteins
CC (GPI-AP). Has phospholipase A2 activity that removes an acyl-chain at
CC the sn-2 position of GPI-anchors during the remodeling of GPI. Required
CC for the shedding of the GPI-AP TDGF1, but not CFC1, at the cell
CC surface. Shedding of TDGF1 modulates Nodal signaling by allowing
CC soluble TDGF1 to act as a Nodal coreceptor on other cells. Also
CC indirectly involved in the translocation of RAC1 from the cytosol to
CC the plasma membrane by maintaining the steady state amount of CAV1-
CC enriched plasma membrane subdomains, stabilizing RAC1 at the plasma
CC membrane. {ECO:0000250|UniProtKB:Q9HCN3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000250|UniProtKB:Q9HCN3};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9HCN3};
CC Multi-pass membrane protein {ECO:0000255}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9HCN3}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha;
CC IsoId=Q9ESN3-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=Q9ESN3-2; Sequence=VSP_004005;
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q9HCN3}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal with anterior-posterior axis
CC formation defects in embryos from 6.7 dpc on until cessation of
CC development at latest in 10 dpc. {ECO:0000269|PubMed:27881714}.
CC -!- SIMILARITY: Belongs to the TMEM8 family. {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; AB045293; BAB16377.1; -; mRNA.
DR EMBL; AK044384; BAC31896.1; -; mRNA.
DR EMBL; BC005722; AAH05722.1; -; mRNA.
DR CCDS; CCDS28546.1; -. [Q9ESN3-1]
DR RefSeq; NP_068565.1; NM_021793.2. [Q9ESN3-1]
DR AlphaFoldDB; Q9ESN3; -.
DR STRING; 10090.ENSMUSP00000025010; -.
DR GlyGen; Q9ESN3; 2 sites.
DR PhosphoSitePlus; Q9ESN3; -.
DR PaxDb; Q9ESN3; -.
DR PRIDE; Q9ESN3; -.
DR ProteomicsDB; 259433; -. [Q9ESN3-1]
DR ProteomicsDB; 259434; -. [Q9ESN3-2]
DR Antibodypedia; 55489; 20 antibodies from 9 providers.
DR DNASU; 60455; -.
DR Ensembl; ENSMUST00000025010; ENSMUSP00000025010; ENSMUSG00000024180. [Q9ESN3-1]
DR Ensembl; ENSMUST00000128597; ENSMUSP00000121651; ENSMUSG00000024180. [Q9ESN3-2]
DR GeneID; 60455; -.
DR KEGG; mmu:60455; -.
DR UCSC; uc008bdj.2; mouse. [Q9ESN3-1]
DR UCSC; uc008bdk.1; mouse. [Q9ESN3-2]
DR CTD; 58986; -.
DR MGI; MGI:1926283; Pgap6.
DR VEuPathDB; HostDB:ENSMUSG00000024180; -.
DR eggNOG; ENOG502QQ7Q; Eukaryota.
DR GeneTree; ENSGT00940000160060; -.
DR HOGENOM; CLU_012979_1_0_1; -.
DR InParanoid; Q9ESN3; -.
DR OMA; PVMREDM; -.
DR OrthoDB; 704708at2759; -.
DR PhylomeDB; Q9ESN3; -.
DR TreeFam; TF331003; -.
DR BioGRID-ORCS; 60455; 0 hits in 76 CRISPR screens.
DR ChiTaRS; Tmem8; mouse.
DR PRO; PR:Q9ESN3; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9ESN3; protein.
DR Bgee; ENSMUSG00000024180; Expressed in right kidney and 147 other tissues.
DR ExpressionAtlas; Q9ESN3; baseline and differential.
DR Genevisible; Q9ESN3; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004623; F:phospholipase A2 activity; IEA:UniProtKB-EC.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR021910; NGX6/PGAP6/MYMK.
DR PANTHER; PTHR14319; PTHR14319; 1.
DR Pfam; PF12036; DUF3522; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond; EGF-like domain;
KW Glycoprotein; Hydrolase; Lipid metabolism; Lysosome; Membrane;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..769
FT /note="Post-GPI attachment to proteins factor 6"
FT /id="PRO_0000022540"
FT TOPO_DOM 34..543
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 544..564
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 565..567
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 568..588
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 589..603
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 604..624
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 625..627
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 628..648
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 649..651
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 652..672
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 673..688
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 689..709
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 710..715
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 716..736
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 737..769
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 495..531
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 496..506
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 500..519
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 521..530
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 1..39
FT /note="MGRVGAGGTAREAATGSLLLLLLLLARPPPAAASNSKES -> MLPVCLPHL
FT PDCHLFPV (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004005"
FT CONFLICT 88
FT /note="S -> G (in Ref. 3; AAH05722)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="D -> A (in Ref. 3; AAH05722)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 769 AA; 85329 MW; A0B886EE571B7B60 CRC64;
MGRVGAGGTA REAATGSLLL LLLLLARPPP AAASNSKESE AGLVSEHFSQ APQKLSFYSW
YGSTRLFHFR VPPDTVLLRW LLHVSQGSPS CTDEEITVHF RYGAPPVINP LGTSFPDNTL
SHASFHIRAL LSTLMLDNTS VNISHPAPGD WFLVAHLPPS SQKIQVKGFV PTCAYIFQPD
MLVMRVVEVS TLEPDVPLPQ TLLSYPSYLK IFVPEYTQEL RLELQGCVSS VSPGCPVRVT
VGATTLPRNF QRVLTCTGLA PSCHLLLSSP PWGRWLQVTF ESLAEPHVTV GFTAKAVFTV
CRPWSVTIHH LIQNNPNQTY DTSAIQLSQS AVHRDLGRSS RVDSGPFCLL NYPVLREDTD
VVSVHFQPLN GAFVLVHSSM PSVMQLRLDT GMDSGGSFII VLRTNKTEVT NGTLVAACVN
AASPFLSFNT SLNCTTAFFQ GYPMFLRASS HMANLIMPFP ETDNWYLSLQ LVCPESPEDC
EQAVVRVETI LYLVPCLNDC GPYGQCLLLR RYGYVYAGCS CKAGWRGWSC TDNSTAQTVA
QQRAAALLLT LSNLMFLAPI AISLHRSFLV EASVYFYTMF FSTFYHACDQ PGEAVLCILS
YDTLQYCDFL GSGASTWVTI LCMARLKTIL KQVLLVLGTL VIAMSLQMDR RGIWNLMGPC
VFAFVIMASM WIYRCGHRGQ CYPTSWQRWV FYLLPGISMA SVGIAMYTSM MTSDNYYYTH
SIWHILLAGS AAFLLPPREE KAGSWACLQK FPCHYQICRN DRDELYTVT
