PISD_MOUSE
ID PISD_MOUSE Reviewed; 406 AA.
AC Q8BSF4; Q8BSD6;
DT 30-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Phosphatidylserine decarboxylase proenzyme, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03208};
DE EC=4.1.1.65 {ECO:0000250|UniProtKB:Q9UG56, ECO:0000255|HAMAP-Rule:MF_03208};
DE Contains:
DE RecName: Full=Phosphatidylserine decarboxylase beta chain {ECO:0000255|HAMAP-Rule:MF_03208};
DE Contains:
DE RecName: Full=Phosphatidylserine decarboxylase alpha chain {ECO:0000255|HAMAP-Rule:MF_03208};
DE Flags: Precursor;
GN Name=Pisd {ECO:0000255|HAMAP-Rule:MF_03208};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Colon;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP SUBCELLULAR LOCATION.
RX PubMed=6862014; DOI=10.1016/0014-5793(83)81141-7;
RA Zborowski J., Dygas A., Wojtczak L.;
RT "Phosphatidylserine decarboxylase is located on the external side of the
RT inner mitochondrial membrane.";
RL FEBS Lett. 157:179-182(1983).
RN [4]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=16192276; DOI=10.1074/jbc.m506510200;
RA Steenbergen R., Nanowski T.S., Beigneux A., Kulinski A., Young S.G.,
RA Vance J.E.;
RT "Disruption of the phosphatidylserine decarboxylase gene in mice causes
RT embryonic lethality and mitochondrial defects.";
RL J. Biol. Chem. 280:40032-40040(2005).
CC -!- FUNCTION: Catalyzes the formation of phosphatidylethanolamine (PtdEtn)
CC from phosphatidylserine (PtdSer). Plays a central role in phospholipid
CC metabolism and in the interorganelle trafficking of phosphatidylserine.
CC {ECO:0000255|HAMAP-Rule:MF_03208}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine + H(+) = a 1,2-
CC diacyl-sn-glycero-3-phosphoethanolamine + CO2; Xref=Rhea:RHEA:20828,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57262,
CC ChEBI:CHEBI:64612; EC=4.1.1.65; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03208};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20829;
CC Evidence={ECO:0000250|UniProtKB:Q9UG56};
CC -!- COFACTOR:
CC Name=pyruvate; Xref=ChEBI:CHEBI:15361;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03208};
CC Note=Binds 1 pyruvoyl group covalently per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_03208};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylethanolamine
CC biosynthesis. {ECO:0000250|UniProtKB:Q9UG56}.
CC -!- SUBUNIT: Heterodimer of a large membrane-associated beta subunit and a
CC small pyruvoyl-containing alpha subunit. {ECO:0000255|HAMAP-
CC Rule:MF_03208}.
CC -!- SUBCELLULAR LOCATION: [Phosphatidylserine decarboxylase beta chain]:
CC Mitochondrion inner membrane {ECO:0000255|HAMAP-Rule:MF_03208,
CC ECO:0000269|PubMed:6862014}; Single-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03208}; Intermembrane side
CC {ECO:0000255|HAMAP-Rule:MF_03208}.
CC -!- SUBCELLULAR LOCATION: [Phosphatidylserine decarboxylase alpha chain]:
CC Mitochondrion inner membrane {ECO:0000255|HAMAP-Rule:MF_03208,
CC ECO:0000269|PubMed:6862014}; Peripheral membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03208}; Intermembrane side
CC {ECO:0000255|HAMAP-Rule:MF_03208}. Note=Anchored to the mitochondrial
CC inner membrane through its interaction with the integral membrane beta
CC chain. {ECO:0000255|HAMAP-Rule:MF_03208}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in testis,
CC including Sertoli cells, followed by liver.
CC {ECO:0000269|PubMed:16192276}.
CC -!- DEVELOPMENTAL STAGE: Expressed during development in tissues rich in
CC mitochondria, such as heart. In liver, low expression level observed in
CC embryos and newborn animals increases 10-fold in adult.
CC {ECO:0000269|PubMed:16192276}.
CC -!- PTM: Is synthesized initially as an inactive proenzyme. Formation of
CC the active enzyme involves a self-maturation process in which the
CC active site pyruvoyl group is generated from an internal serine residue
CC via an autocatalytic post-translational modification. Two non-identical
CC subunits are generated from the proenzyme in this reaction, and the
CC pyruvate is formed at the N-terminus of the alpha chain, which is
CC derived from the carboxyl end of the proenzyme. The autoendoproteolytic
CC cleavage occurs by a canonical serine protease mechanism, in which the
CC side chain hydroxyl group of the serine supplies its oxygen atom to
CC form the C-terminus of the beta chain, while the remainder of the
CC serine residue undergoes an oxidative deamination to produce ammonia
CC and the pyruvoyl prosthetic group on the alpha chain. During this
CC reaction, the Ser that is part of the protease active site of the
CC proenzyme becomes the pyruvoyl prosthetic group, which constitutes an
CC essential element of the active site of the mature decarboxylase.
CC {ECO:0000255|HAMAP-Rule:MF_03208}.
CC -!- DISRUPTION PHENOTYPE: Mutant embryos die in utero between 8 and 10 dpc.
CC They exhibit large numbers of aberrantly shaped mitochondria. In mutant
CC embryonic fibroblasts, fragmented, rounded mitochondria of irregular
CC diameter are widely dispersed throughout the cell rather than being
CC concentrated around the nucleus. {ECO:0000269|PubMed:16192276}.
CC -!- SIMILARITY: Belongs to the phosphatidylserine decarboxylase family.
CC PSD-B subfamily. Eukaryotic type I sub-subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_03208}.
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DR EMBL; AK033483; BAC28313.1; -; mRNA.
DR EMBL; AK034656; BAC28786.1; -; mRNA.
DR EMBL; BC070408; AAH70408.1; -; mRNA.
DR CCDS; CCDS19194.1; -.
DR RefSeq; NP_796272.2; NM_177298.3.
DR AlphaFoldDB; Q8BSF4; -.
DR SMR; Q8BSF4; -.
DR BioGRID; 236418; 2.
DR STRING; 10090.ENSMUSP00000051438; -.
DR iPTMnet; Q8BSF4; -.
DR PhosphoSitePlus; Q8BSF4; -.
DR EPD; Q8BSF4; -.
DR MaxQB; Q8BSF4; -.
DR PaxDb; Q8BSF4; -.
DR PeptideAtlas; Q8BSF4; -.
DR PRIDE; Q8BSF4; -.
DR ProteomicsDB; 288168; -.
DR DNASU; 320951; -.
DR Ensembl; ENSMUST00000061895; ENSMUSP00000051438; ENSMUSG00000023452.
DR GeneID; 320951; -.
DR KEGG; mmu:320951; -.
DR UCSC; uc008wzv.1; mouse.
DR CTD; 23761; -.
DR MGI; MGI:2445114; Pisd.
DR VEuPathDB; HostDB:ENSMUSG00000023452; -.
DR eggNOG; KOG2420; Eukaryota.
DR GeneTree; ENSGT00390000013484; -.
DR InParanoid; Q8BSF4; -.
DR OrthoDB; 1226492at2759; -.
DR PhylomeDB; Q8BSF4; -.
DR TreeFam; TF313148; -.
DR UniPathway; UPA00558; -.
DR BioGRID-ORCS; 320951; 19 hits in 75 CRISPR screens.
DR ChiTaRS; Pisd; mouse.
DR PRO; PR:Q8BSF4; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BSF4; protein.
DR Bgee; ENSMUSG00000023452; Expressed in hypothalamus and 115 other tissues.
DR ExpressionAtlas; Q8BSF4; baseline and differential.
DR Genevisible; Q8BSF4; MM.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0004609; F:phosphatidylserine decarboxylase activity; ISS:UniProtKB.
DR GO; GO:0035694; P:mitochondrial protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006646; P:phosphatidylethanolamine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IEA:UniProtKB-UniRule.
DR GO; GO:0010821; P:regulation of mitochondrion organization; ISS:UniProtKB.
DR HAMAP; MF_03208; PS_decarb_PSD_B_type1_euk; 1.
DR InterPro; IPR003817; PS_Dcarbxylase.
DR InterPro; IPR033177; PSD.
DR InterPro; IPR033661; PSD_type1_euk.
DR PANTHER; PTHR10067; PTHR10067; 1.
DR Pfam; PF02666; PS_Dcarbxylase; 1.
DR TIGRFAMs; TIGR00163; PS_decarb; 1.
PE 2: Evidence at transcript level;
KW Decarboxylase; Lipid biosynthesis; Lipid metabolism; Lyase; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Phospholipid biosynthesis;
KW Phospholipid metabolism; Pyruvate; Reference proteome; Transit peptide;
KW Transmembrane; Transmembrane helix; Zymogen.
FT TRANSIT 1..49
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT CHAIN 50..406
FT /note="Phosphatidylserine decarboxylase proenzyme,
FT mitochondrial"
FT /id="PRO_0000435572"
FT CHAIN 50..374
FT /note="Phosphatidylserine decarboxylase beta chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT /id="PRO_0000029837"
FT CHAIN 375..406
FT /note="Phosphatidylserine decarboxylase alpha chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT /id="PRO_0000029838"
FT TOPO_DOM 50..60
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT TRANSMEM 61..79
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT TOPO_DOM 80..406
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT ACT_SITE 188
FT /note="Charge relay system; for autoendoproteolytic
FT cleavage activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT ACT_SITE 264
FT /note="Charge relay system; for autoendoproteolytic
FT cleavage activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT ACT_SITE 375
FT /note="Charge relay system; for autoendoproteolytic
FT cleavage activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT ACT_SITE 375
FT /note="Schiff-base intermediate with substrate; via pyruvic
FT acid; for decarboxylase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT SITE 374..375
FT /note="Cleavage (non-hydrolytic); by autocatalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT MOD_RES 375
FT /note="Pyruvic acid (Ser); by autocatalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03208"
FT CONFLICT 338..340
FT /note="SPR -> KPK (in Ref. 1; BAC28786)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 406 AA; 45927 MW; 6614312FA8BA9704 CRC64;
MAASGGRACV RSLRGGVLWR SSPCHYESTA TRHFLGTLQK LPLQAGVRNF HTAPVRSLFL
LRPVPILLAT GGGYAGYRQY EKYRERKLEK LGLEIPPKLA SHWEVSLYKS VPTRLLSRAC
GRLNQVELPY WLRRPVYSLY IWTFGVNMTE AAVEDLHHYR NLSEFFRRKL KPQARPVCGL
HCVTSPSDGK ILTFGQVKNS EVEQVKGVTY SLESFLGPRA NTEDLPFPPA SSSDSFRNQL
VTREGNELYH CVIYLAPGDY HCFHSPTDWT ISHRRHFPGS LMSVNPGMAR WIKELFCHNE
RVVLTGDWKH GFFSLTAVGA TNVGSIRIHF DRDLHTNSPR YSKGSYNDLS FVTHANKEGI
PMRKGEPLGE FNLGSTIVLI FEAPKDFNFR LKAGQKIRFG EALGSL
