Q9UG56 · PISD_HUMAN

  • Protein
    Phosphatidylserine decarboxylase proenzyme, mitochondrial
  • Gene
    PISD
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Catalyzes the formation of phosphatidylethanolamine (PtdEtn) from phosphatidylserine (PtdSer) (PubMed:30488656, PubMed:30858161).
Plays a central role in phospholipid metabolism and in the interorganelle trafficking of phosphatidylserine. May be involved in lipid droplet biogenesis at the endoplasmic reticulum membrane (By similarity).

Catalytic activity

Cofactor

pyruvate (UniProtKB | Rhea| CHEBI:15361 )

Note: Binds 1 pyruvoyl group covalently per subunit.

Pathway

Phospholipid metabolism; phosphatidylethanolamine biosynthesis.

Features

Showing features for active site, site.

TypeIDPosition(s)Description
Active site191Charge relay system; for autoendoproteolytic cleavage activity
Active site267Charge relay system; for autoendoproteolytic cleavage activity
Site377-378Cleavage (non-hydrolytic); by autocatalysis
Active site378Charge relay system; for autoendoproteolytic cleavage activity
Active site378Schiff-base intermediate with substrate; via pyruvic acid; for decarboxylase activity

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular ComponentGolgi apparatus
Cellular Componentlipid droplet
Cellular Componentmitochondrial inner membrane
Cellular Componentmitochondrion
Cellular Componentnucleus
Molecular Functionphosphatidylserine decarboxylase activity
Biological Processlipid droplet formation
Biological Processmitochondrial protein catabolic process
Biological Processphosphatidylethanolamine biosynthetic process
Biological Processprotein autoprocessing
Biological Processregulation of mitochondrion organization

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

Gene names

    • Name
      PISD

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q9UG56
  • Secondary accessions
    • B1AKM7
    • O43207
    • O95535
    • Q6IC28
    • Q96GQ2
    • Q9UGA9

Proteomes

Organism-specific databases

Subcellular Location

Phosphatidylserine decarboxylase beta chain

Mitochondrion inner membrane
; Single-pass membrane protein

Phosphatidylserine decarboxylase alpha chain

Mitochondrion inner membrane
; Peripheral membrane protein
Cytoplasm
Note: Anchored to the mitochondrial inner membrane through its interaction with the integral membrane beta chain.

Isoform 1

Isoform 2

Lipid droplet
Note: Predominantly localizes to lipid droplets in lipid-replete conditions, and to mitochondria in lipid-deplete conditions.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain53-63Mitochondrial matrix
Transmembrane64-82Helical
Topological domain83-409Mitochondrial intermembrane

Keywords

Disease & Variants

Involvement in disease

Liberfarb syndrome (LIBF)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An autosomal recessive multisystem disorder affecting the eye, ear, bone, and brain development. Clinical features include early-onset retinal degeneration, congenital cataracts, sensorineural hearing loss, microcephaly, intellectual disability, white matter changes, mild facial dysmorphism, and skeletal dysplasia with platyspondyly, scoliosis and short stature.
  • See also
    MIM:618889
Natural variants in LIBF
Variant IDPosition(s)ChangeDescription
VAR_084458277R>Qin LIBF; loss of autocatalytic processing; decreased protein abundance; decreased phosphatidylserine decarboxylase activity; changed mitochondrion organization; dbSNP:rs147371584
VAR_084459300C>Yin LIBF; loss of autocatalytic processing; probably decreased phosphatidylserine decarboxylase activity; changed mitochondrion organization; patient-derived fibroblasts show fragmented mitochondrial morphology around the nucleus; decreased cell viability with increased CASP3 and CASP7 activation; dbSNP:rs2072505076

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_084458277in LIBF; loss of autocatalytic processing; decreased protein abundance; decreased phosphatidylserine decarboxylase activity; changed mitochondrion organization; dbSNP:rs147371584
Natural variantVAR_084459300in LIBF; loss of autocatalytic processing; probably decreased phosphatidylserine decarboxylase activity; changed mitochondrion organization; patient-derived fibroblasts show fragmented mitochondrial morphology around the nucleus; decreased cell viability with increased CASP3 and CASP7 activation; dbSNP:rs2072505076
Mutagenesis378Loss of autocatalytic processing.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 521 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for transit peptide, chain, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
Transit peptide1-52UniProtMitochondrion
ChainPRO_000002983553-377UniProtPhosphatidylserine decarboxylase beta chain
ChainPRO_000043557153-409UniProtPhosphatidylserine decarboxylase proenzyme, mitochondrial
Modified residue (large scale data)341PRIDEPhosphoserine
Modified residue378UniProtPyruvic acid (Ser); by autocatalysis
ChainPRO_0000029836378-409UniProtPhosphatidylserine decarboxylase alpha chain

Post-translational modification

Is synthesized initially as an inactive proenzyme. Formation of the active enzyme involves a self-maturation process in which the active site pyruvoyl group is generated from an internal serine residue via an autocatalytic post-translational modification. Two non-identical subunits are generated from the proenzyme in this reaction, and the pyruvate is formed at the N-terminus of the alpha chain, which is derived from the carboxyl end of the proenzyme. The autoendoproteolytic cleavage occurs by a canonical serine protease mechanism, in which the side chain hydroxyl group of the serine supplies its oxygen atom to form the C-terminus of the beta chain, while the remainder of the serine residue undergoes an oxidative deamination to produce ammonia and the pyruvoyl prosthetic group on the alpha chain. During this reaction, the Ser that is part of the protease active site of the proenzyme becomes the pyruvoyl prosthetic group, which constitutes an essential element of the active site of the mature decarboxylase.

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

Heterodimer of a large membrane-associated beta subunit and a small pyruvoyl-containing alpha subunit.

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q9UG56-2CIDEB Q9UHD43EBI-17870882, EBI-7062247

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region36-103In isoform Q9UG56-2; Necessary for localization to both lipid droplets and mitochondria

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 2 isoforms produced by Alternative splicing.

Q9UG56-3

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    1
  • Synonyms
    PISD-M
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    409
  • Mass (Da)
    46,672
  • Last updated
    2010-11-02 v4
  • Checksum
    6A5148265369D9DF
MATSVGHRCLGLLHGVAPWRSSLHPCEITALSQSLQPLRKLPFRAFRTDARKIHTAPARTMFLLRPLPILLVTGGGYAGYRQYEKYRERELEKLGLEIPPKLAGHWEVALYKSVPTRLLSRAWGRLNQVELPHWLRRPVYSLYIWTFGVNMKEAAVEDLHHYRNLSEFFRRKLKPQARPVCGLHSVISPSDGRILNFGQVKNCEVEQVKGVTYSLESFLGPRMCTEDLPFPPAASCDSFKNQLVTREGNELYHCVIYLAPGDYHCFHSPTDWTVSHRRHFPGSLMSVNPGMARWIKELFCHNERVVLTGDWKHGFFSLTAVGATNVGSIRIYFDRDLHTNSPRHSKGSYNDFSFVTHTNREGVPMRKGEHLGEFNLGSTIVLIFEAPKDFNFQLKTGQKIRFGEALGSL

Q9UG56-2

  • Name
    2
  • Synonyms
    PISD-LD
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-107: MATSVGHRCLGLLHGVAPWRSSLHPCEITALSQSLQPLRKLPFRAFRTDARKIHTAPARTMFLLRPLPILLVTGGGYAGYRQYEKYRERELEKLGLEIPPKLAGHWE → MMCQSEARQGPELRAAKWLHFPQLALRRRLGQLSCMSRPALKLRSWPLTVLYYLLPFGALRPLSRVGWRPVSR

Computationally mapped potential isoform sequences

There are 6 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
F8WCS6F8WCS6_HUMANPISD56
H0Y7P7H0Y7P7_HUMANPISD362
B1AKM6B1AKM6_HUMANPISD262
B1AKM8B1AKM8_HUMANPISD228
B1AKM9B1AKM9_HUMANPISD81
B1AKN0B1AKN0_HUMANPISD73

Sequence caution

The sequence CAB43678.2 differs from that shown. Reason: Erroneous translation

Features

Showing features for alternative sequence.

TypeIDPosition(s)Description
Alternative sequenceVSP_0075401-107in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
CR456540
EMBL· GenBank· DDBJ
CAG30426.1
EMBL· GenBank· DDBJ
mRNA
AL050371
EMBL· GenBank· DDBJ
CAB43678.2
EMBL· GenBank· DDBJ
Transcribed RNA Sequence problems.
AL096768
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL031255
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471095
EMBL· GenBank· DDBJ
EAW59984.1
EMBL· GenBank· DDBJ
Genomic DNA
BC001482
EMBL· GenBank· DDBJ
AAH01482.1
EMBL· GenBank· DDBJ
mRNA
BC009315
EMBL· GenBank· DDBJ
AAH09315.1
EMBL· GenBank· DDBJ
mRNA
AF035304
EMBL· GenBank· DDBJ
AAB88186.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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