LPIN1 (lipin 1)

Gene

• Entrez ID: 23175
• Gene name: Lipin 1
• Gene symbol: LPIN1
• Synonyms: PAP1
• Chromosome: 2
• Chromosome location: 2p25.1
• Summary: This gene encodes a magnesium-ion-dependent phosphatidic acid phosphohydrolase enzyme that catalyzes the penultimate step in triglyceride synthesis including the dephosphorylation of phosphatidic acid to yield diacylglycerol. Expression of this gene is required for adipocyte differentiation and it also functions as a nuclear transcriptional coactivator with some peroxisome proliferator-activated receptors to modulate expression of other genes involved in lipid metabolism. Mutations in this gene are associated with metabolic syndrome, type 2 diabetes, acute recurrent rhabdomyolysis, and autosomal recessive acute recurrent myoglobinuria (ARARM). This gene is also a candidate for several human lipodystrophy syndromes. [provided by RefSeq, Mar 2017]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs119480071	G>T	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs119480072	C>T	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs119480073	C>A,T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained, genic downstream transcript variant, synonymous variant
rs730880306	T>C	Pathogenic	Splice donor variant, downstream transcript variant, genic downstream transcript variant
rs886041544	->GA	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant, 3 prime UTR variant
rs1572770217	G>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1572931008	->GTGTCACCACGCAGTACCA	Likely-pathogenic	Coding sequence variant, non coding transcript variant, genic downstream transcript variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018934	hsa-miR-335-5p	Microarray	18185580
MIRT049016	hsa-miR-92a-3p	CLASH	23622248
MIRT050981	hsa-miR-17-5p	CLASH	23622248
MIRT437695	hsa-miR-27a-3p	Microarray, qRT-PCR	22815788
MIRT437704	hsa-miR-27b-3p	Microarray, qRT-PCR	22815788
MIRT440316	hsa-miR-485-5p	HITS-CLIP	24374217
MIRT440317	hsa-miR-432-3p	HITS-CLIP	24374217
MIRT732617	hsa-miR-122-5p	Luciferase reporter assay, qRT-PCR, Western blot	28287811
MIRT783401	hsa-miR-1289	HITS-CLIP	27418678
MIRT783523	hsa-miR-129-5p	HITS-CLIP	27418678
MIRT784816	hsa-miR-3198	HITS-CLIP	27418678
MIRT785622	hsa-miR-4294	HITS-CLIP	27418678
MIRT785689	hsa-miR-4309	HITS-CLIP	27418678
MIRT786851	hsa-miR-4802-3p	HITS-CLIP	27418678
MIRT786893	hsa-miR-489-3p	HITS-CLIP	27418678
MIRT787159	hsa-miR-514a-3p	HITS-CLIP	27418678
MIRT787171	hsa-miR-514b-3p	HITS-CLIP	27418678
MIRT788348	hsa-miR-6514-5p	HITS-CLIP	27418678

Transcription factors

Transcription factor	Regulation	Reference
NFYA	Unknown	19553673
NFYB	Unknown	19553673
NFYC	Unknown	19553673
SREBF1	Unknown	19553673

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003713	Function	Transcription coactivator activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	32814053
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	ISS	11138012
GO:0005635	Component	Nuclear envelope	TAS
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	ISS
GO:0005741	Component	Mitochondrial outer membrane	IBA	21873635
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005829	Component	Cytosol	IEA
GO:0006642	Process	Triglyceride mobilization	ISS
GO:0006646	Process	Phosphatidylethanolamine biosynthetic process	TAS
GO:0006656	Process	Phosphatidylcholine biosynthetic process	TAS
GO:0007077	Process	Mitotic nuclear envelope disassembly	TAS
GO:0008195	Function	Phosphatidate phosphatase activity	IBA	21873635
GO:0009062	Process	Fatty acid catabolic process	IBA	21873635
GO:0009062	Process	Fatty acid catabolic process	ISS
GO:0016311	Process	Dephosphorylation	IEA
GO:0019432	Process	Triglyceride biosynthetic process	IBA	21873635
GO:0019432	Process	Triglyceride biosynthetic process	TAS
GO:0031100	Process	Animal organ regeneration	IEA
GO:0031965	Component	Nuclear membrane	ISS
GO:0032869	Process	Cellular response to insulin stimulus	IBA	21873635
GO:0044255	Process	Cellular lipid metabolic process	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	23028044

Other IDs

• MIM: 605518
• HGNC: 13345
• e!Ensembl: ENSG00000134324

Protein

• UniProt ID: Q14693
• Protein name: Phosphatidate phosphatase LPIN1 (EC 3.1.3.4) (Lipin-1)
• Protein function: Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis and therefore controls the metabolism of fatty acids at different levels (PubMed:20231281). Acts also as nuclear transcriptional coactivator for PPARGC1A/PPARA regulatory pathway to modulate lipid metabolism gene expression. Is involved in adipocyte differentiation. Isoform 1 is recruited at the mitochondrion outer membrane and is involved in mitochondrial fission by converting phosphatidic acid to diacylglycerol (By similarity).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04571	Lipin_N	1 → 107	lipin, N-terminal conserved region	Family
  PF16876	Lipin_mid	464 → 557	Lipin/Ned1/Smp2 multi-domain protein middle domain	Family
  PF08235	LNS2	626 → 851	LNS2 (Lipin/Ned1/Smp2)	Domain

• Sequence:

  MNYVGQLAGQVFVTVKELYKGLNPATLSGCIDIIVIRQPNGNLQCSPFHVRFGKMGVLRS
  REKVVDIEINGESVDLHMKLGDNGEAFFVQETDNDQEVIPMHLATSPILSEGASRMECQL
  KRGSVDRMRGLDPSTPAQVIAPSETPSSSSVVKKRRKRRRKSQLDSLKRDDNMNTSEDED
  MFPIEMSSDEAMELLESSRTLPNDIPPFQDDIPEENLSLAVIYPQSASYPNSDREWSPTP
  SPSGSRPSTPKSDSELVSKSTERTGQKNPEMLWLWGELPQAAKSSSPHKMKESSPLSSRK
  ICDKSHFQAIHSESSDTFSDQSPTLVGGALLDQNKPQTEMQFVNEEDLETLGAAAPLLPM
  IEELKPPSASVVQTANKTDSPSRKRDKRSRHLGADGVYLDDLTDMDPEVAALYFPKNGDP
  SGLAKHASDNGARSANQSPQSVGSSGVDSGVESTSDGLRDLPSIAISLCGGLSDHREITK
  DAFLEQAVSYQQFVDNPAIIDDPNLVVKIGSKYYNWTTAAPLLLAMQAFQKPLPKATVES
  IMRDKMPKKGGRWWFSWRGRNTTIKEESKPEQCLAGKAHSTGEQPPQLSLATRVKHESSS
  SDEERAAAKPSNAGHLPLLPNVSYKKTLRLTSEQLKSLKLKNGPNDVVFSVTTQYQGTCR
  CEGTIYLWNWDDKVIISDIDGTITRSDTLGHILPTLGKDWTHQGIAKLYHKVSQNGYKFL
  YCSARAIGMADMTRGYLHWVNERGTVLPQGPLLLSPSSLFSALHREVIEKKPEKFKVQCL
  TDIKNLFFPNTEPFYAAFGNRPADVYSYKQVGVSLNRIFTVNPKGELVQEHAKTNISSYV
  RLCEVVDHVFPLLKRSHSSDFPCSDTFSNFTFWREPLPPFENQDIHSASA

• Sequence length: 890