Q92539 (LPIN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidate phosphatase LPIN2
EC=3.1.3.4

Alternative name(s):
Lipin-2

Gene names

Name:	LPIN2
Synonyms:	KIAA0249

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	896 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays important roles in controlling the metabolism of fatty acids at differents levels. Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis in the reticulum endoplasmic membrane. Acts also as a nuclear transcriptional coactivator for PPARGC1A to modulate lipid metabolism By similarity.
Catalytic activity	A 1,2-diacylglycerol 3-phosphate + H2O = a 1,2-diacyl-sn-glycerol + phosphate.
Cofactor	Mg2+ By similarity.
Enzyme regulation	Inhibited by N-ethylmaleimide By similarity.
Subcellular location	Nucleus By similarity. Cytoplasm › cytosol By similarity. Endoplasmic reticulum membrane By similarity. Note: Translocates to endoplasmic reticulum membrane with increasing levels of oleate By similarity.
Tissue specificity	Expressed in liver, lung, kidney, placenta, spleen, thymus, lymph node, prostate, testes, small intestine, and colon. Ref.5 Ref.9
Domain	Contains 1 Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif known to be essential for phosphatidate phosphatase activity By similarity. Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, a motif known to be a transcriptional binding motif By similarity.
Involvement in disease	Majeed syndrome (MAJEEDS) [MIM:609628]: An autosomal recessive syndrome characterized by chronic recurrent multifocal osteomyelitis that is of early onset with a lifelong course, congenital dyserythropoietic anemia that presents as hypochromic, microcytic anemia during the first year of life and ranges from mild to transfusion-dependent, and transient inflammatory dermatosis, often manifesting as Sweet syndrome (neutrophilic skin infiltration). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the lipin family.
Sequence caution	The sequence BAA13380.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism Transcription Transcription regulation
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Nucleus
Disease	Congenital dyserythropoietic anemia Disease mutation Hereditary hemolytic anemia
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylcholine biosynthetic process Traceable author statement. Source: Reactome phosphatidylethanolamine biosynthetic process Traceable author statement. Source: Reactome positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW triglyceride biosynthetic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	phosphatidate phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB transcription coactivator activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 896	896	Phosphatidate phosphatase LPIN2		PRO_0000209881
Regions
	Region	1 – 108	108	N-LIP
	Region	635 – 837	203	C-LIP
	Motif	153 – 158	6	Nuclear localization signal Potential
	Motif	689 – 693	5	DXDXT motif
	Motif	700 – 704	5	LXXIL motif
Amino acid modifications
	Modified residue	106	1	Phosphoserine By similarity
	Modified residue	186	1	Phosphoserine By similarity
	Modified residue	187	1	Phosphoserine By similarity
	Modified residue	243	1	Phosphoserine By similarity
	Modified residue	245	1	Phosphoserine By similarity
Natural variations
	Natural variant	734	1	S → L in MAJEEDS. Ref.9		VAR_023817

Sequences

	Sequence		Length	Mass (Da)
	Q92539 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 080113FCCA533272	FASTA	896	99,399
	10 20 30 40 50 60 MNYVGQLAGQ VIVTVKELYK GINQATLSGC IDVIVVQQQD GSYQCSPFHV RFGKLGVLRS 70 80 90 100 110 120 KEKVIDIEIN GSAVDLHMKL GDNGEAFFVE ETEEEYEKLP AYLATSPIPT EDQFFKDIDT 130 140 150 160 170 180 PLVKSGGDET PSQSSDISHV LETETIFTPS SVKKKKRRRK KYKQDSKKEE QAASAAAEDT 190 200 210 220 230 240 CDVGVSSDDD KGAQAARGSS NASLKEEECK EPLLFHSGDH YPLSDGDWSP LETTYPQTAC 250 260 270 280 290 300 PKSDSELEVK PAESLLRSES HMEWTWGGFP ESTKVSKRER SDHHPRTATI TPSENTHFRV 310 320 330 340 350 360 IPSEDNLISE VEKDASMEDT VCTIVKPKPR ALGTQMSDPT SVAELLEPPL ESTQISSMLD 370 380 390 400 410 420 ADHLPNAALA EAPSESKPAA KVDSPSKKKG VHKRSQHQGP DDIYLDDLKG LEPEVAALYF 430 440 450 460 470 480 PKSESEPGSR QWPESDTLSG SQSPQSVGSA AADSGTECLS DSAMDLPDVT LSLCGGLSEN 490 500 510 520 530 540 GEISKEKFME HIITYHEFAE NPGLIDNPNL VIRIYNRYYN WALAAPMILS LQVFQKSLPK 550 560 570 580 590 600 ATVESWVKDK MPKKSGRWWF WRKRESMTKQ LPESKEGKSE APPASDLPSS SKEPAGARPA 610 620 630 640 650 660 ENDSSSDEGS QELEESITVD PIPTEPLSHG STTSYKKSLR LSSDQIAKLK LHDGPNDVVF 670 680 690 700 710 720 SITTQYQGTC RCAGTIYLWN WNDKIIISDI DGTITKSDAL GQILPQLGKD WTHQGIAKLY 730 740 750 760 770 780 HSINENGYKF LYCSARAIGM ADMTRGYLHW VNDKGTILPR GPLMLSPSSL FSAFHREVIE 790 800 810 820 830 840 KKPEKFKIEC LNDIKNLFAP SKQPFYAAFG NRPNDVYAYT QVGVPDCRIF TVNPKGELIQ 850 860 870 880 890 ERTKGNKSSY HRLSELVEHV FPLLSKEQNS AFPCPEFSSF CYWRDPIPEV DLDDLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow.
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[5]	"Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns." Donkor J., Sariahmetoglu M., Dewald J., Brindley D.N., Reue K. J. Biol. Chem. 282:3450-3457(2007) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Platelet.
[7]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome)." Ferguson P.J., Chen S., Tayeh M.K., Ochoa L., Leal S.M., Pelet A., Munnich A., Lyonnet S., Majeed H.A., El-Shanti H. J. Med. Genet. 42:551-557(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MAJEEDS LEU-734, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Web resources

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

Cross-references

Sequence databases
EMBL GenBank DDBJ	D87436 mRNA. Translation: BAA13380.2. Different initiation. CH471113 Genomic DNA. Translation: EAX01686.1. CH471113 Genomic DNA. Translation: EAX01687.1. BC152448 mRNA. Translation: AAI52449.1.
IPI	IPI00021956.
RefSeq	NP_055461.1. NM_014646.2.
UniGene	Hs.132342.
3D structure databases
ProteinModelPortal	Q92539.
SMR	Q92539. Positions 684-751.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92539. 2 interactions.
STRING	9606.ENSP00000261596.
PTM databases
PhosphoSite	Q92539.
Polymorphism databases
DMDM	2495724.
Proteomic databases
PaxDb	Q92539.
PRIDE	Q92539.
Protocols and materials databases
DNASU	9663.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261596; ENSP00000261596; ENSG00000101577.
GeneID	9663.
KEGG	hsa:9663.
UCSC	uc002klo.3. human.
Organism-specific databases
CTD	9663.
GeneCards	GC18M002906.
HGNC	HGNC:14450. LPIN2.
HPA	CAB015223. HPA017857.
MIM	605519. gene. 609628. phenotype.
neXtProt	NX_Q92539.
Orphanet	77297. Majeed syndrome.
PharmGKB	PA30437.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5083.
HOGENOM	HOG000230954.
HOVERGEN	HBG052338.
InParanoid	Q92539.
KO	K15728.
OMA	YLWNWND.
OrthoDB	EOG4X97GK.
PhylomeDB	Q92539.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
Bgee	Q92539.
CleanEx	HS_LPIN2.
Genevestigator	Q92539.
GermOnline	ENSG00000101577. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.1000. 1 hit.
InterPro	IPR023214. HAD-like_dom. IPR026058. LIPIN. IPR007651. Lipin_N. IPR013209. LNS2. IPR026744. LPIN2. [Graphical view]
PANTHER	PTHR12181. PTHR12181. 1 hit. PTHR12181:SF11. PTHR12181:SF11. 1 hit.
Pfam	PF04571. Lipin_N. 1 hit. PF08235. LNS2. 1 hit. [Graphical view]
SMART	SM00775. LNS2. 1 hit. [Graphical view]
SUPFAM	SSF56784. HAD-like_dom. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	9663.
NextBio	36287.
SOURCE	Search...

Entry information

Entry name

LPIN2_HUMAN

Accession

Primary (citable) accession number: Q92539
Secondary accession number(s): A7MD25, D3DUH3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 1, 1997
Last modified:	May 1, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.