O95476 (CNEP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CTD nuclear envelope phosphatase 1
EC=3.1.3.16

Alternative name(s):
Serine/threonine-protein phosphatase dullard

Gene names

Name:	CTDNEP1
Synonyms:	DULLARD

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	244 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine protein phosphatase forming with CNEP1R1 an active phosphatase complex that dephosphorylates and may activate LPIN1 and LPIN2. LPIN1 and LPIN2 are phosphatidate phosphatases that catalyze the conversion of phosphatidic acid to diacylglycerol and control the metabolism of fatty acids at differents levels. May indirectly modulate the lipid composition of nuclear and/or endoplasmic reticulum membranes and be required for proper nuclear membrane morphology and/or dynamics. May also indirectly regulate the production of lipid droplets and triacylglycerol. May antagonize BMP signaling. Ref.7 Ref.9
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Subunit structure	Interacts with CNEP1R1; the complex dephosphorylates LPIN1 and LPIN2. Ref.9
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein Ref.2 Ref.7 Ref.9.
Tissue specificity	Muscle specific with lower expression in other metabolic tissues. Ref.9
Sequence similarities	Belongs to the dullard family. Contains 1 FCP1 homology domain.
Biophysicochemical properties	Kinetic parameters: KM=18 mM for p-nitrophenylphosphate Ref.7 pH dependence: Optimum pH is 5.5.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase Protein phosphatase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nuclear envelope organization Inferred from direct assay Ref.7. Source: UniProtKB positive regulation of triglyceride biosynthetic process Inferred from genetic interaction Ref.9. Source: UniProtKB protein dephosphorylation Inferred from direct assay Ref.7Ref.9. Source: UniProtKB protein localization to nucleus Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	Nem1-Spo7 phosphatase complex Inferred from direct assay Ref.9. Source: UniProtKB endoplasmic reticulum membrane Inferred from direct assay Ref.7. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nuclear membrane Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	protein serine/threonine phosphatase activity Inferred from mutant phenotype Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CNEP1R1	Q8N9A8	4	EBI-5323433,EBI-5323455

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 244	244	CTD nuclear envelope phosphatase 1		PRO_0000297967
Regions
	Transmembrane	7 – 29	23	Helical; Potential
	Domain	57 – 224	168	FCP1 homology
Natural variations
	Natural variant	12	1	T → A. Ref.1 Ref.2 Corresponds to variant rs3744399 [ dbSNP | Ensembl ].		VAR_034699
Experimental info
	Mutagenesis	67	1	D → N or E: Abolishes phosphatase activity. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	O95476 [UniParc]. Last modified November 3, 2009. Version 2. Checksum: 062952A90F74575A	FASTA	244	28,377
	10 20 30 40 50 60 MMRTQCLLGL RTFVAFAAKL WSFFIYLLRR QIRTVIQYQT VRYDILPLSP VSRNRLAQVK 70 80 90 100 110 120 RKILVLDLDE TLIHSHHDGV LRPTVRPGTP PDFILKVVID KHPVRFFVHK RPHVDFFLEV 130 140 150 160 170 180 VSQWYELVVF TASMEIYGSA VADKLDNSRS ILKRRYYRQH CTLELGSYIK DLSVVHSDLS 190 200 210 220 230 240 SIVILDNSPG AYRSHPDNAI PIKSWFSDPS DTALLNLLPM LDALRFTADV RSVLSRNLHQ HRLW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Keen J., Inglehearn C. Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-12. Tissue: Brain.
[2]	"NovelFam3000 -- uncharacterized human protein domains conserved across model organisms." Kemmer D., Podowski R.M., Arenillas D., Lim J., Hodges E., Roth P., Sonnhammer E.L.L., Hoeoeg C., Wasserman W.W. BMC Genomics 7:48-48(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, VARIANT ALA-12.
[3]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[5]	"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]. Tissue: Muscle.
[6]	"Molecular cloning and characterization of dullard: a novel gene required for neural development." Satow R., Chan T.C., Asashima M. Biochem. Biophys. Res. Commun. 295:85-91(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
[7]	"A conserved phosphatase cascade that regulates nuclear membrane biogenesis." Kim Y., Gentry M.S., Harris T.E., Wiley S.E., Lawrence J.C. Jr., Dixon J.E. Proc. Natl. Acad. Sci. U.S.A. 104:6596-6601(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-67, SUBCELLULAR LOCATION.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[9]	"Nuclear envelope phosphatase-regulatory subunit 1 (formerly TMEM188) is the metazoan SPO7 ortholog and functions in the lipin activation pathway." Han S., Bahmanyar S., Zhang P., Grishin N., Oegema K., Crooke R., Graham M., Reue K., Dixon J.E., Goodman J.M. J. Biol. Chem. 287:3123-3137(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LPIN1 AND LPIN2 DEPHOSPHORYLATION, INTERACTION WITH CNEP1R1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ011916 mRNA. Translation: CAA09865.1. AY364239 mRNA. Translation: AAQ76798.1. AC003688 Genomic DNA. No translation available. AC120057 Genomic DNA. No translation available. CH471108 Genomic DNA. Translation: EAW90233.1. CH471108 Genomic DNA. Translation: EAW90235.1. CH471108 Genomic DNA. Translation: EAW90236.1. BC009295 mRNA. Translation: AAH09295.1.
IPI	IPI00383704.
RefSeq	NP_001137247.1. NM_001143775.1. NP_056158.2. NM_015343.4.
UniGene	Hs.741244.
3D structure databases
HSSP	HSSP built from PDB template 1TA0 based on UniProtKB Q9GZU7.
ProteinModelPortal	O95476.
SMR	O95476. Positions 57-234.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95476. 2 interactions.
STRING	9606.ENSP00000321732.
PTM databases
PhosphoSite	O95476.
Proteomic databases
PaxDb	O95476.
PRIDE	O95476.
Protocols and materials databases
DNASU	23399.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000318988; ENSP00000321732; ENSG00000175826. ENST00000573600; ENSP00000461749; ENSG00000175826. ENST00000574205; ENSP00000458758; ENSG00000175826. ENST00000574322; ENSP00000460683; ENSG00000175826.
GeneID	23399.
KEGG	hsa:23399.
UCSC	uc002gfd.2. human.
Organism-specific databases
CTD	23399.
GeneCards	GC17M007147.
HGNC	HGNC:19085. CTDNEP1.
HPA	HPA037439.
MIM	610684. gene.
neXtProt	NX_O95476.
PharmGKB	PA134937999.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5190.
HOGENOM	HOG000236379.
HOVERGEN	HBG098153.
InParanoid	O95476.
OMA	SRNRLGQ.
OrthoDB	EOG4J6RRP.
PhylomeDB	O95476.
Enzyme and pathway databases
SABIO-RK	O95476.
Gene expression databases
ArrayExpress	O95476.
Bgee	O95476.
CleanEx	HS_DULLARD.
Genevestigator	O95476.
Family and domain databases
Gene3D	3.40.50.1000. 1 hit.
InterPro	IPR011948. Dullard_phosphatase. IPR023214. HAD-like_dom. IPR004274. NIF. [Graphical view]
Pfam	PF03031. NIF. 1 hit. [Graphical view]
SMART	SM00577. CPDc. 1 hit. [Graphical view]
SUPFAM	SSF56784. HAD-like_dom. 1 hit.
TIGRFAMs	TIGR02251. HIF-SF_euk. 1 hit.
PROSITE	PS50969. FCP1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CTDNEP1. human.
GenomeRNAi	23399.
NextBio	45549.
SOURCE	Search...

Entry information

Entry name

CNEP1_HUMAN

Accession

Primary (citable) accession number: O95476
Secondary accession number(s): D3DTN7, Q96GQ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 21, 2007
Last sequence update:	November 3, 2009
Last modified:	May 1, 2013
This is version 81 of the entry and version 2 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.