ID   CNEP1_HUMAN             Reviewed;         244 AA.
AC   O95476; D3DTN7; Q96GQ9;
DT   21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT   03-NOV-2009, sequence version 2.
DT   27-MAR-2024, entry version 154.
DE   RecName: Full=CTD nuclear envelope phosphatase 1;
DE            EC=3.1.3.16;
DE   AltName: Full=Serine/threonine-protein phosphatase dullard;
GN   Name=CTDNEP1; Synonyms=DULLARD;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-12.
RC   TISSUE=Brain;
RA   Keen J., Inglehearn C.;
RL   Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND VARIANT ALA-12.
RX   PubMed=16533400; DOI=10.1186/1471-2164-7-48;
RA   Kemmer D., Podowski R.M., Arenillas D., Lim J., Hodges E., Roth P.,
RA   Sonnhammer E.L.L., Hoeoeg C., Wasserman W.W.;
RT   "NovelFam3000 -- uncharacterized human protein domains conserved across
RT   model organisms.";
RL   BMC Genomics 7:48-48(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Muscle;
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   [6]
RP   IDENTIFICATION.
RX   PubMed=12083771; DOI=10.1016/s0006-291x(02)00641-1;
RA   Satow R., Chan T.C., Asashima M.;
RT   "Molecular cloning and characterization of dullard: a novel gene required
RT   for neural development.";
RL   Biochem. Biophys. Res. Commun. 295:85-91(2002).
RN   [7]
RP   FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-67, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=17420445; DOI=10.1073/pnas.0702099104;
RA   Kim Y., Gentry M.S., Harris T.E., Wiley S.E., Lawrence J.C. Jr.,
RA   Dixon J.E.;
RT   "A conserved phosphatase cascade that regulates nuclear membrane
RT   biogenesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:6596-6601(2007).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [9]
RP   FUNCTION IN LPIN1 AND LPIN2 DEPHOSPHORYLATION, INTERACTION WITH CNEP1R1,
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=22134922; DOI=10.1074/jbc.m111.324350;
RA   Han S., Bahmanyar S., Zhang P., Grishin N., Oegema K., Crooke R.,
RA   Graham M., Reue K., Dixon J.E., Goodman J.M.;
RT   "Nuclear envelope phosphatase-regulatory subunit 1 (formerly TMEM188) is
RT   the metazoan SPO7 ortholog and functions in the lipin activation pathway.";
RL   J. Biol. Chem. 287:3123-3137(2012).
CC   -!- FUNCTION: Serine/threonine protein phosphatase forming with CNEP1R1 an
CC       active phosphatase complex that dephosphorylates and may activate LPIN1
CC       and LPIN2. LPIN1 and LPIN2 are phosphatidate phosphatases that catalyze
CC       the conversion of phosphatidic acid to diacylglycerol and control the
CC       metabolism of fatty acids at different levels. May indirectly modulate
CC       the lipid composition of nuclear and/or endoplasmic reticulum membranes
CC       and be required for proper nuclear membrane morphology and/or dynamics.
CC       May also indirectly regulate the production of lipid droplets and
CC       triacylglycerol. May antagonize BMP signaling.
CC       {ECO:0000269|PubMed:17420445, ECO:0000269|PubMed:22134922}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:83421; EC=3.1.3.16;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:61977; EC=3.1.3.16;
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=18 mM for p-nitrophenylphosphate {ECO:0000269|PubMed:17420445};
CC       pH dependence:
CC         Optimum pH is 5.5. {ECO:0000269|PubMed:17420445};
CC   -!- SUBUNIT: Interacts with CNEP1R1; the complex dephosphorylates LPIN1 and
CC       LPIN2. {ECO:0000269|PubMed:22134922}.
CC   -!- INTERACTION:
CC       O95476; Q8N9A8: CNEP1R1; NbExp=4; IntAct=EBI-5323433, EBI-5323455;
CC       O95476; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-5323433, EBI-947187;
CC       O95476; Q9WH76: M; Xeno; NbExp=3; IntAct=EBI-5323433, EBI-10823897;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC       membrane protein. Nucleus membrane; Single-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Muscle specific with lower expression in other
CC       metabolic tissues. {ECO:0000269|PubMed:22134922}.
CC   -!- SIMILARITY: Belongs to the dullard family. {ECO:0000305}.
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DR   EMBL; AJ011916; CAA09865.1; -; mRNA.
DR   EMBL; AY364239; AAQ76798.1; -; mRNA.
DR   EMBL; AC003688; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC120057; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471108; EAW90233.1; -; Genomic_DNA.
DR   EMBL; CH471108; EAW90235.1; -; Genomic_DNA.
DR   EMBL; CH471108; EAW90236.1; -; Genomic_DNA.
DR   EMBL; BC009295; AAH09295.1; -; mRNA.
DR   CCDS; CCDS11093.1; -.
DR   RefSeq; NP_001137247.1; NM_001143775.1.
DR   RefSeq; NP_056158.2; NM_015343.4.
DR   AlphaFoldDB; O95476; -.
DR   SMR; O95476; -.
DR   BioGRID; 116972; 76.
DR   IntAct; O95476; 49.
DR   MINT; O95476; -.
DR   STRING; 9606.ENSP00000460683; -.
DR   DEPOD; CTDNEP1; -.
DR   iPTMnet; O95476; -.
DR   PhosphoSitePlus; O95476; -.
DR   SwissPalm; O95476; -.
DR   BioMuta; CTDNEP1; -.
DR   EPD; O95476; -.
DR   jPOST; O95476; -.
DR   MassIVE; O95476; -.
DR   MaxQB; O95476; -.
DR   PaxDb; 9606-ENSP00000461749; -.
DR   PeptideAtlas; O95476; -.
DR   ProteomicsDB; 50907; -.
DR   Pumba; O95476; -.
DR   TopDownProteomics; O95476; -.
DR   Antibodypedia; 23976; 157 antibodies from 23 providers.
DR   DNASU; 23399; -.
DR   Ensembl; ENST00000318988.10; ENSP00000321732.6; ENSG00000175826.12.
DR   Ensembl; ENST00000573600.5; ENSP00000461749.1; ENSG00000175826.12.
DR   Ensembl; ENST00000574205.5; ENSP00000458758.1; ENSG00000175826.12.
DR   Ensembl; ENST00000574322.6; ENSP00000460683.1; ENSG00000175826.12.
DR   GeneID; 23399; -.
DR   KEGG; hsa:23399; -.
DR   MANE-Select; ENST00000574322.6; ENSP00000460683.1; NM_001143775.2; NP_001137247.1.
DR   UCSC; uc002gfd.3; human.
DR   AGR; HGNC:19085; -.
DR   CTD; 23399; -.
DR   DisGeNET; 23399; -.
DR   GeneCards; CTDNEP1; -.
DR   HGNC; HGNC:19085; CTDNEP1.
DR   HPA; ENSG00000175826; Tissue enhanced (skeletal).
DR   MIM; 610684; gene.
DR   neXtProt; NX_O95476; -.
DR   OpenTargets; ENSG00000175826; -.
DR   PharmGKB; PA134937999; -.
DR   VEuPathDB; HostDB:ENSG00000175826; -.
DR   eggNOG; KOG1605; Eukaryota.
DR   GeneTree; ENSGT01040000240503; -.
DR   InParanoid; O95476; -.
DR   OMA; RIWGFFM; -.
DR   OrthoDB; 5473812at2759; -.
DR   PhylomeDB; O95476; -.
DR   TreeFam; TF313962; -.
DR   PathwayCommons; O95476; -.
DR   Reactome; R-HSA-4419969; Depolymerization of the Nuclear Lamina.
DR   SABIO-RK; O95476; -.
DR   SignaLink; O95476; -.
DR   SIGNOR; O95476; -.
DR   BioGRID-ORCS; 23399; 283 hits in 1168 CRISPR screens.
DR   ChiTaRS; CTDNEP1; human.
DR   GenomeRNAi; 23399; -.
DR   Pharos; O95476; Tbio.
DR   PRO; PR:O95476; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; O95476; Protein.
DR   Bgee; ENSG00000175826; Expressed in hindlimb stylopod muscle and 95 other cell types or tissues.
DR   ExpressionAtlas; O95476; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR   GO; GO:0005811; C:lipid droplet; IDA:HPA.
DR   GO; GO:0071595; C:Nem1-Spo7 phosphatase complex; IDA:UniProtKB.
DR   GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR   GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR   GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004722; F:protein serine/threonine phosphatase activity; IMP:UniProtKB.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR   GO; GO:0007276; P:gamete generation; IEA:Ensembl.
DR   GO; GO:0007498; P:mesoderm development; IEA:Ensembl.
DR   GO; GO:0007077; P:mitotic nuclear membrane disassembly; TAS:Reactome.
DR   GO; GO:0006998; P:nuclear envelope organization; IDA:UniProtKB.
DR   GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR   GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; IGI:UniProtKB.
DR   GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR   GO; GO:0034504; P:protein localization to nucleus; IDA:UniProtKB.
DR   CDD; cd07521; HAD_FCP1-like; 1.
DR   Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 1.
DR   InterPro; IPR011948; Dullard_phosphatase.
DR   InterPro; IPR004274; FCP1_dom.
DR   InterPro; IPR036412; HAD-like_sf.
DR   InterPro; IPR023214; HAD_sf.
DR   NCBIfam; TIGR02251; HIF-SF_euk; 1.
DR   PANTHER; PTHR12210:SF70; CTD NUCLEAR ENVELOPE PHOSPHATASE 1; 1.
DR   PANTHER; PTHR12210; DULLARD PROTEIN PHOSPHATASE; 1.
DR   Pfam; PF03031; NIF; 1.
DR   SMART; SM00577; CPDc; 1.
DR   SUPFAM; SSF56784; HAD-like; 1.
DR   PROSITE; PS50969; FCP1; 1.
DR   Genevisible; O95476; HS.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Hydrolase; Membrane; Nucleus; Protein phosphatase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..244
FT                   /note="CTD nuclear envelope phosphatase 1"
FT                   /id="PRO_0000297967"
FT   TRANSMEM        7..29
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          57..224
FT                   /note="FCP1 homology"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00336"
FT   VARIANT         12
FT                   /note="T -> A (in dbSNP:rs3744399)"
FT                   /evidence="ECO:0000269|PubMed:16533400, ECO:0000269|Ref.1"
FT                   /id="VAR_034699"
FT   MUTAGEN         67
FT                   /note="D->N,E: Abolishes phosphatase activity."
FT                   /evidence="ECO:0000269|PubMed:17420445"
SQ   SEQUENCE   244 AA;  28377 MW;  062952A90F74575A CRC64;
     MMRTQCLLGL RTFVAFAAKL WSFFIYLLRR QIRTVIQYQT VRYDILPLSP VSRNRLAQVK
     RKILVLDLDE TLIHSHHDGV LRPTVRPGTP PDFILKVVID KHPVRFFVHK RPHVDFFLEV
     VSQWYELVVF TASMEIYGSA VADKLDNSRS ILKRRYYRQH CTLELGSYIK DLSVVHSDLS
     SIVILDNSPG AYRSHPDNAI PIKSWFSDPS DTALLNLLPM LDALRFTADV RSVLSRNLHQ
     HRLW
//