ID   NEPR1_HUMAN             Reviewed;         125 AA.
AC   Q8N9A8; Q4G1A9; Q5H9V0; Q8NE06;
DT   15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   24-JAN-2024, entry version 128.
DE   RecName: Full=Nuclear envelope phosphatase-regulatory subunit 1;
DE            Short=NEP1-R1;
DE   AltName: Full=Transmembrane protein 188;
GN   Name=CNEP1R1; Synonyms=C16orf69, TMEM188;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Adipose tissue;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA   Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA   Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA   Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA   Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA   Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA   Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA   Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA   Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA   Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA   Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA   Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA   Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA   Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA   Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA   Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA   Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA   DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA   Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA   Myers R.M., Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC   TISSUE=Brain, and Testis;
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   [5]
RP   FUNCTION IN LPIN1 AND LPIN2 DEPHOSPHORYLATION, INTERACTION WITH CTDNEP1,
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).
RN   [6]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC   -!- FUNCTION: Forms with the serine/threonine protein phosphatase CTDNEP1
CC       an active complex which dephosphorylates and may activate LPIN1 and
CC       LPIN2. LPIN1 and LPIN2 are phosphatidate phosphatases that catalyze the
CC       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. {ECO:0000269|PubMed:22134922}.
CC   -!- SUBUNIT: Interacts with CTDNEP1; the complex dephosphorylates LPIN1 and
CC       LPIN2. {ECO:0000269|PubMed:22134922}.
CC   -!- INTERACTION:
CC       Q8N9A8; O95476: CTDNEP1; NbExp=4; IntAct=EBI-5323455, EBI-5323433;
CC   -!- SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000269|PubMed:22134922};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:22134922}. Cytoplasm
CC       {ECO:0000269|PubMed:22134922}. Note=Filamentous pattern in the
CC       cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q8N9A8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8N9A8-2; Sequence=VSP_025126;
CC       Name=3;
CC         IsoId=Q8N9A8-3; Sequence=VSP_025127, VSP_025128;
CC   -!- TISSUE SPECIFICITY: Muscle specific with lower expression in other
CC       metabolic tissues. {ECO:0000269|PubMed:22134922}.
CC   -!- SIMILARITY: Belongs to the CNEP1R1 family. {ECO:0000305}.
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DR   EMBL; AK095420; BAC04545.1; -; mRNA.
DR   EMBL; CR933600; CAI45924.1; -; mRNA.
DR   EMBL; AC007610; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC022550; AAH22550.1; -; mRNA.
DR   EMBL; BC036683; AAH36683.1; -; mRNA.
DR   CCDS; CCDS45480.1; -. [Q8N9A8-2]
DR   CCDS; CCDS61931.1; -. [Q8N9A8-1]
DR   RefSeq; NP_001268718.1; NM_001281789.1. [Q8N9A8-1]
DR   RefSeq; NP_694993.2; NM_153261.5. [Q8N9A8-2]
DR   AlphaFoldDB; Q8N9A8; -.
DR   BioGRID; 129126; 7.
DR   IntAct; Q8N9A8; 3.
DR   STRING; 9606.ENSP00000405635; -.
DR   iPTMnet; Q8N9A8; -.
DR   PhosphoSitePlus; Q8N9A8; -.
DR   BioMuta; CNEP1R1; -.
DR   DMDM; 74729639; -.
DR   EPD; Q8N9A8; -.
DR   jPOST; Q8N9A8; -.
DR   MassIVE; Q8N9A8; -.
DR   MaxQB; Q8N9A8; -.
DR   PeptideAtlas; Q8N9A8; -.
DR   ProteomicsDB; 72513; -. [Q8N9A8-1]
DR   ProteomicsDB; 72514; -. [Q8N9A8-2]
DR   ProteomicsDB; 72515; -. [Q8N9A8-3]
DR   Pumba; Q8N9A8; -.
DR   Antibodypedia; 49431; 15 antibodies from 9 providers.
DR   DNASU; 255919; -.
DR   Ensembl; ENST00000427478.7; ENSP00000394224.2; ENSG00000205423.12. [Q8N9A8-1]
DR   Ensembl; ENST00000458059.7; ENSP00000405635.3; ENSG00000205423.12. [Q8N9A8-2]
DR   Ensembl; ENST00000565457.5; ENSP00000456686.1; ENSG00000205423.12. [Q8N9A8-1]
DR   Ensembl; ENST00000566482.5; ENSP00000456294.1; ENSG00000205423.12. [Q8N9A8-3]
DR   Ensembl; ENST00000568890.5; ENSP00000456913.1; ENSG00000205423.12. [Q8N9A8-3]
DR   GeneID; 255919; -.
DR   KEGG; hsa:255919; -.
DR   MANE-Select; ENST00000427478.7; ENSP00000394224.2; NM_001281789.2; NP_001268718.1.
DR   UCSC; uc002eft.5; human. [Q8N9A8-1]
DR   AGR; HGNC:26759; -.
DR   CTD; 255919; -.
DR   GeneCards; CNEP1R1; -.
DR   HGNC; HGNC:26759; CNEP1R1.
DR   HPA; ENSG00000205423; Low tissue specificity.
DR   neXtProt; NX_Q8N9A8; -.
DR   OpenTargets; ENSG00000205423; -.
DR   PharmGKB; PA162406208; -.
DR   VEuPathDB; HostDB:ENSG00000205423; -.
DR   GeneTree; ENSGT00390000008576; -.
DR   HOGENOM; CLU_207390_0_0_1; -.
DR   InParanoid; Q8N9A8; -.
DR   OMA; DQTVCED; -.
DR   OrthoDB; 2871883at2759; -.
DR   PhylomeDB; Q8N9A8; -.
DR   TreeFam; TF313179; -.
DR   PathwayCommons; Q8N9A8; -.
DR   Reactome; R-HSA-4419969; Depolymerization of the Nuclear Lamina.
DR   SignaLink; Q8N9A8; -.
DR   BioGRID-ORCS; 255919; 82 hits in 1162 CRISPR screens.
DR   GenomeRNAi; 255919; -.
DR   Pharos; Q8N9A8; Tbio.
DR   PRO; PR:Q8N9A8; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q8N9A8; Protein.
DR   Bgee; ENSG00000205423; Expressed in left ventricle myocardium and 188 other cell types or tissues.
DR   ExpressionAtlas; Q8N9A8; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0071595; C:Nem1-Spo7 phosphatase complex; IDA:UniProtKB.
DR   GO; GO:0005635; C:nuclear envelope; TAS:Reactome.
DR   GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR   GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0035307; P:positive regulation of protein dephosphorylation; IDA:UniProtKB.
DR   GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; IGI:UniProtKB.
DR   GO; GO:0034504; P:protein localization to nucleus; IDA:UniProtKB.
DR   InterPro; IPR019168; NEP1-R1.
DR   PANTHER; PTHR20996:SF1; NUCLEAR ENVELOPE PHOSPHATASE-REGULATORY SUBUNIT 1; 1.
DR   PANTHER; PTHR20996; UNCHARACTERIZED; 1.
DR   Pfam; PF09771; Tmemb_18A; 1.
DR   Genevisible; Q8N9A8; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Cytoplasm; Lipid metabolism; Membrane;
KW   Nucleus; Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..125
FT                   /note="Nuclear envelope phosphatase-regulatory subunit 1"
FT                   /id="PRO_0000286615"
FT   TRANSMEM        33..53
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        65..85
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   VAR_SEQ         8
FT                   /note="E -> EAPRVVSLIPAVVSGNCQ (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17974005"
FT                   /id="VSP_025126"
FT   VAR_SEQ         33..47
FT                   /note="MLLIVVSVCTATGAW -> SVLLHIIMESPIFHH (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_025127"
FT   VAR_SEQ         48..125
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_025128"
FT   CONFLICT        15
FT                   /note="R -> G (in Ref. 2; CAI45924)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   125 AA;  14267 MW;  546EB9BEFE8EA593 CRC64;
     MNSLEQAEDL KAFERRLTEY IHCLQPATGR WRMLLIVVSV CTATGAWNWL IDPETQKVSF
     FTSLWNHPFF TISCITLIGL FFAGIHKRVV APSIIAARCR TVLAEYNMSC DDTGKLILKP
     RPHVQ
//