NOSIP_MOUSE
ID NOSIP_MOUSE Reviewed; 301 AA.
AC Q9D6T0; Q9D8J9;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Nitric oxide synthase-interacting protein;
DE AltName: Full=E3 ubiquitin-protein ligase NOSIP {ECO:0000303|PubMed:25546391};
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase NOSIP {ECO:0000305};
GN Name=Nosip;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Pancreas, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH PP2A HOLOENZYME.
RX PubMed=25546391; DOI=10.1371/journal.pone.0116150;
RA Hoffmeister M., Prelle C., Kuechler P., Kovacevic I., Moser M.,
RA Mueller-Esterl W., Oess S.;
RT "The ubiquitin E3 ligase NOSIP modulates protein phosphatase 2A activity in
RT craniofacial development.";
RL PLoS ONE 9:E116150-E116150(2014).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that is essential for proper
CC development of the forebrain, the eye and the face. Catalyzes
CC monoubiquitination of serine/threonine-protein phosphatase 2A (PP2A)
CC catalytic subunit PPP2CA/PPP2CB (PubMed:25546391). Negatively regulates
CC nitric oxide production by inducing NOS1 and NOS3 translocation to
CC actin cytoskeleton and inhibiting their enzymatic activity (By
CC similarity). {ECO:0000250|UniProtKB:Q9Y314,
CC ECO:0000269|PubMed:25546391}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with NOS1 and NOS3 (By similarity). Interacts with
CC PP2A holoenzyme, containing PPP2CA, PPP2CB, PPP2R1A and PPP2R2A
CC subunits (PubMed:25546391). {ECO:0000250|UniProtKB:Q9Y314,
CC ECO:0000269|PubMed:25546391}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y314}. Nucleus
CC {ECO:0000250|UniProtKB:Q9Y314}. Note=Translocates from nucleus to
CC cytoplasm in the G2 phase of the cell cycle.
CC {ECO:0000250|UniProtKB:Q9Y314}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9D6T0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9D6T0-2; Sequence=VSP_023795;
CC -!- DOMAIN: The U-box-like region is a truncated U-box domain. It is
CC unknown whether it is functional or not.
CC -!- DISRUPTION PHENOTYPE: Although mutant embryos are present at the
CC expected Mendelian rate at 18.5 dpc, they die shortly after birth with
CC signs of respiratory distress and cyanosis, likely due to craniofacial
CC malformations. Malformations in knockout mice range from ocular
CC hypotelorism, narrow snout, laterally cleft lip, and cleft secondary
CC palate to cyclopia and presence of proboscis or a single head-like
CC protrusion devoid of facial features. In addition, the weight of
CC knockout embryos is significantly reduced. In knockout animals, PP2A
CC activity is increased in palatal and facial tissues as compared to
CC wild-type, but not in lungs, which do not seem to be affected by the
CC mutation. {ECO:0000269|PubMed:25546391}.
CC -!- SIMILARITY: Belongs to the NOSIP family. {ECO:0000305}.
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DR EMBL; AK007962; BAB25373.1; -; mRNA.
DR EMBL; AK010006; BAB26637.1; -; mRNA.
DR EMBL; BC089029; AAH89029.1; -; mRNA.
DR CCDS; CCDS21228.1; -. [Q9D6T0-1]
DR CCDS; CCDS52242.1; -. [Q9D6T0-2]
DR RefSeq; NP_001157156.1; NM_001163684.1. [Q9D6T0-2]
DR RefSeq; NP_079809.1; NM_025533.3. [Q9D6T0-1]
DR RefSeq; XP_017167721.1; XM_017312232.1. [Q9D6T0-1]
DR AlphaFoldDB; Q9D6T0; -.
DR BioGRID; 211438; 3.
DR IntAct; Q9D6T0; 1.
DR STRING; 10090.ENSMUSP00000103461; -.
DR iPTMnet; Q9D6T0; -.
DR PhosphoSitePlus; Q9D6T0; -.
DR EPD; Q9D6T0; -.
DR MaxQB; Q9D6T0; -.
DR PaxDb; Q9D6T0; -.
DR PeptideAtlas; Q9D6T0; -.
DR PRIDE; Q9D6T0; -.
DR ProteomicsDB; 293677; -. [Q9D6T0-1]
DR ProteomicsDB; 293678; -. [Q9D6T0-2]
DR Antibodypedia; 32058; 185 antibodies from 27 providers.
DR DNASU; 66394; -.
DR Ensembl; ENSMUST00000003513; ENSMUSP00000003513; ENSMUSG00000003421. [Q9D6T0-1]
DR Ensembl; ENSMUST00000107829; ENSMUSP00000103460; ENSMUSG00000003421. [Q9D6T0-2]
DR GeneID; 66394; -.
DR KEGG; mmu:66394; -.
DR UCSC; uc009gsx.2; mouse. [Q9D6T0-1]
DR UCSC; uc009gsy.2; mouse. [Q9D6T0-2]
DR CTD; 51070; -.
DR MGI; MGI:1913644; Nosip.
DR VEuPathDB; HostDB:ENSMUSG00000003421; -.
DR eggNOG; KOG3039; Eukaryota.
DR GeneTree; ENSGT00390000015505; -.
DR HOGENOM; CLU_053742_0_0_1; -.
DR InParanoid; Q9D6T0; -.
DR OMA; AKEKRPM; -.
DR OrthoDB; 1567031at2759; -.
DR PhylomeDB; Q9D6T0; -.
DR TreeFam; TF314268; -.
DR Reactome; R-MMU-203754; NOSIP mediated eNOS trafficking.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 66394; 9 hits in 75 CRISPR screens.
DR ChiTaRS; Nosip; mouse.
DR PRO; PR:Q9D6T0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9D6T0; protein.
DR Bgee; ENSMUSG00000003421; Expressed in spermatid and 258 other tissues.
DR ExpressionAtlas; Q9D6T0; baseline and differential.
DR Genevisible; Q9D6T0; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISO:MGI.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; ISO:MGI.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR016818; NOSIP.
DR InterPro; IPR031790; Znf-NOSIP.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR13063; PTHR13063; 1.
DR Pfam; PF15906; zf-NOSIP; 1.
DR PIRSF; PIRSF023577; ENOS_interacting; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Developmental protein; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation pathway.
FT CHAIN 1..301
FT /note="Nitric oxide synthase-interacting protein"
FT /id="PRO_0000280587"
FT REGION 55..75
FT /note="U-box-like"
FT REGION 131..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 78..101
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y314"
FT VAR_SEQ 180..204
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023795"
SQ SEQUENCE 301 AA; 33209 MW; 9953A7F6E6B4A5FF CRC64;
MTRHGKNCTA GAVYTYHEKK KDTAASGYGT QNIRLSRDAV KDFDCCCLSL QPCHDPVVTP
DGYLYEREAI LEYILHQKRE IARQVKAYEK QRGARREEQK ELQRAAAQDQ VRGFLEKEAA
IVSRPLNPFM PKAATLPNTE GEQPGPSVGP VGKDKDKALP SFWIPSLTPE AKATKLEKPS
RTVTCPMSGK PLRMSDLTSV RFTQLDDSVD RVGLITRSER YVCAVTRDSL SNATPCAVLR
PSGAVVTLEC VEKLIRKDMV DPVNGDTLTE RDIIVLQRGG TGFAGSGVKL QAEMSRPVMQ
A
