NOSIP_HUMAN
ID NOSIP_HUMAN Reviewed; 301 AA.
AC Q9Y314; Q96FD2;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Nitric oxide synthase-interacting protein;
DE AltName: Full=E3 ubiquitin-protein ligase NOSIP;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase NOSIP {ECO:0000305};
DE AltName: Full=eNOS-interacting protein;
GN Name=NOSIP; ORFNames=CGI-25;
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], TISSUE SPECIFICITY, INTERACTION WITH NOS3, AND
RP FUNCTION.
RX PubMed=11149895; DOI=10.1096/fj.00-0078com;
RA Dedio J., Koenig P., Wohlfart P., Schroeder C., Kummer W.,
RA Mueller-Esterl W.;
RT "NOSIP, a novel modulator of endothelial nitric oxide synthase activity.";
RL FASEB J. 15:79-89(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-168.
RC TISSUE=B-cell, Brain, and Placenta;
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 [4]
RP INTERACTION WITH NOS1, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=15548660; DOI=10.1523/jneurosci.2265-04.2004;
RA Dreyer J., Schleicher M., Tappe A., Schilling K., Kuner T.,
RA Kusumawidijaja G., Mueller-Esterl W., Oess S., Kuner R.;
RT "Nitric oxide synthase (NOS)-interacting protein interacts with neuronal
RT NOS and regulates its distribution and activity.";
RL J. Neurosci. 24:10454-10465(2004).
RN [5]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=16135813; DOI=10.1128/mcb.25.18.8251-8258.2005;
RA Schleicher M., Brundin F., Gross S., Mueller-Esterl W., Oess S.;
RT "Cell cycle-regulated inactivation of endothelial NO synthase through
RT NOSIP-dependent targeting to the cytoskeleton.";
RL Mol. Cell. Biol. 25:8251-8258(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-107, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(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 (By similarity). Negatively regulates
CC nitric oxide production by inducing NOS1 and NOS3 translocation to
CC actin cytoskeleton and inhibiting their enzymatic activity
CC (PubMed:11149895, PubMed:15548660, PubMed:16135813).
CC {ECO:0000250|UniProtKB:Q9D6T0, ECO:0000269|PubMed:11149895,
CC ECO:0000269|PubMed:15548660, ECO:0000269|PubMed:16135813}.
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 -!- SUBUNIT: Interacts with NOS1 and NOS3 (PubMed:11149895,
CC PubMed:15548660). Interacts with PP2A holoenzyme, containing PPP2CA,
CC PPP2CB, PPP2R1A and PPP2R2A subunits (By similarity).
CC {ECO:0000250|UniProtKB:Q9D6T0, ECO:0000269|PubMed:11149895,
CC ECO:0000269|PubMed:15548660}.
CC -!- INTERACTION:
CC Q9Y314; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-1051889, EBI-11741890;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15548660,
CC ECO:0000269|PubMed:16135813}. Nucleus {ECO:0000269|PubMed:15548660,
CC ECO:0000269|PubMed:16135813}. Note=Translocates from nucleus to
CC cytoplasm in the G2 phase of the cell cycle (PubMed:16135813).
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain and lung. Present in
CC endothelial cells (at protein level). {ECO:0000269|PubMed:11149895}.
CC -!- DOMAIN: The U-box-like region is a truncated U-box domain. It is
CC unknown whether it is functional or not.
CC -!- SIMILARITY: Belongs to the NOSIP family. {ECO:0000305}.
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DR EMBL; AF132959; AAD27734.1; -; mRNA.
DR EMBL; BC009299; AAH09299.1; -; mRNA.
DR EMBL; BC010077; AAH10077.1; -; mRNA.
DR EMBL; BC011249; AAH11249.1; -; mRNA.
DR CCDS; CCDS12772.1; -.
DR RefSeq; NP_001257889.1; NM_001270960.1.
DR RefSeq; NP_057037.1; NM_015953.4.
DR RefSeq; XP_016882340.1; XM_017026851.1.
DR RefSeq; XP_016882341.1; XM_017026852.1.
DR AlphaFoldDB; Q9Y314; -.
DR BioGRID; 119261; 63.
DR IntAct; Q9Y314; 15.
DR MINT; Q9Y314; -.
DR STRING; 9606.ENSP00000470034; -.
DR GlyGen; Q9Y314; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y314; -.
DR PhosphoSitePlus; Q9Y314; -.
DR SwissPalm; Q9Y314; -.
DR BioMuta; NOSIP; -.
DR DMDM; 74735248; -.
DR EPD; Q9Y314; -.
DR jPOST; Q9Y314; -.
DR MassIVE; Q9Y314; -.
DR MaxQB; Q9Y314; -.
DR PaxDb; Q9Y314; -.
DR PeptideAtlas; Q9Y314; -.
DR PRIDE; Q9Y314; -.
DR ProteomicsDB; 85958; -.
DR Antibodypedia; 32058; 185 antibodies from 27 providers.
DR DNASU; 51070; -.
DR Ensembl; ENST00000596358.6; ENSP00000470034.1; ENSG00000142546.14.
DR GeneID; 51070; -.
DR KEGG; hsa:51070; -.
DR MANE-Select; ENST00000596358.6; ENSP00000470034.1; NM_001270960.2; NP_001257889.1.
DR UCSC; uc002pol.5; human.
DR CTD; 51070; -.
DR DisGeNET; 51070; -.
DR GeneCards; NOSIP; -.
DR HGNC; HGNC:17946; NOSIP.
DR HPA; ENSG00000142546; Low tissue specificity.
DR MIM; 616759; gene.
DR neXtProt; NX_Q9Y314; -.
DR OpenTargets; ENSG00000142546; -.
DR PharmGKB; PA134989259; -.
DR VEuPathDB; HostDB:ENSG00000142546; -.
DR eggNOG; KOG3039; Eukaryota.
DR GeneTree; ENSGT00390000015505; -.
DR HOGENOM; CLU_053742_0_0_1; -.
DR InParanoid; Q9Y314; -.
DR OrthoDB; 1567031at2759; -.
DR PhylomeDB; Q9Y314; -.
DR TreeFam; TF314268; -.
DR PathwayCommons; Q9Y314; -.
DR Reactome; R-HSA-203754; NOSIP mediated eNOS trafficking.
DR SignaLink; Q9Y314; -.
DR BioGRID-ORCS; 51070; 79 hits in 1139 CRISPR screens.
DR GeneWiki; NOSIP; -.
DR GenomeRNAi; 51070; -.
DR Pharos; Q9Y314; Tbio.
DR PRO; PR:Q9Y314; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9Y314; protein.
DR Bgee; ENSG00000142546; Expressed in left testis and 201 other tissues.
DR ExpressionAtlas; Q9Y314; baseline and differential.
DR Genevisible; Q9Y314; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; IDA:UniProtKB.
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 Cytoplasm; Developmental protein; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation pathway.
FT CHAIN 1..301
FT /note="Nitric oxide synthase-interacting protein"
FT /id="PRO_0000280585"
FT REGION 55..75
FT /note="U-box-like"
FT REGION 132..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 78..101
FT /note="Nuclear localization signal"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 168
FT /note="T -> M (in dbSNP:rs17850728)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031169"
SQ SEQUENCE 301 AA; 33172 MW; FB77D6E31511C884 CRC64;
MTRHGKNCTA GAVYTYHEKK KDTAASGYGT QNIRLSRDAV KDFDCCCLSL QPCHDPVVTP
DGYLYEREAI LEYILHQKKE IARQMKAYEK QRGTRREEQK ELQRAASQDH VRGFLEKESA
IVSRPLNPFT AKALSGTSPD DVQPGPSVGP PSKDKDKVLP SFWIPSLTPE AKATKLEKPS
RTVTCPMSGK PLRMSDLTPV HFTPLDSSVD RVGLITRSER YVCAVTRDSL SNATPCAVLR
PSGAVVTLEC VEKLIRKDMV DPVTGDKLTD RDIIVLQRGG TGFAGSGVKL QAEKSRPVMQ
A
