NOE2_MOUSE
ID NOE2_MOUSE Reviewed; 448 AA.
AC Q8BM13; Q0VFZ0; Q0VG58;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Noelin-2;
DE AltName: Full=Olfactomedin-2;
DE Flags: Precursor;
GN Name=Olfm2;
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].
RC STRAIN=C57BL/6J; TISSUE=Skin;
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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=21228389; DOI=10.1167/iovs.10-6356;
RA Sultana A., Nakaya N., Senatorov V.V., Tomarev S.I.;
RT "Olfactomedin 2: expression in the eye and interaction with other
RT olfactomedin domain-containing proteins.";
RL Invest. Ophthalmol. Vis. Sci. 52:2584-2592(2011).
RN [5]
RP IDENTIFICATION IN AMPAR COMPLEX, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=22632720; DOI=10.1016/j.neuron.2012.03.034;
RA Schwenk J., Harmel N., Brechet A., Zolles G., Berkefeld H., Muller C.S.,
RA Bildl W., Baehrens D., Huber B., Kulik A., Klocker N., Schulte U.,
RA Fakler B.;
RT "High-resolution proteomics unravel architecture and molecular diversity of
RT native AMPA receptor complexes.";
RL Neuron 74:621-633(2012).
RN [6]
RP FUNCTION, INTERACTION WITH GRIA2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=25218043; DOI=10.1016/j.expneurol.2014.09.002;
RA Sultana A., Nakaya N., Dong L., Abu-Asab M., Qian H., Tomarev S.I.;
RT "Deletion of olfactomedin 2 induces changes in the AMPA receptor complex
RT and impairs visual, olfactory, and motor functions in mice.";
RL Exp. Neurol. 261:802-811(2014).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=28062493; DOI=10.1161/atvbaha.116.308606;
RA Shi N., Li C.X., Cui X.B., Tomarev S.I., Chen S.Y.;
RT "Olfactomedin 2 regulates smooth muscle phenotypic modulation and vascular
RT remodeling through mediating Runt-related transcription factor 2 binding to
RT serum response factor.";
RL Arterioscler. Thromb. Vasc. Biol. 37:446-454(2017).
CC -!- FUNCTION: Involved in transforming growth factor beta (TGF-beta)-
CC induced smooth muscle differentiation (By similarity). TGF-beta induces
CC expression and nuclear translocation of OLFM2 where it binds to SRF,
CC causing its dissociation from the transcriptional repressor HEY2/HERP1
CC and facilitating binding of SRF to target genes (By similarity). Plays
CC a role in AMPAR complex organization (PubMed:25218043). Is a regulator
CC of vascular smooth-muscle cell (SMC) phenotypic switching, that acts by
CC promoting RUNX2 and inhibiting MYOCD binding to SRF. SMC phenotypic
CC switching is the process through which vascular SMCs undergo transition
CC between a quiescent contractile phenotype and a proliferative synthetic
CC phenotype in response to pathological stimuli. SMC phenotypic
CC plasticity is essential for vascular development and remodeling (By
CC similarity). {ECO:0000250|UniProtKB:O95897,
CC ECO:0000250|UniProtKB:Q568Y7, ECO:0000269|PubMed:25218043}.
CC -!- SUBUNIT: Peripherally associated with AMPAR complex. AMPAR complex
CC consists of an inner core made of 4 pore-forming GluA/GRIA proteins
CC (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged
CC in a twofold symmetry. One of the two pairs of distinct binding sites
CC is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors
CC CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR
CC complex is complemented by outer core constituents binding directly to
CC the GluA/GRIA proteins at sites distinct from the interaction sites of
CC the inner core constituents. Outer core constituents include at least
CC PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the
CC inner and outer core serve as a platform for other, more peripherally
CC associated AMPAR constituents, including OLFM2. Alone or in
CC combination, these auxiliary subunits control the gating and
CC pharmacology of the AMPAR complex and profoundly impact their
CC biogenesis and protein processing (PubMed:22632720). Interacts with
CC GRIA2 (PubMed:25218043). Interacts with OLFM1 and OLFM3 (By
CC similarity). Interacts with SRF; the interaction promotes dissociation
CC of SRF from the transcriptional repressor HEY2 (By similarity).
CC Interacts with RUNX2 (By similarity). {ECO:0000250|UniProtKB:O95897,
CC ECO:0000250|UniProtKB:Q568Y7, ECO:0000269|PubMed:22632720,
CC ECO:0000269|PubMed:25218043}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:O95897}. Synapse
CC {ECO:0000269|PubMed:25218043, ECO:0000305|PubMed:22632720}. Membrane
CC {ECO:0000269|PubMed:25218043}. Nucleus {ECO:0000250|UniProtKB:O95897}.
CC Cytoplasm {ECO:0000250|UniProtKB:O95897}. Note=Nuclear localization is
CC induced by TGF-beta. {ECO:0000250|UniProtKB:O95897}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level)
CC (PubMed:22632720). In the developing eye, first detected at 12 dpc in
CC the retinal pigmented epithelium and preferentially expressed in
CC differentiating retinal ganglion cells between 15 and 18 dpc
CC (PubMed:21228389). In the brain, expression is detected mainly in the
CC olfactory bulb, cortex, piriform cortex, olfactory trabeculae, and
CC inferior and superior colliculus (PubMed:25218043). In the adult eye,
CC expression is detected mainly in retinal ganglion cells
CC (PubMed:25218043). Expressed in carotid arteries (PubMed:28062493).
CC {ECO:0000269|PubMed:21228389, ECO:0000269|PubMed:22632720,
CC ECO:0000269|PubMed:25218043, ECO:0000269|PubMed:28062493}.
CC -!- DEVELOPMENTAL STAGE: During embryonic eye development, first detected
CC at 12 dpc with maximum levels at 19.5 dpc and down-regulation of
CC expression postnatally. In brain, levels increase from 13.5 dpc to
CC postnatal day 6 and decrease in the adult.
CC {ECO:0000269|PubMed:21228389}.
CC -!- DISRUPTION PHENOTYPE: No gross abnormalities with normal lifespan but
CC mutants display reduced exploration, locomotion and olfactory
CC sensitivity, reduced amplitude of the first negative wave in the visual
CC evoked potential test, abnormal motor coordination, anxiety-related
CC behavior and changes in AMPAR complex composition.
CC {ECO:0000269|PubMed:25218043}.
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DR EMBL; AK037199; BAC29750.1; -; mRNA.
DR EMBL; CH466522; EDL25128.1; -; Genomic_DNA.
DR EMBL; BC115981; AAI15982.1; -; mRNA.
DR EMBL; BC117536; AAI17537.1; -; mRNA.
DR CCDS; CCDS40546.1; -.
DR RefSeq; NP_776138.2; NM_173777.3.
DR AlphaFoldDB; Q8BM13; -.
DR SMR; Q8BM13; -.
DR BioGRID; 232687; 3.
DR IntAct; Q8BM13; 1.
DR MINT; Q8BM13; -.
DR STRING; 10090.ENSMUSP00000034692; -.
DR GlyConnect; 2566; 2 N-Linked glycans (2 sites).
DR GlyGen; Q8BM13; 6 sites, 2 N-linked glycans (2 sites).
DR PhosphoSitePlus; Q8BM13; -.
DR MaxQB; Q8BM13; -.
DR PaxDb; Q8BM13; -.
DR PeptideAtlas; Q8BM13; -.
DR PRIDE; Q8BM13; -.
DR ProteomicsDB; 293869; -.
DR Antibodypedia; 42819; 54 antibodies from 16 providers.
DR DNASU; 244723; -.
DR Ensembl; ENSMUST00000034692; ENSMUSP00000034692; ENSMUSG00000032172.
DR GeneID; 244723; -.
DR KEGG; mmu:244723; -.
DR UCSC; uc009oje.1; mouse.
DR CTD; 93145; -.
DR MGI; MGI:3045350; Olfm2.
DR VEuPathDB; HostDB:ENSMUSG00000032172; -.
DR eggNOG; KOG3545; Eukaryota.
DR GeneTree; ENSGT00940000159148; -.
DR HOGENOM; CLU_035236_0_0_1; -.
DR InParanoid; Q8BM13; -.
DR PhylomeDB; Q8BM13; -.
DR TreeFam; TF315964; -.
DR BioGRID-ORCS; 244723; 5 hits in 71 CRISPR screens.
DR ChiTaRS; Olfm2; mouse.
DR PRO; PR:Q8BM13; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8BM13; protein.
DR Bgee; ENSMUSG00000032172; Expressed in embryonic brain and 98 other tissues.
DR ExpressionAtlas; Q8BM13; baseline and differential.
DR Genevisible; Q8BM13; MM.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; IDA:MGI.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0099243; C:extrinsic component of synaptic membrane; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0097060; C:synaptic membrane; IDA:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0009306; P:protein secretion; ISO:MGI.
DR GO; GO:1905174; P:regulation of vascular associated smooth muscle cell dedifferentiation; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; IMP:MGI.
DR InterPro; IPR031219; Noelin-2.
DR InterPro; IPR022082; Noelin_dom.
DR InterPro; IPR003112; Olfac-like_dom.
DR PANTHER; PTHR23192:SF27; PTHR23192:SF27; 1.
DR Pfam; PF12308; Noelin-1; 1.
DR Pfam; PF02191; OLF; 1.
DR SMART; SM00284; OLF; 1.
DR PROSITE; PS51132; OLF; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Disulfide bond; Glycoprotein; Membrane; Nucleus;
KW Reference proteome; Secreted; Signal; Synapse.
FT SIGNAL 1..14
FT /evidence="ECO:0000250"
FT CHAIN 15..448
FT /note="Noelin-2"
FT /id="PRO_0000020079"
FT DOMAIN 188..440
FT /note="Olfactomedin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446"
FT COILED 52..79
FT /evidence="ECO:0000255"
FT COILED 130..187
FT /evidence="ECO:0000255"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 269
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 304
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 393
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 189..371
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446"
FT CONFLICT 405
FT /note="H -> N (in Ref. 1; BAC29750)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 448 AA; 50720 MW; C29ADDE209697A5F CRC64;
MRKLRQTGTT IAGGQTLFQS PEEGWQLYTS AQAPDGKCVC TAVIPAQSTC ARDGRSRELR
QLMEKVQNVS QSMEVLELRT FRDLQYVRSM ETLMRSLDAR LRAADGSVSA KSFQELKDRM
TELLPLSSVL EQYKADTRTI VRLREEVRNL SGNLAAIQEE MGAYGYEDLQ QRVMALEARL
HACAQKLGCG KLTGVSNPIT IRAMGSRFGS WMTDTMAPSA DSRVWYMDGY YKGRRVLEFR
TLGDFIKGQN FIQHLLPQPW AGTGHVVYNG SLFYNKYQSN VVVKYHFRSR SVLVQRSLPG
AGYNNTFPYS WGGFSDMDFM VDESGLWAVY TTNQNAGNIV VSRLDPHTLE VVRSWDTGYP
KRSAGEAFMI CGVLYVTNSH LAGAKVYFAY FTNTSSYEYT DVPFHNQYSH ISMLDYNPRE
RALYTWNNGH QVLYNVTLFH VISTAGDP
