ID   NOE2_HUMAN              Reviewed;         454 AA.
AC   O95897; Q6IMJ3; Q96FC2;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2005, sequence version 2.
DT   13-FEB-2019, entry version 146.
DE   RecName: Full=Noelin-2;
DE   AltName: Full=Olfactomedin-2;
DE   Flags: Precursor;
GN   Name=OLFM2; Synonyms=NOE2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLN-106 AND
RP   MET-127.
RC   TISSUE=Brain;
RA   Mei G., Yu W., Gibbs R.A.;
RL   Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA   Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA   Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA   Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA   Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA   Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA   Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA   Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA   Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA   Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA   Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA   Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA   Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA   Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA   Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   IDENTIFICATION OF GENOMIC DNA.
RX   PubMed=15123989;
RA   Mukhopadhyay A., Talukdar S., Bhattacharjee A., Ray K.;
RT   "Bioinformatic approaches for identification and characterization of
RT   olfactomedin related genes with a potential role in pathogenesis of
RT   ocular disorders.";
RL   Mol. Vis. 10:304-314(2004).
RN   [5]
RP   SUBCELLULAR LOCATION, INTERACTION WITH OLFM1 AND OLFM3, GLYCOSYLATION,
RP   CHARACTERIZATION OF VARIANT MET-86, AND MUTAGENESIS OF ARG-144 AND
RP   LEU-420.
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   [6]
RP   FUNCTION, INTERACTION WITH SRF, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND INDUCTION.
RX   PubMed=25298399; DOI=10.1091/mbc.E14-08-1255;
RA   Shi N., Guo X., Chen S.Y.;
RT   "Olfactomedin 2, a novel regulator for transforming growth factor-
RT   beta-induced smooth muscle differentiation of human embryonic stem
RT   cell-derived mesenchymal cells.";
RL   Mol. Biol. Cell 25:4106-4114(2014).
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=27844144; DOI=10.1007/s00439-016-1745-8;
RA   Holt R., Ugur Iseri S.A., Wyatt A.W., Bax D.A., Gold Diaz D.,
RA   Santos C., Broadgate S., Dunn R., Bruty J., Wallis Y., McMullan D.,
RA   Ogilvie C., Gerrelli D., Zhang Y., Ragge N.;
RT   "Identification and functional characterisation of genetic variants in
RT   OLFM2 in children with developmental eye disorders.";
RL   Hum. Genet. 136:119-127(2017).
RN   [8]
RP   VARIANT [LARGE SCALE ANALYSIS] MET-86.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Involved in transforming growth factor beta (TGF-beta)-
CC       induced smooth muscle differentiation. TGF-beta induces expression
CC       and translocation of OLFM2 to the nucleus where it binds to SRF,
CC       causing its dissociation from the transcriptional repressor
CC       HEY2/HERP1 and facilitating binding of SRF to target genes
CC       (PubMed:25298399). Plays a role in AMPAR complex organization (By
CC       similarity). Is a regulator of vascular smooth-muscle cell (SMC)
CC       phenotypic switching, that acts by promoting RUNX2 and inhibiting
CC       MYOCD binding to SRF. SMC phenotypic switching is the process
CC       through which vascular SMCs undergo transition between a quiescent
CC       contractile phenotype and a proliferative synthetic phenotype in
CC       response to pathological stimuli. SMC phenotypic plasticity is
CC       essential for vascular development and remodeling (By similarity).
CC       {ECO:0000250|UniProtKB:Q568Y7, ECO:0000250|UniProtKB:Q8BM13,
CC       ECO:0000269|PubMed:25298399}.
CC   -!- SUBUNIT: Peripherally associated with AMPAR complex. AMPAR complex
CC       consists of an inner core made of 4 pore-forming GluA/GRIA
CC       proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary
CC       subunits arranged in a twofold symmetry. One of the two pairs of
CC       distinct binding sites is occupied either by CNIH2, CNIH3 or
CC       CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8
CC       or GSG1L. This inner core of AMPAR complex is complemented by
CC       outer core constituents binding directly to the GluA/GRIA proteins
CC       at sites distinct from the interaction sites of the inner core
CC       constituents. Outer core constituents include at least PRRT1,
CC       PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner
CC       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. Interacts with GRIA2 (By
CC       similarity). Interacts with OLFM1 and OLFM3 (PubMed:21228389).
CC       Interacts with SRF; the interaction promotes dissociation of SRF
CC       from the transcriptional repressor HEY2 (PubMed:25298399).
CC       Interacts with RUNX2 (By similarity).
CC       {ECO:0000250|UniProtKB:Q568Y7, ECO:0000250|UniProtKB:Q8BM13,
CC       ECO:0000269|PubMed:21228389, ECO:0000269|PubMed:25298399}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21228389}. Cell
CC       junction, synapse {ECO:0000250|UniProtKB:Q8BM13}. Membrane
CC       {ECO:0000250|UniProtKB:Q8BM13}. Nucleus
CC       {ECO:0000269|PubMed:25298399}. Cytoplasm
CC       {ECO:0000269|PubMed:25298399}. Note=Nuclear localization is
CC       induced by TGF-beta. {ECO:0000269|PubMed:25298399}.
CC   -!- TISSUE SPECIFICITY: Expressed in aortic smooth muscle (at protein
CC       level) (PubMed:25298399). In the fetus, expressed in the brain and
CC       ocular tissues including lens vesicle and optic cup
CC       (PubMed:27844144). {ECO:0000269|PubMed:25298399,
CC       ECO:0000269|PubMed:27844144}.
CC   -!- INDUCTION: By TGF-beta. {ECO:0000269|PubMed:25298399}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:21228389}.
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   -----------------------------------------------------------------------
DR   EMBL; AF131839; AAD20056.1; -; mRNA.
DR   EMBL; AC008742; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC011361; AAH11361.1; -; mRNA.
DR   EMBL; BK001428; DAA01550.1; -; Genomic_DNA.
DR   CCDS; CCDS12221.1; -.
DR   RefSeq; NP_001291276.1; NM_001304347.1.
DR   RefSeq; NP_001291277.1; NM_001304348.1.
DR   RefSeq; NP_477512.1; NM_058164.3.
DR   UniGene; Hs.169743; -.
DR   ProteinModelPortal; O95897; -.
DR   SMR; O95897; -.
DR   BioGrid; 125007; 47.
DR   IntAct; O95897; 12.
DR   STRING; 9606.ENSP00000264833; -.
DR   GlyConnect; 1963; -.
DR   iPTMnet; O95897; -.
DR   PhosphoSitePlus; O95897; -.
DR   BioMuta; OLFM2; -.
DR   EPD; O95897; -.
DR   jPOST; O95897; -.
DR   MaxQB; O95897; -.
DR   PaxDb; O95897; -.
DR   PeptideAtlas; O95897; -.
DR   PRIDE; O95897; -.
DR   ProteomicsDB; 51119; -.
DR   DNASU; 93145; -.
DR   Ensembl; ENST00000264833; ENSP00000264833; ENSG00000105088.
DR   GeneID; 93145; -.
DR   KEGG; hsa:93145; -.
DR   UCSC; uc002mmp.4; human.
DR   CTD; 93145; -.
DR   DisGeNET; 93145; -.
DR   EuPathDB; HostDB:ENSG00000105088.8; -.
DR   GeneCards; OLFM2; -.
DR   HGNC; HGNC:17189; OLFM2.
DR   HPA; HPA049961; -.
DR   HPA; HPA057771; -.
DR   MIM; 617492; gene.
DR   neXtProt; NX_O95897; -.
DR   OpenTargets; ENSG00000105088; -.
DR   PharmGKB; PA31916; -.
DR   eggNOG; ENOG410INP8; Eukaryota.
DR   eggNOG; ENOG410ZRHT; LUCA.
DR   GeneTree; ENSGT00940000159148; -.
DR   HOGENOM; HOG000232069; -.
DR   HOVERGEN; HBG006513; -.
DR   InParanoid; O95897; -.
DR   OMA; YVRNTEN; -.
DR   OrthoDB; 421994at2759; -.
DR   PhylomeDB; O95897; -.
DR   TreeFam; TF315964; -.
DR   ChiTaRS; OLFM2; human.
DR   GeneWiki; OLFM2; -.
DR   GenomeRNAi; 93145; -.
DR   PRO; PR:O95897; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   Bgee; ENSG00000105088; Expressed in 119 organ(s), highest expression level in dorsolateral prefrontal cortex.
DR   ExpressionAtlas; O95897; baseline and differential.
DR   Genevisible; O95897; HS.
DR   GO; GO:0032281; C:AMPA glutamate receptor complex; ISS:UniProtKB.
DR   GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IDA:MGI.
DR   GO; GO:0099243; C:extrinsic component of synaptic membrane; IEA:Ensembl.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR   GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; IMP:UniProtKB.
DR   GO; GO:0009306; P:protein secretion; IDA:MGI.
DR   GO; GO:1905174; P:regulation of vascular smooth muscle cell dedifferentiation; ISS:UniProtKB.
DR   GO; GO:0007601; P:visual perception; IEA:Ensembl.
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   Cell junction; Coiled coil; Complete proteome; Cytoplasm;
KW   Disulfide bond; Glycoprotein; Membrane; Nucleus; Polymorphism;
KW   Reference proteome; Secreted; Signal; Synapse.
FT   SIGNAL        1     20       {ECO:0000255}.
FT   CHAIN        21    454       Noelin-2.
FT                                /FTId=PRO_0000020078.
FT   DOMAIN      194    446       Olfactomedin-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00446}.
FT   COILED       58     85       {ECO:0000255}.
FT   COILED      136    193       {ECO:0000255}.
FT   CARBOHYD     74     74       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    155    155       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    275    275       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    310    310       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    399    399       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    441    441       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    195    377       {ECO:0000255|PROSITE-ProRule:PRU00446}.
FT   VARIANT      86     86       T -> M (in a colorectal cancer sample;
FT                                somatic mutation; no effect on secretion;
FT                                dbSNP:rs1298178636).
FT                                {ECO:0000269|PubMed:16959974,
FT                                ECO:0000269|PubMed:21228389}.
FT                                /FTId=VAR_036532.
FT   VARIANT     106    106       R -> Q (in dbSNP:rs2303100).
FT                                {ECO:0000269|Ref.1}.
FT                                /FTId=VAR_022550.
FT   VARIANT     127    127       T -> M (in dbSNP:rs11556087).
FT                                {ECO:0000269|Ref.1}.
FT                                /FTId=VAR_050423.
FT   MUTAGEN     144    144       R->Q: No effect on secretion.
FT                                {ECO:0000269|PubMed:21228389}.
FT   MUTAGEN     420    420       L->S: Completely blocks secretion. Also
FT                                significantly inhibits secretion of OLFM1
FT                                and OLFM3. {ECO:0000269|PubMed:21228389}.
SQ   SEQUENCE   454 AA;  51386 MW;  EBF4AE8DF909C77F CRC64;
     MWPLTVPPPL LLLLCSGLAG QTLFQNPEEG WQLYTSAQAP DGKCICTAVI PAQSTCSRDG
     RSRELRQLME KVQNVSQSME VLELRTYRDL QYVRGMETLM RSLDARLRAA DGSLSAKSFQ
     ELKDRMTELL PLSSVLEQYK ADTRTIVRLR EEVRNLSGSL AAIQEEMGAY GYEDLQQRVM
     ALEARLHACA QKLGCGKLTG VSNPITVRAM GSRFGSWMTD TMAPSADSRV WYMDGYYKGR
     RVLEFRTLGD FIKGQNFIQH LLPQPWAGTG HVVYNGSLFY NKYQSNVVVK YHFRSRSVLV
     QRSLPGAGYN NTFPYSWGGF SDMDFMVDES GLWAVYTTNQ NAGNIVVSRL DPHTLEVMRS
     WDTGYPKRSA GEAFMICGVL YVTNSHLAGA KVYFAYFTNT SSYEYTDVPF HNQYSHISML
     DYNPRERALY TWNNGHQVLY NVTLFHVIST SGDP
//