NOE2_HUMAN
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 03-AUG-2022, entry version 165.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLN-106 AND 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., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., 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 project:
RT 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 ocular
RT 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 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 SPECIFICITY,
RP 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-beta-
RT induced smooth muscle differentiation of human embryonic stem cell-derived
RT 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., Santos C.,
RA Broadgate S., Dunn R., Bruty J., Wallis Y., McMullan D., Ogilvie C.,
RA 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., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal 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 and
CC translocation of OLFM2 to the nucleus where it binds to SRF, causing
CC its dissociation from the transcriptional repressor HEY2/HERP1 and
CC facilitating binding of SRF to target genes (PubMed:25298399). Plays a
CC role in AMPAR complex organization (By similarity). Is a regulator of
CC 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:Q568Y7,
CC ECO:0000250|UniProtKB:Q8BM13, 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 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. Interacts with GRIA2 (By
CC similarity). Interacts with OLFM1 and OLFM3 (PubMed:21228389).
CC Interacts with SRF; the interaction promotes dissociation of SRF from
CC the transcriptional repressor HEY2 (PubMed:25298399). Interacts with
CC RUNX2 (By similarity). {ECO:0000250|UniProtKB:Q568Y7,
CC ECO:0000250|UniProtKB:Q8BM13, ECO:0000269|PubMed:21228389,
CC ECO:0000269|PubMed:25298399}.
CC -!- INTERACTION:
CC O95897; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-721741, EBI-11749135;
CC O95897; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-721741, EBI-22310682;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21228389}. Synapse
CC {ECO:0000250|UniProtKB:Q8BM13}. Membrane
CC {ECO:0000250|UniProtKB:Q8BM13}. Nucleus {ECO:0000269|PubMed:25298399}.
CC Cytoplasm {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 (PubMed:27844144).
CC {ECO:0000269|PubMed:25298399, ECO:0000269|PubMed:27844144}.
CC -!- INDUCTION: By TGF-beta. {ECO:0000269|PubMed:25298399}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:21228389}.
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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 AlphaFoldDB; O95897; -.
DR SMR; O95897; -.
DR BioGRID; 125007; 122.
DR IntAct; O95897; 45.
DR STRING; 9606.ENSP00000264833; -.
DR GlyConnect; 1963; 5 N-Linked glycans (1 site).
DR GlyGen; O95897; 6 sites, 5 N-linked glycans (1 site).
DR iPTMnet; O95897; -.
DR PhosphoSitePlus; O95897; -.
DR BioMuta; OLFM2; -.
DR EPD; O95897; -.
DR jPOST; O95897; -.
DR MassIVE; O95897; -.
DR MaxQB; O95897; -.
DR PaxDb; O95897; -.
DR PeptideAtlas; O95897; -.
DR PRIDE; O95897; -.
DR ProteomicsDB; 51119; -.
DR Antibodypedia; 42819; 54 antibodies from 16 providers.
DR DNASU; 93145; -.
DR Ensembl; ENST00000264833.9; ENSP00000264833.3; ENSG00000105088.9.
DR GeneID; 93145; -.
DR KEGG; hsa:93145; -.
DR MANE-Select; ENST00000264833.9; ENSP00000264833.3; NM_058164.4; NP_477512.1.
DR UCSC; uc002mmp.4; human.
DR CTD; 93145; -.
DR DisGeNET; 93145; -.
DR GeneCards; OLFM2; -.
DR HGNC; HGNC:17189; OLFM2.
DR HPA; ENSG00000105088; Tissue enhanced (brain, skin).
DR MIM; 617492; gene.
DR neXtProt; NX_O95897; -.
DR OpenTargets; ENSG00000105088; -.
DR PharmGKB; PA31916; -.
DR VEuPathDB; HostDB:ENSG00000105088; -.
DR eggNOG; KOG3545; Eukaryota.
DR GeneTree; ENSGT00940000159148; -.
DR InParanoid; O95897; -.
DR OMA; KADMRTI; -.
DR OrthoDB; 421994at2759; -.
DR PhylomeDB; O95897; -.
DR TreeFam; TF315964; -.
DR PathwayCommons; O95897; -.
DR SignaLink; O95897; -.
DR BioGRID-ORCS; 93145; 17 hits in 1072 CRISPR screens.
DR ChiTaRS; OLFM2; human.
DR GeneWiki; OLFM2; -.
DR GenomeRNAi; 93145; -.
DR Pharos; O95897; Tbio.
DR PRO; PR:O95897; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O95897; protein.
DR Bgee; ENSG00000105088; Expressed in cortical plate and 105 other tissues.
DR ExpressionAtlas; O95897; baseline and differential.
DR Genevisible; O95897; HS.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; ISS:UniProtKB.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
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 associated smooth muscle cell dedifferentiation; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
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..20
FT /evidence="ECO:0000255"
FT CHAIN 21..454
FT /note="Noelin-2"
FT /id="PRO_0000020078"
FT DOMAIN 194..446
FT /note="Olfactomedin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446"
FT COILED 58..85
FT /evidence="ECO:0000255"
FT COILED 136..193
FT /evidence="ECO:0000255"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 399
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 195..377
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446"
FT VARIANT 86
FT /note="T -> M (in a colorectal cancer sample; somatic
FT mutation; no effect on secretion; dbSNP:rs1298178636)"
FT /evidence="ECO:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:21228389"
FT /id="VAR_036532"
FT VARIANT 106
FT /note="R -> Q (in dbSNP:rs2303100)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_022550"
FT VARIANT 127
FT /note="T -> M (in dbSNP:rs11556087)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_050423"
FT MUTAGEN 144
FT /note="R->Q: No effect on secretion."
FT /evidence="ECO:0000269|PubMed:21228389"
FT MUTAGEN 420
FT /note="L->S: Completely blocks secretion. Also
FT significantly inhibits secretion of OLFM1 and OLFM3."
FT /evidence="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
