NRARP_MOUSE
ID NRARP_MOUSE Reviewed; 114 AA.
AC Q91ZA8; Q80UV7; Q9CZM1;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Notch-regulated ankyrin repeat-containing protein;
GN Name=Nrarp;
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 [MRNA] (ISOFORM 1), FUNCTION, INDUCTION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=AKR/J;
RX PubMed=11783997; DOI=10.1006/dbio.2001.0408;
RA Krebs L.T., Deftos M.L., Bevan M.J., Gridley T.;
RT "The Nrarp gene encodes an ankyrin-repeat protein that is transcriptionally
RT regulated by the notch signaling pathway.";
RL Dev. Biol. 238:110-119(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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 [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=19268448; DOI=10.1016/j.ydbio.2009.02.023;
RA Sewell W., Sparrow D.B., Smith A.J., Gonzalez D.M., Rappaport E.F.,
RA Dunwoodie S.L., Kusumi K.;
RT "Cyclical expression of the Notch/Wnt regulator Nrarp requires modulation
RT by Dll3 in somitogenesis.";
RL Dev. Biol. 329:400-409(2009).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND INTERACTION WITH LEF1.
RX PubMed=19154719; DOI=10.1016/j.devcel.2008.12.009;
RA Phng L.K., Potente M., Leslie J.D., Babbage J., Nyqvist D., Lobov I.,
RA Ondr J.K., Rao S., Lang R.A., Thurston G., Gerhardt H.;
RT "Nrarp coordinates endothelial Notch and Wnt signaling to control vessel
RT density in angiogenesis.";
RL Dev. Cell 16:70-82(2009).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21795391; DOI=10.1091/mbc.e11-02-0139;
RA Kim W., Matsui T., Yamao M., Ishibashi M., Tamada K., Takumi T., Kohno K.,
RA Oba S., Ishii S., Sakumura Y., Bessho Y.;
RT "The period of the somite segmentation clock is sensitive to Notch
RT activity.";
RL Mol. Biol. Cell 22:3541-3549(2011).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21998026; DOI=10.1002/dvg.20813;
RA Krebs L.T., Bradley C.K., Norton C.R., Xu J., Oram K.F., Starling C.,
RA Deftos M.L., Bevan M.J., Gridley T.;
RT "The Notch-regulated ankyrin repeat protein is required for proper
RT anterior-posterior somite patterning in mice.";
RL Genesis 50:366-374(2012).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=24015274; DOI=10.1371/journal.pone.0072767;
RA Murta D., Batista M., Silva E., Trindade A., Henrique D., Duarte A.,
RA Lopes-da-Costa L.;
RT "Dynamics of Notch pathway expression during mouse testis post-natal
RT development and along the spermatogenic cycle.";
RL PLoS ONE 8:E72767-E72767(2013).
CC -!- FUNCTION: Downstream effector of Notch signaling. Involved in the
CC regulation of liver cancer cells self-renewal (By similarity). Involved
CC in the regulation of canonical Wnt signaling by stabilizing LEF1 (By
CC similarity). Involved in angiogenesis acting downstream of Notch at
CC branch points to regulate vascular density. Proposed to integrate
CC endothelial Notch and Wnt signaling to control stalk cell proliferation
CC and to stablilize new endothelial connections during angiogenesis
CC (PubMed:19154719). During somitogenesis involved in maintenance of
CC proper somite segmentation and proper numbers of somites and vertebrae.
CC Required for proper anterior-posterior somite patterning. Proposed to
CC function in a negative feedback loop to destabilize Notch 1
CC intracellular domain (NICD) and down-regulate the Notch signal,
CC preventing expansion of the Notch signal into the anterior somite
CC domain (PubMed:21795391, PubMed:21998026).
CC {ECO:0000250|UniProtKB:Q7T3Y0, ECO:0000250|UniProtKB:Q7Z6K4,
CC ECO:0000269|PubMed:11783997, ECO:0000269|PubMed:19154719,
CC ECO:0000269|PubMed:21795391, ECO:0000269|PubMed:21998026,
CC ECO:0000305|PubMed:21998026}.
CC -!- SUBUNIT: Interacts with LEF1. {ECO:0000269|PubMed:19154719}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q91ZA8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91ZA8-2; Sequence=VSP_032380, VSP_032381;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the brain, heart,
CC colon, kidney, liver, lung and small intestine. Expressed in retina,
CC most prominent in endothelial cells at the migrating point of the
CC vasculature behind leading tip cells. Expressed in testis.
CC {ECO:0000269|PubMed:11783997, ECO:0000269|PubMed:19154719,
CC ECO:0000269|PubMed:24015274}.
CC -!- DEVELOPMENTAL STAGE: During embryogenesis, expressed in several tissues
CC in which cellular differentiation is regulated by the notch signaling
CC pathway. At 10.5 dpc expressed in intersomatic vessels and in vessels
CC of the limb buds with strongest expression at vascular branch points.
CC Cyclic expression between 8.5 dpc and 10.5 dpc somitogenesis is
CC dependent on DLL3. {ECO:0000269|PubMed:11783997,
CC ECO:0000269|PubMed:19154719, ECO:0000269|PubMed:19268448}.
CC -!- INDUCTION: By Notch signaling via a CBF1/Su(H)/Lag-1 (CSL)-dependent
CC pathway. {ECO:0000269|PubMed:11783997}.
CC -!- DISRUPTION PHENOTYPE: Axial skeletal defects in newborn mice such as
CC rib fusions, fused vertebral bodies and fused pedicles of the
CC vertebrae; defects are influenced by the strain-specific genetic
CC background. Embryos exhibit expansion and fusion of myotomes, dorsal
CC root ganglia fusions and defects in projection of the spinal nerves.
CC Embryos show increased level of Notch 1 intracellular domain (NICD)
CC expression in presomitic mesoderm and somites (PubMed:21998026). In
CC contrast, fewer somites and vertebrae found in -/- are linked to a
CC longer segmentation clock period (PubMed:21795391). Defects in the
CC radial expansion of the vascular plexus from the optic nerve head to
CC the periphery, reduction of retinal vessel density; however, most of
CC the defects in angiogenesis resolve over time (PubMed:19154719).
CC {ECO:0000269|PubMed:19154719, ECO:0000269|PubMed:21795391,
CC ECO:0000269|PubMed:21998026}.
CC -!- SIMILARITY: Belongs to the NRARP family. {ECO:0000305}.
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DR EMBL; AY046077; AAL05944.1; -; mRNA.
DR EMBL; AK012426; BAB28231.1; ALT_SEQ; mRNA.
DR EMBL; AL732309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC048088; AAH48088.1; -; mRNA.
DR EMBL; BC069891; AAH69891.1; -; mRNA.
DR CCDS; CCDS38066.1; -. [Q91ZA8-1]
DR RefSeq; NP_080256.2; NM_025980.2. [Q91ZA8-1]
DR AlphaFoldDB; Q91ZA8; -.
DR SMR; Q91ZA8; -.
DR IntAct; Q91ZA8; 1.
DR STRING; 10090.ENSMUSP00000100615; -.
DR PhosphoSitePlus; Q91ZA8; -.
DR MaxQB; Q91ZA8; -.
DR PaxDb; Q91ZA8; -.
DR PRIDE; Q91ZA8; -.
DR Antibodypedia; 19006; 154 antibodies from 25 providers.
DR DNASU; 67122; -.
DR Ensembl; ENSMUST00000104999; ENSMUSP00000100615; ENSMUSG00000078202. [Q91ZA8-1]
DR GeneID; 67122; -.
DR KEGG; mmu:67122; -.
DR UCSC; uc008iqk.1; mouse. [Q91ZA8-1]
DR CTD; 441478; -.
DR MGI; MGI:1914372; Nrarp.
DR VEuPathDB; HostDB:ENSMUSG00000078202; -.
DR eggNOG; KOG0505; Eukaryota.
DR GeneTree; ENSGT00940000161928; -.
DR HOGENOM; CLU_000134_41_1_1; -.
DR InParanoid; Q91ZA8; -.
DR OMA; NMTSCEF; -.
DR OrthoDB; 1514637at2759; -.
DR PhylomeDB; Q91ZA8; -.
DR BioGRID-ORCS; 67122; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Nrarp; mouse.
DR PRO; PR:Q91ZA8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q91ZA8; protein.
DR Bgee; ENSMUSG00000078202; Expressed in paraxial mesoderm and 242 other tissues.
DR Genevisible; Q91ZA8; MM.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IMP:MGI.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:MGI.
DR GO; GO:0001935; P:endothelial cell proliferation; IMP:MGI.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IMP:MGI.
DR GO; GO:1902367; P:negative regulation of Notch signaling pathway involved in somitogenesis; IMP:MGI.
DR GO; GO:0045581; P:negative regulation of T cell differentiation; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IBA:GO_Central.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IMP:MGI.
DR GO; GO:0022407; P:regulation of cell-cell adhesion; IMP:MGI.
DR GO; GO:0032525; P:somite rostral/caudal axis specification; IMP:MGI.
DR GO; GO:0002040; P:sprouting angiogenesis; IMP:MGI.
DR GO; GO:0030217; P:T cell differentiation; IDA:MGI.
DR GO; GO:0101023; P:vascular endothelial cell proliferation; IMP:MGI.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF12796; Ank_2; 1.
DR SMART; SM00248; ANK; 2.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Developmental protein;
KW Reference proteome; Repeat.
FT CHAIN 1..114
FT /note="Notch-regulated ankyrin repeat-containing protein"
FT /id="PRO_0000325080"
FT REPEAT 50..79
FT /note="ANK 1"
FT REPEAT 83..112
FT /note="ANK 2"
FT VAR_SEQ 79..80
FT /note="LA -> RS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032380"
FT VAR_SEQ 81..114
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032381"
SQ SEQUENCE 114 AA; 12492 MW; C8B84B648DB47F4F CRC64;
MSQAELSTCS APQTQRIFQE AVRKGNTQEL QSLLQNMTNC EFNVNSFGPE GQTALHQSVI
DGNLELVKLL VKFGADIRLA NRDGWSALHI AAFGGHQDIV LYLITKAKYA ASGR
