ID   NRARP_HUMAN             Reviewed;         114 AA.
AC   Q7Z6K4; B8A4K5;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   03-AUG-2022, entry version 136.
DE   RecName: Full=Notch-regulated ankyrin repeat-containing protein;
GN   Name=NRARP;
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 GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
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   [3]
RP   FUNCTION, AND INDUCTION.
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   [4]
RP   FUNCTION.
RX   PubMed=25985737; DOI=10.1038/ncomms8122;
RA   Zhu P., Wang Y., Du Y., He L., Huang G., Zhang G., Yan X., Fan Z.;
RT   "C8orf4 negatively regulates self-renewal of liver cancer stem cells via
RT   suppression of NOTCH2 signalling.";
RL   Nat. Commun. 6:7122-7122(2015).
CC   -!- FUNCTION: Downstream effector of Notch signaling. Involved in the
CC       regulation of liver cancer cells self-renewal (PubMed:25985737).
CC       Involved in angiogenesis acting downstream of Notch at branch points to
CC       regulate vascular density. Proposed to integrate endothelial Notch and
CC       Wnt signaling to control stalk cell proliferation and to stablilize new
CC       endothelial connections during angiogenesis (PubMed:19154719). During
CC       somitogenesis involved in maintenance of proper somite segmentation and
CC       proper numbers of somites and vertebrae. Required for proper anterior-
CC       posterior somite patterning. Proposed to function in a negative
CC       feedback loop to destabilize Notch 1 intracellular domain (NICD) and
CC       down-regulate the Notch signal, preventing expansion of the Notch
CC       signal into the anterior somite domain (By similarity).
CC       {ECO:0000250|UniProtKB:Q91ZA8, ECO:0000269|PubMed:19154719,
CC       ECO:0000269|PubMed:25985737, ECO:0000305|PubMed:25985737}.
CC   -!- SUBUNIT: Interacts with LEF1. {ECO:0000250|UniProtKB:Q91ZA8}.
CC   -!- INTERACTION:
CC       Q7Z6K4; P29083: GTF2E1; NbExp=3; IntAct=EBI-5773228, EBI-5462215;
CC   -!- INDUCTION: In endothelial cells by Notch signaling.
CC       {ECO:0000269|PubMed:19154719}.
CC   -!- SIMILARITY: Belongs to the NRARP family. {ECO:0000305}.
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DR   EMBL; BX255925; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC053618; AAH53618.1; -; mRNA.
DR   CCDS; CCDS35188.1; -.
DR   RefSeq; NP_001004354.1; NM_001004354.2.
DR   PDB; 6PY8; X-ray; 3.75 A; B/G=1-114.
DR   PDBsum; 6PY8; -.
DR   AlphaFoldDB; Q7Z6K4; -.
DR   SMR; Q7Z6K4; -.
DR   BioGRID; 137507; 3.
DR   IntAct; Q7Z6K4; 2.
DR   STRING; 9606.ENSP00000349041; -.
DR   GlyGen; Q7Z6K4; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q7Z6K4; -.
DR   PhosphoSitePlus; Q7Z6K4; -.
DR   BioMuta; NRARP; -.
DR   DMDM; 74750170; -.
DR   MassIVE; Q7Z6K4; -.
DR   PaxDb; Q7Z6K4; -.
DR   PeptideAtlas; Q7Z6K4; -.
DR   PRIDE; Q7Z6K4; -.
DR   Antibodypedia; 19006; 154 antibodies from 25 providers.
DR   DNASU; 441478; -.
DR   Ensembl; ENST00000356628.4; ENSP00000349041.2; ENSG00000198435.4.
DR   GeneID; 441478; -.
DR   KEGG; hsa:441478; -.
DR   MANE-Select; ENST00000356628.4; ENSP00000349041.2; NM_001004354.3; NP_001004354.1.
DR   UCSC; uc004cmo.3; human.
DR   CTD; 441478; -.
DR   DisGeNET; 441478; -.
DR   GeneCards; NRARP; -.
DR   HGNC; HGNC:33843; NRARP.
DR   HPA; ENSG00000198435; Tissue enhanced (intestine).
DR   neXtProt; NX_Q7Z6K4; -.
DR   OpenTargets; ENSG00000198435; -.
DR   PharmGKB; PA164724205; -.
DR   VEuPathDB; HostDB:ENSG00000198435; -.
DR   eggNOG; KOG0505; Eukaryota.
DR   GeneTree; ENSGT00940000161928; -.
DR   HOGENOM; CLU_000134_41_1_1; -.
DR   InParanoid; Q7Z6K4; -.
DR   OMA; NMTSCEF; -.
DR   OrthoDB; 1514637at2759; -.
DR   PhylomeDB; Q7Z6K4; -.
DR   PathwayCommons; Q7Z6K4; -.
DR   SignaLink; Q7Z6K4; -.
DR   SIGNOR; Q7Z6K4; -.
DR   BioGRID-ORCS; 441478; 12 hits in 1072 CRISPR screens.
DR   ChiTaRS; NRARP; human.
DR   GenomeRNAi; 441478; -.
DR   Pharos; Q7Z6K4; Tbio.
DR   PRO; PR:Q7Z6K4; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; Q7Z6K4; protein.
DR   Bgee; ENSG00000198435; Expressed in mucosa of sigmoid colon and 176 other tissues.
DR   Genevisible; Q7Z6K4; HS.
DR   GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IBA:GO_Central.
DR   GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IBA:GO_Central.
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; IEA:Ensembl.
DR   GO; GO:0045581; P:negative regulation of T cell differentiation; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
DR   GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP: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; IEA:Ensembl.
DR   GO; GO:0032525; P:somite rostral/caudal axis specification; IEA:Ensembl.
DR   GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
DR   GO; GO:0101023; P:vascular endothelial cell proliferation; IEA:Ensembl.
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   3D-structure; ANK repeat; Developmental protein; Reference proteome;
KW   Repeat.
FT   CHAIN           1..114
FT                   /note="Notch-regulated ankyrin repeat-containing protein"
FT                   /id="PRO_0000325079"
FT   REPEAT          50..79
FT                   /note="ANK 1"
FT   REPEAT          83..112
FT                   /note="ANK 2"
SQ   SEQUENCE   114 AA;  12492 MW;  C8B84B648DB47F4F CRC64;
     MSQAELSTCS APQTQRIFQE AVRKGNTQEL QSLLQNMTNC EFNVNSFGPE GQTALHQSVI
     DGNLELVKLL VKFGADIRLA NRDGWSALHI AAFGGHQDIV LYLITKAKYA ASGR