NEPRO_HUMAN
ID NEPRO_HUMAN Reviewed; 567 AA.
AC Q6NW34; D3DN69; Q68DM6; Q9H7U0; Q9UFM4;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 3.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Nucleolus and neural progenitor protein {ECO:0000305};
GN Name=NEPRO {ECO:0000312|HGNC:HGNC:24496}; Synonyms=C3orf17;
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] (ISOFORM 1), AND VARIANT ILE-357.
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP PRO-490.
RC TISSUE=Cerebellum, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-357.
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP INVOLVEMENT IN ANXD3, AND VARIANT ANXD3 CYS-94.
RX PubMed=26633546; DOI=10.1038/gim.2015.147;
RA Shaheen R., Patel N., Shamseldin H., Alzahrani F., Al-Yamany R.,
RA Almoisheer A., Ewida N., Anazi S., Alnemer M., Elsheikh M., Alfaleh K.,
RA Alshammari M., Alhashem A., Alangari A.A., Salih M.A., Kircher M.,
RA Daza R.M., Ibrahim N., Wakil S.M., Alaqeel A., Altowaijri I., Shendure J.,
RA Al-Habib A., Faqieh E., Alkuraya F.S.;
RT "Accelerating matchmaking of novel dysmorphology syndromes through clinical
RT and genomic characterization of a large cohort.";
RL Genet. Med. 18:686-695(2016).
RN [10]
RP VARIANT ANXD3 CYS-94.
RX PubMed=29620724; DOI=10.1038/gim.2018.50;
RA Maddirevula S., Alsahli S., Alhabeeb L., Patel N., Alzahrani F.,
RA Shamseldin H.E., Anazi S., Ewida N., Alsaif H.S., Mohamed J.Y.,
RA Alazami A.M., Ibrahim N., Abdulwahab F., Hashem M., Abouelhoda M.,
RA Monies D., Al Tassan N., Alshammari M., Alsagheir A., Seidahmed M.Z.,
RA Sogati S., Aglan M.S., Hamad M.H., Salih M.A., Hamed A.A., Alhashmi N.,
RA Nabil A., Alfadli F., Abdel-Salam G.M.H., Alkuraya H., Peitee W.O.,
RA Keng W.T., Qasem A., Mushiba A.M., Zaki M.S., Fassad M.R., Alfadhel M.,
RA Alexander S., Sabr Y., Temtamy S., Ekbote A.V., Ismail S., Hosny G.A.,
RA Otaify G.A., Amr K., Al Tala S., Khan A.O., Rizk T., Alaqeel A.,
RA Alsiddiky A., Singh A., Kapoor S., Alhashem A., Faqeih E., Shaheen R.,
RA Alkuraya F.S.;
RT "Expanding the phenome and variome of skeletal dysplasia.";
RL Genet. Med. 20:1609-1616(2018).
RN [11]
RP VARIANT ANXD3 PHE-145.
RX PubMed=31250547; DOI=10.1002/ajmg.a.61267;
RA Narayanan D.L., Shukla A., Kausthubham N., Bhavani G.S., Shah H.,
RA Mortier G., Girisha K.M.;
RT "An emerging ribosomopathy affecting the skeleton due to biallelic
RT variations in NEPRO.";
RL Am. J. Med. Genet. A 179:1709-1717(2019).
CC -!- FUNCTION: May play a role in cortex development as part of the Notch
CC signaling pathway. Downstream of Notch may repress the expression of
CC proneural genes and inhibit neuronal differentiation thereby
CC maintaining neural progenitors. May also play a role in preimplentation
CC embryo development. {ECO:0000250|UniProtKB:Q8R2U2}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8R2U2}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:Q8R2U2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6NW34-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NW34-2; Sequence=VSP_017342, VSP_017343;
CC -!- DISEASE: Anauxetic dysplasia 3 (ANXD3) [MIM:618853]: An autosomal
CC recessive skeletal dysplasia characterized by severe short stature,
CC brachydactyly, skin laxity, joint hypermobility and dislocations, short
CC metacarpals, broad middle phalanges, and metaphyseal irregularities.
CC Most patients also exhibit motor and cognitive delays.
CC {ECO:0000269|PubMed:26633546, ECO:0000269|PubMed:29620724,
CC ECO:0000269|PubMed:31250547}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the nepro family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB55998.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK024325; BAB14885.1; -; mRNA.
DR EMBL; AL117573; CAB55998.1; ALT_INIT; mRNA.
DR EMBL; CR749341; CAH18194.1; -; mRNA.
DR EMBL; CH471052; EAW79648.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79649.1; -; Genomic_DNA.
DR EMBL; BC067743; AAH67743.1; -; mRNA.
DR CCDS; CCDS33824.1; -. [Q6NW34-1]
DR CCDS; CCDS82820.1; -. [Q6NW34-2]
DR PIR; T17308; T17308.
DR RefSeq; NP_001306038.1; NM_001319109.1. [Q6NW34-2]
DR RefSeq; NP_001306039.1; NM_001319110.1.
DR RefSeq; NP_001306040.1; NM_001319111.1.
DR RefSeq; NP_001306041.1; NM_001319112.1.
DR RefSeq; NP_001306043.1; NM_001319114.1.
DR RefSeq; NP_001306044.1; NM_001319115.1.
DR RefSeq; NP_056227.2; NM_015412.3. [Q6NW34-1]
DR AlphaFoldDB; Q6NW34; -.
DR BioGRID; 117387; 104.
DR IntAct; Q6NW34; 30.
DR MINT; Q6NW34; -.
DR STRING; 9606.ENSP00000320251; -.
DR iPTMnet; Q6NW34; -.
DR PhosphoSitePlus; Q6NW34; -.
DR BioMuta; NEPRO; -.
DR DMDM; 134047717; -.
DR EPD; Q6NW34; -.
DR jPOST; Q6NW34; -.
DR MassIVE; Q6NW34; -.
DR MaxQB; Q6NW34; -.
DR PaxDb; Q6NW34; -.
DR PeptideAtlas; Q6NW34; -.
DR PRIDE; Q6NW34; -.
DR ProteomicsDB; 66738; -. [Q6NW34-1]
DR ProteomicsDB; 66739; -. [Q6NW34-2]
DR Antibodypedia; 32543; 91 antibodies from 18 providers.
DR DNASU; 25871; -.
DR Ensembl; ENST00000314400.10; ENSP00000320251.5; ENSG00000163608.15. [Q6NW34-1]
DR Ensembl; ENST00000383675.6; ENSP00000373173.2; ENSG00000163608.15. [Q6NW34-2]
DR GeneID; 25871; -.
DR KEGG; hsa:25871; -.
DR MANE-Select; ENST00000314400.10; ENSP00000320251.5; NM_015412.4; NP_056227.2.
DR UCSC; uc003dzr.4; human. [Q6NW34-1]
DR CTD; 25871; -.
DR DisGeNET; 25871; -.
DR GeneCards; NEPRO; -.
DR HGNC; HGNC:24496; NEPRO.
DR HPA; ENSG00000163608; Low tissue specificity.
DR MalaCards; NEPRO; -.
DR MIM; 617089; gene.
DR MIM; 618853; phenotype.
DR neXtProt; NX_Q6NW34; -.
DR OpenTargets; ENSG00000163608; -.
DR Orphanet; 93347; Anauxetic dysplasia.
DR PharmGKB; PA134948355; -.
DR VEuPathDB; HostDB:ENSG00000163608; -.
DR eggNOG; ENOG502QTP3; Eukaryota.
DR GeneTree; ENSGT00390000007644; -.
DR HOGENOM; CLU_035014_0_0_1; -.
DR InParanoid; Q6NW34; -.
DR OMA; INKHNTS; -.
DR OrthoDB; 480212at2759; -.
DR PhylomeDB; Q6NW34; -.
DR TreeFam; TF335999; -.
DR PathwayCommons; Q6NW34; -.
DR SignaLink; Q6NW34; -.
DR BioGRID-ORCS; 25871; 744 hits in 1080 CRISPR screens.
DR ChiTaRS; NEPRO; human.
DR GenomeRNAi; 25871; -.
DR Pharos; Q6NW34; Tbio.
DR PRO; PR:Q6NW34; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q6NW34; protein.
DR Bgee; ENSG00000163608; Expressed in secondary oocyte and 183 other tissues.
DR ExpressionAtlas; Q6NW34; baseline and differential.
DR Genevisible; Q6NW34; HS.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB.
DR InterPro; IPR027951; DUF4477.
DR Pfam; PF14780; DUF4477; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Disease variant; Dwarfism;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..567
FT /note="Nucleolus and neural progenitor protein"
FT /id="PRO_0000225012"
FT REGION 437..457
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..460
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q8R2U2"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 114
FT /note="N -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017342"
FT VAR_SEQ 115..184
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017343"
FT VARIANT 94
FT /note="R -> C (in ANXD3; unknown pathological significance;
FT dbSNP:rs1236015814)"
FT /evidence="ECO:0000269|PubMed:26633546,
FT ECO:0000269|PubMed:29620724"
FT /id="VAR_084136"
FT VARIANT 101
FT /note="E -> K (in dbSNP:rs2291465)"
FT /id="VAR_025418"
FT VARIANT 145
FT /note="L -> F (in ANXD3; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31250547"
FT /id="VAR_084137"
FT VARIANT 352
FT /note="P -> S (in dbSNP:rs2306858)"
FT /id="VAR_025419"
FT VARIANT 357
FT /note="F -> I (in dbSNP:rs2306857)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_025420"
FT VARIANT 476
FT /note="T -> A (in dbSNP:rs3732813)"
FT /id="VAR_025421"
FT VARIANT 490
FT /note="S -> P (in dbSNP:rs7628368)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_025422"
FT CONFLICT 35
FT /note="L -> I (in Ref. 4; AAH67743)"
FT /evidence="ECO:0000305"
FT CONFLICT 509
FT /note="S -> N (in Ref. 4; AAH67743)"
FT /evidence="ECO:0000305"
FT CONFLICT 520
FT /note="E -> G (in Ref. 4; AAH67743)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 567 AA; 64552 MW; 88CB0CEE2A0CA0A2 CRC64;
MMAAVPPGLE PWNRVRIPKA GNRSAVTVQN PGAALDLCIA AVIKECHLVI LSLKSQTLDA
ETDVLCAVLY SNHNRMGRHK PHLALKQVEQ CLKRLKNMNL EGSIQDLFEL FSSNENQPLT
TKVCVVPSQP VVELVLMKVL GACKLLLRLL DCCCKTFLLT VKHLGLQEFI ILNLVMVGLV
SRLWVLYKGV LKRLILLYEP LFGLLQEVAR IQPMPYFKDF TFPSDITEFL GQPYFEAFKK
KMPIAFAAKG INKLLNKLFL INEQSPRASE ETLLGISKKA KQMKINVQNN VDLGQPVKNK
RVFKEESSEF DVRAFCNQLK HKATQETSFD FKCSQSRLKT TKYSSQKVIG TPHAKSFVQR
FREAESFTQL SEEIQMAVVW CRSKKLKAQA IFLGNKLLKS NRLKHLEAQG TSLPKKLECI
KTSICNHLLR GSGIKTSKHH LRQRRSQNKF LRRQRKPQRK LQSTLLREIQ QFSQGTRKSA
TDTSAKWRLS HCTVHRTDLY PNSKQLLNSG VSMPVIQTKE KMIHENLRGI HENETDSWTV
MQINKNSTSG TIKETDDIDD IFALMGV
