NEPN_MOUSE
ID NEPN_MOUSE Reviewed; 512 AA.
AC Q9CQ76;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Nephrocan {ECO:0000312|MGI:MGI:1913900};
DE Flags: Precursor;
GN Name=Nepn {ECO:0000312|MGI:MGI:1913900};
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] {ECO:0000312|EMBL:AAX23973.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND GLYCOSYLATION.
RC STRAIN=NIH-III {ECO:0000312|EMBL:AAX23973.1};
RC TISSUE=Kidney {ECO:0000312|EMBL:AAX23973.1};
RX PubMed=16990280; DOI=10.1074/jbc.m604787200;
RA Mochida Y., Parisuthiman D., Kaku M., Hanai J., Sukhatme V.P., Yamauchi M.;
RT "Nephrocan, a novel member of the small leucine-rich repeat protein family,
RT is an inhibitor of transforming growth factor-beta signaling.";
RL J. Biol. Chem. 281:36044-36051(2006).
RN [2] {ECO:0000312|EMBL:BAB30857.1, ECO:0000312|EMBL:BAB30928.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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] {ECO:0000312|Proteomes:UP000000589}
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] {ECO:0000312|EMBL:EDL05079.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000312|EMBL:AAI32047.1, ECO:0000312|EMBL:AAI32049.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6] {ECO:0000305}
RP DEVELOPMENTAL STAGE.
RX PubMed=17683524; DOI=10.1186/1471-213x-7-92;
RA Hou J., Charters A.M., Lee S.C., Zhao Y., Wu M.K., Jones S.J., Marra M.A.,
RA Hoodless P.A.;
RT "A systematic screen for genes expressed in definitive endoderm by Serial
RT Analysis of Gene Expression (SAGE).";
RL BMC Dev. Biol. 7:92-92(2007).
CC -!- FUNCTION: May inhibit TGF-beta signaling.
CC {ECO:0000269|PubMed:16990280}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16990280}.
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in the kidney, where it
CC is primarily detected in the epithelial cells of distal tubules and
CC collecting ducts, and more weakly in proximal epithelial cells.
CC Expressed at lower levels in heart and lung (at protein level).
CC Detected in skeletal muscle. {ECO:0000269|PubMed:16990280}.
CC -!- DEVELOPMENTAL STAGE: Detected in the definitive endoderm from 7.5 dpc
CC onwards (PubMed:17683524). Strongly expressed in the developing midgut
CC by 9 dpc, but then at 9.5 dpc expression appears to decrease
CC (PubMed:17683524). Global expression levels peak during 11 dpc: also
CC detected at slightly lower levels during 7 dpc, 15 dpc and 17 dpc
CC (PubMed:16990280). {ECO:0000269|PubMed:16990280,
CC ECO:0000269|PubMed:17683524}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16990280}.
CC -!- SIMILARITY: Belongs to the small leucine-rich proteoglycan (SLRP)
CC family. {ECO:0000305}.
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DR EMBL; AY938536; AAX23973.1; -; mRNA.
DR EMBL; AK017656; BAB30857.1; -; mRNA.
DR EMBL; AK017780; BAB30928.1; -; mRNA.
DR EMBL; AC153526; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466540; EDL05079.1; -; Genomic_DNA.
DR EMBL; BC132046; AAI32047.1; -; mRNA.
DR EMBL; BC132048; AAI32049.1; -; mRNA.
DR CCDS; CCDS23840.1; -.
DR RefSeq; NP_079960.1; NM_025684.2.
DR AlphaFoldDB; Q9CQ76; -.
DR SMR; Q9CQ76; -.
DR STRING; 10090.ENSMUSP00000070130; -.
DR GlyGen; Q9CQ76; 1 site.
DR PaxDb; Q9CQ76; -.
DR PRIDE; Q9CQ76; -.
DR ProteomicsDB; 252948; -.
DR Ensembl; ENSMUST00000067085; ENSMUSP00000070130; ENSMUSG00000038624.
DR GeneID; 66650; -.
DR KEGG; mmu:66650; -.
DR UCSC; uc007fbh.1; mouse.
DR CTD; 66650; -.
DR MGI; MGI:1913900; Nepn.
DR VEuPathDB; HostDB:ENSMUSG00000038624; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000162914; -.
DR HOGENOM; CLU_000288_18_6_1; -.
DR InParanoid; Q9CQ76; -.
DR OMA; TCPRRCS; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q9CQ76; -.
DR TreeFam; TF336377; -.
DR BioGRID-ORCS; 66650; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q9CQ76; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9CQ76; protein.
DR Bgee; ENSMUSG00000038624; Expressed in pancreatic epithelial bud and 30 other tissues.
DR ExpressionAtlas; Q9CQ76; baseline and differential.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005614; C:interstitial matrix; IDA:MGI.
DR GO; GO:0046696; C:lipopolysaccharide receptor complex; IBA:GO_Central.
DR GO; GO:0001530; F:lipopolysaccharide binding; IBA:GO_Central.
DR GO; GO:0030198; P:extracellular matrix organization; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:MGI.
DR GO; GO:0002718; P:regulation of cytokine production involved in immune response; IBA:GO_Central.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IBA:GO_Central.
DR Gene3D; 3.80.10.10; -; 5.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF13855; LRR_8; 3.
DR SMART; SM00369; LRR_TYP; 9.
DR PROSITE; PS51450; LRR; 14.
PE 1: Evidence at protein level;
KW Glycoprotein; Leucine-rich repeat; Reference proteome; Repeat; Secreted;
KW Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..512
FT /note="Nephrocan"
FT /id="PRO_5004324983"
FT DOMAIN 20..44
FT /note="LRRNT"
FT /evidence="ECO:0000305"
FT REPEAT 45..69
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 71..93
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 94..117
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 119..138
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 139..162
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 164..185
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 186..208
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 210..232
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 234..253
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 254..276
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT REPEAT 277..299
FT /note="LRR 11"
FT /evidence="ECO:0000255"
FT REPEAT 301..320
FT /note="LRR 12"
FT /evidence="ECO:0000255"
FT REPEAT 321..344
FT /note="LRR 13"
FT /evidence="ECO:0000255"
FT REPEAT 346..371
FT /note="LRR 14"
FT /evidence="ECO:0000255"
FT REPEAT 373..389
FT /note="LRR 15"
FT /evidence="ECO:0000255"
FT REPEAT 390..413
FT /note="LRR 16"
FT /evidence="ECO:0000255"
FT REPEAT 415..442
FT /note="LRR 17"
FT /evidence="ECO:0000255"
FT REGION 474..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 474..499
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 512 AA; 57705 MW; BA8F0C4B6F809FAF CRC64;
MHPLWAFLLG LSLTNGLSAN CPGRCSCDSM QSVQCYRLME LPSGIPSTTK RLYISHSRIQ
HLQLSNFTGL LALEDFILLA SGTESIENDT FKTLSTLKTL ELWKNKLRQV PSALPANLEV
LKLNDNAICA LRGSEFEGLK NLKVLELKNN LISSLSPSML SPLASLQSLM VDGNNIESVV
GPLSLPHLKY MSMENNQLHL IPGNVFTSLQ NLQFLSFSGN FLTKIPINLP KSLLSLKMER
NQLKVVRFRD MKHLENLSHL YLSENFLSSI DGAQQLTNLT TLEVSQNQLQ MLPPRLPSRL
QKLDCSSNFI QRVTAPEFQD LRDLKHLFLD NNVVSLFEAG ALQRCSQLSN LALEQNLLLS
IPLRLPKTLA RLDLKGNAIQ DMAERELRDL KQLQVLNLRN NRISALDFKA LEGLPRLRHL
YLDGNPWNCT CSLLRAREVL KAKGTDVKGG QCAAPAERQG ESWMSSKKIL RQCEHHLQQS
EKSKETKKKP KPEDSSSIRL NMDDDDDDYE ID