NPNT_MOUSE
ID NPNT_MOUSE Reviewed; 561 AA.
AC Q91V88; Q6NV58; Q80VP6; Q91XL5; Q91ZD3; Q923T5;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Nephronectin;
DE AltName: Full=Preosteoblast EGF-like repeat protein with MAM domain;
DE Flags: Precursor;
GN Name=Npnt; Synonyms=Neph1, Poem;
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, OLIGOMERIZATION,
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF ASP-384.
RC STRAIN=C57BL/6J; TISSUE=Preosteoblast;
RX PubMed=11546798; DOI=10.1074/jbc.m103216200;
RA Morimura N., Tezuka Y., Watanabe N., Yasuda M., Miyatani S., Hozumi N.,
RA Tezuka Ki K.;
RT "Molecular cloning of POEM: a novel adhesion molecule that interacts with
RT alpha8beta1 integrin.";
RL J. Biol. Chem. 276:42172-42181(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J, and NIH Swiss; TISSUE=Kidney;
RX PubMed=11470831; DOI=10.1083/jcb.200103069;
RA Brandenberger R., Schmidt A., Linton J., Wang D., Backus C., Denda S.,
RA Mueller U., Reichardt L.F.;
RT "Identification and characterization of a novel extracellular matrix
RT protein nephronectin that is associated with integrin alpha8beta1 in the
RT embryonic kidney.";
RL J. Cell Biol. 154:447-458(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Pancreas;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Kidney, and 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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17537792; DOI=10.1242/dev.005033;
RA Linton J.M., Martin G.R., Reichardt L.F.;
RT "The ECM protein nephronectin promotes kidney development via integrin
RT alpha8beta1-mediated stimulation of Gdnf expression.";
RL Development 134:2501-2509(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Functional ligand of integrin alpha-8/beta-1 in kidney
CC development. Regulates the expression of GDNF with integrin alpha-
CC 8/beta-1 which is essential for kidney development. May also play a
CC role in the development and function of various tissues, regulating
CC cell adhesion, spreading and survival through the binding of several
CC integrins. {ECO:0000269|PubMed:11470831, ECO:0000269|PubMed:11546798,
CC ECO:0000269|PubMed:17537792}.
CC -!- SUBUNIT: Homodimer and homotrimer.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:11470831, ECO:0000269|PubMed:11546798}.
CC Note=Trapped on the cell surface or in the extracellular matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Short;
CC IsoId=Q91V88-1; Sequence=Displayed;
CC Name=2; Synonyms=Long;
CC IsoId=Q91V88-2; Sequence=VSP_026989;
CC Name=3;
CC IsoId=Q91V88-3; Sequence=VSP_026990;
CC Name=4;
CC IsoId=Q91V88-4; Sequence=VSP_026989, VSP_026990;
CC -!- TISSUE SPECIFICITY: Expressed in kidney (at protein level).
CC {ECO:0000269|PubMed:11470831}.
CC -!- DEVELOPMENTAL STAGE: Expressed from 10.5 dpc onward mainly at
CC epithelial-mesenchymal interfaces in kidney and other tissues
CC undergoing morphogenesis (at protein level).
CC {ECO:0000269|PubMed:11470831, ECO:0000269|PubMed:11546798}.
CC -!- DOMAIN: The MAM domain is required for localization at the cell
CC surface.
CC -!- DISRUPTION PHENOTYPE: Mice display renal agenesis at birth due to a
CC developmental delay. This delay is associated with a reduced expression
CC of Gdnf and is similar to the one found in mice lacking Itga8.
CC {ECO:0000269|PubMed:17537792}.
CC -!- MISCELLANEOUS: Was named nephronectin based on its potential role in
CC kidney development.
CC -!- SIMILARITY: Belongs to the nephronectin family. {ECO:0000305}.
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DR EMBL; AB059656; BAB69692.1; -; mRNA.
DR EMBL; AF397007; AAK84391.1; -; mRNA.
DR EMBL; AF397008; AAK84392.1; -; mRNA.
DR EMBL; AY035898; AAK96010.1; -; mRNA.
DR EMBL; AY035899; AAK96011.1; -; mRNA.
DR EMBL; AK050484; BAC34283.1; -; mRNA.
DR EMBL; BC046642; AAH46642.1; -; mRNA.
DR EMBL; BC068308; AAH68308.1; -; mRNA.
DR CCDS; CCDS17845.1; -. [Q91V88-1]
DR CCDS; CCDS17846.1; -. [Q91V88-2]
DR CCDS; CCDS71322.1; -. [Q91V88-3]
DR CCDS; CCDS71323.1; -. [Q91V88-4]
DR RefSeq; NP_001025007.1; NM_001029836.2. [Q91V88-1]
DR RefSeq; NP_001274030.1; NM_001287101.1. [Q91V88-4]
DR RefSeq; NP_001274031.1; NM_001287102.1. [Q91V88-3]
DR RefSeq; NP_277060.2; NM_033525.3. [Q91V88-2]
DR AlphaFoldDB; Q91V88; -.
DR SMR; Q91V88; -.
DR BioGRID; 227625; 3.
DR IntAct; Q91V88; 2.
DR STRING; 10090.ENSMUSP00000040071; -.
DR iPTMnet; Q91V88; -.
DR PhosphoSitePlus; Q91V88; -.
DR MaxQB; Q91V88; -.
DR PaxDb; Q91V88; -.
DR PRIDE; Q91V88; -.
DR ProteomicsDB; 293683; -. [Q91V88-1]
DR ProteomicsDB; 293684; -. [Q91V88-2]
DR ProteomicsDB; 293685; -. [Q91V88-3]
DR ProteomicsDB; 293686; -. [Q91V88-4]
DR Antibodypedia; 1021; 130 antibodies from 22 providers.
DR DNASU; 114249; -.
DR Ensembl; ENSMUST00000042729; ENSMUSP00000040071; ENSMUSG00000040998. [Q91V88-2]
DR Ensembl; ENSMUST00000042744; ENSMUSP00000040684; ENSMUSG00000040998. [Q91V88-1]
DR Ensembl; ENSMUST00000093971; ENSMUSP00000091505; ENSMUSG00000040998. [Q91V88-4]
DR Ensembl; ENSMUST00000117164; ENSMUSP00000113419; ENSMUSG00000040998. [Q91V88-3]
DR GeneID; 114249; -.
DR KEGG; mmu:114249; -.
DR UCSC; uc008rkc.3; mouse. [Q91V88-2]
DR UCSC; uc008rkd.3; mouse. [Q91V88-1]
DR UCSC; uc008rke.3; mouse. [Q91V88-4]
DR UCSC; uc008rkf.3; mouse. [Q91V88-3]
DR CTD; 255743; -.
DR MGI; MGI:2148811; Npnt.
DR VEuPathDB; HostDB:ENSMUSG00000040998; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00930000150973; -.
DR InParanoid; Q91V88; -.
DR OMA; GKTCNQG; -.
DR OrthoDB; 766075at2759; -.
DR PhylomeDB; Q91V88; -.
DR TreeFam; TF330819; -.
DR BioGRID-ORCS; 114249; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q91V88; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q91V88; protein.
DR Bgee; ENSMUSG00000040998; Expressed in ascending aorta and 287 other tissues.
DR ExpressionAtlas; Q91V88; baseline and differential.
DR Genevisible; Q91V88; MM.
DR GO; GO:0005604; C:basement membrane; IDA:BHF-UCL.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0030485; C:smooth muscle contractile fiber; IDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005178; F:integrin binding; IDA:BHF-UCL.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IMP:MGI.
DR GO; GO:0033631; P:cell-cell adhesion mediated by integrin; IDA:BHF-UCL.
DR GO; GO:0007160; P:cell-matrix adhesion; IDA:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:BHF-UCL.
DR GO; GO:0045184; P:establishment of protein localization; IMP:BHF-UCL.
DR GO; GO:0030198; P:extracellular matrix organization; IDA:MGI.
DR GO; GO:0097195; P:pilomotor reflex; IMP:BHF-UCL.
DR GO; GO:0010694; P:positive regulation of alkaline phosphatase activity; IDA:BHF-UCL.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IDA:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:BHF-UCL.
DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:MGI.
DR GO; GO:0051145; P:smooth muscle cell differentiation; IDA:BHF-UCL.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:MGI.
DR GO; GO:0001657; P:ureteric bud development; IMP:MGI.
DR CDD; cd06263; MAM; 1.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR000998; MAM_dom.
DR Pfam; PF07645; EGF_CA; 3.
DR Pfam; PF00629; MAM; 1.
DR SMART; SM00181; EGF; 5.
DR SMART; SM00179; EGF_CA; 3.
DR SMART; SM00137; MAM; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF57184; SSF57184; 2.
DR PROSITE; PS00010; ASX_HYDROXYL; 3.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 3.
DR PROSITE; PS50026; EGF_3; 4.
DR PROSITE; PS01187; EGF_CA; 3.
DR PROSITE; PS50060; MAM_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell adhesion; Developmental protein;
KW Differentiation; Disulfide bond; EGF-like domain; Extracellular matrix;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..561
FT /note="Nephronectin"
FT /id="PRO_0000295685"
FT DOMAIN 52..87
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 89..128
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 132..168
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 169..213
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 214..254
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 420..561
FT /note="MAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00128"
FT REGION 266..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 382..384
FT /note="Integrin interaction"
FT COMPBIAS 315..352
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..370
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 56..69
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 60..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 77..86
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 93..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 100..113
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 115..127
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 173..186
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 180..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 197..212
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 218..231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 225..240
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 242..253
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 58
FT /note="P -> PFYVLRQRLARIRCQLKA (in isoform 2 and isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:11470831"
FT /id="VSP_026989"
FT VAR_SEQ 88
FT /note="Q -> QDESFHPTPLDQGSEQPLFQPPDHQATNVPSR (in isoform 3
FT and isoform 4)"
FT /evidence="ECO:0000303|PubMed:11470831"
FT /id="VSP_026990"
FT MUTAGEN 384
FT /note="D->E: Reduced cell spreading- and survival-promoting
FT activities."
FT /evidence="ECO:0000269|PubMed:11546798"
FT CONFLICT 24
FT /note="R -> G (in Ref. 4; AAH68308)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 561 AA; 61490 MW; 69E7ACAA0EE3F506 CRC64;
MAVLLAAVLA SSLYLQVAAD FDGRWPRQIV SSIGLCRYGG RIDCCWGWAR QSWGQCQPVC
QPQCKHGECV GPNKCKCHPG FAGKTCNQDL NECGLKPRPC KHRCMNTFGS YKCYCLNGYM
LLPDGSCSSA LSCSMANCQY GCDVVKGQVR CQCPSPGLQL APDGRTCVDI DECATGRVSC
PRFRQCVNTF GSYICKCHTG FDLMYIGGKY QCHDIDECSL GQHQCSSYAR CYNIHGSYKC
QCRDGYEGDG LNCVYIPKVM IEPSGPIHMP ERNGTISKGD GGHANRIPDA GSTRWPLKTP
YIPPVITNRP TSKPTTRPTP NPTPQPTPPP PPPLPTEPRT TPLPPTPERP STRPTTIAPA
TSTTTRVITV DNRIQTDPQK PRGDVFIPRQ PTNDLFEIFE IERGVSADEE VKDDPGILIH
SCNFDHGLCG WIREKDSDLH WETARDPAGG QYLTVSAAKA PGGKAARLVL RLGHLMHSGD
LCLSFRHKVT GLHSGTLQVF VRKHGTHGAA LWGRNGGHGW RQTQITLRGA DVKSVIFKGE
KRRGHTGEIG LDDVSLKRGR C
