NPHN_RAT
ID NPHN_RAT Reviewed; 1252 AA.
AC Q9R044; Q9JIX2; Q9QXX7;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 08-MAR-2011, sequence version 2.
DT 25-MAY-2022, entry version 166.
DE RecName: Full=Nephrin;
DE AltName: Full=Renal glomerulus-specific cell adhesion receptor;
DE Flags: Precursor;
GN Name=Nphs1; Synonyms=Nphn;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=10820162; DOI=10.1681/asn.v116991;
RA Putaala H., Sainio K., Sariola H., Tryggvason K.;
RT "Primary structure of mouse and rat nephrin cDNA and structure and
RT expression of the mouse gene.";
RL J. Am. Soc. Nephrol. 11:991-1001(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RC STRAIN=Wistar; TISSUE=Renal glomerulus;
RX PubMed=10792613; DOI=10.1046/j.1523-1755.2000.00044.x;
RA Kawachi H., Koike H., Kurihara H., Yaoita E., Orikasa M., Shia M.A.,
RA Sakai T., Yamamoto T., Salant D.J., Shimizu F.;
RT "Cloning of rat nephrin: expression in developing glomeruli and in
RT proteinuric states.";
RL Kidney Int. 57:1949-1961(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 19-1252 (ISOFORMS 1; 2 AND 3), FUNCTION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Renal glomerulus;
RX PubMed=10487848; DOI=10.1016/s0002-9440(10)65190-5;
RA Ahola H., Wang S.-X., Luimula P., Solin M.-L., Holzman L.B., Holthoefer H.;
RT "Cloning and expression of the rat nephrin homolog.";
RL Am. J. Pathol. 155:907-913(1999).
RN [4]
RP INDUCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=11012881; DOI=10.1046/j.1523-1755.2000.00308.x;
RA Luimula P., Ahola H., Wang S.X., Solin M.L., Aaltonen P., Tikkanen I.,
RA Kerjaschki D., Holthofer H.;
RT "Nephrin in experimental glomerular disease.";
RL Kidney Int. 58:1461-1468(2000).
RN [5]
RP FUNCTION.
RX PubMed=11880318; DOI=10.1152/ajprenal.00290.2001;
RA Yuan H., Takeuchi E., Salant D.J.;
RT "Podocyte slit-diaphragm protein nephrin is linked to the actin
RT cytoskeleton.";
RL Am. J. Physiol. 282:F585-F591(2002).
RN [6]
RP INTERACTION WITH MAGI1.
RX PubMed=16155592; DOI=10.1038/labinvest.3700347;
RA Hirabayashi S., Mori H., Kansaku A., Kurihara H., Sakai T., Shimizu F.,
RA Kawachi H., Hata Y.;
RT "MAGI-1 is a component of the glomerular slit diaphragm that is tightly
RT associated with nephrin.";
RL Lab. Invest. 85:1528-1543(2005).
RN [7]
RP INTERACTION WITH ACTN4; CASK; IQGAP1; MAGI2; SPTAN1 AND SPTBN1.
RC STRAIN=Sprague-Dawley; TISSUE=Renal glomerulus;
RX PubMed=15994232; DOI=10.1073/pnas.0504166102;
RA Lehtonen S., Ryan J.J., Kudlicka K., Iino N., Zhou H., Farquhar M.G.;
RT "Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and
RT alpha-actinin are components of the nephrin multiprotein complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:9814-9819(2005).
RN [8]
RP INTERACTION WITH DDN.
RX PubMed=17537921; DOI=10.1073/pnas.0700917104;
RA Asanuma K., Campbell K.N., Kim K., Faul C., Mundel P.;
RT "Nuclear relocation of the nephrin and CD2AP-binding protein dendrin
RT promotes apoptosis of podocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10134-10139(2007).
RN [9]
RP PHOSPHORYLATION AT TYR-1204 BY FYN.
RX PubMed=19179337; DOI=10.1074/jbc.m806851200;
RA Harita Y., Kurihara H., Kosako H., Tezuka T., Sekine T., Igarashi T.,
RA Ohsawa I., Ohta S., Hattori S.;
RT "Phosphorylation of nephrin triggers Ca2+ signaling by recruitment and
RT activation of phospholipase C-{gamma}1.";
RL J. Biol. Chem. 284:8951-8962(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1112; THR-1115 AND SER-1119,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Seems to play a role in the development or function of the
CC kidney glomerular filtration barrier. Regulates glomerular vascular
CC permeability. May anchor the podocyte slit diaphragm to the actin
CC cytoskeleton. Plays a role in skeletal muscle formation through
CC regulation of myoblast fusion. {ECO:0000269|PubMed:10487848,
CC ECO:0000269|PubMed:11880318}.
CC -!- SUBUNIT: Interacts with NPHS2 and with CD2AP (via C-terminal domain).
CC Self-associates (via the Ig-like domains). Also interacts (via the Ig-
CC like domains) with KIRREL1/NEPH1 and KIRREL2; the interaction with
CC KIRREL1 is dependent on KIRREL1 glycosylation. Interacts with KIRREL3
CC (By similarity). Interacts with MAGI1 (via PDZ 2 and 3 domains) forming
CC a tripartite complex with IGSF5/JAM4. Interacts with DDN; the
CC interaction is direct. Forms a complex with ACTN4, CASK, IQGAP1, MAGI2,
CC SPTAN1 and SPTBN1. {ECO:0000250|UniProtKB:Q9QZS7,
CC ECO:0000269|PubMed:15994232, ECO:0000269|PubMed:16155592,
CC ECO:0000269|PubMed:17537921}.
CC -!- INTERACTION:
CC Q9R044; P97710: Sirpa; NbExp=2; IntAct=EBI-7945021, EBI-7945080;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Note=Located at podocyte slit diaphragm
CC between podocyte foot processes. {ECO:0000269|PubMed:10792613}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=Q9R044-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha;
CC IsoId=Q9R044-2; Sequence=VSP_002599;
CC Name=3; Synonyms=Beta;
CC IsoId=Q9R044-3; Sequence=VSP_002600;
CC -!- TISSUE SPECIFICITY: Strongly expressed in the podocytes of kidney
CC glomeruli (at protein level) and at lower levels in the spleen.
CC {ECO:0000269|PubMed:10487848, ECO:0000269|PubMed:11012881}.
CC -!- INDUCTION: Following injection with puromycin which induces nephrosis,
CC down-regulated by 40% 3 days post-injection and by 80% at day 10. Also
CC down-regulated by HgCl2 with rapid decrease at day 3.
CC {ECO:0000269|PubMed:11012881}.
CC -!- PTM: Phosphorylated at Tyr-1204 by FYN, leading to the recruitment and
CC activation of phospholipase C-gamma-1/PLCG1.
CC {ECO:0000269|PubMed:19179337}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. {ECO:0000305}.
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DR EMBL; AF172255; AAF91086.1; -; mRNA.
DR EMBL; AF161715; AAF14884.1; -; mRNA.
DR EMBL; AF125521; AAF12734.1; -; mRNA.
DR RefSeq; NP_072150.1; NM_022628.1.
DR AlphaFoldDB; Q9R044; -.
DR BioGRID; 249144; 8.
DR CORUM; Q9R044; -.
DR IntAct; Q9R044; 1.
DR MINT; Q9R044; -.
DR STRING; 10116.ENSRNOP00000049922; -.
DR GlyGen; Q9R044; 6 sites.
DR iPTMnet; Q9R044; -.
DR PhosphoSitePlus; Q9R044; -.
DR PaxDb; Q9R044; -.
DR GeneID; 64563; -.
DR KEGG; rno:64563; -.
DR UCSC; RGD:620460; rat. [Q9R044-1]
DR CTD; 4868; -.
DR RGD; 620460; Nphs1.
DR eggNOG; KOG3515; Eukaryota.
DR InParanoid; Q9R044; -.
DR OrthoDB; 269917at2759; -.
DR PhylomeDB; Q9R044; -.
DR Reactome; R-RNO-373753; Nephrin family interactions.
DR PRO; PR:Q9R044; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005604; C:basement membrane; IDA:RGD.
DR GO; GO:0042995; C:cell projection; ISO:RGD.
DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005925; C:focal adhesion; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0036057; C:slit diaphragm; IDA:UniProtKB.
DR GO; GO:0051393; F:alpha-actinin binding; IPI:RGD.
DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0030507; F:spectrin binding; IPI:RGD.
DR GO; GO:0007155; P:cell adhesion; ISO:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0003094; P:glomerular filtration; IC:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0007520; P:myoblast fusion; ISO:RGD.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISO:RGD.
DR GO; GO:0044062; P:regulation of excretion; ISO:RGD.
DR GO; GO:0007519; P:skeletal muscle tissue development; ISO:RGD.
DR GO; GO:0036060; P:slit diaphragm assembly; ISS:UniProtKB.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 10.
DR InterPro; IPR013162; CD80_C2-set.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR Pfam; PF08205; C2-set_2; 5.
DR Pfam; PF00041; fn3; 1.
DR SMART; SM00060; FN3; 1.
DR SMART; SM00409; IG; 8.
DR SMART; SM00408; IGc2; 7.
DR SUPFAM; SSF48726; SSF48726; 9.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS50835; IG_LIKE; 7.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell membrane; Developmental protein;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane; Myogenesis;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..1252
FT /note="Nephrin"
FT /id="PRO_0000015054"
FT TOPO_DOM 36..1078
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1079..1099
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1100..1252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 39..144
FT /note="Ig-like C2-type 1"
FT DOMAIN 149..247
FT /note="Ig-like C2-type 2"
FT DOMAIN 256..347
FT /note="Ig-like C2-type 3"
FT DOMAIN 354..448
FT /note="Ig-like C2-type 4"
FT DOMAIN 454..554
FT /note="Ig-like C2-type 5"
FT DOMAIN 558..649
FT /note="Ig-like C2-type 6"
FT DOMAIN 754..846
FT /note="Ig-like C2-type 7"
FT DOMAIN 852..953
FT /note="Ig-like C2-type 8"
FT DOMAIN 957..1052
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 1043..1067
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1113..1144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1113..1135
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60500"
FT MOD_RES 1112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1115
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1204
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000269|PubMed:19179337"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 561
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 578
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 591
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 722
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 67..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 174..231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 279..331
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 375..431
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 479..542
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 581..637
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 775..830
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 877..934
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1070..1155
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10487848"
FT /id="VSP_002600"
FT VAR_SEQ 1070..1082
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10487848"
FT /id="VSP_002599"
FT CONFLICT 19
FT /note="M -> T (in Ref. 2; AAF14884)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="R -> Q (in Ref. 2; AAF14884)"
FT /evidence="ECO:0000305"
FT CONFLICT 1229
FT /note="D -> N (in Ref. 3; AAF12734)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1252 AA; 136281 MW; 6A3550AB907883EC CRC64;
MGAKRVTVRG ARTSPIHRMS SLTPLLLMGM LTSGLAESPV PTSAPRGFWA LSENLTAVEG
TTVKLWCGVR APGSVVQWAK DGLLLGPNPK MPGFPRYSLE GDRAKGEFHL LIEACDLSDD
AEYECQVGRS ELGPELVSPK VILSILVSPK VLLLTPEAGS TVTWVAGQEY VVTCVSGDAK
PAPDITFIQS GRTILDVSSN VNEGSEEKLC ITEAEARVIP QSSDNGQLLV CEGSNPALDT
PIKASFTMNI LFPPGPPVID WPGLNEGHVR AGENLELPCT ARGGNPPATL QWLKNGKPVS
TAWGTEHAQA VAHSVLVMTV RPEDHGARLS CQSYNSVSAG TQERSITLQV TFPPSAITIL
GSVSQSENKN VTLCCLTKSS RPRVLLRWWL GGRQLLPTDE TVMDGLHGGH ISMSNLTFLV
RREDNGLPLT CEAFSDAFSK ETFKKSLTLN VKYPAQKLWI EGPPEGQYIR TGTRVRLVCL
AIGGNPDPSL IWFKDSRPVS EPRQPQEPRR VQLGSVEKSG STFSRELVLI IGPPDNRAKF
SCKAGQLSAS TQLVVQFPPT NLTILANSSA LRPGDALNLT CVSISSNPPV NLSWDKEGER
LEDVAAKPQS APFKGSAASR SVFLRVSSRD HGQRVTCRAH SEALRETVSS FYRFNVLYPP
EFLGEQVRAV TVVEQGQVLL PVSVSANPAP EAFNWTFRGY RLSPAGGPRH RILSGGALQL
WNVTRADDGF YQLHCQNSEG TAEALLKLDV HYAPTIRALR DPTEVNVGGS VDIVCTVDAN
PILPEMFSWE RLGEEEEDLN LDDMEKVSKG STGRLRIRQA KLSQAGAYQC IVDNGVAPAA
RGLVRLVVRF APQVDQPTPL TKVAAAGDST SSATLHCRAR GVPNIDFTWT KNGVPLDLQD
PRYTEHRYHQ GVVHSSLLTI ANVSAAQDYA LFKCTATNAL GSDHTNIQLV SISRPDPPLG
LKVVSISPHS VGLEWKPGFD GGLPQRFQIR YEALETPGFL HVDVLPTQAT TFTLTGLKPS
TRYRIWLLAS NALGDSGLTD KGIQVSVTTP GPDQAPEDTD HQLPTELPPG PPRLPLLPVL
FAVGGLLLLS NASCVGGLLW RRRLRRLAEE ISEKTEAGSE DRIRNEYEES QWTGDRDTRS
STVSTAEVDP NYYSMRDFSP QLPPTLEEVL YHQGAEGEDM AFPGHLHDEV ERAYGPPGAW
GPLYDEVRMD PYDLRWPEVQ CEDPRGIYDQ VAADMDAVEA SSLPFELRGH LV
