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Nephrin (Renal glomerulus-specific cell adhesion receptor)

 NPHN_HUMAN              Reviewed;        1241 AA.
O60500; A6NDH2; C3RX61;
16-APR-2002, integrated into UniProtKB/Swiss-Prot.
01-AUG-1998, sequence version 1.
23-MAY-2018, entry version 167.
RecName: Full=Nephrin;
AltName: Full=Renal glomerulus-specific cell adhesion receptor;
Flags: Precursor;
Name=NPHS1; Synonyms=NPHN;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INVOLVEMENT IN NPHS1.
PubMed=9660941; DOI=10.1016/S1097-2765(00)80057-X;
Kestilae M., Lenkkeri U., Maennikkoe M., Lamerdin J.E., McCready P.,
Putaala H., Ruotsalainen V., Morita T., Nissinen M., Herva R.,
Kashtan C.E., Peltonen L., Holmberg C., Olsen A., Tryggvason K.;
"Positionally cloned gene for a novel glomerular protein -- nephrin
-- is mutated in congenital nephrotic syndrome.";
Mol. Cell 1:575-582(1998).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LYS-117.
PubMed=19309778;
Tikhomirov E., Voznesenskaya T., Tsygin A.;
"Novel human pathological mutations. Gene symbol: NPHS1. Disease:
congenital nephrotic syndrome, Finnish type.";
Hum. Genet. 125:334-334(2009).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Grunkemeyer J.A., Kumar N., Kalluri R.;
"Human nephrin (NPHS1) cDNA sequence.";
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15057824; DOI=10.1038/nature02399;
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
Rubin E.M., Lucas S.M.;
"The DNA sequence and biology of human chromosome 19.";
Nature 428:529-535(2004).
[5]
NUCLEOTIDE SEQUENCE [MRNA] OF 1032-1134 (ISOFORM 2), AND SUBCELLULAR
LOCATION.
PubMed=10550324; DOI=10.1016/S0002-9440(10)65483-1;
Holthoefer H., Ahola H., Solin M.-L., Wang S.-X., Palmen T.,
Luimula P., Miettinen A., Kerjaschki D.;
"Nephrin localizes at the podocyte filtration slit area and is
characteristically spliced in the human kidney.";
Am. J. Pathol. 155:1681-1687(1999).
[6]
SUBCELLULAR LOCATION.
PubMed=10393930; DOI=10.1073/pnas.96.14.7962;
Ruotsalainen V., Ljungberg P., Wartiovaara J., Lenkkeri U.,
Kestilae M., Jalanko H., Holmberg C., Tryggvason K.;
"Nephrin is specifically located at the slit diaphragm of glomerular
podocytes.";
Proc. Natl. Acad. Sci. U.S.A. 96:7962-7967(1999).
[7]
INTERACTION WITH NPHS2.
PubMed=11562357; DOI=10.1074/jbc.C100452200;
Huber T.B., Kottgen M., Schilling B., Walz G., Benzing T.;
"Interaction with podocin facilitates nephrin signaling.";
J. Biol. Chem. 276:41543-41546(2001).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Platelet;
PubMed=18088087; DOI=10.1021/pr0704130;
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
[9]
VARIANTS LYS-117; GLN-408 AND SER-1077, AND VARIANTS NPHS1 SER-64;
ASN-171; THR-172 DEL; ASN-173; 205-THR--ARG-207 DELINS ILE; CYS-270;
PRO-350; ARG-366; CYS-367; SER-368; VAL-376; TYR-465; PHE-528;
GLN-610; PHE-623; CYS-724; CYS-743; TRP-802; PRO-802; ASP-806; CYS-831
AND CYS-1140.
PubMed=9915943; DOI=10.1086/302182;
Lenkkeri U., Maennikkoe M., McCready P., Lamerdin J., Gribouval O.,
Niaudet P.M., Antignac C.K., Kashtan C.E., Homberg C., Olsen A.,
Kestilae M., Tryggvason K.;
"Structure of the gene for congenital nephrotic syndrome of the
Finnish type (NPHS1) and characterization of mutations.";
Am. J. Hum. Genet. 64:51-61(1999).
[10]
VARIANT NPHS1 VAL-819, AND VARIANT LYS-447.
PubMed=10652016; DOI=10.1046/j.1523-1755.2000.00859.x;
Aya K., Tanaka H., Seino Y.;
"Novel mutation in the nephrin gene of a Japanese patient with
congenital nephrotic syndrome of the Finnish type.";
Kidney Int. 57:401-404(2000).
[11]
CHARACTERIZATION OF VARIANTS NPHS1 SER-64; ASN-171; ASN-173; CYS-270;
PRO-350; ARG-366; CYS-367; SER-368; VAL-376; TYR-465; PHE-528;
GLN-610; PHE-623; CYS-724; CYS-743; TRP-802; PRO-802; ASP-806; CYS-831
AND CYS-1140, AND CHARACTERIZATION OF VARIANT GLN-408.
PubMed=11726550; DOI=10.1093/hmg/10.23.2637;
Liu L., Done S.C., Khoshnoodi J., Bertorello A., Wartiovaara J.,
Berggren P.O., Tryggvason K.;
"Defective nephrin trafficking caused by missense mutations in the
NPHS1 gene: insight into the mechanisms of congenital nephrotic
syndrome.";
Hum. Mol. Genet. 10:2637-2644(2001).
[12]
VARIANTS NPHS1 SER-64; ASN-171; THR-172 DEL; ASN-173; CYS-270;
PRO-350; ARG-366; CYS-367; LEU-368; SER-368; VAL-376; TRP-379;
PHE-417; GLN-460; TYR-465; PHE-528; CYS-558; GLN-610; PHE-623;
CYS-724; VAL-739; CYS-743; TRP-802; PRO-802; ASP-806; VAL-819 AND
PHE-834, AND VARIANTS LYS-117; ARG-264; GLN-408; LYS-447; ARG-617;
ASP-725; VAL-851 AND SER-1077.
PubMed=11317351; DOI=10.1002/humu.1111;
Beltcheva O., Martin P., Lenkkeri U., Tryggvason K.;
"Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic
syndrome.";
Hum. Mutat. 17:368-373(2001).
[13]
VARIANTS NPHS1 ARG-265 AND MET-822.
PubMed=17290294; DOI=10.1038/sj.ki.5002110;
Kitamura A., Tsukaguchi H., Hiramoto R., Shono A., Doi T., Kagami S.,
Iijima K.;
"A familial childhood-onset relapsing nephrotic syndrome.";
Kidney Int. 71:946-951(2007).
[14]
VARIANTS NPHS1 VAL-96; THR-107; GLN-460; GLN-575; PRO-832 AND SER-976,
AND CHARACTERIZATION OF VARIANT NPHS1 PRO-832.
PubMed=18614772; DOI=10.1681/ASN.2008010059;
Philippe A., Nevo F., Esquivel E.L., Reklaityte D., Gribouval O.,
Tete M.J., Loirat C., Dantal J., Fischbach M., Pouteil-Noble C.,
Decramer S., Hoehne M., Benzing T., Charbit M., Niaudet P.,
Antignac C.;
"Nephrin mutations can cause childhood-onset steroid-resistant
nephrotic syndrome.";
J. Am. Soc. Nephrol. 19:1871-1878(2008).
[15]
VARIANTS NPHS1 TRP-256; CYS-367; CYS-412; SER-519; ARG-569 AND
GLY-709.
PubMed=18503012; DOI=10.1093/ndt/gfn271;
Heeringa S.F., Vlangos C.N., Chernin G., Hinkes B., Gbadegesin R.,
Liu J., Hoskins B.E., Ozaltin F., Hildebrandt F.;
"Thirteen novel NPHS1 mutations in a large cohort of children with
congenital nephrotic syndrome.";
Nephrol. Dial. Transplant. 23:3527-3533(2008).
[16]
VARIANTS NPHS1 VAL-107; LEU-167; THR-172 DEL; 205-THR--ARG-207 DELINS
ILE; CYS-299; HIS-340; GLU-347; PRO-350; ARG-366; CYS-367; TRP-407;
GLN-460; CYS-558; ASN-572; GLY-586; ARG-587; PHE-623; LYS-673;
CYS-681; CYS-743; PRO-910; SER-976 AND CYS-1140, AND VARIANT GLN-408.
PubMed=20172850; DOI=10.1093/ndt/gfq088;
Schoeb D.S., Chernin G., Heeringa S.F., Matejas V., Held S.,
Vega-Warner V., Bockenhauer D., Vlangos C.N., Moorani K.N.,
Neuhaus T.J., Kari J.A., MacDonald J., Saisawat P., Ashraf S.,
Ovunc B., Zenker M., Hildebrandt F.;
"Nineteen novel NPHS1 mutations in a worldwide cohort of patients with
congenital nephrotic syndrome (CNS).";
Nephrol. Dial. Transplant. 25:2970-2976(2010).
[17]
VARIANT NPHS1 THR-742, AND VARIANT LYS-117.
PubMed=22009864; DOI=10.4238/2011.October.18.1;
Wu L.Q., Hu J.J., Xue J.J., Liang D.S.;
"Two novel NPHS1 mutations in a Chinese family with congenital
nephrotic syndrome.";
Genet. Mol. Res. 10:2517-2522(2011).
[18]
VARIANTS NPHS1 GLU-107; THR-172 DEL; ILE-188; 205-THR--ARG-207 DELINS
ILE; SER-567; PHE-623; VAL-851 AND CYS-1096.
PubMed=20798252; DOI=10.2215/CJN.01190210;
Buescher A.K., Kranz B., Buescher R., Hildebrandt F., Dworniczak B.,
Pennekamp P., Kuwertz-Broeking E., Wingen A.M., John U., Kemper M.,
Monnens L., Hoyer P.F., Weber S., Konrad M.;
"Immunosuppression and renal outcome in congenital and pediatric
steroid-resistant nephrotic syndrome.";
Clin. J. Am. Soc. Nephrol. 5:2075-2084(2010).
[19]
VARIANTS NPHS1 LEU-368 AND CYS-412.
PubMed=22732337;
Buescher A.K., Konrad M., Nagel M., Witzke O., Kribben A., Hoyer P.F.,
Weber S.;
"Mutations in podocyte genes are a rare cause of primary FSGS
associated with ESRD in adult patients.";
Clin. Nephrol. 78:47-53(2012).
[20]
VARIANTS NPHS1 ILE-188; LYS-189; PRO-237; TRP-256; ARG-264; ILE-294;
ILE-608; THR-912; ASN-1016 AND VAL-1020, AND VARIANT GLN-408.
PubMed=22565185; DOI=10.1016/j.gene.2012.04.063;
Abid A., Khaliq S., Shahid S., Lanewala A., Mubarak M., Hashmi S.,
Kazi J., Masood T., Hafeez F., Naqvi S.A., Rizvi S.A., Mehdi S.Q.;
"A spectrum of novel NPHS1 and NPHS2 gene mutations in pediatric
nephrotic syndrome patients from Pakistan.";
Gene 502:133-137(2012).
[21]
VARIANT NPHS1 ARG-264.
PubMed=25804400; DOI=10.1038/ejhg.2015.46;
Evers C., Paramasivam N., Hinderhofer K., Fischer C., Granzow M.,
Schmidt-Bacher A., Eils R., Steinbeisser H., Schlesner M., Moog U.;
"SIPA1L3 identified by linkage analysis and whole-exome sequencing as
a novel gene for autosomal recessive congenital cataract.";
Eur. J. Hum. Genet. 23:1627-1633(2015).
[22]
VARIANTS NPHS1 THR-172 DEL; ARG-264; ASN-446; HIS-711 AND MET-736, AND
VARIANT SER-1077.
PubMed=26560236; DOI=10.1111/nep.12667;
Guaragna M.S., Cleto T.L., Souza M.L., Lutaif A.C., de Castro L.C.,
Penido M.G., Maciel-Guerra A.T., Belangero V.M., Guerra-Junior G.,
De Mello M.P.;
"NPHS1 gene mutations confirm congenital nephrotic syndrome in four
Brazilian cases: a novel mutation is described.";
Nephrology 21:753-757(2016).
-!- FUNCTION: Seems to play a role in the development or function of
the kidney glomerular filtration barrier. Regulates glomerular
vascular permeability. May anchor the podocyte slit diaphragm to
the actin cytoskeleton. Plays a role in skeletal muscle formation
through regulation of myoblast fusion (By similarity).
{ECO:0000250|UniProtKB:Q9QZS7, ECO:0000250|UniProtKB:Q9R044}.
-!- SUBUNIT: Interacts with CD2AP (via C-terminal domain). Interacts
with MAGI1 (via PDZ 2 and 3 domains) forming a tripartite complex
with IGSF5/JAM4. Interacts with DDN; the interaction is direct.
Self-associates (via the Ig-like domains). Also interacts (via the
Ig-like domains) with KIRREL1/NEPH1 and KIRREL2; the interaction
with KIRREL1 is dependent on KIRREL1 glycosylation. Interacts with
KIRREL3. Forms a complex with ACTN4, CASK, IQGAP1, MAGI2, SPTAN1
and SPTBN1 (By similarity). Interacts with NPHS2
(PubMed:11562357). {ECO:0000250|UniProtKB:Q9QZS7,
ECO:0000250|UniProtKB:Q9R044, ECO:0000269|PubMed:11562357}.
-!- INTERACTION:
P46940:IQGAP1; NbExp=5; IntAct=EBI-996920, EBI-297509;
P16333:NCK1; NbExp=3; IntAct=EBI-996920, EBI-389883;
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass
type I membrane protein {ECO:0000305}. Note=Predominantly located
at podocyte slit diaphragm between podocyte foot processes. Also
associated with podocyte apical plasma membrane.
{ECO:0000269|PubMed:10393930, ECO:0000269|PubMed:10550324}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=O60500-1; Sequence=Displayed;
Name=2; Synonyms=Alpha;
IsoId=O60500-2; Sequence=VSP_002598;
-!- TISSUE SPECIFICITY: Specifically expressed in podocytes of kidney
glomeruli.
-!- DEVELOPMENTAL STAGE: In 23-week-old embryo found in epithelial
podocytes of the periphery of mature and developing glomeruli.
-!- PTM: Phosphorylated at Tyr-1193 by FYN, leading to the recruitment
and activation of phospholipase C-gamma-1/PLCG1. {ECO:0000250}.
-!- DISEASE: Nephrotic syndrome 1 (NPHS1) [MIM:256300]: A form of
nephrotic syndrome, a renal disease clinically characterized by
severe proteinuria, resulting in complications such as
hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show
non-specific histologic changes such as focal segmental
glomerulosclerosis and diffuse mesangial proliferation. Some
affected individuals have an inherited steroid-resistant form and
progress to end-stage renal failure. {ECO:0000269|PubMed:10652016,
ECO:0000269|PubMed:11317351, ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:17290294, ECO:0000269|PubMed:18503012,
ECO:0000269|PubMed:18614772, ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:22009864,
ECO:0000269|PubMed:22565185, ECO:0000269|PubMed:22732337,
ECO:0000269|PubMed:25804400, ECO:0000269|PubMed:26560236,
ECO:0000269|PubMed:9660941, ECO:0000269|PubMed:9915943}. Note=The
disease is caused by mutations affecting the gene represented in
this entry.
-!- SIMILARITY: Belongs to the immunoglobulin superfamily.
{ECO:0000305}.
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EMBL; AF035835; AAC39687.1; -; mRNA.
EMBL; EU642886; ACH99862.1; -; mRNA.
EMBL; AF190637; AAG17141.1; -; mRNA.
EMBL; AC002133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AF126957; AAF36451.1; -; mRNA.
CCDS; CCDS32996.1; -. [O60500-1]
PIR; T37190; T37190.
RefSeq; NP_004637.1; NM_004646.3. [O60500-1]
UniGene; Hs.122186; -.
PDB; 4ZRT; X-ray; 1.74 A; B=1188-1198.
PDBsum; 4ZRT; -.
ProteinModelPortal; O60500; -.
SMR; O60500; -.
BioGrid; 110928; 16.
DIP; DIP-36424N; -.
ELM; O60500; -.
IntAct; O60500; 9.
STRING; 9606.ENSP00000368190; -.
iPTMnet; O60500; -.
PhosphoSitePlus; O60500; -.
BioMuta; NPHS1; -.
PaxDb; O60500; -.
PeptideAtlas; O60500; -.
PRIDE; O60500; -.
DNASU; 4868; -.
Ensembl; ENST00000353632; ENSP00000343634; ENSG00000161270. [O60500-2]
Ensembl; ENST00000378910; ENSP00000368190; ENSG00000161270. [O60500-1]
GeneID; 4868; -.
KEGG; hsa:4868; -.
UCSC; uc002oby.4; human. [O60500-1]
CTD; 4868; -.
DisGeNET; 4868; -.
EuPathDB; HostDB:ENSG00000161270.19; -.
GeneCards; NPHS1; -.
HGNC; HGNC:7908; NPHS1.
HPA; CAB035555; -.
MalaCards; NPHS1; -.
MIM; 256300; phenotype.
MIM; 602716; gene.
neXtProt; NX_O60500; -.
OpenTargets; ENSG00000161270; -.
Orphanet; 839; Congenital nephrotic syndrome, Finnish type.
Orphanet; 93214; Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation.
Orphanet; 93213; Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
Orphanet; 93216; Familial idiopathic steroid-resistant nephrotic syndrome with minimal changes.
PharmGKB; PA31709; -.
eggNOG; KOG3515; Eukaryota.
eggNOG; ENOG410XRJN; LUCA.
GeneTree; ENSGT00550000074545; -.
HOGENOM; HOG000113844; -.
HOVERGEN; HBG031752; -.
InParanoid; O60500; -.
OMA; LYMDVLP; -.
OrthoDB; EOG091G00UN; -.
PhylomeDB; O60500; -.
TreeFam; TF327139; -.
Reactome; R-HSA-373753; Nephrin family interactions.
SignaLink; O60500; -.
SIGNOR; O60500; -.
GeneWiki; Nephrin; -.
GenomeRNAi; 4868; -.
PRO; PR:O60500; -.
Proteomes; UP000005640; Chromosome 19.
Bgee; ENSG00000161270; -.
CleanEx; HS_NPHS1; -.
Genevisible; O60500; HS.
GO; GO:0042995; C:cell projection; IEA:Ensembl.
GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
GO; GO:0005622; C:intracellular; IEA:GOC.
GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO; GO:0036057; C:slit diaphragm; ISS:UniProtKB.
GO; GO:0017022; F:myosin binding; IPI:UniProtKB.
GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
GO; GO:0007588; P:excretion; TAS:ProtInc.
GO; GO:0032836; P:glomerular basement membrane development; IEP:UniProtKB.
GO; GO:0072015; P:glomerular visceral epithelial cell development; IEP:UniProtKB.
GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
GO; GO:0007520; P:myoblast fusion; IEA:Ensembl.
GO; GO:0030838; P:positive regulation of actin filament polymerization; IEA:Ensembl.
GO; GO:0035418; P:protein localization to synapse; IGI:UniProtKB.
GO; GO:0044062; P:regulation of excretion; IEA:Ensembl.
GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl.
CDD; cd00063; FN3; 1.
Gene3D; 2.60.40.10; -; 10.
InterPro; IPR013162; CD80_C2-set.
InterPro; IPR003961; FN3_dom.
InterPro; IPR036116; FN3_sf.
InterPro; IPR007110; Ig-like_dom.
InterPro; IPR036179; Ig-like_dom_sf.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR003599; Ig_sub.
InterPro; IPR003598; Ig_sub2.
InterPro; IPR013106; Ig_V-set.
Pfam; PF08205; C2-set_2; 5.
Pfam; PF00041; fn3; 1.
Pfam; PF07686; V-set; 1.
SMART; SM00060; FN3; 1.
SMART; SM00409; IG; 8.
SMART; SM00408; IGc2; 7.
SUPFAM; SSF48726; SSF48726; 9.
SUPFAM; SSF49265; SSF49265; 1.
PROSITE; PS50853; FN3; 1.
PROSITE; PS50835; IG_LIKE; 7.
1: Evidence at protein level;
3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
Complete proteome; Developmental protein; Disease mutation;
Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
Myogenesis; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
Signal; Transmembrane; Transmembrane helix.
SIGNAL 1 22 {ECO:0000255}.
CHAIN 23 1241 Nephrin.
/FTId=PRO_0000015052.
TOPO_DOM 23 1055 Extracellular. {ECO:0000255}.
TRANSMEM 1056 1076 Helical. {ECO:0000255}.
TOPO_DOM 1077 1241 Cytoplasmic. {ECO:0000255}.
DOMAIN 27 130 Ig-like C2-type 1.
DOMAIN 143 234 Ig-like C2-type 2.
DOMAIN 242 333 Ig-like C2-type 3.
DOMAIN 340 434 Ig-like C2-type 4.
DOMAIN 440 540 Ig-like C2-type 5.
DOMAIN 544 635 Ig-like C2-type 6.
DOMAIN 740 832 Ig-like C2-type 7.
DOMAIN 838 939 Ig-like C2-type 8.
DOMAIN 943 1038 Fibronectin type-III.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
REGION 1160 1241 Binds to NPHS2.
MOD_RES 432 432 Phosphoserine.
{ECO:0000244|PubMed:18088087}.
MOD_RES 1098 1098 Phosphoserine.
{ECO:0000250|UniProtKB:Q9R044}.
MOD_RES 1101 1101 Phosphothreonine.
{ECO:0000250|UniProtKB:Q9R044}.
MOD_RES 1105 1105 Phosphoserine.
{ECO:0000250|UniProtKB:Q9R044}.
MOD_RES 1193 1193 Phosphotyrosine; by FYN.
{ECO:0000250|UniProtKB:Q9R044}.
CARBOHYD 40 40 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 356 356 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 401 401 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 547 547 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 553 553 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 564 564 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 577 577 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 680 680 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 708 708 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 908 908 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 53 111 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 160 217 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 265 317 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 361 417 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 465 528 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 567 623 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 761 816 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 863 920 {ECO:0000255|PROSITE-ProRule:PRU00114}.
VAR_SEQ 1056 1095 Missing (in isoform 2).
{ECO:0000303|PubMed:10550324}.
/FTId=VSP_002598.
VARIANT 64 64 W -> S (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833897).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013029.
VARIANT 96 96 L -> V (in NPHS1; dbSNP:rs386833929).
{ECO:0000269|PubMed:18614772}.
/FTId=VAR_064194.
VARIANT 107 107 A -> E (in NPHS1).
{ECO:0000269|PubMed:20798252}.
/FTId=VAR_079794.
VARIANT 107 107 A -> T (in NPHS1; dbSNP:rs386833933).
{ECO:0000269|PubMed:18614772}.
/FTId=VAR_064195.
VARIANT 107 107 A -> V (in NPHS1; dbSNP:rs386833934).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064196.
VARIANT 117 117 E -> K (in dbSNP:rs3814995).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:19309778,
ECO:0000269|PubMed:22009864,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013030.
VARIANT 167 167 P -> L (in NPHS1; dbSNP:rs386833945).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064197.
VARIANT 171 171 I -> N (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833946).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013031.
VARIANT 172 172 Missing (in NPHS1).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:20798252,
ECO:0000269|PubMed:26560236,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013032.
VARIANT 173 173 I -> N (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833949).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013033.
VARIANT 188 188 N -> I (in NPHS1; dbSNP:rs145125791).
{ECO:0000269|PubMed:20798252,
ECO:0000269|PubMed:22565185}.
/FTId=VAR_072375.
VARIANT 189 189 E -> K (in NPHS1; dbSNP:rs139598219).
{ECO:0000269|PubMed:22565185}.
/FTId=VAR_072376.
VARIANT 205 207 TPR -> I (in NPHS1).
{ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:20798252,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013034.
VARIANT 233 233 T -> A (in dbSNP:rs35238405).
/FTId=VAR_049970.
VARIANT 237 237 L -> P (in NPHS1; dbSNP:rs373835033).
{ECO:0000269|PubMed:22565185}.
/FTId=VAR_072161.
VARIANT 256 256 R -> W (in NPHS1; dbSNP:rs386833960).
{ECO:0000269|PubMed:18503012,
ECO:0000269|PubMed:22565185}.
/FTId=VAR_064198.
VARIANT 264 264 P -> R (in NPHS1; unknown pathological
significance; dbSNP:rs34982899).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:22565185,
ECO:0000269|PubMed:25804400,
ECO:0000269|PubMed:26560236}.
/FTId=VAR_064199.
VARIANT 265 265 C -> R (in NPHS1; dbSNP:rs267606917).
{ECO:0000269|PubMed:17290294}.
/FTId=VAR_064200.
VARIANT 270 270 G -> C (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833961).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013035.
VARIANT 294 294 T -> I (in NPHS1; dbSNP:rs113825926).
{ECO:0000269|PubMed:22565185}.
/FTId=VAR_072377.
VARIANT 299 299 R -> C (in NPHS1; dbSNP:rs753476209).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064201.
VARIANT 340 340 P -> H (in NPHS1; dbSNP:rs386833861).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064202.
VARIANT 347 347 G -> E (in NPHS1; dbSNP:rs386833862).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064203.
VARIANT 350 350 S -> P (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833863).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013036.
VARIANT 366 366 S -> R (in NPHS1; lack of protein
expression on the cell surface; the
mutant protein is retained in the
endoplasmic reticulum;
dbSNP:rs386833864).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013037.
VARIANT 367 367 R -> C (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833865).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:18503012,
ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013038.
VARIANT 368 368 P -> L (in NPHS1; dbSNP:rs386833867).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:22732337}.
/FTId=VAR_064204.
VARIANT 368 368 P -> S (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833866).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013039.
VARIANT 376 376 L -> V (in NPHS1; does not affect protein
expression on the cell surface;
dbSNP:rs386833868).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013040.
VARIANT 379 379 R -> W (in NPHS1; dbSNP:rs386833871).
{ECO:0000269|PubMed:11317351}.
/FTId=VAR_064205.
VARIANT 392 392 L -> P (in dbSNP:rs34320609).
/FTId=VAR_049971.
VARIANT 407 407 R -> W (in NPHS1; dbSNP:rs386833874).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064206.
VARIANT 408 408 R -> Q (polymorphism; does not affect
protein expression on the cell surface;
dbSNP:rs33950747).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:22565185,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013041.
VARIANT 412 412 G -> C (in NPHS1; dbSNP:rs142008044).
{ECO:0000269|PubMed:18503012,
ECO:0000269|PubMed:22732337}.
/FTId=VAR_064207.
VARIANT 417 417 C -> F (in NPHS1; dbSNP:rs386833875).
{ECO:0000269|PubMed:11317351}.
/FTId=VAR_064208.
VARIANT 446 446 I -> N (in NPHS1; unknown pathological
significance; dbSNP:rs386833879).
{ECO:0000269|PubMed:26560236}.
/FTId=VAR_075252.
VARIANT 447 447 E -> K (in dbSNP:rs28939695).
{ECO:0000269|PubMed:10652016,
ECO:0000269|PubMed:11317351}.
/FTId=VAR_013042.
VARIANT 460 460 R -> Q (in NPHS1; dbSNP:rs386833880).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:18614772,
ECO:0000269|PubMed:20172850}.
/FTId=VAR_064209.
VARIANT 465 465 C -> Y (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833881).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013043.
VARIANT 519 519 P -> S (in NPHS1; dbSNP:rs386833884).
{ECO:0000269|PubMed:18503012}.
/FTId=VAR_064210.
VARIANT 528 528 C -> F (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833885).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013044.
VARIANT 558 558 R -> C (in NPHS1; dbSNP:rs386833886).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:20172850}.
/FTId=VAR_064211.
VARIANT 567 567 C -> S (in NPHS1).
{ECO:0000269|PubMed:20798252}.
/FTId=VAR_079795.
VARIANT 569 569 S -> R (in NPHS1; dbSNP:rs386833888).
{ECO:0000269|PubMed:18503012}.
/FTId=VAR_064212.
VARIANT 572 572 S -> N (in NPHS1; dbSNP:rs386833889).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064213.
VARIANT 575 575 P -> Q (in NPHS1; dbSNP:rs386833890).
{ECO:0000269|PubMed:18614772}.
/FTId=VAR_064214.
VARIANT 586 586 R -> G (in NPHS1; dbSNP:rs730880174).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064215.
VARIANT 587 587 L -> R (in NPHS1; dbSNP:rs386833892).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064216.
VARIANT 608 608 V -> I (in NPHS1; dbSNP:rs367976914).
{ECO:0000269|PubMed:22565185}.
/FTId=VAR_072378.
VARIANT 610 610 L -> Q (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833894).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013045.
VARIANT 617 617 H -> R (found in patients with nephrotic
syndrome; unknown pathological
significance; dbSNP:rs764058957).
{ECO:0000269|PubMed:11317351}.
/FTId=VAR_064217.
VARIANT 623 623 C -> F (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833895).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:20798252,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013046.
VARIANT 673 673 N -> K (in NPHS1; dbSNP:rs191807913).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064218.
VARIANT 681 681 W -> C (in NPHS1; dbSNP:rs386833900).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064219.
VARIANT 709 709 V -> G (in NPHS1; dbSNP:rs386833902).
{ECO:0000269|PubMed:18503012}.
/FTId=VAR_064220.
VARIANT 711 711 R -> H (in NPHS1; unknown pathological
significance; dbSNP:rs926025297).
{ECO:0000269|PubMed:26560236}.
/FTId=VAR_075253.
VARIANT 724 724 S -> C (in NPHS1; does not affect protein
expression on the cell surface;
dbSNP:rs386833905).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013047.
VARIANT 725 725 E -> D (found in patients with nephrotic
syndrome; unknown pathological
significance).
{ECO:0000269|PubMed:11317351}.
/FTId=VAR_064221.
VARIANT 736 736 V -> M (in NPHS1; unknown pathological
significance).
{ECO:0000269|PubMed:26560236}.
/FTId=VAR_075254.
VARIANT 739 739 A -> V (in NPHS1; dbSNP:rs386833907).
{ECO:0000269|PubMed:11317351}.
/FTId=VAR_064222.
VARIANT 742 742 I -> T (in NPHS1; dbSNP:rs386833908).
{ECO:0000269|PubMed:22009864}.
/FTId=VAR_067252.
VARIANT 743 743 R -> C (in NPHS1; does not affect protein
expression on the cell surface;
dbSNP:rs386833909).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013048.
VARIANT 802 802 R -> P (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs114203578).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013050.
VARIANT 802 802 R -> W (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833911).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013049.
VARIANT 806 806 A -> D (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833912).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013051.
VARIANT 819 819 D -> V (in NPHS1; dbSNP:rs387906357).
{ECO:0000269|PubMed:10652016,
ECO:0000269|PubMed:11317351}.
/FTId=VAR_013052.
VARIANT 822 822 V -> M (in NPHS1; dbSNP:rs267606918).
{ECO:0000269|PubMed:17290294}.
/FTId=VAR_064223.
VARIANT 831 831 R -> C (in NPHS1; lack of protein
expression on the cell surface;
dbSNP:rs386833915).
{ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013053.
VARIANT 832 832 L -> P (in NPHS1; the mutant protein is
retained in the endoplasmic reticulum;
dbSNP:rs386833916).
{ECO:0000269|PubMed:18614772}.
/FTId=VAR_064224.
VARIANT 834 834 V -> F (in NPHS1; dbSNP:rs386833917).
{ECO:0000269|PubMed:11317351}.
/FTId=VAR_064225.
VARIANT 851 851 A -> V (in NPHS1; unknown pathological
significance).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:20798252}.
/FTId=VAR_064226.
VARIANT 910 910 S -> P (in NPHS1; dbSNP:rs143649022).
{ECO:0000269|PubMed:20172850}.
/FTId=VAR_064227.
VARIANT 912 912 A -> T (in NPHS1; dbSNP:rs763162233).
{ECO:0000269|PubMed:22565185}.
/FTId=VAR_072162.
VARIANT 976 976 R -> S (in NPHS1; dbSNP:rs138656762).
{ECO:0000269|PubMed:18614772,
ECO:0000269|PubMed:20172850}.
/FTId=VAR_064228.
VARIANT 991 991 V -> L (in dbSNP:rs34736717).
/FTId=VAR_049972.
VARIANT 1016 1016 S -> N (in NPHS1; dbSNP:rs367986918).
{ECO:0000269|PubMed:22565185}.
/FTId=VAR_072379.
VARIANT 1020 1020 G -> V (in NPHS1; dbSNP:rs749003854).
{ECO:0000269|PubMed:22565185}.
/FTId=VAR_072163.
VARIANT 1077 1077 N -> S (in dbSNP:rs4806213).
{ECO:0000269|PubMed:11317351,
ECO:0000269|PubMed:26560236,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013054.
VARIANT 1096 1096 G -> C (in NPHS1; unknown pathological
significance).
{ECO:0000269|PubMed:20798252}.
/FTId=VAR_079796.
VARIANT 1140 1140 R -> C (in NPHS1; does not affect protein
expression on the cell surface;
dbSNP:rs143092783).
{ECO:0000269|PubMed:11726550,
ECO:0000269|PubMed:20172850,
ECO:0000269|PubMed:9915943}.
/FTId=VAR_013055.
SEQUENCE 1241 AA; 134742 MW; 7F5AFAF078BCF532 CRC64;
MALGTTLRAS LLLLGLLTEG LAQLAIPASV PRGFWALPEN LTVVEGASVE LRCGVSTPGS
AVQWAKDGLL LGPDPRIPGF PRYRLEGDPA RGEFHLHIEA CDLSDDAEYE CQVGRSEMGP
ELVSPRVILS ILVPPKLLLL TPEAGTMVTW VAGQEYVVNC VSGDAKPAPD ITILLSGQTI
SDISANVNEG SQQKLFTVEA TARVTPRSSD NRQLLVCEAS SPALEAPIKA SFTVNVLFPP
GPPVIEWPGL DEGHVRAGQS LELPCVARGG NPLATLQWLK NGQPVSTAWG TEHTQAVARS
VLVMTVRPED HGAQLSCEAH NSVSAGTQEH GITLQVTFPP SAIIILGSAS QTENKNVTLS
CVSKSSRPRV LLRWWLGWRQ LLPMEETVMD GLHGGHISMS NLTFLARRED NGLTLTCEAF
SEAFTKETFK KSLILNVKYP AQKLWIEGPP EGQKLRAGTR VRLVCLAIGG NPEPSLMWYK
DSRTVTESRL PQESRRVHLG SVEKSGSTFS RELVLVTGPS DNQAKFTCKA GQLSASTQLA
VQFPPTNVTI LANASALRPG DALNLTCVSV SSNPPVNLSW DKEGERLEGV AAPPRRAPFK
GSAAARSVLL QVSSRDHGQR VTCRAHSAEL RETVSSFYRL NVLYRPEFLG EQVLVVTAVE
QGEALLPVSV SANPAPEAFN WTFRGYRLSP AGGPRHRILS SGALHLWNVT RADDGLYQLH
CQNSEGTAEA RLRLDVHYAP TIRALQDPTE VNVGGSVDIV CTVDANPILP GMFNWERLGE
DEEDQSLDDM EKISRGPTGR LRIHHAKLAQ AGAYQCIVDN GVAPPARRLL RLVVRFAPQV
EHPTPLTKVA AAGDSTSSAT LHCRARGVPN IVFTWTKNGV PLDLQDPRYT EHTYHQGGVH
SSLLTIANVS AAQDYALFTC TATNALGSDQ TNIQLVSISR PDPPSGLKVV SLTPHSVGLE
WKPGFDGGLP QRFCIRYEAL GTPGFHYVDV VPPQATTFTL TGLQPSTRYR VWLLASNALG
DSGLADKGTQ LPITTPGLHQ PSGEPEDQLP TEPPSGPSGL PLLPVLFALG GLLLLSNASC
VGGVLWQRRL RRLAEGISEK TEAGSEEDRV RNEYEESQWT GERDTQSSTV STTEAEPYYR
SLRDFSPQLP PTQEEVSYSR GFTGEDEDMA FPGHLYDEVE RTYPPSGAWG PLYDEVQMGP
WDLHWPEDTY QDPRGIYDQV AGDLDTLEPD SLPFELRGHL V


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