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Q9QZS7 (NPHN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nephrin
Alternative name(s):
Renal glomerulus-specific cell adhesion receptor
Gene names
Name:Nphs1
Synonyms:Nphn
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1256 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.3 Ref.8 Ref.13

Subunit structure

Interacts with NPHS2 and with CD2AP (via C-terminal domain). Interacts with MAGI1 (via PDZ 2 and 3 domains) forming a tripartite complex with IGSF5/JAM4. Forms a complex with ACTN4, CASK, IQGAP1, MAGI2, SPTAN1 and SPTBN1 By similarity. Interacts with DDN; the interaction is direct. Self-associates (via the Ig-like domains). Also interacts (via the Ig-like domains) with KIRREL/NEPH1 and KIRREL2; the interaction with KIRREL is dependent on KIRREL glycosylation. Ref.4 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12

Subcellular location

Cell membrane; Single-pass type I membrane protein Potential. Note: Located at podocyte slit diaphragm between podocyte foot processes. Ref.1

Tissue specificity

Expressed in kidney glomeruli. In the embryo, expressed in the mesonephric kidney at E11 with strong expression in cranial tubules with podocyte-like structures. Expression is observed in the podocytes of the developing kidney from E13. High expression is also detected in the developing cerebellum, hindbrain, spinal cord, retina and hypothalamus. Expressed in skeletal muscle during myoblast fusion such as in the adult following acute injury and in the embryo but not detected in uninjured adult skeletal muscle. Isoform 1 and isoform 2 are expressed in the newborn brain and developing cerebellum. Isoform 1 is the predominant isoform inadult kidney. Ref.2 Ref.4 Ref.6 Ref.8 Ref.13

Post-translational modification

Phosphorylated at Tyr-1208 by FYN, leading to the recruitment and activation of phospholipase C-gamma-1/PLCG1 By similarity.

Disruption phenotype

Death by postnatal day 2 associated with proteinuria, edema and massive glomerular vascular leak. Kidneys display enlarged Bowman's spaces, dilated tubuli, effacement of podocyte foot processes and an absence of the glomerular epithelial slit diaphragm. Impaired skeletal muscle development characterized by incomplete myoblast fusion. Ref.3 Ref.8 Ref.13

Sequence similarities

Belongs to the immunoglobulin superfamily.

Contains 1 fibronectin type-III domain.

Contains 8 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
   Biological processCell adhesion
Myogenesis
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Inferred from direct assay PubMed 11562357. Source: MGI

MAPK cascade

Inferred from direct assay PubMed 11562357. Source: MGI

cell adhesion

Inferred from genetic interaction PubMed 21306299. Source: MGI

glomerular basement membrane development

Inferred from electronic annotation. Source: Ensembl

glomerular visceral epithelial cell development

Inferred from electronic annotation. Source: Ensembl

myoblast fusion

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of actin filament polymerization

Inferred from genetic interaction PubMed 17923684. Source: MGI

regulation of excretion

Inferred from mutant phenotype Ref.8. Source: UniProtKB

skeletal muscle tissue development

Inferred from mutant phenotype Ref.13. Source: UniProtKB

   Cellular_componentcell projection

Inferred from direct assay PubMed 20534871. Source: UniProtKB

integral component of membrane

Traceable author statement Ref.9. Source: MGI

integral component of plasma membrane

Traceable author statement PubMed 11562357. Source: MGI

membrane raft

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex

Inferred from electronic annotation. Source: Ensembl

slit diaphragm

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9QZS7-1)

Also known as: NephrinA;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9QZS7-2)

Also known as: NephrinB;

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: MGAKEATVRGPGASPVHRTCHLIPLLLAGMLTT → MEKWRAWDPQSIQRRKTAK

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3535 Potential
Chain36 – 12561221Nephrin
PRO_0000015053

Regions

Topological domain36 – 10781043Extracellular Potential
Transmembrane1079 – 109921Helical; Potential
Topological domain1100 – 1256157Cytoplasmic Potential
Domain39 – 144106Ig-like C2-type 1
Domain149 – 24799Ig-like C2-type 2
Domain256 – 34792Ig-like C2-type 3
Domain354 – 44895Ig-like C2-type 4
Domain454 – 554101Ig-like C2-type 5
Domain558 – 64992Ig-like C2-type 6
Domain754 – 84693Ig-like C2-type 7
Domain852 – 953102Ig-like C2-type 8
Domain957 – 105195Fibronectin type-III

Amino acid modifications

Modified residue4461Phosphoserine By similarity
Modified residue12081Phosphotyrosine; by FYN By similarity
Glycosylation541N-linked (GlcNAc...) Potential
Glycosylation3701N-linked (GlcNAc...) Potential
Glycosylation4151N-linked (GlcNAc...) Potential
Glycosylation5611N-linked (GlcNAc...) Potential
Glycosylation5781N-linked (GlcNAc...) Potential
Glycosylation5911N-linked (GlcNAc...) Potential
Glycosylation7221N-linked (GlcNAc...) Potential
Disulfide bond67 ↔ 125 By similarity
Disulfide bond174 ↔ 231 By similarity
Disulfide bond279 ↔ 331 By similarity
Disulfide bond375 ↔ 431 By similarity
Disulfide bond479 ↔ 542 By similarity
Disulfide bond581 ↔ 637 By similarity
Disulfide bond775 ↔ 830 By similarity
Disulfide bond877 ↔ 934 By similarity

Natural variations

Alternative sequence1 – 3333MGAKE…GMLTT → MEKWRAWDPQSIQRRKTAK in isoform 2.
VSP_040676

Experimental info

Sequence conflict1 – 2424MGAKE…CHLIP → MALGTTLRAS in AAF03368. Ref.1
Sequence conflict61A → V in AAF91087. Ref.2
Sequence conflict211H → R in AAF91087. Ref.2
Sequence conflict431S → P in AAF91085. Ref.2
Sequence conflict431S → P in AAG17142. Ref.3
Sequence conflict431S → P in AAK38483. Ref.3
Sequence conflict431S → P in BAI63574. Ref.4
Sequence conflict631V → I in AAF03368. Ref.1
Sequence conflict631V → I in AAF91087. Ref.2
Sequence conflict1401S → R in AAF03368. Ref.1
Sequence conflict1401S → R in AAF91087. Ref.2
Sequence conflict1451I → V in AAF03368. Ref.1
Sequence conflict1451I → V in AAF91087. Ref.2
Sequence conflict1481S → P in AAF03368. Ref.1
Sequence conflict1481S → P in AAF91087. Ref.2
Sequence conflict1781D → G in AAF03368. Ref.1
Sequence conflict1781D → G in AAF91087. Ref.2
Sequence conflict7631T → A in AAF03368. Ref.1
Sequence conflict9961S → T in AAF03368. Ref.1
Sequence conflict9961S → T in AAF91087. Ref.2
Sequence conflict10761L → Q in AAF03368. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (NephrinA) [UniParc].

Last modified March 8, 2011. Version 2.
Checksum: 339A670F2AF000A2

FASTA1,256136,336
        10         20         30         40         50         60 
MGAKEATVRG PGASPVHRTC HLIPLLLAGM LTTGLAQSPV PTSAPRGFWA LSENLTVVEG 

        70         80         90        100        110        120 
STVKLWCGVR APGSVVQWAK DGLLLGPNPK IPGFPRYSLE GDSAKGEFHL LIEACDLSDD 

       130        140        150        160        170        180 
AEYECQVGRS ELGPELVSPS VILSILVSPK VLQLTPEAGS TVTWVAGQEY VVTCVSGDAK 

       190        200        210        220        230        240 
PAPDIIFIQG GRTVEDVSSS VNEGSEEKLF FTEAEARVTP QSSDNGQLLV CEGSNPALAT 

       250        260        270        280        290        300 
PIKASFTMNI LFPPGPPVID WPGLNEGHVR AGENLELPCI ARGGNPPATL QWLKNGKPVS 

       310        320        330        340        350        360 
IAWGTEHAQA VAHSVLVMTV RPEDHGARLS CQSYNSVSAE TQERSITLQV TFPPSAVTIL 

       370        380        390        400        410        420 
GSTSQSENKN VTLCCLTKSS RPRVLLRWWL GGRQLLPTDE TVMDGLHGGH ISMSNLTLLV 

       430        440        450        460        470        480 
KREDNGLSLT CEAFSDAFSK ETFKKSLTLN VKYPAQKLWI EGPPEGQSIR TGTRVRLVCL 

       490        500        510        520        530        540 
AIGGNPEPSL TWLKDSRPVN DPRQSQEPRR VQLGSVEKSG STFSRELVLI IGPPDNLAKF 

       550        560        570        580        590        600 
SCKAGQLSAS TQLVVQFPPT NLTILANSSA LRPGDALNLT CVSISSNPPV NLSLDKEGER 

       610        620        630        640        650        660 
LDDVAAKPQS APFKGSAASR SVFLRVSSRD HGHRVTCRAH SEALRETVSS FYRLNVLYPP 

       670        680        690        700        710        720 
EFLGEQVRAV TVVEQGQALL PVSVSANPAP EAFNWTFRGY RLSPAGGPRH RILSGGALQL 

       730        740        750        760        770        780 
WNVTRADDGF YQLHCQNSEG TAEALLKLDV HYAPTIRALK DPTEVNVGGS VDIVCTVDAN 

       790        800        810        820        830        840 
PILPEMFSWE RLGEDEEELN LDDMEKMSKG STGRLRIRQA KLSQAGAYQC IVDNGVAPAA 

       850        860        870        880        890        900 
RGLVRLVVRF APQVDHPTPL TKVAAAGDST SSATLHCRAR GVPNIDFTWT KNGVPLDLQD 

       910        920        930        940        950        960 
PRYTEHKYHQ GVVHSSLLTI ANVSAAQDYA LFKCTATNAL GSDHTNIQLV SISRPDPPLG 

       970        980        990       1000       1010       1020 
LKVVSVSPHS VGLEWKPGFD GGLPQRFQIR YEALESPGFL YMDVLPAQAT TFTLTGLKPS 

      1030       1040       1050       1060       1070       1080 
TRYRIWLLAS NALGDSGLTD KGIQVSITTP GLDQAPEDTD QPLPTEQPPG PPRLPLLPVL 

      1090       1100       1110       1120       1130       1140 
FAVGGLLLLS NASCVGGLLW RRRLRRLAEE ISEKTEAGSE EDRIRNEYEE SQWTGDRDTR 

      1150       1160       1170       1180       1190       1200 
SSTVSTAEVD PHYYSMRDFS PQLPPTLEEV SYRQAFTGIE DEDMAFPGHL YDEVERVYGP 

      1210       1220       1230       1240       1250 
PGVWGPLYDE VQMDPYDLRW PEVKYEDPRG IYDQVAADMD AGEPGSLPFE LRGHLV 

« Hide

Isoform 2 (NephrinB) [UniParc].

Checksum: 5DA81EAA712A3EBB
Show »

FASTA1,242135,352

References

« Hide 'large scale' references
[1]"Nephrin localizes to the slit pore of the glomerular epithelial cell."
Holzman L.B., St John P.L., Kovari I.A., Verma R., Holthoefer H., Abrahamson D.R.
Kidney Int. 56:1481-1491(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
[2]"Primary structure of mouse and rat nephrin cDNA and structure and expression of the mouse gene."
Putaala H., Sainio K., Sariola H., Tryggvason K.
J. Am. Soc. Nephrol. 11:991-1001(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Kidney.
[3]"Determinants of vascular permeability in the kidney glomerulus."
Hamano Y., Grunkemeyer J.A., Sudhakar A., Zeisberg M., Cosgrove D., Morello R., Lee B., Sugimoto H., Kalluri R.
J. Biol. Chem. 277:31154-31162(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-494 (ISOFORM 1), FUNCTION, DISRUPTION PHENOTYPE.
Strain: 129/SvEv and C57BL/6J.
[4]"Ptf1a directly controls expression of immunoglobulin superfamily molecules Nephrin and Neph3 in the developing central nervous system."
Nishida K., Hoshino M., Kawaguchi Y., Murakami F.
J. Biol. Chem. 285:373-380(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SELF-ASSOCIATION, INTERACTION WITH KIRREL2, TISSUE SPECIFICITY.
[5]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[6]"Alternatively used promoters and distinct elements direct tissue-specific expression of nephrin."
Beltcheva O., Kontusaari S., Fetissov S., Putaala H., Kilpelainen P., Hokfelt T., Tryggvason K.
J. Am. Soc. Nephrol. 14:352-358(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19 (ISOFORM 2), TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
Strain: 129/Sv.
[7]"CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain."
Shih N.Y., Li J., Cotran R., Mundel P., Miner J.H., Shaw A.S.
Am. J. Pathol. 159:2303-2308(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD2AP.
[8]"The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death."
Putaala H., Soininen R., Kilpelainen P., Wartiovaara J., Tryggvason K.
Hum. Mol. Genet. 10:1-8(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[9]"Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin."
Schwarz K., Simons M., Reiser J., Saleem M.A., Faul C., Kriz W., Shaw A.S., Holzman L.B., Mundel P.
J. Clin. Invest. 108:1621-1629(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD2AP AND NPHS2.
[10]"NEPH1 defines a novel family of podocin interacting proteins."
Sellin L., Huber T.B., Gerke P., Quack I., Pavenstaedt H., Walz G.
FASEB J. 17:115-117(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KIRREL1.
Strain: Swiss Webster.
Tissue: Brain.
[11]"Homodimerization and heterodimerization of the glomerular podocyte proteins nephrin and NEPH1."
Gerke P., Huber T.B., Sellin L., Benzing T., Walz G.
J. Am. Soc. Nephrol. 14:918-926(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SELF-ASSOCIATION, INTERACTION WITH KIRREL.
[12]"Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes."
Asanuma K., Campbell K.N., Kim K., Faul C., Mundel P.
Proc. Natl. Acad. Sci. U.S.A. 104:10134-10139(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDN.
[13]"A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion."
Sohn R.L., Huang P., Kawahara G., Mitchell M., Guyon J., Kalluri R., Kunkel L.M., Gussoni E.
Proc. Natl. Acad. Sci. U.S.A. 106:9274-9279(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF168466 mRNA. Translation: AAF03368.1.
AF172254 expand/collapse EMBL AC list , AF172247, AF172248, AF172249, AF172250, AF172251, AF172252, AF172253 Genomic DNA. Translation: AAF91085.1.
AF172256 mRNA. Translation: AAF91087.1.
AF190638 Genomic DNA. Translation: AAG17142.1.
AF191090 mRNA. Translation: AAK38483.1.
AB513652 mRNA. Translation: BAI63574.1.
AC167970 mRNA. No translation available.
AY183460 Genomic DNA. Translation: AAO22850.1.
RefSeqNP_062332.2. NM_019459.2.
XP_006540278.1. XM_006540215.1.
UniGeneMm.437830.

3D structure databases

ProteinModelPortalQ9QZS7.
SMRQ9QZS7. Positions 48-633, 648-1036.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid207694. 1 interaction.
STRING10090.ENSMUSP00000006825.

PTM databases

PhosphoSiteQ9QZS7.

Proteomic databases

PaxDbQ9QZS7.
PRIDEQ9QZS7.

Protocols and materials databases

DNASU54631.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000006825; ENSMUSP00000006825; ENSMUSG00000006649. [Q9QZS7-1]
GeneID54631.
KEGGmmu:54631.
UCSCuc009gem.1. mouse. [Q9QZS7-2]
uc009gen.1. mouse. [Q9QZS7-1]

Organism-specific databases

CTD4868.
MGIMGI:1859637. Nphs1.

Phylogenomic databases

eggNOGNOG251936.
GeneTreeENSGT00550000074545.
HOVERGENHBG031752.
InParanoidQ9ET59.
OMANVNEGSQ.
OrthoDBEOG7RBZ7J.
PhylomeDBQ9QZS7.
TreeFamTF327139.

Gene expression databases

ArrayExpressQ9QZS7.
BgeeQ9QZS7.
CleanExMM_NPHS1.
GenevestigatorQ9QZS7.

Family and domain databases

Gene3D2.60.40.10. 10 hits.
InterProIPR013162. CD80_C2-set.
IPR003961. Fibronectin_type3.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
[Graphical view]
PfamPF08205. C2-set_2. 5 hits.
PF00041. fn3. 1 hit.
PF07679. I-set. 2 hits.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 1 hit.
SM00409. IG. 5 hits.
SM00408. IGc2. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 1 hit.
PROSITEPS50853. FN3. 1 hit.
PS50835. IG_LIKE. 8 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio311448.
PROQ9QZS7.
SOURCESearch...

Entry information

Entry nameNPHN_MOUSE
AccessionPrimary (citable) accession number: Q9QZS7
Secondary accession number(s): D2KXA7 expand/collapse secondary AC list , Q811S5, Q925S5, Q9ESC6, Q9ET59, Q9JIX1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: March 8, 2011
Last modified: April 16, 2014
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot