O60500 (NPHN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nephrin

Alternative name(s):
Renal glomerulus-specific cell adhesion receptor

Gene names

Name:	NPHS1
Synonyms:	NPHN

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1241 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 By similarity.
Subunit structure	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 KIRREL/NEPH1 and KIRREL2; the interaction with KIRREL is dependent on KIRREL glycosylation. Forms a complex with ACTN4, CASK, IQGAP1, MAGI2, SPTAN1 and SPTBN1 By similarity. Interacts with NPHS2. Ref.7
Subcellular location	Cell membrane; Single-pass type I membrane protein Potential. Note: Predominantly located at podocyte slit diaphragm between podocyte foot processes. Also associated with podocyte apical plasma membrane. Ref.5 Ref.6
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.
Post-translational modification	Phosphorylated at Tyr-1193 by FYN, leading to the recruitment and activation of phospholipase C-gamma-1/PLCG1 By similarity.
Involvement in disease	Nephrotic syndrome 1 (NPHS1) [MIM:256300]: A renal disease characterized clinically by proteinuria, 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
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 process	Cell adhesion Myogenesis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JNK cascade Inferred from electronic annotation. Source: Compara cell adhesion Traceable author statement Ref.1. Source: ProtInc excretion Traceable author statement Ref.1. Source: ProtInc glomerular basement membrane development Inferred from expression pattern PubMed 17464107. Source: UniProtKB glomerular visceral epithelial cell development Inferred from expression pattern PubMed 17464107. Source: UniProtKB myoblast fusion Inferred from electronic annotation. Source: Compara positive regulation of actin filament polymerization Inferred from electronic annotation. Source: Compara regulation of excretion Inferred from electronic annotation. Source: Compara
Cellular_component	cell projection Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc slit diaphragm Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	3	EBI-996920,EBI-389883

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60500-1)

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: O60500-2)

Also known as: Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     1056-1095: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 1241	1219	Nephrin		PRO_0000015052
Regions
	Topological domain	23 – 1055	1033	Extracellular Potential
	Transmembrane	1056 – 1076	21	Helical; Potential
	Topological domain	1077 – 1241	165	Cytoplasmic Potential
	Domain	27 – 130	104	Ig-like C2-type 1
	Domain	143 – 234	92	Ig-like C2-type 2
	Domain	242 – 333	92	Ig-like C2-type 3
	Domain	340 – 434	95	Ig-like C2-type 4
	Domain	440 – 540	101	Ig-like C2-type 5
	Domain	544 – 635	92	Ig-like C2-type 6
	Domain	740 – 832	93	Ig-like C2-type 7
	Domain	838 – 939	102	Ig-like C2-type 8
	Domain	941 – 1035	95	Fibronectin type-III
	Region	1160 – 1241	82	Binds to NPHS2
Amino acid modifications
	Modified residue	432	1	Phosphoserine Ref.8
	Modified residue	1193	1	Phosphotyrosine; by FYN By similarity
	Glycosylation	40	1	N-linked (GlcNAc...) Potential
	Glycosylation	356	1	N-linked (GlcNAc...) Potential
	Glycosylation	401	1	N-linked (GlcNAc...) Potential
	Glycosylation	547	1	N-linked (GlcNAc...) Potential
	Glycosylation	553	1	N-linked (GlcNAc...) Potential
	Glycosylation	564	1	N-linked (GlcNAc...) Potential
	Glycosylation	577	1	N-linked (GlcNAc...) Potential
	Glycosylation	680	1	N-linked (GlcNAc...) Potential
	Glycosylation	708	1	N-linked (GlcNAc...) Potential
	Glycosylation	908	1	N-linked (GlcNAc...) Potential
	Disulfide bond	53 ↔ 111		Potential
	Disulfide bond	160 ↔ 217		Potential
	Disulfide bond	265 ↔ 317		Potential
	Disulfide bond	361 ↔ 417		Potential
	Disulfide bond	465 ↔ 528		Potential
	Disulfide bond	567 ↔ 623		Potential
	Disulfide bond	761 ↔ 816		Potential
	Disulfide bond	863 ↔ 920		Potential
Natural variations
	Alternative sequence	1056 – 1095	40	Missing in isoform 2.		VSP_002598
	Natural variant	64	1	W → S in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013029
	Natural variant	96	1	L → V in NPHS1. Ref.14		VAR_064194
	Natural variant	107	1	A → T in NPHS1. Ref.14		VAR_064195
	Natural variant	107	1	A → V in NPHS1. Ref.16		VAR_064196
	Natural variant	117	1	E → K. Ref.2 Ref.9 Ref.12 Ref.17 Corresponds to variant rs3814995 [ dbSNP | Ensembl ].		VAR_013030
	Natural variant	167	1	P → L in NPHS1. Ref.16		VAR_064197
	Natural variant	171	1	I → N in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013031
	Natural variant	172	1	Missing in NPHS1. Ref.9 Ref.12 Ref.16		VAR_013032
	Natural variant	173	1	I → N in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013033
	Natural variant	205 – 207	3	TPR → I in NPHS1.		VAR_013034
	Natural variant	233	1	T → A. Corresponds to variant rs35238405 [ dbSNP | Ensembl ].		VAR_049970
	Natural variant	256	1	R → W in NPHS1. Ref.15		VAR_064198
	Natural variant	264	1	P → R Found in patients with nephrotic syndrome; unknown pathological significance. Ref.12		VAR_064199
	Natural variant	265	1	C → R in NPHS1. Ref.13		VAR_064200
	Natural variant	270	1	G → C in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013035
	Natural variant	299	1	R → C in NPHS1. Ref.16		VAR_064201
	Natural variant	340	1	P → H in NPHS1. Ref.16		VAR_064202
	Natural variant	347	1	G → E in NPHS1. Ref.16		VAR_064203
	Natural variant	350	1	S → P in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12 Ref.16		VAR_013036
	Natural variant	366	1	S → R in NPHS1; lack of protein expression on the cell surface; the mutant protein is retained in the endoplasmic reticulum. Ref.9 Ref.11 Ref.12 Ref.16		VAR_013037
	Natural variant	367	1	R → C in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12 Ref.15 Ref.16		VAR_013038
	Natural variant	368	1	P → L in NPHS1. Ref.12		VAR_064204
	Natural variant	368	1	P → S in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013039
	Natural variant	376	1	L → V in NPHS1; does not affect protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013040
	Natural variant	379	1	R → W in NPHS1. Ref.12		VAR_064205
	Natural variant	392	1	L → P. Corresponds to variant rs34320609 [ dbSNP | Ensembl ].		VAR_049971
	Natural variant	407	1	R → W in NPHS1. Ref.16		VAR_064206
	Natural variant	408	1	R → Q in NPHS1; uncertain pathological significance; does not affect protein expression on the cell surface. Ref.9 Ref.11 Ref.12 Ref.16 Corresponds to variant rs33950747 [ dbSNP | Ensembl ].		VAR_013041
	Natural variant	412	1	G → C in NPHS1. Ref.15		VAR_064207
	Natural variant	417	1	C → F in NPHS1. Ref.12		VAR_064208
	Natural variant	447	1	E → K. Ref.10 Ref.12 Corresponds to variant rs28939695 [ dbSNP | Ensembl ].		VAR_013042
	Natural variant	460	1	R → Q in NPHS1. Ref.12 Ref.14 Ref.16		VAR_064209
	Natural variant	465	1	C → Y in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013043
	Natural variant	519	1	P → S in NPHS1. Ref.15		VAR_064210
	Natural variant	528	1	C → F in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013044
	Natural variant	558	1	R → C in NPHS1. Ref.12 Ref.16		VAR_064211
	Natural variant	569	1	S → R in NPHS1. Ref.15		VAR_064212
	Natural variant	572	1	S → N in NPHS1. Ref.16		VAR_064213
	Natural variant	575	1	P → Q in NPHS1. Ref.14		VAR_064214
	Natural variant	586	1	R → G in NPHS1. Ref.16		VAR_064215
	Natural variant	587	1	L → R in NPHS1. Ref.16		VAR_064216
	Natural variant	610	1	L → Q in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013045
	Natural variant	617	1	H → R Found in patients with nephrotic syndrome; unknown pathological significance. Ref.12		VAR_064217
	Natural variant	623	1	C → F in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12 Ref.16		VAR_013046
	Natural variant	673	1	N → K in NPHS1. Ref.16		VAR_064218
	Natural variant	681	1	W → C in NPHS1. Ref.16		VAR_064219
	Natural variant	709	1	V → G in NPHS1. Ref.15		VAR_064220
	Natural variant	724	1	S → C in NPHS1; does not affect protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013047
	Natural variant	725	1	E → D Found in patients with nephrotic syndrome; unknown pathological significance. Ref.12		VAR_064221
	Natural variant	739	1	A → V in NPHS1. Ref.12		VAR_064222
	Natural variant	742	1	I → T in NPHS1. Ref.17		VAR_067252
	Natural variant	743	1	R → C in NPHS1; does not affect protein expression on the cell surface. Ref.9 Ref.11 Ref.12 Ref.16		VAR_013048
	Natural variant	802	1	R → P in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013050
	Natural variant	802	1	R → W in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013049
	Natural variant	806	1	A → D in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11 Ref.12		VAR_013051
	Natural variant	819	1	D → V in NPHS1. Ref.10 Ref.12		VAR_013052
	Natural variant	822	1	V → M in NPHS1. Ref.13		VAR_064223
	Natural variant	831	1	R → C in NPHS1; lack of protein expression on the cell surface. Ref.9 Ref.11		VAR_013053
	Natural variant	832	1	L → P in NPHS1; the mutant protein is retained in the endoplasmic reticulum. Ref.14		VAR_064224
	Natural variant	834	1	V → F in NPHS1. Ref.12		VAR_064225
	Natural variant	851	1	A → V Found in patients with nephrotic syndrome; unknown pathological significance. Ref.12		VAR_064226
	Natural variant	910	1	S → P in NPHS1. Ref.16		VAR_064227
	Natural variant	976	1	R → S in NPHS1. Ref.14 Ref.16		VAR_064228
	Natural variant	991	1	V → L. Corresponds to variant rs34736717 [ dbSNP | Ensembl ].		VAR_049972
	Natural variant	1077	1	N → S. Ref.9 Ref.12 Corresponds to variant rs4806213 [ dbSNP | Ensembl ].		VAR_013054
	Natural variant	1140	1	R → C in NPHS1; does not affect protein expression on the cell surface. Ref.9 Ref.11 Ref.16		VAR_013055

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 7F5AFAF078BCF532	FASTA	1,241	134,742
	10 20 30 40 50 60 MALGTTLRAS LLLLGLLTEG LAQLAIPASV PRGFWALPEN LTVVEGASVE LRCGVSTPGS 70 80 90 100 110 120 AVQWAKDGLL LGPDPRIPGF PRYRLEGDPA RGEFHLHIEA CDLSDDAEYE CQVGRSEMGP 130 140 150 160 170 180 ELVSPRVILS ILVPPKLLLL TPEAGTMVTW VAGQEYVVNC VSGDAKPAPD ITILLSGQTI 190 200 210 220 230 240 SDISANVNEG SQQKLFTVEA TARVTPRSSD NRQLLVCEAS SPALEAPIKA SFTVNVLFPP 250 260 270 280 290 300 GPPVIEWPGL DEGHVRAGQS LELPCVARGG NPLATLQWLK NGQPVSTAWG TEHTQAVARS 310 320 330 340 350 360 VLVMTVRPED HGAQLSCEAH NSVSAGTQEH GITLQVTFPP SAIIILGSAS QTENKNVTLS 370 380 390 400 410 420 CVSKSSRPRV LLRWWLGWRQ LLPMEETVMD GLHGGHISMS NLTFLARRED NGLTLTCEAF 430 440 450 460 470 480 SEAFTKETFK KSLILNVKYP AQKLWIEGPP EGQKLRAGTR VRLVCLAIGG NPEPSLMWYK 490 500 510 520 530 540 DSRTVTESRL PQESRRVHLG SVEKSGSTFS RELVLVTGPS DNQAKFTCKA GQLSASTQLA 550 560 570 580 590 600 VQFPPTNVTI LANASALRPG DALNLTCVSV SSNPPVNLSW DKEGERLEGV AAPPRRAPFK 610 620 630 640 650 660 GSAAARSVLL QVSSRDHGQR VTCRAHSAEL RETVSSFYRL NVLYRPEFLG EQVLVVTAVE 670 680 690 700 710 720 QGEALLPVSV SANPAPEAFN WTFRGYRLSP AGGPRHRILS SGALHLWNVT RADDGLYQLH 730 740 750 760 770 780 CQNSEGTAEA RLRLDVHYAP TIRALQDPTE VNVGGSVDIV CTVDANPILP GMFNWERLGE 790 800 810 820 830 840 DEEDQSLDDM EKISRGPTGR LRIHHAKLAQ AGAYQCIVDN GVAPPARRLL RLVVRFAPQV 850 860 870 880 890 900 EHPTPLTKVA AAGDSTSSAT LHCRARGVPN IVFTWTKNGV PLDLQDPRYT EHTYHQGGVH 910 920 930 940 950 960 SSLLTIANVS AAQDYALFTC TATNALGSDQ TNIQLVSISR PDPPSGLKVV SLTPHSVGLE 970 980 990 1000 1010 1020 WKPGFDGGLP QRFCIRYEAL GTPGFHYVDV VPPQATTFTL TGLQPSTRYR VWLLASNALG 1030 1040 1050 1060 1070 1080 DSGLADKGTQ LPITTPGLHQ PSGEPEDQLP TEPPSGPSGL PLLPVLFALG GLLLLSNASC 1090 1100 1110 1120 1130 1140 VGGVLWQRRL RRLAEGISEK TEAGSEEDRV RNEYEESQWT GERDTQSSTV STTEAEPYYR 1150 1160 1170 1180 1190 1200 SLRDFSPQLP PTQEEVSYSR GFTGEDEDMA FPGHLYDEVE RTYPPSGAWG PLYDEVQMGP 1210 1220 1230 1240 WDLHWPEDTY QDPRGIYDQV AGDLDTLEPD SLPFELRGHL V
	Isoform 2 (Alpha) [UniParc]. Checksum: 189283B140D831DF	FASTA	1,201	130,546
	10 20 30 40 50 60 MALGTTLRAS LLLLGLLTEG LAQLAIPASV PRGFWALPEN LTVVEGASVE LRCGVSTPGS 70 80 90 100 110 120 AVQWAKDGLL LGPDPRIPGF PRYRLEGDPA RGEFHLHIEA CDLSDDAEYE CQVGRSEMGP 130 140 150 160 170 180 ELVSPRVILS ILVPPKLLLL TPEAGTMVTW VAGQEYVVNC VSGDAKPAPD ITILLSGQTI 190 200 210 220 230 240 SDISANVNEG SQQKLFTVEA TARVTPRSSD NRQLLVCEAS SPALEAPIKA SFTVNVLFPP 250 260 270 280 290 300 GPPVIEWPGL DEGHVRAGQS LELPCVARGG NPLATLQWLK NGQPVSTAWG TEHTQAVARS 310 320 330 340 350 360 VLVMTVRPED HGAQLSCEAH NSVSAGTQEH GITLQVTFPP SAIIILGSAS QTENKNVTLS 370 380 390 400 410 420 CVSKSSRPRV LLRWWLGWRQ LLPMEETVMD GLHGGHISMS NLTFLARRED NGLTLTCEAF 430 440 450 460 470 480 SEAFTKETFK KSLILNVKYP AQKLWIEGPP EGQKLRAGTR VRLVCLAIGG NPEPSLMWYK 490 500 510 520 530 540 DSRTVTESRL PQESRRVHLG SVEKSGSTFS RELVLVTGPS DNQAKFTCKA GQLSASTQLA 550 560 570 580 590 600 VQFPPTNVTI LANASALRPG DALNLTCVSV SSNPPVNLSW DKEGERLEGV AAPPRRAPFK 610 620 630 640 650 660 GSAAARSVLL QVSSRDHGQR VTCRAHSAEL RETVSSFYRL NVLYRPEFLG EQVLVVTAVE 670 680 690 700 710 720 QGEALLPVSV SANPAPEAFN WTFRGYRLSP AGGPRHRILS SGALHLWNVT RADDGLYQLH 730 740 750 760 770 780 CQNSEGTAEA RLRLDVHYAP TIRALQDPTE VNVGGSVDIV CTVDANPILP GMFNWERLGE 790 800 810 820 830 840 DEEDQSLDDM EKISRGPTGR LRIHHAKLAQ AGAYQCIVDN GVAPPARRLL RLVVRFAPQV 850 860 870 880 890 900 EHPTPLTKVA AAGDSTSSAT LHCRARGVPN IVFTWTKNGV PLDLQDPRYT EHTYHQGGVH 910 920 930 940 950 960 SSLLTIANVS AAQDYALFTC TATNALGSDQ TNIQLVSISR PDPPSGLKVV SLTPHSVGLE 970 980 990 1000 1010 1020 WKPGFDGGLP QRFCIRYEAL GTPGFHYVDV VPPQATTFTL TGLQPSTRYR VWLLASNALG 1030 1040 1050 1060 1070 1080 DSGLADKGTQ LPITTPGLHQ PSGEPEDQLP TEPPSGISEK TEAGSEEDRV RNEYEESQWT 1090 1100 1110 1120 1130 1140 GERDTQSSTV STTEAEPYYR SLRDFSPQLP PTQEEVSYSR GFTGEDEDMA FPGHLYDEVE 1150 1160 1170 1180 1190 1200 RTYPPSGAWG PLYDEVQMGP WDLHWPEDTY QDPRGIYDQV AGDLDTLEPD SLPFELRGHL V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Positionally cloned gene for a novel glomerular protein -- nephrin --is mutated in congenital nephrotic syndrome." 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. Mol. Cell 1:575-582(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN NPHS1.
[2]	"Novel human pathological mutations. Gene symbol: NPHS1. Disease: congenital nephrotic syndrome, Finnish type." Tikhomirov E., Voznesenskaya T., Tsygin A. Hum. Genet. 125:334-334(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LYS-117.
[3]	"Human nephrin (NPHS1) cDNA sequence." Grunkemeyer J.A., Kumar N., Kalluri R. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"The DNA sequence and biology of human chromosome 19." 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. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Nephrin localizes at the podocyte filtration slit area and is characteristically spliced in the human kidney." Holthoefer H., Ahola H., Solin M.-L., Wang S.-X., Palmen T., Luimula P., Miettinen A., Kerjaschki D. Am. J. Pathol. 155:1681-1687(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1032-1134 (ISOFORM 2), SUBCELLULAR LOCATION.
[6]	"Nephrin is specifically located at the slit diaphragm of glomerular podocytes." Ruotsalainen V., Ljungberg P., Wartiovaara J., Lenkkeri U., Kestilae M., Jalanko H., Holmberg C., Tryggvason K. Proc. Natl. Acad. Sci. U.S.A. 96:7962-7967(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	"Interaction with podocin facilitates nephrin signaling." Huber T.B., Kottgen M., Schilling B., Walz G., Benzing T. J. Biol. Chem. 276:41543-41546(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NPHS2.
[8]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, MASS SPECTROMETRY. Tissue: Platelet.
[9]	"Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations." 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. Am. J. Hum. Genet. 64:51-61(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-117 AND SER-1077, 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; GLN-408; TYR-465; PHE-528; GLN-610; PHE-623; CYS-724; CYS-743; TRP-802; PRO-802; ASP-806; CYS-831 AND CYS-1140.
[10]	"Novel mutation in the nephrin gene of a Japanese patient with congenital nephrotic syndrome of the Finnish type." Aya K., Tanaka H., Seino Y. Kidney Int. 57:401-404(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NPHS1 VAL-819, VARIANT LYS-447.
[11]	"Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: insight into the mechanisms of congenital nephrotic syndrome." Liu L., Done S.C., Khoshnoodi J., Bertorello A., Wartiovaara J., Berggren P.O., Tryggvason K. Hum. Mol. Genet. 10:2637-2644(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS NPHS1 SER-64; ASN-171; ASN-173; CYS-270; PRO-350; ARG-366; CYS-367; SER-368; VAL-376; GLN-408; TYR-465; PHE-528; GLN-610; PHE-623; CYS-724; CYS-743; TRP-802; PRO-802; ASP-806; CYS-831 AND CYS-1140.
[12]	"Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome." Beltcheva O., Martin P., Lenkkeri U., Tryggvason K. Hum. Mutat. 17:368-373(2001) [PubMed] [Europe PMC] [Abstract] Cited for: 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; GLN-408; 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, VARIANTS LYS-117; ARG-264; LYS-447; ARG-617; ASP-725; VAL-851 AND SER-1077.
[13]	"A familial childhood-onset relapsing nephrotic syndrome." Kitamura A., Tsukaguchi H., Hiramoto R., Shono A., Doi T., Kagami S., Iijima K. Kidney Int. 71:946-951(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NPHS1 ARG-265 AND MET-822.
[14]	"Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome." 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. J. Am. Soc. Nephrol. 19:1871-1878(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NPHS1 VAL-96; THR-107; GLN-460; GLN-575; PRO-832 AND SER-976, CHARACTERIZATION OF VARIANT NPHS1 PRO-832.
[15]	"Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome." Heeringa S.F., Vlangos C.N., Chernin G., Hinkes B., Gbadegesin R., Liu J., Hoskins B.E., Ozaltin F., Hildebrandt F. Nephrol. Dial. Transplant. 23:3527-3533(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NPHS1 TRP-256; CYS-367; CYS-412; SER-519; ARG-569 AND GLY-709.
[16]	"Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS)." 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. Nephrol. Dial. Transplant. 25:2970-2976(2010) [PubMed] [Europe PMC] [Abstract] Cited for: 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-408; 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.
[17]	"Two novel NPHS1 mutations in a Chinese family with congenital nephrotic syndrome." Wu L.Q., Hu J.J., Xue J.J., Liang D.S. Genet. Mol. Res. 10:2517-2522(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NPHS1 THR-742, VARIANT LYS-117.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF035835 mRNA. Translation: AAC39687.1. EU642886 mRNA. Translation: ACH99862.1. AF190637 mRNA. Translation: AAG17141.1. AC002133 Genomic DNA. No translation available. AF126957 mRNA. Translation: AAF36451.1.
IPI	IPI00219898. IPI00747010.
PIR	T37190.
RefSeq	NP_004637.1. NM_004646.3.
UniGene	Hs.122186.
3D structure databases
ProteinModelPortal	O60500.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60500. 6 interactions.
STRING	9606.ENSP00000368190.
PTM databases
PhosphoSite	O60500.
Proteomic databases
PaxDb	O60500.
PRIDE	O60500.
Protocols and materials databases
DNASU	4868.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000353632; ENSP00000343634; ENSG00000161270. ENST00000378910; ENSP00000368190; ENSG00000161270.
GeneID	4868.
KEGG	hsa:4868.
UCSC	uc002oby.3. human.
Organism-specific databases
CTD	4868.
GeneCards	GC19M036316.
HGNC	HGNC:7908. NPHS1.
HPA	CAB035555.
MIM	256300. phenotype. 602716. gene.
neXtProt	NX_O60500.
Orphanet	839. Congenital nephrotic syndrome, Finnish type. 93214. Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation. 93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis. 93216. Familial idiopathic steroid-resistant nephrotic syndrome with minimal changes.
PharmGKB	PA31709.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG251936.
HOGENOM	HOG000113844.
HOVERGEN	HBG031752.
InParanoid	O60500.
OMA	ATLTWYK.
Enzyme and pathway databases
Reactome	REACT_111155. Cell-Cell communication.
Gene expression databases
Bgee	O60500.
CleanEx	HS_NPHS1.
Genevestigator	O60500.
GermOnline	ENSG00000161270. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 10 hits.
InterPro	IPR013162. CD80_C2-set. IPR003961. Fibronectin_type3. IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR003598. Ig_sub2. IPR013106. Ig_V-set. [Graphical view]
Pfam	PF08205. C2-set_2. 5 hits. PF00041. fn3. 1 hit. PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00060. FN3. 1 hit. SM00409. IG. 5 hits. SM00408. IGc2. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 1 hit.
PROSITE	PS50853. FN3. 1 hit. PS50835. IG_LIKE. 7 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4868.
NextBio	18748.
SOURCE	Search...

Entry information

Entry name

NPHN_HUMAN

Accession

Primary (citable) accession number: O60500
Secondary accession number(s): A6NDH2, C3RX61

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	August 1, 1998
Last modified:	May 1, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.