O15259 (NPHP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nephrocystin-1

Alternative name(s):
Juvenile nephronophthisis 1 protein

Gene names

Name:	NPHP1
Synonyms:	NPH1

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	732 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Together with BCAR1 it may play a role in the control of epithelial cell polarity. Involved in the organization of apical junctions in kidney cells together with NPHP4 and RPGRIP1L/NPHP8 By similarity. Does not seem to be strictly required for ciliogenesis By similarity. Seems to help to recruit PTK2B/PYK2 to cell matrix adhesions, thereby initiating phosphorylation of PTK2B/PYK2 and PTK2B/PYK2-dependent signaling. May play a role in the regulation of intraflagellar transport (IFT) during cilia assembly. Required for normal retina development. In connecting photoreceptor cilia influences the movement of some IFT proteins such as IFT88 and WDR19. Involved in spermatogenesis By similarity.
Subunit structure	Interacts with BCAR1, PTK2B/PYK2 and tensin. Interacts with INVS and NPHP3. Interacts with PACS1; the interaction is dependent on NPHP1 phosphorylation by CK2. Interacts with KIF7. Interacts with AHI1 and TNK2. Interacts with NPHP4 in a complex containing NPHP1, NPHP4 and RPGRIP1L. Interacts with IQCB1; the interaction likely requires additional interactors. Ref.6 Ref.7 Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Subcellular location	Cell junction › adherens junction By similarity. Cell projection › cilium. Cytoplasm › cytoskeleton › cilium axoneme. Cell junction › tight junction. Note: Colocalizes with E-cadherin and BCAR1 at or near the cell-cell adherens junctions By similarity. Localized to respiratory cilia axoneme. Localized to the transition zone of respiratory cilia, photoreceptor-connecting cilia and renal monocilia. In cultured renal cells, it localizes diffusely in the cytoplasm but, as cells approach confluence, it accumulates to basolateral tight junctions. Ref.9 Ref.11 Ref.15
Tissue specificity	Widespread expression, with highest levels in pituitary gland, spinal cord, thyroid gland, testis, skeletal muscle, lymph node and trachea. Weakly expressed in heart, kidney and pancreas. Expressed in nasal epithelial cells (at protein level). Ref.9
Developmental stage	During in vitro ciliogenesis translocalizes from the cytoplasm to the ciliary transition zone during epithelial cell polarization. Ref.11
Domain	The SH3 domain mediates the stable interaction with Cas By similarity.
Post-translational modification	Phosphorylation by CK2 is required for the interaction with PACS1 and the targeting to the base region of cilia.
Involvement in disease	Nephronophthisis 1 (NPHP1) [MIM:256100]: An autosomal recessive inherited disease characterized by anemia, polyuria, polydipsia, isosthenuria and death in uremia. Symmetrical destruction of the kidneys involving both tubules and glomeruli occurs. The underlying pathology is a chronic tubulo-interstitial nephropathy with characteristic tubular basement membrane thickening and medullary cyst formation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. The age at death ranges from about 4 to 15 years. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Senior-Loken syndrome 1 (SLSN1) [MIM:266900]: A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Joubert syndrome 4 (JBTS4) [MIM:609583]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 4 is a phenotypically mild form. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Miscellaneous	Nephronophthisis type 1 patients deficient for NPHP1 show normal overall integrity of respiratory cilia.
Sequence similarities	Belongs to the nephrocystin-1 family. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Cilium biogenesis/degradation Differentiation Spermatogenesis
Cellular component	Cell junction Cell projection Cilium Cytoplasm Cytoskeleton Tight junction
Coding sequence diversity	Alternative splicing
Disease	Ciliopathy Disease mutation Joubert syndrome Nephronophthisis Senior-Loken syndrome
Domain	Coiled coil SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Non-traceable author statement PubMed 12006559. Source: UniProtKB cell projection organization Inferred from sequence or structural similarity. Source: UniProtKB cell-cell adhesion Non-traceable author statement PubMed 12006559. Source: UniProtKB cellular protein localization Inferred from electronic annotation. Source: Compara excretion Traceable author statement Ref.1. Source: ProtInc photoreceptor cell outer segment organization Inferred from electronic annotation. Source: Compara retina development in camera-type eye Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Non-traceable author statement Ref.6. Source: UniProtKB spermatid differentiation Inferred from sequence or structural similarity. Source: UniProtKB visual behavior Non-traceable author statement PubMed 12205563. Source: UniProtKB
Cellular_component	adherens junction Inferred from electronic annotation. Source: UniProtKB-SubCell cell-cell junction Inferred from direct assay Ref.15. Source: UniProtKB cilium axoneme Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeleton Inferred from electronic annotation. Source: UniProtKB-KW membrane Non-traceable author statement PubMed 10665934. Source: UniProtKB motile cilium Inferred from direct assay Ref.11. Source: UniProtKB photoreceptor connecting cilium Inferred from sequence or structural similarity. Source: UniProtKB tight junction Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	structural molecule activity Non-traceable author statement PubMed 12006559. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O15259-1)

Also known as: NPHP1;

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: O15259-2)

Also known as: NPHP1-8A;

The sequence of this isoform differs from the canonical sequence as follows:
     258-312: Missing.

Isoform 3 (identifier: O15259-3)

The sequence of this isoform differs from the canonical sequence as follows:
     49-110: Missing.
     258-313: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: O15259-4)

The sequence of this isoform differs from the canonical sequence as follows:
     313-313: Q → QQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 732

732

Nephrocystin-1

PRO_0000159585

Regions

Domain

152 – 212

61

SH3

Coiled coil

3 – 105

103

Potential

Coiled coil

127 – 150

24

Potential

Compositional bias

116 – 147

32

Glu-rich

Compositional bias

212 – 227

16

Glu-rich

Amino acid modifications

Modified residue

46

1

Phosphotyrosine; by FAK2 Ref.16

Modified residue

121

1

Phosphoserine; by CK2 Probable

Modified residue

123

1

Phosphoserine; by CK2 Probable

Modified residue

126

1

Phosphoserine; by CK2 Probable

Modified residue

349

1

Phosphotyrosine; by FAK2 Ref.16

Modified residue

721

1

Phosphotyrosine; by SRC Ref.16

Natural variations

Alternative sequence

49 – 110

62

Missing in isoform 3.

VSP_010073

Alternative sequence

258 – 313

56

Missing in isoform 3.

VSP_010074

Alternative sequence

258 – 312

55

Missing in isoform 2.

VSP_003424

Alternative sequence

313

1

Q → QQ in isoform 4.

VSP_024381

Natural variant

342

1

G → R in NPHP1; associated with Cogan-type congenital ocular motor apraxia. Ref.19

VAR_012160

Experimental info

Mutagenesis

121

1

S → A: Impairs interaction with PACS1; when associated with A-123 and A-126. Ref.9

Mutagenesis

123

1

S → A: Impairs interaction with PACS1; when associated with A-121 and A-126. Ref.9

Mutagenesis

126

1

S → A: Impairs interaction with PACS1; when associated with A-121 and A-123. Ref.9

Mutagenesis

180

1

L → P: Loss of SH3 domain fold. Ref.18

Mutagenesis

203

1

P → L: Does not affect fold stability, as assessed by circular dichroism thermal denaturation melting curves and by NMR spectroscopy. Affects interaction with PKD1. Ref.14

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

732

Helix Strand Turn

Details...

Beta strand

155 – 159

5

Beta strand

166 – 169

4

Beta strand

175 – 181

7

Beta strand

186 – 193

8

Beta strand

195 – 197

3

Beta strand

199 – 204

6

Beta strand

207 – 209

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (NPHP1) [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 270125F56F2C50F7	FASTA	732	83,299
	10 20 30 40 50 60 MLARRQRDPL QALRRRNQEL KQQVDSLLSE SQLKEALEPN KRQHIYQRCI QLKQAIDENK 70 80 90 100 110 120 NALQKLSKAD ESAPVANYNQ RKEEEHTLLD KLTQQLQGLA VTISRENITE VGAPTEEEEE 130 140 150 160 170 180 SESEDSEDSG GEEEDAEEEE EEKEENESHK WSTGEEYIAV GDFTAQQVGD LTFKKGEILL 190 200 210 220 230 240 VIEKKPDGWW IAKDAKGNEG LVPRTYLEPY SEEEEGQESS EEGSEEDVEA VDETADGAEV 250 260 270 280 290 300 KQRTDPHWSA VQKAISEAGI FCLVNHVSFC YLIVLMRNRM ETVEDTNGSE TGFRAWNVQS 310 320 330 340 350 360 RGRIFLVSKP VLQINTVDVL TTMGAIPAGF RPSTLSQLLE EGNQFRANYF LQPELMPSQL 370 380 390 400 410 420 AFRDLMWDAT EGTIRSRPSR ISLILTLWSC KMIPLPGMSI QVLSRHVRLC LFDGNKVLSN 430 440 450 460 470 480 IHTVRATWQP KKPKTWTFSP QVTRILPCLL DGDCFIRSNS ASPDLGILFE LGISYIRNST 490 500 510 520 530 540 GERGELSCGW VFLKLFDASG VPIPAKTYEL FLNGGTPYEK GIEVDPSISR RAHGSVFYQI 550 560 570 580 590 600 MTMRRQPQLL VKLRSLNRRS RNVLSLLPET LIGNMCSIHL LIFYRQILGD VLLKDRMSLQ 610 620 630 640 650 660 STDLISHPML ATFPMLLEQP DVMDALRSSW AGKESTLKRS EKRDKEFLKS TFLLVYHDCV 670 680 690 700 710 720 LPLLHSTRLP PFRWAEEETE TARWKVITDF LKQNQENQGA LQALLSPDGV HEPFDLSEQT 730 YDFLGEMRKN AV
	Isoform 2 (NPHP1-8A) [UniParc]. Checksum: EB4C60DC4967021D	FASTA	677	77,041
	10 20 30 40 50 60 MLARRQRDPL QALRRRNQEL KQQVDSLLSE SQLKEALEPN KRQHIYQRCI QLKQAIDENK 70 80 90 100 110 120 NALQKLSKAD ESAPVANYNQ RKEEEHTLLD KLTQQLQGLA VTISRENITE VGAPTEEEEE 130 140 150 160 170 180 SESEDSEDSG GEEEDAEEEE EEKEENESHK WSTGEEYIAV GDFTAQQVGD LTFKKGEILL 190 200 210 220 230 240 VIEKKPDGWW IAKDAKGNEG LVPRTYLEPY SEEEEGQESS EEGSEEDVEA VDETADGAEV 250 260 270 280 290 300 KQRTDPHWSA VQKAISEQIN TVDVLTTMGA IPAGFRPSTL SQLLEEGNQF RANYFLQPEL 310 320 330 340 350 360 MPSQLAFRDL MWDATEGTIR SRPSRISLIL TLWSCKMIPL PGMSIQVLSR HVRLCLFDGN 370 380 390 400 410 420 KVLSNIHTVR ATWQPKKPKT WTFSPQVTRI LPCLLDGDCF IRSNSASPDL GILFELGISY 430 440 450 460 470 480 IRNSTGERGE LSCGWVFLKL FDASGVPIPA KTYELFLNGG TPYEKGIEVD PSISRRAHGS 490 500 510 520 530 540 VFYQIMTMRR QPQLLVKLRS LNRRSRNVLS LLPETLIGNM CSIHLLIFYR QILGDVLLKD 550 560 570 580 590 600 RMSLQSTDLI SHPMLATFPM LLEQPDVMDA LRSSWAGKES TLKRSEKRDK EFLKSTFLLV 610 620 630 640 650 660 YHDCVLPLLH STRLPPFRWA EEETETARWK VITDFLKQNQ ENQGALQALL SPDGVHEPFD 670 LSEQTYDFLG EMRKNAV
	Isoform 3 [UniParc]. Checksum: BBBDED56BF312D45	FASTA	614	69,909
	10 20 30 40 50 60 MLARRQRDPL QALRRRNQEL KQQVDSLLSE SQLKEALEPN KRQHIYQRVG APTEEEEESE 70 80 90 100 110 120 SEDSEDSGGE EEDAEEEEEE KEENESHKWS TGEEYIAVGD FTAQQVGDLT FKKGEILLVI 130 140 150 160 170 180 EKKPDGWWIA KDAKGNEGLV PRTYLEPYSE EEEGQESSEE GSEEDVEAVD ETADGAEVKQ 190 200 210 220 230 240 RTDPHWSAVQ KAISEINTVD VLTTMGAIPA GFRPSTLSQL LEEGNQFRAN YFLQPELMPS 250 260 270 280 290 300 QLAFRDLMWD ATEGTIRSRP SRISLILTLW SCKMIPLPGM SIQVLSRHVR LCLFDGNKVL 310 320 330 340 350 360 SNIHTVRATW QPKKPKTWTF SPQVTRILPC LLDGDCFIRS NSASPDLGIL FELGISYIRN 370 380 390 400 410 420 STGERGELSC GWVFLKLFDA SGVPIPAKTY ELFLNGGTPY EKGIEVDPSI SRRAHGSVFY 430 440 450 460 470 480 QIMTMRRQPQ LLVKLRSLNR RSRNVLSLLP ETLIGNMCSI HLLIFYRQIL GDVLLKDRMS 490 500 510 520 530 540 LQSTDLISHP MLATFPMLLE QPDVMDALRS SWAGKESTLK RSEKRDKEFL KSTFLLVYHD 550 560 570 580 590 600 CVLPLLHSTR LPPFRWAEEE TETARWKVIT DFLKQNQENQ GALQALLSPD GVHEPFDLSE 610 QTYDFLGEMR KNAV
	Isoform 4 [UniParc]. Checksum: B3222151828658D8	FASTA	733	83,428
	10 20 30 40 50 60 MLARRQRDPL QALRRRNQEL KQQVDSLLSE SQLKEALEPN KRQHIYQRCI QLKQAIDENK 70 80 90 100 110 120 NALQKLSKAD ESAPVANYNQ RKEEEHTLLD KLTQQLQGLA VTISRENITE VGAPTEEEEE 130 140 150 160 170 180 SESEDSEDSG GEEEDAEEEE EEKEENESHK WSTGEEYIAV GDFTAQQVGD LTFKKGEILL 190 200 210 220 230 240 VIEKKPDGWW IAKDAKGNEG LVPRTYLEPY SEEEEGQESS EEGSEEDVEA VDETADGAEV 250 260 270 280 290 300 KQRTDPHWSA VQKAISEAGI FCLVNHVSFC YLIVLMRNRM ETVEDTNGSE TGFRAWNVQS 310 320 330 340 350 360 RGRIFLVSKP VLQQINTVDV LTTMGAIPAG FRPSTLSQLL EEGNQFRANY FLQPELMPSQ 370 380 390 400 410 420 LAFRDLMWDA TEGTIRSRPS RISLILTLWS CKMIPLPGMS IQVLSRHVRL CLFDGNKVLS 430 440 450 460 470 480 NIHTVRATWQ PKKPKTWTFS PQVTRILPCL LDGDCFIRSN SASPDLGILF ELGISYIRNS 490 500 510 520 530 540 TGERGELSCG WVFLKLFDAS GVPIPAKTYE LFLNGGTPYE KGIEVDPSIS RRAHGSVFYQ 550 560 570 580 590 600 IMTMRRQPQL LVKLRSLNRR SRNVLSLLPE TLIGNMCSIH LLIFYRQILG DVLLKDRMSL 610 620 630 640 650 660 QSTDLISHPM LATFPMLLEQ PDVMDALRSS WAGKESTLKR SEKRDKEFLK STFLLVYHDC 670 680 690 700 710 720 VLPLLHSTRL PPFRWAEEET ETARWKVITD FLKQNQENQG ALQALLSPDG VHEPFDLSEQ 730 TYDFLGEMRK NAV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisis." Saunier S., Calado J., Heilig R., Silbermann F., Benessy F., Morin G., Konrad M., Broyer M., Gubler M.-C., Weissenbach J., Antignac C. Hum. Mol. Genet. 6:2317-2323(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Fetal kidney.
[2]	"A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1." Hildebrandt F., Otto E., Rensing C., Nothwang H.G., Vollmer M., Adolphs J., Hanusch H., Brandis M. Nat. Genet. 17:149-153(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-732 (ISOFORM 4), ALTERNATIVE SPLICING.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]	"Renal-retinal syndromes: association of retinal anomalies and recessive nephronophthisis in patients with homozygous deletion of the NPH1 locus." Caridi G., Murer L., Bellantuono R., Sorino P., Caringella D.A., Gusmano R., Ghiggeri G.M. Am. J. Kidney Dis. 32:1059-1062(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SLSN1.
[6]	"The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin." Mollet G., Salomon R., Gribouval O., Silbermann F., Bacq D., Landthaler G., Milford D., Nayir A., Rizzoni G., Antignac C., Saunier S. Nat. Genet. 32:300-305(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NPHP4.
[7]	"Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination." Otto E.A., Schermer B., Obara T., O'Toole J.F., Hiller K.S., Mueller A.M., Ruf R.G., Hoefele J., Beekmann F., Landau D., Foreman J.W., Goodship J.A., Strachan T., Kispert A., Wolf M.T., Gagnadoux M.F., Nivet H., Antignac C. , Walz G., Drummond I.A., Benzing T., Hildebrandt F. Nat. Genet. 34:413-420(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INVS.
[8]	"Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis." Olbrich H., Fliegauf M., Hoefele J., Kispert A., Otto E., Volz A., Wolf M.T., Sasmaz G., Trauer U., Reinhardt R., Sudbrak R., Antignac C., Gretz N., Walz G., Schermer B., Benzing T., Hildebrandt F., Omran H. Nat. Genet. 34:455-459(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NPHP3.
[9]	"Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia." Schermer B., Hoepker K., Omran H., Ghenoiu C., Fliegauf M., Fekete A., Horvath J., Koettgen M., Hackl M., Zschiedrich S., Huber T.B., Kramer-Zucker A., Zentgraf H., Blaukat A., Walz G., Benzing T. EMBO J. 24:4415-4424(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-121; SER-123 AND SER-126, MUTAGENESIS OF SER-121; SER-123 AND SER-126, INTERACTION WITH PACS1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]	"The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome." Parisi M.A., Bennett C.L., Eckert M.L., Dobyns W.B., Gleeson J.G., Shaw D.W.W., McDonald R., Eddy A., Chance P.F., Glass I.A. Am. J. Hum. Genet. 75:82-91(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN JBTS4.
[11]	"Nephrocystin specifically localizes to the transition zone of renal and respiratory cilia and photoreceptor connecting cilia." Fliegauf M., Horvath J., von Schnakenburg C., Olbrich H., Mueller D., Thumfart J., Schermer B., Pazour G.J., Neumann H.P., Zentgraf H., Benzing T., Omran H. J. Am. Soc. Nephrol. 17:2424-2433(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[12]	"Nephrocystin-1 interacts directly with Ack1 and is expressed in human collecting duct." Eley L., Moochhala S.H., Simms R., Hildebrandt F., Sayer J.A. Biochem. Biophys. Res. Commun. 371:877-882(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNK2.
[13]	"Jouberin localizes to collecting ducts and interacts with nephrocystin-1." Eley L., Gabrielides C., Adams M., Johnson C.A., Hildebrandt F., Sayer J.A. Kidney Int. 74:1139-1149(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AHI1.
[14]	"Nephrocystin-1 forms a complex with polycystin-1 via a polyproline motif/SH3 domain interaction and regulates the apoptotic response in mammals." Wodarczyk C., Distefano G., Rowe I., Gaetani M., Bricoli B., Muorah M., Spitaleri A., Mannella V., Ricchiuto P., Pema M., Castelli M., Casanova A.E., Mollica L., Banzi M., Boca M., Antignac C., Saunier S., Musco G., Boletta A. PLoS ONE 5:E12719-E12719(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PKD1, MUTAGENESIS OF PRO-203.
[15]	"Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways." Sang L., Miller J.J., Corbit K.C., Giles R.H., Brauer M.J., Otto E.A., Baye L.M., Wen X., Scales S.J., Kwong M., Huntzicker E.G., Sfakianos M.K., Sandoval W., Bazan J.F., Kulkarni P., Garcia-Gonzalo F.R., Seol A.D., O'Toole J.F. , Held S., Reutter H.M., Lane W.S., Rafiq M.A., Noor A., Ansar M., Devi A.R., Sheffield V.C., Slusarski D.C., Vincent J.B., Doherty D.A., Hildebrandt F., Reiter J.F., Jackson P.K. Cell 145:513-528(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH IQCB1; INVS AND NPHP4.
[16]	"Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylation of nephrocystin-1 to control targeting to monocilia." Liebau M.C., Hopker K., Muller R.U., Schmedding I., Zank S., Schairer B., Fabretti F., Hohne M., Bartram M.P., Dafinger C., Hackl M., Burst V., Habbig S., Zentgraf H., Blaukat A., Walz G., Benzing T., Schermer B. J. Biol. Chem. 286:14237-14245(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTK2B/PYK2, PHOSPHORYLATION AT TYR-46; TYR-349 AND TYR-721.
[17]	"Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics." Dafinger C., Liebau M.C., Elsayed S.M., Hellenbroich Y., Boltshauser E., Korenke G.C., Fabretti F., Janecke A.R., Ebermann I., Nurnberg G., Nurnberg P., Zentgraf H., Koerber F., Addicks K., Elsobky E., Benzing T., Schermer B., Bolz H.J. J. Clin. Invest. 121:2662-2667(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KIF7.
[18]	"Solution NMR structure of the SH3 domain of human nephrocystin and analysis of a mutation-causing juvenile nephronophthisis." le Maire A., Weber T., Saunier S., Broutin I., Antignac C., Ducruix A., Dardel F. Proteins 59:347-355(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 147-212, MUTAGENESIS OF LEU-180.
[19]	"Children with ocular motor apraxia type Cogan carry deletions in the gene (NPHP1) for juvenile nephronophthisis." Betz R., Rensing C., Otto E., Mincheva A., Zehnder D., Lichter P., Hildebrandt F. J. Pediatr. 136:828-831(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NPHP1 ARG-342.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ001815 mRNA. Translation: CAA05030.1.
AF023674 mRNA. Translation: AAC51771.1.
AC013268 Genomic DNA. No translation available.
AC140479 Genomic DNA. No translation available.
BC009789 mRNA. No translation available.
BC062574 mRNA. Translation: AAH62574.1.

IPI

IPI00028739.
IPI00410302.
IPI00843954.
IPI01015576.

RefSeq

NP_000263.2. NM_000272.3.
NP_001121650.1. NM_001128178.1.
NP_001121651.1. NM_001128179.1.
NP_997064.2. NM_207181.2.

UniGene

Hs.280388.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S1N	NMR	-	A	147-212	[»]

ProteinModelPortal

O15259.

ModBase

Search...

Protein-protein interaction databases

IntAct

O15259. 1 interaction.

MINT

MINT-2792475.

STRING

9606.ENSP00000313169.

PTM databases

PhosphoSite

O15259.

Proteomic databases

PaxDb

O15259.

PRIDE

O15259.

Protocols and materials databases

DNASU

4867.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000316534; ENSP00000313169; ENSG00000144061.
ENST00000355301; ENSP00000347452; ENSG00000144061.
ENST00000393272; ENSP00000376953; ENSG00000144061.
ENST00000445609; ENSP00000389879; ENSG00000144061.

GeneID

4867.

KEGG

hsa:4867.

UCSC

uc002tfl.4. human.
uc002tfm.4. human.
uc002tfn.4. human.
uc002tfo.4. human.

Organism-specific databases

CTD

4867.

GeneCards

GC02M110879.

HGNC

HGNC:7905. NPHP1.

HPA

HPA046093.

MIM

256100. phenotype.
266900. phenotype.
607100. gene.
609583. phenotype.

neXtProt

NX_O15259.

Orphanet

655. Autosomal recessive medullary cystic kidney disease.
220497. Joubert syndrome with renal defect.
3156. Senior-Loken syndrome.

PharmGKB

PA31706.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG85120.

HOGENOM

HOG000231753.

HOVERGEN

HBG019088.

OMA

EQTYDFL.

Gene expression databases

ArrayExpress

O15259.

Bgee

O15259.

CleanEx

HS_NPHP1.

Genevestigator

O15259.

GermOnline

ENSG00000144061. Homo sapiens.

Family and domain databases

InterPro

IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00018. SH3_1. 1 hit.
[Graphical view]

SMART

SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.

PROSITE

PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

NPHP1. human.

EvolutionaryTrace

O15259.

GenomeRNAi

4867.

NextBio

18742.

SOURCE

Search...

Entry information

Entry name

NPHP1_HUMAN

Accession

Primary (citable) accession number: O15259
Secondary accession number(s): O14837

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 130 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.