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Reviewed, UniProtKB/Swiss-Prot O15259 (NPHP1_HUMAN)

Last modified March 2, 2010. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
Nephrocystin-1
Alternative name(s):
Juvenile nephronophthisis 1 protein
Gene names
Name:NPHP1
Synonyms:NPH1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length732 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Together with Cas it may play a role in the control of epithelial cell polarity. Seems to help to recruit protein tyrosine kinase 2 beta (PTK2B) to cell matrix adhesions, thereby initiating phosphorylation of PTK2B and PTK2B-dependent signaling By similarity.

Subunit structure

Interacts with Crk-associated substrate (Cas), NPHP4, PTK2B and tensin. Interacts with INVS and NPHP3. Ref.4 Ref.5

Subcellular location

Cell junction › adherens junction By similarity. Note: Localizes at or near the cell-cell adherens junctions By similarity.

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.

Domain

The SH3 domain mediates the stable interaction with Cas By similarity.

Involvement in disease

Defects in NPHP1 are the cause of nephronophthisis type 1 (NPHP1) [MIM:256100]; also known as familial juvenile nephronophthisis 1. NPHP1 is 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. Ref.7

Defects in NPHP1 are the cause of Senior-Loken syndrome type 1 (SLSN1) [MIM:266900]; also known as juvenile nephronophthisis with Leber amaurosis. SLSN is a renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney, with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. Ref.6

Defects in NPHP1 are the cause of Joubert syndrome type 4 (JBTS4) [MIM:609583]. JBTS is an autosomal recessive 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. JBTS4 is a phenotypically mild form. Ref.8

Sequence similarities

Belongs to the nephrocystin-1 family.

Contains 1 SH3 domain.

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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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 732732Nephrocystin-1
PRO_0000159585

Regions

Domain152 – 21261SH3
Coiled coil3 – 105103 Potential
Coiled coil127 – 15024 Potential
Compositional bias116 – 14732Glu-rich
Compositional bias212 – 22716Glu-rich

Natural variations

Alternative sequence49 – 11062Missing in isoform 3.
VSP_010073
Alternative sequence258 – 31356Missing in isoform 3.
VSP_010074
Alternative sequence258 – 31255Missing in isoform 2.
VSP_003424
Alternative sequence3131Q → QQ in isoform 4.
VSP_024381
Natural variant3421G → R in NPHP1; associated with Cogan-type congenital ocular motor apraxia. Ref.7
VAR_012160

Secondary structure

1 ............... 732
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (NPHP1) [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 270125F56F2C50F7

FASTA73283,299
        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

« Hide

Isoform 2 (NPHP1-8A).

Checksum: EB4C60DC4967021D
Show »

FASTA67777,041
Isoform 3.

Checksum: BBBDED56BF312D45
Show »

FASTA61469,909
Isoform 4.

Checksum: B3222151828658D8
Show »

FASTA73383,428

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References

« Hide '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: 9361039] [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: 9326933] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-732 (ISOFORM 4), ALTERNATIVE SPLICING.
[3]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]"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. expand/collapse author list , Walz G., Drummond I.A., Benzing T., Hildebrandt F.
Nat. Genet. 34:413-420(2003) [PubMed: 12872123] [Abstract]
Cited for: INTERACTION WITH INVS.
[5]"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: 12872122] [Abstract]
Cited for: INTERACTION WITH NPHP3.
[6]"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: 9856524] [Abstract]
Cited for: INVOLVEMENT IN SLSN1.
[7]"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: 10839884] [Abstract]
Cited for: VARIANT NPHP1 ARG-342.
[8]"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: 15138899] [Abstract]
Cited for: INVOLVEMENT IN JBTS4.
+Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AJ001815 mRNA. Translation: CAA05030.1.
AF023674 mRNA. Translation: AAC51771.1.
BC009789 mRNA. No translation available.
BC062574 mRNA. Translation: AAH62574.1.
IPIIPI00028739.
IPI00218974.
IPI00410302.
IPI00843954.
RefSeqNP_000263.2.
NP_001121650.1.
NP_001121651.1.
NP_997064.2.
UniGeneHs.280388

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S1NNMR-A147-212[»]
ModBaseSearch...

Protein-protein interaction databases

IntActO15259. 1 interaction.
STRINGO15259.

Proteomic databases

PRIDEO15259.

Genome annotation databases

EnsemblENST00000393272; ENSP00000376953; ENSG00000144061; Homo sapiens. [Genome view]
GeneID4867.
KEGGhsa:4867.
UCSCuc002tfl.2. human.
uc002tfm.2. human.
uc002tfn.2. human.
uc002tfo.2. human.

Organism-specific databases

CTD4867.
GeneCardsGC02M110237.
H-InvDBHIX0023912.
HGNCHGNC:7905. NPHP1.
MIM256100. phenotype.
266900. phenotype.
607100. gene.
609583. phenotype.
Orphanet475. Joubert syndrome.
655. Medullary cystic kidney disease, autosomal recessive.
3156. Senior-Loken syndrome.
PharmGKBPA31706.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG13493.
HOVERGENHBG019088.
OMAEQTYDFL.
OrthoDBEOG97Q0SB.
PhylomeDBO15259.

Gene expression databases

ArrayExpressO15259.
BgeeO15259.
CleanExHS_NPHP1.
GenevestigatorO15259.
GermOnlineENSG00000144061. Homo sapiens.

Family and domain databases

InterProIPR001452. SH3_domain.
[Graphical view]
PfamPF00018. SH3_1. 1 hit.
[Graphical view]
SMARTSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SH3. 1 hit.
PROSITEPS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio18742.
SOURCESearch...

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Entry information

Entry nameNPHP1_HUMAN
AccessionPrimary (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: March 2, 2010
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

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Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents