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Protein

Nephrocystin-1

Gene

NPHP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  • structural molecule activity Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton organization Source: UniProtKB
  • cell projection organization Source: UniProtKB
  • excretion Source: ProtInc
  • retina development in camera-type eye Source: UniProtKB
  • signal transduction Source: UniProtKB
  • single organismal cell-cell adhesion Source: UniProtKB
  • spermatid differentiation Source: UniProtKB
  • visual behavior Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cilium biogenesis/degradation, Differentiation, Spermatogenesis

Enzyme and pathway databases

ReactomeiR-HSA-5620912. Anchoring of the basal body to the plasma membrane.
SignaLinkiO15259.
SIGNORiO15259.

Names & Taxonomyi

Protein namesi
Recommended name:
Nephrocystin-1
Alternative name(s):
Juvenile nephronophthisis 1 protein
Gene namesi
Name:NPHP1
Synonyms:NPH1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:7905. NPHP1.

Subcellular locationi

GO - Cellular componenti

  • adherens junction Source: UniProtKB-SubCell
  • bicellular tight junction Source: UniProtKB-SubCell
  • cell-cell junction Source: UniProtKB
  • cytoskeleton Source: UniProtKB-KW
  • cytosol Source: Reactome
  • membrane Source: UniProtKB
  • motile cilium Source: UniProtKB
  • photoreceptor connecting cilium Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell projection, Cilium, Cytoplasm, Cytoskeleton, Tight junction

Pathology & Biotechi

Involvement in diseasei

Nephronophthisis 1 (NPHP1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:256100
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti342 – 3421G → R in NPHP1; associated with Cogan-type congenital ocular motor apraxia. 1 Publication
Corresponds to variant rs121907899 [ dbSNP | Ensembl ].
VAR_012160
Senior-Loken syndrome 1 (SLSN1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:266900
Joubert syndrome 4 (JBTS4)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:609583

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi121 – 1211S → A: Impairs interaction with PACS1; when associated with A-123 and A-126. 1 Publication
Mutagenesisi123 – 1231S → A: Impairs interaction with PACS1; when associated with A-121 and A-126. 1 Publication
Mutagenesisi126 – 1261S → A: Impairs interaction with PACS1; when associated with A-121 and A-123. 1 Publication
Mutagenesisi180 – 1801L → P: Loss of SH3 domain fold. 1 Publication
Mutagenesisi203 – 2031P → L: Does not affect fold stability, as assessed by circular dichroism thermal denaturation melting curves and by NMR spectroscopy. Affects interaction with PKD1. 1 Publication

Keywords - Diseasei

Ciliopathy, Disease mutation, Joubert syndrome, Nephronophthisis, Senior-Loken syndrome

Organism-specific databases

MalaCardsiNPHP1.
MIMi256100. phenotype.
266900. phenotype.
609583. phenotype.
Orphaneti110. Bardet-Biedl syndrome.
220497. Joubert syndrome with renal defect.
93592. Juvenile nephronophthisis.
3156. Senior-Loken syndrome.
PharmGKBiPA31706.

Polymorphism and mutation databases

BioMutaiNPHP1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 732732Nephrocystin-1PRO_0000159585Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei46 – 461Phosphotyrosine; by FAK21 Publication
Modified residuei121 – 1211Phosphoserine; by CK21 Publication
Modified residuei123 – 1231Phosphoserine; by CK21 Publication
Modified residuei126 – 1261Phosphoserine; by CK21 Publication
Modified residuei349 – 3491Phosphotyrosine; by FAK21 Publication
Modified residuei721 – 7211Phosphotyrosine; by SRC1 Publication

Post-translational modificationi

Phosphorylation by CK2 is required for the interaction with PACS1 and the targeting to the base region of cilia.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO15259.
PeptideAtlasiO15259.
PRIDEiO15259.

PTM databases

iPTMnetiO15259.
PhosphoSiteiO15259.

Expressioni

Tissue specificityi

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).1 Publication

Developmental stagei

During in vitro ciliogenesis translocalizes from the cytoplasm to the ciliary transition zone during epithelial cell polarization.1 Publication

Gene expression databases

BgeeiENSG00000144061.
CleanExiHS_NPHP1.
ExpressionAtlasiO15259. baseline and differential.
GenevisibleiO15259. HS.

Organism-specific databases

HPAiHPA046093.

Interactioni

Subunit structurei

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. Interacts with ANKS3 (By similarity).By similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ADAM15Q134442EBI-953828,EBI-77818
AHI1Q8N1574EBI-953828,EBI-1049056
PKD1P981612EBI-953828,EBI-1752013

Protein-protein interaction databases

BioGridi110927. 85 interactions.
IntActiO15259. 74 interactions.
MINTiMINT-2792475.
STRINGi9606.ENSP00000313169.

Structurei

Secondary structure

1
732
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi155 – 1595Combined sources
Beta strandi166 – 1694Combined sources
Beta strandi175 – 1817Combined sources
Beta strandi186 – 1938Combined sources
Beta strandi195 – 1973Combined sources
Beta strandi199 – 2046Combined sources
Beta strandi207 – 2093Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1S1NNMR-A147-212[»]
ProteinModelPortaliO15259.
SMRiO15259. Positions 153-212.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15259.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini152 – 21261SH3PROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili3 – 105103Sequence analysisAdd
BLAST
Coiled coili127 – 15024Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi116 – 14732Glu-richAdd
BLAST
Compositional biasi212 – 22716Glu-richAdd
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the nephrocystin-1 family.Curated
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, SH3 domain

Phylogenomic databases

eggNOGiENOG410IE0Z. Eukaryota.
ENOG410XPXZ. LUCA.
GeneTreeiENSGT00390000007701.
HOGENOMiHOG000231753.
HOVERGENiHBG019088.
InParanoidiO15259.
KOiK19657.
OMAiEGNQFRA.
OrthoDBiEOG091G05R3.
PhylomeDBiO15259.
TreeFamiTF320679.

Family and domain databases

InterProiIPR030642. NPHP1.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR15176:SF1. PTHR15176:SF1. 1 hit.
PfamiPF00018. SH3_1. 1 hit.
[Graphical view]
SMARTiSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
PROSITEiPS50002. SH3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15259-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MLARRQRDPL QALRRRNQEL KQQVDSLLSE SQLKEALEPN KRQHIYQRCI
60 70 80 90 100
QLKQAIDENK NALQKLSKAD ESAPVANYNQ RKEEEHTLLD KLTQQLQGLA
110 120 130 140 150
VTISRENITE VGAPTEEEEE SESEDSEDSG GEEEDAEEEE EEKEENESHK
160 170 180 190 200
WSTGEEYIAV GDFTAQQVGD LTFKKGEILL VIEKKPDGWW IAKDAKGNEG
210 220 230 240 250
LVPRTYLEPY SEEEEGQESS EEGSEEDVEA VDETADGAEV KQRTDPHWSA
260 270 280 290 300
VQKAISEAGI FCLVNHVSFC YLIVLMRNRM ETVEDTNGSE TGFRAWNVQS
310 320 330 340 350
RGRIFLVSKP VLQINTVDVL TTMGAIPAGF RPSTLSQLLE EGNQFRANYF
360 370 380 390 400
LQPELMPSQL AFRDLMWDAT EGTIRSRPSR ISLILTLWSC KMIPLPGMSI
410 420 430 440 450
QVLSRHVRLC LFDGNKVLSN IHTVRATWQP KKPKTWTFSP QVTRILPCLL
460 470 480 490 500
DGDCFIRSNS ASPDLGILFE LGISYIRNST GERGELSCGW VFLKLFDASG
510 520 530 540 550
VPIPAKTYEL FLNGGTPYEK GIEVDPSISR RAHGSVFYQI MTMRRQPQLL
560 570 580 590 600
VKLRSLNRRS RNVLSLLPET LIGNMCSIHL LIFYRQILGD VLLKDRMSLQ
610 620 630 640 650
STDLISHPML ATFPMLLEQP DVMDALRSSW AGKESTLKRS EKRDKEFLKS
660 670 680 690 700
TFLLVYHDCV LPLLHSTRLP PFRWAEEETE TARWKVITDF LKQNQENQGA
710 720 730
LQALLSPDGV HEPFDLSEQT YDFLGEMRKN AV
Length:732
Mass (Da):83,299
Last modified:January 1, 1998 - v1
Checksum:i270125F56F2C50F7
GO
Isoform 2 (identifier: O15259-2) [UniParc]FASTAAdd to basket
Also known as: NPHP1-8A

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

Show »
Length:677
Mass (Da):77,041
Checksum:iEB4C60DC4967021D
GO
Isoform 3 (identifier: O15259-3) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:614
Mass (Da):69,909
Checksum:iBBBDED56BF312D45
GO
Isoform 4 (identifier: O15259-4) [UniParc]FASTAAdd to basket

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

Show »
Length:733
Mass (Da):83,428
Checksum:iB3222151828658D8
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti342 – 3421G → R in NPHP1; associated with Cogan-type congenital ocular motor apraxia. 1 Publication
Corresponds to variant rs121907899 [ dbSNP | Ensembl ].
VAR_012160

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei49 – 11062Missing in isoform 3. 1 PublicationVSP_010073Add
BLAST
Alternative sequencei258 – 31356Missing in isoform 3. 1 PublicationVSP_010074Add
BLAST
Alternative sequencei258 – 31255Missing in isoform 2. 1 PublicationVSP_003424Add
BLAST
Alternative sequencei313 – 3131Q → QQ in isoform 4. 1 PublicationVSP_024381

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2086.1. [O15259-4]
CCDS46384.1. [O15259-3]
CCDS46385.1. [O15259-1]
CCDS46386.1. [O15259-2]
RefSeqiNP_000263.2. NM_000272.3. [O15259-4]
NP_001121650.1. NM_001128178.1. [O15259-2]
NP_001121651.1. NM_001128179.1. [O15259-3]
NP_997064.2. NM_207181.2. [O15259-1]
UniGeneiHs.280388.

Genome annotation databases

EnsembliENST00000316534; ENSP00000313169; ENSG00000144061. [O15259-4]
ENST00000355301; ENSP00000347452; ENSG00000144061. [O15259-3]
ENST00000393272; ENSP00000376953; ENSG00000144061. [O15259-1]
ENST00000445609; ENSP00000389879; ENSG00000144061. [O15259-2]
GeneIDi4867.
KEGGihsa:4867.
UCSCiuc002tfl.6. human. [O15259-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2086.1. [O15259-4]
CCDS46384.1. [O15259-3]
CCDS46385.1. [O15259-1]
CCDS46386.1. [O15259-2]
RefSeqiNP_000263.2. NM_000272.3. [O15259-4]
NP_001121650.1. NM_001128178.1. [O15259-2]
NP_001121651.1. NM_001128179.1. [O15259-3]
NP_997064.2. NM_207181.2. [O15259-1]
UniGeneiHs.280388.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1S1NNMR-A147-212[»]
ProteinModelPortaliO15259.
SMRiO15259. Positions 153-212.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110927. 85 interactions.
IntActiO15259. 74 interactions.
MINTiMINT-2792475.
STRINGi9606.ENSP00000313169.

PTM databases

iPTMnetiO15259.
PhosphoSiteiO15259.

Polymorphism and mutation databases

BioMutaiNPHP1.

Proteomic databases

PaxDbiO15259.
PeptideAtlasiO15259.
PRIDEiO15259.

Protocols and materials databases

DNASUi4867.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316534; ENSP00000313169; ENSG00000144061. [O15259-4]
ENST00000355301; ENSP00000347452; ENSG00000144061. [O15259-3]
ENST00000393272; ENSP00000376953; ENSG00000144061. [O15259-1]
ENST00000445609; ENSP00000389879; ENSG00000144061. [O15259-2]
GeneIDi4867.
KEGGihsa:4867.
UCSCiuc002tfl.6. human. [O15259-1]

Organism-specific databases

CTDi4867.
GeneCardsiNPHP1.
GeneReviewsiNPHP1.
HGNCiHGNC:7905. NPHP1.
HPAiHPA046093.
MalaCardsiNPHP1.
MIMi256100. phenotype.
266900. phenotype.
607100. gene.
609583. phenotype.
neXtProtiNX_O15259.
Orphaneti110. Bardet-Biedl syndrome.
220497. Joubert syndrome with renal defect.
93592. Juvenile nephronophthisis.
3156. Senior-Loken syndrome.
PharmGKBiPA31706.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE0Z. Eukaryota.
ENOG410XPXZ. LUCA.
GeneTreeiENSGT00390000007701.
HOGENOMiHOG000231753.
HOVERGENiHBG019088.
InParanoidiO15259.
KOiK19657.
OMAiEGNQFRA.
OrthoDBiEOG091G05R3.
PhylomeDBiO15259.
TreeFamiTF320679.

Enzyme and pathway databases

ReactomeiR-HSA-5620912. Anchoring of the basal body to the plasma membrane.
SignaLinkiO15259.
SIGNORiO15259.

Miscellaneous databases

ChiTaRSiNPHP1. human.
EvolutionaryTraceiO15259.
GeneWikiiNPHP1.
GenomeRNAii4867.
PROiO15259.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144061.
CleanExiHS_NPHP1.
ExpressionAtlasiO15259. baseline and differential.
GenevisibleiO15259. HS.

Family and domain databases

InterProiIPR030642. NPHP1.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR15176:SF1. PTHR15176:SF1. 1 hit.
PfamiPF00018. SH3_1. 1 hit.
[Graphical view]
SMARTiSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
PROSITEiPS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNPHP1_HUMAN
AccessioniPrimary (citable) accession number: O15259
Secondary accession number(s): O14837
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: January 1, 1998
Last modified: September 7, 2016
This is version 162 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Miscellaneousi

Miscellaneous

Nephronophthisis type 1 patients deficient for NPHP1 show normal overall integrity of respiratory cilia.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.