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UniProtKB - O15259 (NPHP1_HUMAN)

Protein

Nephrocystin-1

Gene

NPHP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

GO - Molecular functioni

  • structural molecule activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processCilium 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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000144061.12
HGNCiHGNC:7905 NPHP1
MIMi607100 gene
neXtProtiNX_O15259

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_012160342G → R in NPHP1; associated with Cogan-type congenital ocular motor apraxia. 1 PublicationCorresponds to variant dbSNP:rs121907899Ensembl.1
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)DescriptionActionsGraphical viewLength
Mutagenesisi121S → A: Impairs interaction with PACS1; when associated with A-123 and A-126. 1 Publication1
Mutagenesisi123S → A: Impairs interaction with PACS1; when associated with A-121 and A-126. 1 Publication1
Mutagenesisi126S → A: Impairs interaction with PACS1; when associated with A-121 and A-123. 1 Publication1
Mutagenesisi180L → P: Loss of SH3 domain fold. 1 Publication1
Mutagenesisi203P → L: Does not affect fold stability, as assessed by circular dichroism thermal denaturation melting curves and by NMR spectroscopy. Affects interaction with PKD1. 1 Publication1

Keywords - Diseasei

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

Organism-specific databases

DisGeNETi4867
GeneReviewsiNPHP1
MalaCardsiNPHP1
MIMi256100 phenotype
266900 phenotype
609583 phenotype
OpenTargetsiENSG00000144061
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)DescriptionActionsGraphical viewLength
ChainiPRO_00001595851 – 732Nephrocystin-1Add BLAST732

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei46Phosphotyrosine; by FAK21 Publication1
Modified residuei121Phosphoserine; by CK21 Publication1
Modified residuei123Phosphoserine; by CK21 Publication1
Modified residuei126Phosphoserine; by CK21 Publication1
Modified residuei349Phosphotyrosine; by FAK21 Publication1
Modified residuei721Phosphotyrosine; by SRC1 Publication1

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
ProteomicsDBi48545
48546 [O15259-2]
48547 [O15259-3]
48548 [O15259-4]

PTM databases

iPTMnetiO15259
PhosphoSitePlusiO15259

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 Expressed in 140 organ(s), highest expression level in muscle of leg
CleanExiHS_NPHP1
ExpressionAtlasiO15259 baseline and differential
GenevisibleiO15259 HS

Organism-specific databases

HPAiHPA046093
HPA074071

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

Protein-protein interaction databases

BioGridi110927, 85 interactors
CORUMiO15259
IntActiO15259, 75 interactors
MINTiO15259
STRINGi9606.ENSP00000313169

Structurei

Secondary structure

1732
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO15259
SMRiO15259
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15259

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini152 – 212SH3PROSITE-ProRule annotationAdd BLAST61

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili3 – 105Sequence analysisAdd BLAST103
Coiled coili127 – 150Sequence analysisAdd BLAST24

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi116 – 147Glu-richAdd BLAST32
Compositional biasi212 – 227Glu-richAdd BLAST16

Domaini

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

Sequence similaritiesi

Belongs to the nephrocystin-1 family.Curated

Keywords - Domaini

Coiled coil, SH3 domain

Phylogenomic databases

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

Family and domain databases

CDDicd11770 SH3_Nephrocystin, 1 hit
InterProiView protein in InterPro
IPR039687 NPHP1
IPR030642 NPHP1_SH3
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR15176 PTHR15176, 1 hit
PfamiView protein in Pfam
PF00018 SH3_1, 1 hit
SMARTiView protein in SMART
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS50002 SH3, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JNM7C9JNM7_HUMAN
Nephrocystin-1
NPHP1
711Annotation score:
C9J082C9J082_HUMAN
Nephrocystin-1
NPHP1 hCG_1988612
121Annotation score:
H7C014H7C014_HUMAN
Nephrocystin-1
NPHP1
47Annotation score:
H7C2K4H7C2K4_HUMAN
Nephrocystin-1
NPHP1
45Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0776335R → L Functional polymorphism; changed function; unable to rescue the corresponding loss of function zebrafish mutant which displays a cilium function alteration phenotype. 1 PublicationCorresponds to variant dbSNP:rs190983114EnsemblClinVar.1
Natural variantiVAR_012160342G → R in NPHP1; associated with Cogan-type congenital ocular motor apraxia. 1 PublicationCorresponds to variant dbSNP:rs121907899Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01007349 – 110Missing in isoform 3. 1 PublicationAdd BLAST62
Alternative sequenceiVSP_010074258 – 313Missing in isoform 3. 1 PublicationAdd BLAST56
Alternative sequenceiVSP_003424258 – 312Missing in isoform 2. 1 PublicationAdd BLAST55
Alternative sequenceiVSP_024381313Q → QQ in isoform 4. 1 Publication1

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, Polymorphism

Similar proteinsi

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S1NNMR-A147-212[»]
ProteinModelPortaliO15259
SMRiO15259
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110927, 85 interactors
CORUMiO15259
IntActiO15259, 75 interactors
MINTiO15259
STRINGi9606.ENSP00000313169

PTM databases

iPTMnetiO15259
PhosphoSitePlusiO15259

Polymorphism and mutation databases

BioMutaiNPHP1

Proteomic databases

PaxDbiO15259
PeptideAtlasiO15259
PRIDEiO15259
ProteomicsDBi48545
48546 [O15259-2]
48547 [O15259-3]
48548 [O15259-4]

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
DisGeNETi4867
EuPathDBiHostDB:ENSG00000144061.12
GeneCardsiNPHP1
GeneReviewsiNPHP1
HGNCiHGNC:7905 NPHP1
HPAiHPA046093
HPA074071
MalaCardsiNPHP1
MIMi256100 phenotype
266900 phenotype
607100 gene
609583 phenotype
neXtProtiNX_O15259
OpenTargetsiENSG00000144061
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
OMAiARWKVIT
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
PROiPR:O15259
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144061 Expressed in 140 organ(s), highest expression level in muscle of leg
CleanExiHS_NPHP1
ExpressionAtlasiO15259 baseline and differential
GenevisibleiO15259 HS

Family and domain databases

CDDicd11770 SH3_Nephrocystin, 1 hit
InterProiView protein in InterPro
IPR039687 NPHP1
IPR030642 NPHP1_SH3
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR15176 PTHR15176, 1 hit
PfamiView protein in Pfam
PF00018 SH3_1, 1 hit
SMARTiView protein in SMART
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNPHP1_HUMAN
AccessioniPrimary (citable) accession number: O15259
Secondary accession number(s): O14837
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 179 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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