UniProtKB - O15259 (NPHP1_HUMAN)
Nephrocystin-1
NPHP1
Functioni
Miscellaneous
GO - Molecular functioni
- structural molecule activity Source: UniProtKB
GO - Biological processi
- actin cytoskeleton organization Source: UniProtKB
- cell-cell adhesion Source: UniProtKB
- cell projection organization Source: UniProtKB
- ciliary basal body-plasma membrane docking Source: Reactome
- excretion Source: ProtInc
- positive regulation of bicellular tight junction assembly Source: UniProtKB
- protein localization involved in establishment of planar polarity Source: GO_Central
- retina development in camera-type eye Source: UniProtKB
- signal transduction Source: UniProtKB
- spermatid differentiation Source: UniProtKB
- visual behavior Source: UniProtKB
Keywordsi
Biological process | Cilium biogenesis/degradation, Differentiation, Spermatogenesis |
Enzyme and pathway databases
PathwayCommonsi | O15259 |
Reactomei | R-HSA-5620912, Anchoring of the basal body to the plasma membrane |
SignaLinki | O15259 |
SIGNORi | O15259 |
Names & Taxonomyi
Protein namesi | Recommended name: Nephrocystin-1Alternative name(s): Juvenile nephronophthisis 1 protein |
Gene namesi | Name:NPHP1 Synonyms:NPH1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7905, NPHP1 |
MIMi | 607100, gene |
neXtProti | NX_O15259 |
VEuPathDBi | HostDB:ENSG00000144061.12 |
Subcellular locationi
Cytoskeleton
- cilium axoneme 2 Publications
Other locations
- Cell junction By similarity
- adherens junction By similarity
- cilium 1 Publication
- tight junction
Note: In the retinal photoreceptor cell layer, localizes at the connecting cilium (By similarity). Colocalizes with E-cadherin and BCAR1 at or near the cell-cell adherens junctions (By similarity). Localized to respiratory cilia axoneme (PubMed:16308564, PubMed:16885411). Localized to the transition zone of respiratory cilia (PubMed:16885411). Localized to the transition zone of photoreceptor-connecting cilia and renal monocilia (By similarity). In cultured renal cells, it localizes diffusely in the cytoplasm but, as cells approach confluence, it accumulates at basolateral tight junctions (By similarity).By similarity2 Publications
Cytoskeleton
- cytoskeleton Source: UniProtKB-KW
Cytosol
- cytosol Source: Reactome
Other locations
- adherens junction Source: UniProtKB-SubCell
- bicellular tight junction Source: UniProtKB-SubCell
- cell-cell junction Source: UniProtKB
- cilium Source: GO_Central
- cytoplasm Source: GO_Central
- membrane Source: UniProtKB
- motile cilium Source: UniProtKB
- photoreceptor connecting cilium Source: UniProtKB
Keywords - Cellular componenti
Cell junction, Cell projection, Cilium, Cytoplasm, Cytoskeleton, Tight junctionPathology & Biotechi
Involvement in diseasei
Nephronophthisis 1 (NPHP1)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_012160 | 342 | G → 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
Joubert syndrome 4 (JBTS4)2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 121 | S → A: Impairs interaction with PACS1; when associated with A-123 and A-126. 1 Publication | 1 | |
Mutagenesisi | 123 | S → A: Impairs interaction with PACS1; when associated with A-121 and A-126. 1 Publication | 1 | |
Mutagenesisi | 126 | S → A: Impairs interaction with PACS1; when associated with A-121 and A-123. 1 Publication | 1 | |
Mutagenesisi | 180 | L → P: Loss of SH3 domain fold. 1 Publication | 1 | |
Mutagenesisi | 203 | P → 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 | 1 |
Keywords - Diseasei
Ciliopathy, Disease variant, Joubert syndrome, Leber congenital amaurosis, Nephronophthisis, Senior-Loken syndromeOrganism-specific databases
DisGeNETi | 4867 |
GeneReviewsi | NPHP1 |
MalaCardsi | NPHP1 |
MIMi | 256100, phenotype 266900, phenotype 609583, phenotype |
OpenTargetsi | ENSG00000144061 |
Orphaneti | 110, Bardet-Biedl syndrome 220497, Joubert syndrome with renal defect 93592, Juvenile nephronophthisis 3156, Senior-Loken syndrome |
PharmGKBi | PA31706 |
Miscellaneous databases
Pharosi | O15259, Tbio |
Genetic variation databases
BioMutai | NPHP1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000159585 | 1 – 732 | Nephrocystin-1Add BLAST | 732 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 46 | Phosphotyrosine; by FAK21 Publication | 1 | |
Modified residuei | 121 | Phosphoserine; by CK21 Publication | 1 | |
Modified residuei | 123 | Phosphoserine; by CK21 Publication | 1 | |
Modified residuei | 126 | Phosphoserine; by CK21 Publication | 1 | |
Modified residuei | 349 | Phosphotyrosine; by FAK21 Publication | 1 | |
Modified residuei | 721 | Phosphotyrosine; by SRC1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
MassIVEi | O15259 |
PaxDbi | O15259 |
PeptideAtlasi | O15259 |
PRIDEi | O15259 |
ProteomicsDBi | 48545 [O15259-1] 48546 [O15259-2] 48547 [O15259-3] 48548 [O15259-4] |
PTM databases
iPTMneti | O15259 |
PhosphoSitePlusi | O15259 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSG00000144061, Expressed in skeletal muscle tissue and 160 other tissues |
ExpressionAtlasi | O15259, baseline and differential |
Genevisiblei | O15259, HS |
Organism-specific databases
HPAi | ENSG00000144061, Tissue enhanced (skeletal) |
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).
Interacts with SPATA7 (By similarity).
Interacts with FLNA (By similarity).
By similarity10 PublicationsBinary interactionsi
Hide detailsO15259
With | #Exp. | IntAct |
---|---|---|
ADAM15 [Q13444] | 4 | EBI-953828,EBI-77818 |
AHI1 [Q8N157] | 4 | EBI-953828,EBI-1049056 |
NPHP4 [O75161] | 18 | EBI-953828,EBI-4281852 |
PKD1 [P98161] | 2 | EBI-953828,EBI-1752013 |
PTK2B [Q14289] | 2 | EBI-953828,EBI-298640 |
Protein-protein interaction databases
BioGRIDi | 110927, 91 interactors |
CORUMi | O15259 |
IntActi | O15259, 81 interactors |
MINTi | O15259 |
STRINGi | 9606.ENSP00000313169 |
Miscellaneous databases
RNActi | O15259, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O15259 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O15259 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 152 – 212 | SH3PROSITE-ProRule annotationAdd BLAST | 61 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 3 – 105 | Sequence analysisAdd BLAST | 103 | |
Coiled coili | 127 – 150 | Sequence analysisAdd BLAST | 24 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 116 – 147 | Glu-richAdd BLAST | 32 | |
Compositional biasi | 212 – 227 | Glu-richAdd BLAST | 16 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Coiled coil, SH3 domainPhylogenomic databases
eggNOGi | ENOG502QU7K, Eukaryota |
GeneTreei | ENSGT00390000007701 |
HOGENOMi | CLU_024987_1_0_1 |
InParanoidi | O15259 |
OMAi | SHYIQPE |
OrthoDBi | 676699at2759 |
PhylomeDBi | O15259 |
TreeFami | TF320679 |
Family and domain databases
CDDi | cd11770, SH3_Nephrocystin, 1 hit |
InterProi | View protein in InterPro IPR039687, NPHP1 IPR030642, NPHP1_SH3 IPR036028, SH3-like_dom_sf IPR001452, SH3_domain |
PANTHERi | PTHR15176:SF1, PTHR15176:SF1, 1 hit |
Pfami | View protein in Pfam PF00018, SH3_1, 1 hit |
SMARTi | View protein in SMART SM00326, SH3, 1 hit |
SUPFAMi | SSF50044, SSF50044, 1 hit |
PROSITEi | View protein in PROSITE PS50002, SH3, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9J082 | C9J082_HUMAN | Nephrocystin-1 | NPHP1 hCG_1988612 | 121 | Annotation score: | ||
C9JNM7 | C9JNM7_HUMAN | Nephrocystin-1 | NPHP1 | 711 | Annotation score: | ||
A0A6Q8PGI7 | A0A6Q8PGI7_HUMAN | Nephrocystin-1 | NPHP1 | 609 | Annotation score: | ||
A0A6Q8PHD4 | A0A6Q8PHD4_HUMAN | Nephrocystin-1 | NPHP1 | 616 | Annotation score: | ||
H7C2K4 | H7C2K4_HUMAN | Nephrocystin-1 | NPHP1 | 45 | Annotation score: | ||
A0A6Q8PH10 | A0A6Q8PH10_HUMAN | Nephrocystin-1 | NPHP1 | 409 | Annotation score: | ||
H7C014 | H7C014_HUMAN | Nephrocystin-1 | NPHP1 | 47 | Annotation score: | ||
A0A6Q8PHS3 | A0A6Q8PHS3_HUMAN | Nephrocystin-1 | NPHP1 hCG_1988612 | 410 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077633 | 5 | R → L 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_012160 | 342 | G → R in NPHP1; associated with Cogan-type congenital ocular motor apraxia. 1 PublicationCorresponds to variant dbSNP:rs121907899Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010073 | 49 – 110 | Missing in isoform 3. 1 PublicationAdd BLAST | 62 | |
Alternative sequenceiVSP_010074 | 258 – 313 | Missing in isoform 3. 1 PublicationAdd BLAST | 56 | |
Alternative sequenceiVSP_003424 | 258 – 312 | Missing in isoform 2. 1 PublicationAdd BLAST | 55 | |
Alternative sequenceiVSP_024381 | 313 | Q → QQ in isoform 4. 1 Publication | 1 |
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 |
CCDSi | CCDS2086.1 [O15259-4] CCDS46384.1 [O15259-3] CCDS46385.1 [O15259-1] CCDS46386.1 [O15259-2] |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000316534; ENSP00000313169; ENSG00000144061 [O15259-4] ENST00000355301; ENSP00000347452; ENSG00000144061 [O15259-3] ENST00000393272; ENSP00000376953; ENSG00000144061 [O15259-1] ENST00000445609; ENSP00000389879; ENSG00000144061 [O15259-2] ENST00000676053; ENSP00000502475; ENSG00000144061 [O15259-3] |
GeneIDi | 4867 |
KEGGi | hsa:4867 |
UCSCi | uc002tfl.6, human [O15259-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS2086.1 [O15259-4] CCDS46384.1 [O15259-3] CCDS46385.1 [O15259-1] CCDS46386.1 [O15259-2] |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1S1N | NMR | - | A | 147-212 | [»] | |
6O1Q | NMR | - | A | 1-115 | [»] | |
SMRi | O15259 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110927, 91 interactors |
CORUMi | O15259 |
IntActi | O15259, 81 interactors |
MINTi | O15259 |
STRINGi | 9606.ENSP00000313169 |
PTM databases
iPTMneti | O15259 |
PhosphoSitePlusi | O15259 |
Genetic variation databases
BioMutai | NPHP1 |
Proteomic databases
MassIVEi | O15259 |
PaxDbi | O15259 |
PeptideAtlasi | O15259 |
PRIDEi | O15259 |
ProteomicsDBi | 48545 [O15259-1] 48546 [O15259-2] 48547 [O15259-3] 48548 [O15259-4] |
Protocols and materials databases
ABCDi | O15259, 1 sequenced antibody |
Antibodypediai | 18009, 146 antibodies |
DNASUi | 4867 |
Genome annotation databases
Ensembli | ENST00000316534; ENSP00000313169; ENSG00000144061 [O15259-4] ENST00000355301; ENSP00000347452; ENSG00000144061 [O15259-3] ENST00000393272; ENSP00000376953; ENSG00000144061 [O15259-1] ENST00000445609; ENSP00000389879; ENSG00000144061 [O15259-2] ENST00000676053; ENSP00000502475; ENSG00000144061 [O15259-3] |
GeneIDi | 4867 |
KEGGi | hsa:4867 |
UCSCi | uc002tfl.6, human [O15259-1] |
Organism-specific databases
CTDi | 4867 |
DisGeNETi | 4867 |
GeneCardsi | NPHP1 |
GeneReviewsi | NPHP1 |
HGNCi | HGNC:7905, NPHP1 |
HPAi | ENSG00000144061, Tissue enhanced (skeletal) |
MalaCardsi | NPHP1 |
MIMi | 256100, phenotype 266900, phenotype 607100, gene 609583, phenotype |
neXtProti | NX_O15259 |
OpenTargetsi | ENSG00000144061 |
Orphaneti | 110, Bardet-Biedl syndrome 220497, Joubert syndrome with renal defect 93592, Juvenile nephronophthisis 3156, Senior-Loken syndrome |
PharmGKBi | PA31706 |
VEuPathDBi | HostDB:ENSG00000144061.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QU7K, Eukaryota |
GeneTreei | ENSGT00390000007701 |
HOGENOMi | CLU_024987_1_0_1 |
InParanoidi | O15259 |
OMAi | SHYIQPE |
OrthoDBi | 676699at2759 |
PhylomeDBi | O15259 |
TreeFami | TF320679 |
Enzyme and pathway databases
PathwayCommonsi | O15259 |
Reactomei | R-HSA-5620912, Anchoring of the basal body to the plasma membrane |
SignaLinki | O15259 |
SIGNORi | O15259 |
Miscellaneous databases
BioGRID-ORCSi | 4867, 11 hits in 988 CRISPR screens |
ChiTaRSi | NPHP1, human |
EvolutionaryTracei | O15259 |
GeneWikii | NPHP1 |
GenomeRNAii | 4867 |
Pharosi | O15259, Tbio |
PROi | PR:O15259 |
RNActi | O15259, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000144061, Expressed in skeletal muscle tissue and 160 other tissues |
ExpressionAtlasi | O15259, baseline and differential |
Genevisiblei | O15259, HS |
Family and domain databases
CDDi | cd11770, SH3_Nephrocystin, 1 hit |
InterProi | View protein in InterPro IPR039687, NPHP1 IPR030642, NPHP1_SH3 IPR036028, SH3-like_dom_sf IPR001452, SH3_domain |
PANTHERi | PTHR15176:SF1, PTHR15176:SF1, 1 hit |
Pfami | View protein in Pfam PF00018, SH3_1, 1 hit |
SMARTi | View protein in SMART SM00326, SH3, 1 hit |
SUPFAMi | SSF50044, SSF50044, 1 hit |
PROSITEi | View protein in PROSITE PS50002, SH3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NPHP1_HUMAN | |
Accessioni | O15259Primary (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: | April 7, 2021 | |
This is version 196 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - 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