UniProtKB - Q9P278 (FNIP2_HUMAN)
Folliculin-interacting protein 2
FNIP2
Functioni
Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:18663353, PubMed:31672913).
In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (PubMed:31672913).
Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (PubMed:31672913).
Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726).
In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:18403135).
Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:18403135).
Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:18403135).
May play a role in the signal transduction pathway of apoptosis induced by O6-methylguanine-mispaired lesions (By similarity).
By similarity4 PublicationsGO - Molecular functioni
- ATPase inhibitor activity Source: UniProtKB
- chaperone binding Source: UniProtKB
GO - Biological processi
- intrinsic apoptotic signaling pathway in response to DNA damage Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
- positive regulation of protein-containing complex assembly Source: ParkinsonsUK-UCL
- protein phosphorylation Source: UniProtKB
- regulation of protein phosphorylation Source: UniProtKB
Keywordsi
Biological process | DNA damage |
Enzyme and pathway databases
PathwayCommonsi | Q9P278 |
Reactomei | R-HSA-9639288, Amino acids regulate mTORC1 |
SignaLinki | Q9P278 |
SIGNORi | Q9P278 |
Names & Taxonomyi
Protein namesi | Recommended name: Folliculin-interacting protein 21 PublicationAlternative name(s): FNIP1-like protein1 Publication O6-methylguanine-induced apoptosis 1 protein1 Publication |
Gene namesi | Name:FNIP21 PublicationImported Synonyms:FNIPL1 Publication, KIAA14501 Publication, MAPO11 Publication |
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:29280, FNIP2 |
MIMi | 612768, gene |
neXtProti | NX_Q9P278 |
VEuPathDBi | HostDB:ENSG00000052795 |
Subcellular locationi
Lysosome
- Lysosome membrane 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 3 Publications
Note: Colocalizes with FLCN in the cytoplasm.2 Publications
Cytoskeleton
- centriolar satellite Source: HPA
Cytosol
- cytosol Source: HPA
Lysosome
- lysosomal membrane Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Lysosome, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 57600 |
OpenTargetsi | ENSG00000052795 |
PharmGKBi | PA162388758 |
Miscellaneous databases
Pharosi | Q9P278, Tbio |
Genetic variation databases
BioMutai | FNIP2 |
DMDMi | 189035874 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000320553 | 1 – 1114 | Folliculin-interacting protein 2Add BLAST | 1114 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 216 | PhosphoserineCombined sources | 1 | |
Modified residuei | 221 | PhosphoserineCombined sources | 1 | |
Modified residuei | 723 | PhosphoserineCombined sources | 1 | |
Modified residuei | 726 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9P278 |
jPOSTi | Q9P278 |
MassIVEi | Q9P278 |
MaxQBi | Q9P278 |
PaxDbi | Q9P278 |
PeptideAtlasi | Q9P278 |
PRIDEi | Q9P278 |
ProteomicsDBi | 83745 [Q9P278-1] 83746 [Q9P278-2] |
PTM databases
iPTMneti | Q9P278 |
PhosphoSitePlusi | Q9P278 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000052795, Expressed in kidney epithelium and 222 other tissues |
ExpressionAtlasi | Q9P278, baseline and differential |
Genevisiblei | Q9P278, HS |
Organism-specific databases
HPAi | ENSG00000052795, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer and homomultimer (PubMed:18403135, PubMed:27353360). Heterodimer and heteromultimer with FNIP1 (PubMed:18403135, PubMed:27353360).
Interacts (via C-terminus) with FLCN (via C-terminus) (PubMed:18403135, PubMed:18663353, PubMed:27353360). Phosphorylated FLCN is preferentially bound (PubMed:18663353).
Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound, and Ragulator (PubMed:31704029, PubMed:31672913).
Interacts with PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase (PubMed:18403135, PubMed:27353360).
Interacts with HSP70, HSP90AA1, STIP1, PTGES3, CDC37, BRAF, GCR and CDK4 (PubMed:27353360).
5 PublicationsBinary interactionsi
GO - Molecular functioni
- chaperone binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 121650, 17 interactors |
CORUMi | Q9P278 |
IntActi | Q9P278, 7 interactors |
MINTi | Q9P278 |
STRINGi | 9606.ENSP00000264433 |
Miscellaneous databases
RNActi | Q9P278, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9P278 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 42 – 460 | uDENN FNIP1/2-typePROSITE-ProRule annotationAdd BLAST | 419 | |
Domaini | 468 – 1040 | cDENN FNIP1/2-typePROSITE-ProRule annotationAdd BLAST | 573 | |
Domaini | 1050 – 1105 | dDENN FNIP1/2-typePROSITE-ProRule annotationAdd BLAST | 56 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 12 – 32 | DisorderedSequence analysisAdd BLAST | 21 | |
Regioni | 93 – 126 | DisorderedSequence analysisAdd BLAST | 34 | |
Regioni | 203 – 237 | DisorderedSequence analysisAdd BLAST | 35 | |
Regioni | 544 – 911 | Interaction with PRKAA11 PublicationAdd BLAST | 368 | |
Regioni | 585 – 632 | DisorderedSequence analysisAdd BLAST | 48 | |
Regioni | 645 – 665 | DisorderedSequence analysisAdd BLAST | 21 | |
Regioni | 747 – 800 | DisorderedSequence analysisAdd BLAST | 54 | |
Regioni | 875 – 900 | DisorderedSequence analysisAdd BLAST | 26 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 93 – 118 | Polar residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 203 – 228 | Polar residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 606 – 623 | Basic and acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 785 – 800 | Basic and acidic residuesSequence analysisAdd BLAST | 16 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3693, Eukaryota |
GeneTreei | ENSGT00390000009391 |
HOGENOMi | CLU_003447_0_0_1 |
InParanoidi | Q9P278 |
OMAi | GFQEPAL |
OrthoDBi | 303571at2759 |
PhylomeDBi | Q9P278 |
TreeFami | TF324090 |
Family and domain databases
InterProi | View protein in InterPro IPR037545, DENN_FNIP1/2 IPR028086, FNIP_C_dom IPR026156, FNIP_fam IPR028085, FNIP_mid_dom IPR028084, FNIP_N_dom |
Pfami | View protein in Pfam PF14638, FNIP_C, 1 hit PF14637, FNIP_M, 1 hit PF14636, FNIP_N, 1 hit |
PRINTSi | PR02073, FOLLICULNIP1 |
PROSITEi | View protein in PROSITE PS51836, DENN_FNIP12, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 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
MAPTLLQKLF NKRGSSGSSA AASAQGRAPK EGPAFSWSCS EFDLNEIRLI
60 70 80 90 100
VYQDCDRRGR QVLFDSKAVQ KIEEVTAQKT EDVPIKISAK CCQGSSSVSS
110 120 130 140 150
SSSSSISSHS SSGGSSHHAK EQLPKYQYTR PASDVNMLGE MMFGSVAMSY
160 170 180 190 200
KGSTLKIHYI RSPPQLMISK VFSARMGSFC GSTNNLQDSF EYINQDPNLG
210 220 230 240 250
KLNTNQNSLG PCRTGSNLAH STPVDMPSRG QNEDRDSGIA RSASLSSLLI
260 270 280 290 300
TPFPSPSSST SSSSSYQRRW LRSQTTSLEN GIIPRRSTDE TFSLAEETCS
310 320 330 340 350
SNPAMVRRKK IAISIIFSLC EKEEAQRNFQ DFFFSHFPLF ESHMNRLKSA
360 370 380 390 400
IEKAMISCRK IAESSLRVQF YVSRLMEALG EFRGTIWNLY SVPRIAEPVW
410 420 430 440 450
LTMMSGTLEK NQLCQRFLKE FTLLIEQINK NQFFAALLTA VLTYHLAWVP
460 470 480 490 500
TVMPVDHPPI KAFSEKRTSQ SVNMLAKTHP YNPLWAQLGD LYGAIGSPVR
510 520 530 540 550
LTRTVVVGKQ KDLVQRILYV LTYFLRCSEL QENQLTWSGN HGEGDQVLNG
560 570 580 590 600
SKIITALEKG EVEESEYVVI TVRNEPALVP PILPPTAAER HNPWPTGFPE
610 620 630 640 650
CPEGTDSRDL GLKPDKEANR RPEQGSEACS AGCLGPASDA SWKPQNAFCG
660 670 680 690 700
DEKNKEAPQD GSSRLPSCEV LGAGMKMDQQ AVCELLKVEM PTRLPDRSVA
710 720 730 740 750
WPCPDRHLRE KPSLEKVTFQ IGSFASPESD FESRMKKMEE RVKACGPSLE
760 770 780 790 800
ASEAADVAQD PQVSRSPFKP GFQENVCCPQ NRLSEGDEGE SDKGFAEDRG
810 820 830 840 850
SRNDMAADIA GQLSHAADLG TASHGAGGTG GRRLEATRGL YVKAAEGPVL
860 870 880 890 900
EPVAPRCVQR GPGLVAGANI PCGDDNKKAN FRTEGDIPRN ESSDSALGDS
910 920 930 940 950
DDEACASAML DLGHGGDRTG GSLEVELPLP RSQSISTQNV RNFGRSLLAG
960 970 980 990 1000
YCPTYMPDLV LHGTGSDEKL KQCLVADLVH TVHHPVLDEP IAEAVCIIAD
1010 1020 1030 1040 1050
TDKWSVQVAT SQRKVTDNMK LGQDVLVSSQ VSSLLQSILQ LYKLHLPADF
1060 1070 1080 1090 1100
CIMHLEDRLQ EMYLKSKMLS EYLRGHTRVH VKELGVVLGI ESNDLPLLTA
1110
IASTHSPYVA QILL
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD6RFH5 | D6RFH5_HUMAN | Folliculin-interacting protein 2 | FNIP2 | 673 | Annotation score: | ||
H0Y8F3 | H0Y8F3_HUMAN | Folliculin-interacting protein 2 | FNIP2 | 241 | Annotation score: |
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_045612 | 298 | T → S. Corresponds to variant dbSNP:rs2276938Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_031656 | 1 – 35 | MAPTL…EGPAF → MCGGTANTTNQPESWQDSAR CVSDAVPGAGRIYRALLCTK IKKHTGVDRSTDHTELDN in isoform 2. 1 PublicationAdd BLAST | 35 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB040883 mRNA Translation: BAA95974.1 Different initiation. BC007861 mRNA Translation: AAH07861.1 Different initiation. BC016638 mRNA Translation: AAH16638.1 Sequence problems. AK022968 mRNA Translation: BAB14338.1 Different initiation. |
CCDSi | CCDS47155.1 [Q9P278-1] |
RefSeqi | NP_001310845.1, NM_001323916.1 [Q9P278-2] NP_001332972.1, NM_001346043.1 NP_065891.1, NM_020840.2 [Q9P278-1] |
Genome annotation databases
Ensembli | ENST00000264433; ENSP00000264433; ENSG00000052795 |
GeneIDi | 57600 |
KEGGi | hsa:57600 |
MANE-Selecti | ENST00000264433.11; ENSP00000264433.6; NM_020840.3; NP_065891.1 |
UCSCi | uc003iqe.5, human [Q9P278-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB040883 mRNA Translation: BAA95974.1 Different initiation. BC007861 mRNA Translation: AAH07861.1 Different initiation. BC016638 mRNA Translation: AAH16638.1 Sequence problems. AK022968 mRNA Translation: BAB14338.1 Different initiation. |
CCDSi | CCDS47155.1 [Q9P278-1] |
RefSeqi | NP_001310845.1, NM_001323916.1 [Q9P278-2] NP_001332972.1, NM_001346043.1 NP_065891.1, NM_020840.2 [Q9P278-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6NZD | electron microscopy | 3.60 | I | 1-1114 | [»] | |
6ULG | electron microscopy | 3.31 | N | 1-1114 | [»] | |
7LSW | X-ray | 3.05 | A/B/C/D/E/F | 552-576 | [»] | |
7LT6 | X-ray | 1.80 | A/B/C | 558-576 | [»] | |
SMRi | Q9P278 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121650, 17 interactors |
CORUMi | Q9P278 |
IntActi | Q9P278, 7 interactors |
MINTi | Q9P278 |
STRINGi | 9606.ENSP00000264433 |
PTM databases
iPTMneti | Q9P278 |
PhosphoSitePlusi | Q9P278 |
Genetic variation databases
BioMutai | FNIP2 |
DMDMi | 189035874 |
Proteomic databases
EPDi | Q9P278 |
jPOSTi | Q9P278 |
MassIVEi | Q9P278 |
MaxQBi | Q9P278 |
PaxDbi | Q9P278 |
PeptideAtlasi | Q9P278 |
PRIDEi | Q9P278 |
ProteomicsDBi | 83745 [Q9P278-1] 83746 [Q9P278-2] |
Protocols and materials databases
Antibodypediai | 28193, 160 antibodies from 26 providers |
DNASUi | 57600 |
Genome annotation databases
Ensembli | ENST00000264433; ENSP00000264433; ENSG00000052795 |
GeneIDi | 57600 |
KEGGi | hsa:57600 |
MANE-Selecti | ENST00000264433.11; ENSP00000264433.6; NM_020840.3; NP_065891.1 |
UCSCi | uc003iqe.5, human [Q9P278-1] |
Organism-specific databases
CTDi | 57600 |
DisGeNETi | 57600 |
GeneCardsi | FNIP2 |
HGNCi | HGNC:29280, FNIP2 |
HPAi | ENSG00000052795, Low tissue specificity |
MIMi | 612768, gene |
neXtProti | NX_Q9P278 |
OpenTargetsi | ENSG00000052795 |
PharmGKBi | PA162388758 |
VEuPathDBi | HostDB:ENSG00000052795 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3693, Eukaryota |
GeneTreei | ENSGT00390000009391 |
HOGENOMi | CLU_003447_0_0_1 |
InParanoidi | Q9P278 |
OMAi | GFQEPAL |
OrthoDBi | 303571at2759 |
PhylomeDBi | Q9P278 |
TreeFami | TF324090 |
Enzyme and pathway databases
PathwayCommonsi | Q9P278 |
Reactomei | R-HSA-9639288, Amino acids regulate mTORC1 |
SignaLinki | Q9P278 |
SIGNORi | Q9P278 |
Miscellaneous databases
BioGRID-ORCSi | 57600, 5 hits in 1048 CRISPR screens |
ChiTaRSi | FNIP2, human |
GenomeRNAii | 57600 |
Pharosi | Q9P278, Tbio |
PROi | PR:Q9P278 |
RNActi | Q9P278, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000052795, Expressed in kidney epithelium and 222 other tissues |
ExpressionAtlasi | Q9P278, baseline and differential |
Genevisiblei | Q9P278, HS |
Family and domain databases
InterProi | View protein in InterPro IPR037545, DENN_FNIP1/2 IPR028086, FNIP_C_dom IPR026156, FNIP_fam IPR028085, FNIP_mid_dom IPR028084, FNIP_N_dom |
Pfami | View protein in Pfam PF14638, FNIP_C, 1 hit PF14637, FNIP_M, 1 hit PF14636, FNIP_N, 1 hit |
PRINTSi | PR02073, FOLLICULNIP1 |
PROSITEi | View protein in PROSITE PS51836, DENN_FNIP12, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | FNIP2_HUMAN | |
Accessioni | Q9P278Primary (citable) accession number: Q9P278 Secondary accession number(s): Q05DC3, Q96I31, Q9H994 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 26, 2008 |
Last sequence update: | February 26, 2008 | |
Last modified: | February 23, 2022 | |
This is version 131 of the entry and version 2 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 4
Human chromosome 4: 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