{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q8R0W6","secondaryAccessions":["Q9EQH8"],"uniProtkbId":"NFIP1_MOUSE","entryAudit":{"firstPublicDate":"2005-12-06","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2002-06-01","entryVersion":158,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"NEDD4 family-interacting protein 1"}},"alternativeNames":[{"fullName":{"value":"NEDD4 WW domain-binding protein 5"}}]},"genes":[{"geneName":{"value":"Ndfip1"},"synonyms":[{"value":"N4wbp5"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BT67"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11748237"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17137798"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20962770"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23897647"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24520172"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25631046"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25632008"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25801959"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26319551"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27088444"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28051111"}],"value":"Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation (PubMed:11748237, PubMed:17137798, PubMed:20962770). Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion (PubMed:26319551). Restricts the production of pro-inflammatory cytokines in effector Th17 T-cells by promoting ITCH-mediated ubiquitination and degradation of RORC (PubMed:28051111). Together with NDFIP2, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (PubMed:27088444). Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells (PubMed:24520172, PubMed:28051111). Negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS (By similarity). Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation (By similarity). In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protection of the cells from cobalt and iron toxicity (By similarity). Important for normal development of dendrites and dendritic spines in cortex (PubMed:23897647). Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1 (PubMed:25631046). Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH (PubMed:25632008). Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate (By similarity). Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity (PubMed:25801959)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BT67"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11042109"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11748237"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17137798"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25632008"}],"value":"Forms heterodimers with NDFIP2 (By similarity). Interacts with several E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L and WWP2 (PubMed:11042109, PubMed:11748237, PubMed:17137798, PubMed:25632008). The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion (PubMed:11748237). Interacts with U2SURP (PubMed:11748237). Interacts with SLC11A2/DMT1 (By similarity). Interacts with PTEN (By similarity). May interact with phosphorylated EGFR (By similarity). Interacts with BRAT1 (By similarity). Interacts with KCNH2 (By similarity). Interacts with MAVS (By similarity). Part of a complex containing ITCH, NDFIP1 and MAP3K7 (PubMed:25632008). Interacts (via N-terminus) with UBE2L3; the interaction mediates recruitment of UBE2L3 to ITCH (PubMed:25632008)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q8R0W6","intActId":"EBI-6304119"},"interactantTwo":{"uniProtKBAccession":"P46935","geneName":"Nedd4","intActId":"EBI-773516"},"numberOfExperiments":5,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BT67"}],"value":"Detected in exosomes and secreted via the exosomal pathway"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BT67"}],"value":"Endosome membrane","id":"SL-0100"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BT67"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11748237"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16822981"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18819914"}],"value":"Golgi apparatus membrane","id":"SL-0134"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23897647"}],"value":"Synapse, synaptosome","id":"SL-0261"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23897647"}],"value":"Cell projection, dendrite","id":"SL-0283"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BT67"}],"value":"Secreted","id":"SL-0243"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11748237"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17137798"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23897647"}],"value":"Highly expressed in embryonic and early postnatal cortex (at protein level) (PubMed:23897647). Widely expressed (PubMed:11748237). Hardly detectable in resting T-cells; up-regulated in T-cells in response to activation (PubMed:17137798)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16822981"}],"value":"Up-regulated after traumatic brain injury in surviving neurons around the lesion site"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11042109"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11748237"}],"value":"The PPxY motifs are required for E3 ubiquitin-protein ligase binding and activation and for ubiquitination"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11748237"}],"value":"Ubiquitinated by NEDD4; mono-, di- and polyubiquitinated forms are detected. Ubiquitination regulates its degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Undergoes transient tyrosine phosphorylation following EGF stimulation, most probably by catalyzed by SRC. Phosphorylation SRC is enhanced in the presence of NDFIP2 which may act as a scaffold to recruit SRC to NDFIP1 (By similarity)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17137798"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18776082"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19706893"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20962770"}],"value":"Mutant mice appear normal at birth, but develop severe skin and gastrointestinal tract inflammation around 6 to 8 weeks of age (PubMed:17137798, PubMed:20962770). They do not survive beyond 14 weeks (PubMed:17137798). This phenotype is due to the lack of activity of ITCH E3 ubiquitin-protein ligase, and consequently, prolongation of JUNB half-life after T-cell activation (PubMed:17137798, PubMed:20962770). This results in an increased production of T-helper 2 (Th2) cytokines and in the promotion of Th2-mediated inflammation (PubMed:17137798, PubMed:20962770). This subsequently leads to increased number of circulating, esophagus and small bowel eosinophils (PubMed:20962770). Mutant mice have thicker small bowel and do not gain as much weight as the wild type (PubMed:20962770). Mutant mice also show an increased iron transport in hepatocytes and iron accumulation in the liver around portal veins, in the villi of duodenum and throughout the brain cortex (PubMed:18776082, PubMed:19706893)"}],"commentType":"DISRUPTION PHENOTYPE"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"AAG44248.1","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Initiator methionine","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1,"modifier":"EXACT"}},"description":"Removed","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BT67"}]},{"type":"Chain","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":221,"modifier":"EXACT"}},"description":"NEDD4 family-interacting protein 1","featureId":"PRO_0000076270"},{"type":"Topological domain","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":116,"modifier":"EXACT"}},"description":"Cytoplasmic","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":117,"modifier":"EXACT"},"end":{"value":137,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Topological domain","location":{"start":{"value":138,"modifier":"EXACT"},"end":{"value":143,"modifier":"EXACT"}},"description":"Extracellular","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":144,"modifier":"EXACT"},"end":{"value":164,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Topological domain","location":{"start":{"value":165,"modifier":"EXACT"},"end":{"value":172,"modifier":"EXACT"}},"description":"Cytoplasmic","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":173,"modifier":"EXACT"},"end":{"value":193,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Topological domain","location":{"start":{"value":194,"modifier":"EXACT"},"end":{"value":221,"modifier":"EXACT"}},"description":"Extracellular","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Region","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":41,"modifier":"EXACT"}},"description":"Interaction with UBE2L3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25632008"}]},{"type":"Region","location":{"start":{"value":18,"modifier":"EXACT"},"end":{"value":44,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":42,"modifier":"EXACT"},"end":{"value":76,"modifier":"EXACT"}},"description":"Interaction with ITCH","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25632008"}]},{"type":"Motif","location":{"start":{"value":39,"modifier":"EXACT"},"end":{"value":42,"modifier":"EXACT"}},"description":"PPxY motif 1"},{"type":"Motif","location":{"start":{"value":64,"modifier":"EXACT"},"end":{"value":67,"modifier":"EXACT"}},"description":"PPxY motif 2"},{"type":"Motif","location":{"start":{"value":74,"modifier":"EXACT"},"end":{"value":76,"modifier":"EXACT"}},"description":"PPxY motif 3"},{"type":"Modified residue","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":2,"modifier":"EXACT"}},"description":"N-acetylalanine","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BT67"}]},{"type":"Mutagenesis","location":{"start":{"value":42,"modifier":"EXACT"},"end":{"value":42,"modifier":"EXACT"}},"description":"Abolishes interaction with NEDD4.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11042109"}],"alternativeSequence":{"originalSequence":"Y","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":67,"modifier":"EXACT"},"end":{"value":67,"modifier":"EXACT"}},"description":"Alters interaction with NEDD4.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11042109"}],"alternativeSequence":{"originalSequence":"Y","alternativeSequences":["A"]}}],"keywords":[{"id":"KW-0007","category":"PTM","name":"Acetylation"},{"id":"KW-0966","category":"Cellular component","name":"Cell projection"},{"id":"KW-0967","category":"Cellular component","name":"Endosome"},{"id":"KW-0333","category":"Cellular component","name":"Golgi apparatus"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0677","category":"Domain","name":"Repeat"},{"id":"KW-0964","category":"Cellular component","name":"Secreted"},{"id":"KW-0770","category":"Cellular component","name":"Synapse"},{"id":"KW-0771","category":"Cellular component","name":"Synaptosome"},{"id":"KW-0812","category":"Domain","name":"Transmembrane"},{"id":"KW-1133","category":"Domain","name":"Transmembrane helix"},{"id":"KW-0832","category":"PTM","name":"Ubl conjugation"}],"references":[{"referenceNumber":1,"citation":{"id":"11042109","citationType":"journal article","authors":["Jolliffe C.N.","Harvey K.F.","Haines B.P.","Parasivam G.","Kumar S."],"citationCrossReferences":[{"database":"PubMed","id":"11042109"},{"database":"DOI","id":"10.1042/bj3510557"}],"title":"Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4.","publicationDate":"2000","journal":"Biochem. J.","firstPage":"557","lastPage":"565","volume":"351"},"referencePositions":["NUCLEOTIDE SEQUENCE [MRNA]","MUTAGENESIS OF TYR-42 AND TYR-67","INTERACTION WITH NEDD4","DOMAINS"],"referenceComments":[{"value":"Embryo","type":"TISSUE"}]},{"referenceNumber":2,"citation":{"id":"16141072","citationType":"journal article","authors":["Carninci P.","Kasukawa T.","Katayama S.","Gough J.","Frith M.C.","Maeda N.","Oyama R.","Ravasi T.","Lenhard B.","Wells C.","Kodzius R.","Shimokawa K.","Bajic V.B.","Brenner S.E.","Batalov S.","Forrest A.R.","Zavolan M.","Davis M.J.","Wilming L.G.","Aidinis V.","Allen J.E.","Ambesi-Impiombato A.","Apweiler R.","Aturaliya R.N.","Bailey T.L.","Bansal M.","Baxter L.","Beisel K.W.","Bersano T.","Bono H.","Chalk A.M.","Chiu K.P.","Choudhary V.","Christoffels A.","Clutterbuck D.R.","Crowe M.L.","Dalla E.","Dalrymple B.P.","de Bono B.","Della Gatta G.","di Bernardo D.","Down T.","Engstrom P.","Fagiolini M.","Faulkner G.","Fletcher C.F.","Fukushima T.","Furuno M.","Futaki S.","Gariboldi M.","Georgii-Hemming P.","Gingeras T.R.","Gojobori T.","Green R.E.","Gustincich S.","Harbers M.","Hayashi Y.","Hensch T.K.","Hirokawa N.","Hill D.","Huminiecki L.","Iacono M.","Ikeo K.","Iwama A.","Ishikawa T.","Jakt M.","Kanapin A.","Katoh M.","Kawasawa Y.","Kelso J.","Kitamura H.","Kitano H.","Kollias G.","Krishnan S.P.","Kruger A.","Kummerfeld S.K.","Kurochkin I.V.","Lareau L.F.","Lazarevic D.","Lipovich L.","Liu J.","Liuni S.","McWilliam S.","Madan Babu M.","Madera M.","Marchionni L.","Matsuda H.","Matsuzawa S.","Miki H.","Mignone F.","Miyake S.","Morris K.","Mottagui-Tabar S.","Mulder N.","Nakano N.","Nakauchi H.","Ng P.","Nilsson R.","Nishiguchi S.","Nishikawa S.","Nori F.","Ohara O.","Okazaki Y.","Orlando V.","Pang K.C.","Pavan W.J.","Pavesi G.","Pesole G.","Petrovsky N.","Piazza S.","Reed J.","Reid J.F.","Ring B.Z.","Ringwald M.","Rost B.","Ruan Y.","Salzberg S.L.","Sandelin A.","Schneider C.","Schoenbach C.","Sekiguchi K.","Semple C.A.","Seno S.","Sessa L.","Sheng Y.","Shibata Y.","Shimada H.","Shimada K.","Silva D.","Sinclair B.","Sperling S.","Stupka E.","Sugiura K.","Sultana R.","Takenaka Y.","Taki K.","Tammoja K.","Tan S.L.","Tang S.","Taylor M.S.","Tegner J.","Teichmann S.A.","Ueda H.R.","van Nimwegen E.","Verardo R.","Wei C.L.","Yagi K.","Yamanishi H.","Zabarovsky E.","Zhu S.","Zimmer A.","Hide W.","Bult C.","Grimmond S.M.","Teasdale R.D.","Liu E.T.","Brusic V.","Quackenbush J.","Wahlestedt C.","Mattick J.S.","Hume D.A.","Kai C.","Sasaki D.","Tomaru Y.","Fukuda S.","Kanamori-Katayama M.","Suzuki M.","Aoki J.","Arakawa T.","Iida J.","Imamura K.","Itoh M.","Kato T.","Kawaji H.","Kawagashira N.","Kawashima T.","Kojima M.","Kondo S.","Konno H.","Nakano K.","Ninomiya N.","Nishio T.","Okada M.","Plessy C.","Shibata K.","Shiraki T.","Suzuki S.","Tagami M.","Waki K.","Watahiki A.","Okamura-Oho Y.","Suzuki H.","Kawai J.","Hayashizaki Y."],"citationCrossReferences":[{"database":"PubMed","id":"16141072"},{"database":"DOI","id":"10.1126/science.1112014"}],"title":"The transcriptional landscape of the mammalian genome.","publicationDate":"2005","journal":"Science","firstPage":"1559","lastPage":"1563","volume":"309"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]"],"referenceComments":[{"value":"C57BL/6J","type":"STRAIN"},{"value":"Pancreas","type":"TISSUE"}]},{"referenceNumber":3,"citation":{"id":"15489334","citationType":"journal article","authoringGroup":["The MGC Project Team"],"citationCrossReferences":[{"database":"PubMed","id":"15489334"},{"database":"DOI","id":"10.1101/gr.2596504"}],"title":"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).","publicationDate":"2004","journal":"Genome Res.","firstPage":"2121","lastPage":"2127","volume":"14"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]"],"referenceComments":[{"value":"FVB/N","type":"STRAIN"},{"value":"Liver","type":"TISSUE"}]},{"referenceNumber":4,"citation":{"id":"11748237","citationType":"journal article","authors":["Harvey K.F.","Shearwin-Whyatt L.M.","Fotia A.","Parton R.G.","Kumar S."],"citationCrossReferences":[{"database":"PubMed","id":"11748237"},{"database":"DOI","id":"10.1074/jbc.m110443200"}],"title":"N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein.","publicationDate":"2002","journal":"J. Biol. Chem.","firstPage":"9307","lastPage":"9317","volume":"277"},"referencePositions":["FUNCTION","TISSUE SPECIFICITY","INTERACTION WITH NEDD4; NEDD4L; U2SURP; WWP2 AND ITCH","DOMAIN","UBIQUITINATION BY NEDD4","SUBCELLULAR LOCATION"]},{"referenceNumber":5,"citation":{"id":"17137798","citationType":"journal article","authors":["Oliver P.M.","Cao X.","Worthen G.S.","Shi P.","Briones N.","MacLeod M.","White J.","Kirby P.","Kappler J.","Marrack P.","Yang B."],"citationCrossReferences":[{"database":"PubMed","id":"17137798"},{"database":"DOI","id":"10.1016/j.immuni.2006.10.012"}],"title":"Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation.","publicationDate":"2006","journal":"Immunity","firstPage":"929","lastPage":"940","volume":"25"},"referencePositions":["FUNCTION","DISRUPTION PHENOTYPE","INTERACTION WITH ITCH","TISSUE SPECIFICITY"]},{"referenceNumber":6,"citation":{"id":"16822981","citationType":"journal article","authors":["Sang Q.","Kim M.H.","Kumar S.","Bye N.","Morganti-Kossman M.C.","Gunnersen J.","Fuller S.","Howitt J.","Hyde L.","Beissbarth T.","Scott H.S.","Silke J.","Tan S.S."],"citationCrossReferences":[{"database":"PubMed","id":"16822981"},{"database":"DOI","id":"10.1523/jneurosci.1398-06.2006"}],"title":"Nedd4-WW domain-binding protein 5 (Ndfip1) is associated with neuronal survival after acute cortical brain injury.","publicationDate":"2006","journal":"J. Neurosci.","firstPage":"7234","lastPage":"7244","volume":"26"},"referencePositions":["SUBCELLULAR LOCATION","INDUCTION BY TRAUMATIC BRAIN INJURY"]},{"referenceNumber":7,"citation":{"id":"18776082","citationType":"journal article","authors":["Foot N.J.","Dalton H.E.","Shearwin-Whyatt L.M.","Dorstyn L.","Tan S.S.","Yang B.","Kumar S."],"citationCrossReferences":[{"database":"PubMed","id":"18776082"},{"database":"DOI","id":"10.1182/blood-2008-04-150953"}],"title":"Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2.","publicationDate":"2008","journal":"Blood","firstPage":"4268","lastPage":"4275","volume":"112"},"referencePositions":["DISRUPTION PHENOTYPE"]},{"referenceNumber":8,"citation":{"id":"18819914","citationType":"journal article","authors":["Putz U.","Howitt J.","Lackovic J.","Foot N.","Kumar S.","Silke J.","Tan S.S."],"citationCrossReferences":[{"database":"PubMed","id":"18819914"},{"database":"DOI","id":"10.1074/jbc.m804120200"}],"title":"Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins.","publicationDate":"2008","journal":"J. Biol. Chem.","firstPage":"32621","lastPage":"32627","volume":"283"},"referencePositions":["SUBCELLULAR LOCATION"]},{"referenceNumber":9,"citation":{"id":"19706893","citationType":"journal article","authors":["Howitt J.","Putz U.","Lackovic J.","Doan A.","Dorstyn L.","Cheng H.","Yang B.","Chan-Ling T.","Silke J.","Kumar S.","Tan S.S."],"citationCrossReferences":[{"database":"PubMed","id":"19706893"},{"database":"DOI","id":"10.1073/pnas.0904880106"}],"title":"Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons.","publicationDate":"2009","journal":"Proc. Natl. Acad. Sci. U.S.A.","firstPage":"15489","lastPage":"15494","volume":"106"},"referencePositions":["DISRUPTION PHENOTYPE"]},{"referenceNumber":10,"citation":{"id":"20962770","citationType":"journal article","authors":["Ramon H.E.","Riling C.R.","Bradfield J.","Yang B.","Hakonarson H.","Oliver P.M."],"citationCrossReferences":[{"database":"PubMed","id":"20962770"},{"database":"DOI","id":"10.1038/mi.2010.69"}],"title":"The ubiquitin ligase adaptor Ndfip1 regulates T cell-mediated gastrointestinal inflammation and inflammatory bowel disease susceptibility.","publicationDate":"2011","journal":"Mucosal Immunol.","firstPage":"314","lastPage":"324","volume":"4"},"referencePositions":["FUNCTION","DISRUPTION PHENOTYPE"]},{"referenceNumber":11,"citation":{"id":"23897647","citationType":"journal article","authors":["Hammond V.E.","Gunnersen J.M.","Goh C.P.","Low L.H.","Hyakumura T.","Tang M.M.","Britto J.M.","Putz U.","Howitt J.A.","Tan S.S."],"citationCrossReferences":[{"database":"PubMed","id":"23897647"},{"database":"DOI","id":"10.1093/cercor/bht191"}],"title":"Ndfip1 is required for the development of pyramidal neuron dendrites and spines in the neocortex.","publicationDate":"2014","journal":"Cereb. Cortex","firstPage":"3289","lastPage":"3300","volume":"24"},"referencePositions":["FUNCTION","SUBCELLULAR LOCATION","TISSUE SPECIFICITY"]},{"referenceNumber":12,"citation":{"id":"24520172","citationType":"journal article","authors":["Altin J.A.","Daley S.R.","Howitt J.","Rickards H.J.","Batkin A.K.","Horikawa K.","Prasad S.J.","Nelms K.A.","Kumar S.","Wu L.C.","Tan S.S.","Cook M.C.","Goodnow C.C."],"citationCrossReferences":[{"database":"PubMed","id":"24520172"},{"database":"DOI","id":"10.1073/pnas.1322739111"}],"title":"Ndfip1 mediates peripheral tolerance to self and exogenous antigen by inducing cell cycle exit in responding CD4+ T cells.","publicationDate":"2014","journal":"Proc. Natl. Acad. Sci. U.S.A.","firstPage":"2067","lastPage":"2074","volume":"111"},"referencePositions":["FUNCTION"]},{"referenceNumber":13,"citation":{"id":"26319551","citationType":"journal article","authors":["Beck A.","Shatz-Azoulay H.","Vinik Y.","Isaac R.","Boura-Halfon S.","Zick Y."],"citationCrossReferences":[{"database":"PubMed","id":"26319551"},{"database":"DOI","id":"10.1016/j.bbrc.2015.08.099"}],"title":"Nedd4 family interacting protein 1 (Ndfip1) promotes death of pancreatic beta cells.","publicationDate":"2015","journal":"Biochem. Biophys. Res. Commun.","firstPage":"851","lastPage":"856","volume":"465"},"referencePositions":["FUNCTION"]},{"referenceNumber":14,"citation":{"id":"25631046","citationType":"journal article","authors":["Low L.H.","Chow Y.L.","Li Y.","Goh C.P.","Putz U.","Silke J.","Ouchi T.","Howitt J.","Tan S.S."],"citationCrossReferences":[{"database":"PubMed","id":"25631046"},{"database":"DOI","id":"10.1074/jbc.m114.613687"}],"title":"Nedd4 family interacting protein 1 (Ndfip1) is required for ubiquitination and nuclear trafficking of BRCA1-associated ATM activator 1 (BRAT1) during the DNA damage response.","publicationDate":"2015","journal":"J. Biol. Chem.","firstPage":"7141","lastPage":"7150","volume":"290"},"referencePositions":["FUNCTION"]},{"referenceNumber":15,"citation":{"id":"25632008","citationType":"journal article","authors":["Kathania M.","Zeng M.","Yadav V.N.","Moghaddam S.J.","Yang B.","Venuprasad K."],"citationCrossReferences":[{"database":"PubMed","id":"25632008"},{"database":"DOI","id":"10.4049/jimmunol.1402742"}],"title":"Ndfip1 regulates itch ligase activity and airway inflammation via UbcH7.","publicationDate":"2015","journal":"J. Immunol.","firstPage":"2160","lastPage":"2167","volume":"194"},"referencePositions":["FUNCTION","INTERACTION WITH UBE2L3 AND ITCH","IDENTIFICATION IN COMPLEX WITH ITCH AND MAP3K7"]},{"referenceNumber":16,"citation":{"id":"25801959","citationType":"journal article","authors":["Howitt J.","Low L.H.","Putz U.","Doan A.","Lackovic J.","Goh C.P.","Gunnersen J.","Silke J.","Tan S.S."],"citationCrossReferences":[{"database":"PubMed","id":"25801959"},{"database":"DOI","id":"10.1093/jmcb/mjv020"}],"title":"Ndfip1 represses cell proliferation by controlling Pten localization and signaling specificity.","publicationDate":"2015","journal":"J. Mol. Cell Biol.","firstPage":"119","lastPage":"131","volume":"7"},"referencePositions":["FUNCTION"]},{"referenceNumber":17,"citation":{"id":"27088444","citationType":"journal article","authors":["O'Leary C.E.","Riling C.R.","Spruce L.A.","Ding H.","Kumar S.","Deng G.","Liu Y.","Seeholzer S.H.","Oliver P.M."],"citationCrossReferences":[{"database":"PubMed","id":"27088444"},{"database":"DOI","id":"10.1038/ncomms11226"}],"title":"Ndfip-mediated degradation of Jak1 tunes cytokine signalling to limit expansion of CD4+ effector T cells.","publicationDate":"2016","journal":"Nat. Commun.","firstPage":"11226","lastPage":"11226","volume":"7"},"referencePositions":["FUNCTION"]},{"referenceNumber":18,"citation":{"id":"28051111","citationType":"journal article","authors":["Kesewa Layman A.A.","Sprout S.L.","Phillips D.","Oliver P.M."],"citationCrossReferences":[{"database":"PubMed","id":"28051111"},{"database":"DOI","id":"10.1038/srep39649"}],"title":"Ndfip1 restricts Th17 cell potency by limiting lineage stability and proinflammatory cytokine production.","publicationDate":"2017","journal":"Sci. Rep.","firstPage":"39649","lastPage":"39649","volume":"7"},"referencePositions":["FUNCTION"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"AF220209","properties":[{"key":"ProteinId","value":"AAG44248.1"},{"key":"Status","value":"ALT_INIT"},{"key":"MoleculeType","value":"mRNA"}]},{"database":"EMBL","id":"AK050560","properties":[{"key":"ProteinId","value":"BAC34324.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"mRNA"}]},{"database":"EMBL","id":"BC026372","properties":[{"key":"ProteinId","value":"AAH26372.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"mRNA"}]},{"database":"CCDS","id":"CCDS37789.1","properties":[{"key":"Description","value":"-"}]},{"database":"RefSeq","id":"NP_001342678.1","properties":[{"key":"NucleotideSequenceId","value":"NM_001355749.1"}]},{"database":"RefSeq","id":"NP_075372.1","properties":[{"key":"NucleotideSequenceId","value":"NM_022996.2"}]},{"database":"AlphaFoldDB","id":"Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"BioGRID","id":"211136","properties":[{"key":"Interactions","value":"14"}]},{"database":"CORUM","id":"Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"FunCoup","id":"Q8R0W6","properties":[{"key":"Number of interactors","value":"2323"}]},{"database":"IntAct","id":"Q8R0W6","properties":[{"key":"Interactions","value":"1"}]},{"database":"STRING","id":"10090.ENSMUSP00000158314","properties":[{"key":"Description","value":"-"}]},{"database":"iPTMnet","id":"Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"PhosphoSitePlus","id":"Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"SwissPalm","id":"Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"PaxDb","id":"10090-ENSMUSP00000158314","properties":[{"key":"Description","value":"-"}]},{"database":"PeptideAtlas","id":"Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"ProteomicsDB","id":"287407","properties":[{"key":"Description","value":"-"}]},{"database":"Pumba","id":"Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"Antibodypedia","id":"2434","properties":[{"key":"antibodies","value":"201 antibodies from 35 providers"}]},{"database":"Ensembl","id":"ENSMUST00000025293.5","properties":[{"key":"ProteinId","value":"ENSMUSP00000025293.4"},{"key":"GeneId","value":"ENSMUSG00000024425.5"}]},{"database":"Ensembl","id":"ENSMUST00000236085.2","properties":[{"key":"ProteinId","value":"ENSMUSP00000158314.2"},{"key":"GeneId","value":"ENSMUSG00000024425.5"}]},{"database":"GeneID","id":"65113","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"mmu:65113","properties":[{"key":"Description","value":"-"}]},{"database":"UCSC","id":"uc008esj.1","properties":[{"key":"OrganismName","value":"mouse"}]},{"database":"AGR","id":"MGI:1929601","properties":[{"key":"Description","value":"-"}]},{"database":"CTD","id":"80762","properties":[{"key":"Description","value":"-"}]},{"database":"MGI","id":"MGI:1929601","properties":[{"key":"GeneName","value":"Ndfip1"}]},{"database":"VEuPathDB","id":"HostDB:ENSMUSG00000024425","properties":[{"key":"Description","value":"-"}]},{"database":"eggNOG","id":"KOG4812","properties":[{"key":"ToxonomicScope","value":"Eukaryota"}]},{"database":"GeneTree","id":"ENSGT00390000012721","properties":[{"key":"Description","value":"-"}]},{"database":"HOGENOM","id":"CLU_074980_2_0_1","properties":[{"key":"Description","value":"-"}]},{"database":"InParanoid","id":"Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"OMA","id":"ASMVKWT","properties":[{"key":"Fingerprint","value":"-"}]},{"database":"OrthoDB","id":"10003116at2759","properties":[{"key":"Description","value":"-"}]},{"database":"PhylomeDB","id":"Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"BioGRID-ORCS","id":"65113","properties":[{"key":"hits","value":"0 hits in 115 CRISPR screens"}]},{"database":"PRO","id":"PR:Q8R0W6","properties":[{"key":"Description","value":"-"}]},{"database":"Proteomes","id":"UP000000589","properties":[{"key":"Component","value":"Chromosome 18"}]},{"database":"RNAct","id":"Q8R0W6","properties":[{"key":"moleculeType","value":"protein"}]},{"database":"Bgee","id":"ENSMUSG00000024425","properties":[{"key":"ExpressionPatterns","value":"Expressed in subparaventricular zone and 275 other cell types or tissues"}]},{"database":"ExpressionAtlas","id":"Q8R0W6","properties":[{"key":"ExpressionPatterns","value":"baseline and differential"}]},{"database":"GO","id":"GO:0005938","properties":[{"key":"GoTerm","value":"C:cell cortex"},{"key":"GoEvidenceType","value":"IDA:MGI"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0030425","properties":[{"key":"GoTerm","value":"C:dendrite"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-SubCell"}]},{"database":"GO","id":"GO:0005783","properties":[{"key":"GoTerm","value":"C:endoplasmic reticulum"},{"key":"GoEvidenceType","value":"IBA:GO_Central"}]},{"database":"GO","id":"GO:0010008","properties":[{"key":"GoTerm","value":"C:endosome membrane"},{"key":"GoEvidenceType","value":"ISO:GO_Central"}]},{"database":"GO","id":"GO:0005576","properties":[{"key":"GoTerm","value":"C:extracellular region"},{"key":"GoEvidenceType","value":"ISO:GO_Central"}]},{"database":"GO","id":"GO:0005794","properties":[{"key":"GoTerm","value":"C:Golgi apparatus"},{"key":"GoEvidenceType","value":"IDA:MGI"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"11748237"}]},{"database":"GO","id":"GO:0000139","properties":[{"key":"GoTerm","value":"C:Golgi membrane"},{"key":"GoEvidenceType","value":"IC:MGI"}],"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"11748237"}]},{"database":"GO","id":"GO:0016020","properties":[{"key":"GoTerm","value":"C:membrane"},{"key":"GoEvidenceType","value":"ISM:MGI"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"PubMed","id":"11748237"}]},{"database":"GO","id":"GO:0048471","properties":[{"key":"GoTerm","value":"C:perinuclear region of cytoplasm"},{"key":"GoEvidenceType","value":"ISO:GO_Central"}]},{"database":"GO","id":"GO:0045202","properties":[{"key":"GoTerm","value":"C:synapse"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-SubCell"}]},{"database":"GO","id":"GO:0050699","properties":[{"key":"GoTerm","value":"F:WW domain binding"},{"key":"GoEvidenceType","value":"IPI:MGI"}],"evidences":[{"evidenceCode":"ECO:0000353","source":"PubMed","id":"11748237"}]},{"database":"GO","id":"GO:0006879","properties":[{"key":"GoTerm","value":"P:intracellular iron ion homeostasis"},{"key":"GoEvidenceType","value":"ISO:GO_Central"}]},{"database":"GO","id":"GO:0030001","properties":[{"key":"GoTerm","value":"P:metal ion transport"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"GO","id":"GO:0010629","properties":[{"key":"GoTerm","value":"P:negative regulation of gene expression"},{"key":"GoEvidenceType","value":"ISO:GO_Central"}]},{"database":"GO","id":"GO:0050728","properties":[{"key":"GoTerm","value":"P:negative regulation of inflammatory response"},{"key":"GoEvidenceType","value":"IMP:MGI"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0032713","properties":[{"key":"GoTerm","value":"P:negative regulation of interleukin-4 production"},{"key":"GoEvidenceType","value":"IMP:MGI"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0048294","properties":[{"key":"GoTerm","value":"P:negative regulation of isotype switching to IgE isotypes"},{"key":"GoEvidenceType","value":"IMP:MGI"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0051224","properties":[{"key":"GoTerm","value":"P:negative regulation of protein transport"},{"key":"GoEvidenceType","value":"ISO:GO_Central"}]},{"database":"GO","id":"GO:0042130","properties":[{"key":"GoTerm","value":"P:negative regulation of T cell proliferation"},{"key":"GoEvidenceType","value":"IMP:MGI"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0002829","properties":[{"key":"GoTerm","value":"P:negative regulation of type 2 immune response"},{"key":"GoEvidenceType","value":"IMP:MGI"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0045732","properties":[{"key":"GoTerm","value":"P:positive regulation of protein catabolic process"},{"key":"GoEvidenceType","value":"IDA:MGI"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0031398","properties":[{"key":"GoTerm","value":"P:positive regulation of protein ubiquitination"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0043161","properties":[{"key":"GoTerm","value":"P:proteasome-mediated ubiquitin-dependent protein catabolic process"},{"key":"GoEvidenceType","value":"ISO:GO_Central"}]},{"database":"GO","id":"GO:0048302","properties":[{"key":"GoTerm","value":"P:regulation of isotype switching to IgG isotypes"},{"key":"GoEvidenceType","value":"IMP:MGI"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0045619","properties":[{"key":"GoTerm","value":"P:regulation of lymphocyte differentiation"},{"key":"GoEvidenceType","value":"IMP:MGI"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0002761","properties":[{"key":"GoTerm","value":"P:regulation of myeloid leukocyte differentiation"},{"key":"GoEvidenceType","value":"IMP:MGI"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"17137798"}]},{"database":"GO","id":"GO:0006511","properties":[{"key":"GoTerm","value":"P:ubiquitin-dependent protein catabolic process"},{"key":"GoEvidenceType","value":"IBA:GO_Central"}]},{"database":"GO","id":"GO:0007034","properties":[{"key":"GoTerm","value":"P:vacuolar transport"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"CDD","id":"cd22305","properties":[{"key":"EntryName","value":"NDFIP1"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR019325","properties":[{"key":"EntryName","value":"NEDD4/Bsd2"}]},{"database":"PANTHER","id":"PTHR13396","properties":[{"key":"EntryName","value":"NEDD4 FAMILY INTERACTING PROTEIN 1/2"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR13396:SF3","properties":[{"key":"EntryName","value":"NEDD4 FAMILY-INTERACTING PROTEIN 1"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF10176","properties":[{"key":"EntryName","value":"NEDD4_Bsd2"},{"key":"MatchStatus","value":"2"}]}],"sequence":{"value":"MALALAALAAVEPACGSGYQQLQNEEEPGEPEQTAGDAPPPYSSITAESAAYFDYKDESGFPKPPSYNVATTLPSYDEAERTKTEATIPLVPGRDEDFVGRDDFDDTDQLRIGNDGIFMLTFFMAFLFNWIGFFLSFCLTTSAAGRYGAISGFGLSLIKWILIVRFSTYFPGYFDGQYWLWWVFLVLGFLLFLRGFINYAKVRKMPETFSNLPRTRVLFIY","length":221,"molWeight":24914,"crc64":"7699A062161AC6A4","md5":"5D89EAA7D138ACEE90B61DA0E3459A17"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"SUBUNIT":1,"INTERACTION":1,"SUBCELLULAR LOCATION":1,"TISSUE SPECIFICITY":1,"INDUCTION":1,"DOMAIN":1,"PTM":2,"DISRUPTION PHENOTYPE":1,"SEQUENCE CAUTION":1},"countByFeatureType":{"Initiator methionine":1,"Chain":1,"Topological domain":4,"Transmembrane":3,"Region":3,"Motif":3,"Modified residue":1,"Mutagenesis":2},"uniParcId":"UPI0000027D02"}}