NFAM1_MOUSE
ID NFAM1_MOUSE Reviewed; 264 AA.
AC Q8R4V1; Q3UAX8; Q9D5Z3;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=NFAT activation molecule 1;
DE AltName: Full=Calcineurin/NFAT-activating ITAM-containing protein;
DE AltName: Full=NFAT-activating protein with ITAM motif 1;
DE Flags: Precursor;
GN Name=Nfam1; Synonyms=Cnaip;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, GLYCOSYLATION,
RP DEVELOPMENTAL STAGE, AND INTERACTION WITH SYK AND ZAP70.
RC STRAIN=C57BL/6J; TISSUE=Spleen;
RX PubMed=15143214; DOI=10.1073/pnas.0401119101;
RA Ohtsuka M., Arase H., Takeuchi A., Yamasaki S., Shiina R., Suenaga T.,
RA Sakurai D., Yokosuka T., Arase N., Iwashima M., Kitamura T., Moriya H.,
RA Saito T.;
RT "NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule
RT that regulates B cell development and signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8126-8131(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Bone marrow, Cerebellum, Spinal cord, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
CC -!- FUNCTION: May function in immune system as a receptor which activates
CC via the calcineurin/NFAT-signaling pathway the downstream cytokine gene
CC promoters. Activates the transcription of IL-13 and TNF-alpha promoters
CC (By similarity). May be involved in the regulation of B-cell, but not
CC T-cell, development. {ECO:0000250}.
CC -!- SUBUNIT: No direct interaction with the B-cell antigen receptor (BCR).
CC Interacts with SYK; probably involved in BCR signaling. Interacts with
CC ZAP70. {ECO:0000269|PubMed:15143214}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Note=Partially recruited to lipid rafts
CC upon BCR stimulation. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8R4V1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8R4V1-2; Sequence=VSP_008044;
CC Name=3;
CC IsoId=Q8R4V1-3; Sequence=VSP_008043;
CC -!- TISSUE SPECIFICITY: Highly expressed in the spleen, expressed by both
CC B- and CD4+ and CD8+ T-cells, as well as non-T- and non-B-cells,
CC including macrophages and neutrophils. Expressed at low levels, if any,
CC in non-immune tissue. {ECO:0000269|PubMed:15143214}.
CC -!- DEVELOPMENTAL STAGE: Highest expression in pro-B-cells decreases with
CC B-cell differentiation. {ECO:0000269|PubMed:15143214}.
CC -!- DOMAIN: The ITAM domain displays no close similarity to any existing
CC ITAMs, except for four conserved positions. The phosphorylated ITAM
CC domain binds ZAP70 and SYK.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15143214}.
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DR EMBL; AF361364; AAL99631.1; -; mRNA.
DR EMBL; AK014802; BAB29558.1; -; mRNA.
DR EMBL; AK048992; BAC33506.1; -; mRNA.
DR EMBL; AK150635; BAE29724.1; -; mRNA.
DR EMBL; AK151187; BAE30186.1; -; mRNA.
DR EMBL; AK151884; BAE30770.1; -; mRNA.
DR EMBL; AK152262; BAE31080.1; -; mRNA.
DR EMBL; AK152499; BAE31268.1; -; mRNA.
DR EMBL; AK152688; BAE31419.1; -; mRNA.
DR EMBL; AK155106; BAE33051.1; -; mRNA.
DR EMBL; AK162939; BAE37125.1; -; mRNA.
DR EMBL; AK169918; BAE41458.1; -; mRNA.
DR EMBL; AK170098; BAE41562.1; -; mRNA.
DR EMBL; AK170593; BAE41900.1; -; mRNA.
DR EMBL; AK170677; BAE41952.1; -; mRNA.
DR EMBL; AK170811; BAE42044.1; -; mRNA.
DR EMBL; AK171086; BAE42239.1; -; mRNA.
DR EMBL; AK171201; BAE42309.1; -; mRNA.
DR CCDS; CCDS27694.1; -. [Q8R4V1-2]
DR CCDS; CCDS70651.1; -. [Q8R4V1-3]
DR CCDS; CCDS70652.1; -. [Q8R4V1-1]
DR RefSeq; NP_001258340.1; NM_001271411.1. [Q8R4V1-1]
DR RefSeq; NP_001258341.1; NM_001271412.1.
DR RefSeq; NP_001258342.1; NM_001271413.1. [Q8R4V1-3]
DR RefSeq; NP_001258343.1; NM_001271414.1. [Q8R4V1-3]
DR RefSeq; NP_083004.1; NM_028728.3. [Q8R4V1-2]
DR AlphaFoldDB; Q8R4V1; -.
DR IntAct; Q8R4V1; 2.
DR MINT; Q8R4V1; -.
DR STRING; 10090.ENSMUSP00000105129; -.
DR GlyGen; Q8R4V1; 2 sites.
DR iPTMnet; Q8R4V1; -.
DR PhosphoSitePlus; Q8R4V1; -.
DR MaxQB; Q8R4V1; -.
DR PaxDb; Q8R4V1; -.
DR PRIDE; Q8R4V1; -.
DR ProteomicsDB; 287403; -. [Q8R4V1-1]
DR ProteomicsDB; 287404; -. [Q8R4V1-2]
DR ProteomicsDB; 287405; -. [Q8R4V1-3]
DR Antibodypedia; 27327; 122 antibodies from 25 providers.
DR DNASU; 74039; -.
DR Ensembl; ENSMUST00000023076; ENSMUSP00000023076; ENSMUSG00000058099. [Q8R4V1-3]
DR Ensembl; ENSMUST00000109503; ENSMUSP00000105129; ENSMUSG00000058099. [Q8R4V1-2]
DR Ensembl; ENSMUST00000231165; ENSMUSP00000154945; ENSMUSG00000058099. [Q8R4V1-1]
DR GeneID; 74039; -.
DR KEGG; mmu:74039; -.
DR UCSC; uc007wzs.2; mouse. [Q8R4V1-2]
DR UCSC; uc007wzt.2; mouse. [Q8R4V1-1]
DR CTD; 150372; -.
DR MGI; MGI:1921289; Nfam1.
DR VEuPathDB; HostDB:ENSMUSG00000058099; -.
DR eggNOG; ENOG502SDBU; Eukaryota.
DR GeneTree; ENSGT00390000000787; -.
DR HOGENOM; CLU_083046_1_0_1; -.
DR InParanoid; Q8R4V1; -.
DR OMA; TYYCSVR; -.
DR OrthoDB; 1285575at2759; -.
DR PhylomeDB; Q8R4V1; -.
DR TreeFam; TF336307; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 74039; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Nfam1; mouse.
DR PRO; PR:Q8R4V1; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8R4V1; protein.
DR Bgee; ENSMUSG00000058099; Expressed in granulocyte and 79 other tissues.
DR ExpressionAtlas; Q8R4V1; baseline and differential.
DR Genevisible; Q8R4V1; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISS:HGNC-UCL.
DR GO; GO:0045121; C:membrane raft; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:HGNC-UCL.
DR GO; GO:0030183; P:B cell differentiation; IMP:HGNC-UCL.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:HGNC-UCL.
DR GO; GO:0050861; P:positive regulation of B cell receptor signaling pathway; IMP:HGNC-UCL.
DR GO; GO:0001819; P:positive regulation of cytokine production; IEA:InterPro.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:HGNC-UCL.
DR GO; GO:0045577; P:regulation of B cell differentiation; IDA:MGI.
DR GO; GO:0007165; P:signal transduction; ISS:HGNC-UCL.
DR InterPro; IPR033549; NFAM1.
DR PANTHER; PTHR35680; PTHR35680; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Phosphoprotein; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..37
FT /evidence="ECO:0000255"
FT CHAIN 38..264
FT /note="NFAT activation molecule 1"
FT /id="PRO_0000015047"
FT TOPO_DOM 38..159
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 160..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..264
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 49..145
FT /note="Ig-like V-type"
FT DOMAIN 212..232
FT /note="ITAM"
FT MOD_RES 215
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 226
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 64..110
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..62
FT /note="MESWLLRRGARVRCLHPPSWLPAWCFLCLLPVPQTLQLTGLVSLTHTSLPIM
FT VSLANTDVFF -> MPGYQLTRQGDIHPNVQSKKDL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008044"
FT VAR_SEQ 1..51
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008043"
SQ SEQUENCE 264 AA; 29988 MW; 3C86F1E9ABF3E538 CRC64;
MESWLLRRGA RVRCLHPPSW LPAWCFLCLL PVPQTLQLTG LVSLTHTSLP IMVSLANTDV
FFSCRIEDFT RLQRDLPVKL FHTDIHGRRR WEKQINCQHR PGMENHTRDC MVKLSQANTS
ATGIYYFIVE GEETYQSDGV VILVRDTVYQ PPAFKVQEAL MLGFTSLMSV LGVLGTALLL
WKKKQISVLG KHTAKTCSGL KSTVGTTKPP AESVYTSLQR RETEVYACMK EETGSPVFSQ
SPATKEKLNR FEDDNEFNLV YENL
