NFAM1_HUMAN
ID NFAM1_HUMAN Reviewed; 270 AA.
AC Q8NET5; B0QYD0; Q20WL2; Q5JZ96; Q8IUY8; Q8TEM8;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 153.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF TYR-220 AND TYR-231.
RX PubMed=12615919; DOI=10.1074/jbc.m211060200;
RA Yang J., Hu G., Wang S.W., Li Y., Martin R., Li K., Yao Z.;
RT "Calcineurin/nuclear factors of activated T cells (NFAT)-activating and
RT immunoreceptor tyrosine-based activation motif (ITAM)-containing protein
RT (CNAIP), a novel ITAM-containing protein that activates the
RT calcineurin/NFAT-signaling pathway.";
RL J. Biol. Chem. 278:16797-16801(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, GLYCOSYLATION, INTERACTION WITH SYK AND ZAP70, AND MUTAGENESIS
RP OF TYR-220 AND TYR-231.
RC TISSUE=T-cell;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 125-270.
RC TISSUE=Spleen;
RX PubMed=12693554; DOI=10.1093/dnares/10.1.49;
RA Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N.,
RA Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen. II. The
RT complete sequences of 81 cDNA clones.";
RL DNA Res. 10:49-57(2003).
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
CC promoters. May be involved in the regulation of B-cell, but not T-cell,
CC development. Overexpression activates downstream effectors without
CC ligand binding or antibody cross-linking. {ECO:0000269|PubMed:12615919,
CC ECO:0000269|PubMed:15143214}.
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 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q8NET5; Q9H165-2: BCL11A; NbExp=3; IntAct=EBI-11990542, EBI-10183342;
CC Q8NET5; Q969L2: MAL2; NbExp=3; IntAct=EBI-11990542, EBI-944295;
CC Q8NET5; P15884-3: TCF4; NbExp=3; IntAct=EBI-11990542, EBI-13636688;
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 -!- TISSUE SPECIFICITY: Highly expressed in neutrophils, primary monocytes,
CC mast cells, monocytic cell lines and lymphocytes. Also expressed in
CC spleen B and T-cells, and lung. Expressed at low level in non-immune
CC tissue. {ECO:0000269|PubMed:12615919, 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; AY247409; AAO91847.1; -; mRNA.
DR EMBL; AY121370; AAM83133.1; -; mRNA.
DR EMBL; CT841509; CAJ86439.1; -; mRNA.
DR EMBL; AL022316; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60505.1; -; Genomic_DNA.
DR EMBL; BC038241; AAH38241.2; -; mRNA.
DR EMBL; AK074094; BAB84920.1; -; mRNA.
DR CCDS; CCDS14034.1; -.
DR RefSeq; NP_001305252.1; NM_001318323.1.
DR RefSeq; NP_666017.1; NM_145912.6.
DR AlphaFoldDB; Q8NET5; -.
DR SMR; Q8NET5; -.
DR BioGRID; 127289; 11.
DR IntAct; Q8NET5; 4.
DR STRING; 9606.ENSP00000333680; -.
DR GlyGen; Q8NET5; 1 site.
DR iPTMnet; Q8NET5; -.
DR PhosphoSitePlus; Q8NET5; -.
DR BioMuta; NFAM1; -.
DR DMDM; 34222694; -.
DR EPD; Q8NET5; -.
DR jPOST; Q8NET5; -.
DR MassIVE; Q8NET5; -.
DR PaxDb; Q8NET5; -.
DR PeptideAtlas; Q8NET5; -.
DR PRIDE; Q8NET5; -.
DR ProteomicsDB; 73214; -.
DR Antibodypedia; 27327; 122 antibodies from 25 providers.
DR DNASU; 150372; -.
DR Ensembl; ENST00000329021.10; ENSP00000333680.5; ENSG00000235568.7.
DR GeneID; 150372; -.
DR KEGG; hsa:150372; -.
DR MANE-Select; ENST00000329021.10; ENSP00000333680.5; NM_145912.8; NP_666017.1.
DR UCSC; uc003bcn.5; human.
DR CTD; 150372; -.
DR DisGeNET; 150372; -.
DR GeneCards; NFAM1; -.
DR HGNC; HGNC:29872; NFAM1.
DR HPA; ENSG00000235568; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 608740; gene.
DR neXtProt; NX_Q8NET5; -.
DR OpenTargets; ENSG00000235568; -.
DR PharmGKB; PA134949664; -.
DR VEuPathDB; HostDB:ENSG00000235568; -.
DR eggNOG; ENOG502SDBU; Eukaryota.
DR GeneTree; ENSGT00390000000787; -.
DR HOGENOM; CLU_083046_1_0_1; -.
DR InParanoid; Q8NET5; -.
DR OMA; TYYCSVR; -.
DR OrthoDB; 1285575at2759; -.
DR PhylomeDB; Q8NET5; -.
DR TreeFam; TF336307; -.
DR PathwayCommons; Q8NET5; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q8NET5; -.
DR BioGRID-ORCS; 150372; 9 hits in 1070 CRISPR screens.
DR ChiTaRS; NFAM1; human.
DR GenomeRNAi; 150372; -.
DR Pharos; Q8NET5; Tbio.
DR PRO; PR:Q8NET5; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q8NET5; protein.
DR Bgee; ENSG00000235568; Expressed in monocyte and 178 other tissues.
DR ExpressionAtlas; Q8NET5; baseline and differential.
DR Genevisible; Q8NET5; HS.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IDA:HGNC-UCL.
DR GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:HGNC-UCL.
DR GO; GO:0030183; P:B cell differentiation; ISS:HGNC-UCL.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; NAS:HGNC-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:HGNC-UCL.
DR GO; GO:0050861; P:positive regulation of B cell receptor signaling pathway; ISS:HGNC-UCL.
DR GO; GO:0001819; P:positive regulation of cytokine production; NAS:HGNC-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:HGNC-UCL.
DR GO; GO:0045577; P:regulation of B cell differentiation; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IDA:HGNC-UCL.
DR InterPro; IPR033549; NFAM1.
DR InterPro; IPR003110; Phos_immunorcpt_sig_ITAM.
DR PANTHER; PTHR35680; PTHR35680; 1.
DR PROSITE; PS51055; ITAM_1; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Membrane; Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..42
FT /evidence="ECO:0000255"
FT CHAIN 43..270
FT /note="NFAT activation molecule 1"
FT /id="PRO_0000015046"
FT TOPO_DOM 43..163
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 50..150
FT /note="Ig-like V-type"
FT DOMAIN 209..237
FT /note="ITAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379"
FT REGION 190..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 234..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 220
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 231
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 65..114
FT /evidence="ECO:0000250"
FT VARIANT 137
FT /note="H -> Y (in dbSNP:rs34296033)"
FT /id="VAR_049964"
FT VARIANT 187
FT /note="N -> K (in dbSNP:rs17003048)"
FT /id="VAR_049965"
FT MUTAGEN 220
FT /note="Y->A,F: Abolishes the ITAM-mediated-activating
FT activity."
FT /evidence="ECO:0000269|PubMed:12615919,
FT ECO:0000269|PubMed:15143214"
FT MUTAGEN 231
FT /note="Y->A,F: Abolishes the ITAM-mediated-activating
FT activity."
FT /evidence="ECO:0000269|PubMed:12615919,
FT ECO:0000269|PubMed:15143214"
SQ SEQUENCE 270 AA; 29686 MW; 0026DBDE1FEAD2B3 CRC64;
MENQPVRWRA LPGLPRPPGL PAAPWLLLGV LLLPGTLRLA GGQSVTHTGL PIMASLANTA
ISFSCRITYP YTPQFKVFTV SYFHEDLQGQ RSPKKPTNCH PGLGTENQSH TLDCQVTLVL
PGASATGTYY CSVHWPHSTV RGSGTFILVR DAGYREPPQS PQKLLLFGFT GLLSVLSVVG
TALLLWNKKR MRGPGKDPTR KCPDPRSASS PKQHPSESVY TALQRRETEV YACIENEDGS
SPTAKQSPLS QERPHRFEDD GELNLVYENL
