FLT3L_MOUSE
ID FLT3L_MOUSE Reviewed; 232 AA.
AC P49772; Q64085;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Fms-related tyrosine kinase 3 ligand;
DE Short=Flt3 ligand;
DE Short=Flt3L;
DE AltName: Full=SL cytokine;
DE Flags: Precursor;
GN Name=Flt3lg; Synonyms=Flt3l;
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].
RX PubMed=8145851; DOI=10.1038/368643a0;
RA Hannum C., Culpepper J., Campbell D., McClanahan T., Zurawski S.,
RA Bazan J.F., Kastelein R., Hudak S., Wagner J., Mattson J., Luh J., Duda G.,
RA Martina N., Peterson D., Menon S., Shanafelt A., Muench M., Kelner G.,
RA Namikawa R., Rennick D., Roncarolo M.G., Zlotnik A., Rosnet O.,
RA Dubreuil P., Birnbaum D., Lee F.;
RT "Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of
RT haematopoietic stem cells and is encoded by variant RNAs.";
RL Nature 368:643-648(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=SJL/J;
RX PubMed=7505204; DOI=10.1016/0092-8674(93)90325-k;
RA Lyman S.D., James L., Vanden Bos T., Devries P., Brasel K., Gliniak B.,
RA Hollingsworth L.T., Picha K.S., McKenna H.J., Splett R.R., Fletcher F.A.,
RA Maraskovsky E., Farrah T., Foxworthe D., Williams D.E., Beckmann M.P.;
RT "Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor:
RT a proliferative factor for primitive hematopoietic cells.";
RL Cell 75:1157-1167(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=7566977;
RA Lyman S.D., Stocking K., Davison B., Fletcher F., Johnson L., Escobar S.;
RT "Structural analysis of human and murine flt3 ligand genomic loci.";
RL Oncogene 11:1165-1172(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RX PubMed=7824267;
RA Lyman S.D., James L., Escobar S., Downey H., de Vries P., Brasel K.,
RA Stocking K., Beckmann M.P., Copeland N.G., Cleveland L.S.;
RT "Identification of soluble and membrane-bound isoforms of the murine flt3
RT ligand generated by alternative splicing of mRNAs.";
RL Oncogene 10:149-157(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA McClanahan T., Culpepper J., Campbell D., Wagner J., Franz-Bacon K.,
RA Mattson J., Tsai S., Luh J., Guimares M.J., Mattei M.-G., Rosnet O.,
RA Birnbaum D., Hannum C.;
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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).
CC -!- FUNCTION: Stimulates the proliferation of early hematopoietic cells by
CC activating FLT3. Synergizes well with a number of other colony
CC stimulating factors and interleukins.
CC -!- SUBUNIT: Homodimer (soluble isoform). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted. Note=Biologically active.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted. Note=Inactive.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=6C;
CC IsoId=P49772-1; Sequence=Displayed;
CC Name=2; Synonyms=5H;
CC IsoId=P49772-2; Sequence=VSP_004253;
CC Name=3; Synonyms=E6;
CC IsoId=P49772-3; Sequence=VSP_004254, VSP_004255;
CC Name=4; Synonyms=E6Delta16;
CC IsoId=P49772-4; Sequence=VSP_004256;
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DR EMBL; U04807; AAA18000.1; -; mRNA.
DR EMBL; L23636; AAA39436.1; -; mRNA.
DR EMBL; U29875; AAA90951.1; -; Genomic_DNA.
DR EMBL; U29875; AAA90952.1; -; Genomic_DNA.
DR EMBL; S76459; AAB33069.1; -; mRNA.
DR EMBL; S76461; AAB33070.1; -; mRNA.
DR EMBL; S76464; AAB33071.1; -; mRNA.
DR EMBL; U44024; AAA93307.1; -; Genomic_DNA.
DR EMBL; U44024; AAA93306.1; -; Genomic_DNA.
DR EMBL; AK020105; BAB31997.1; -; mRNA.
DR CCDS; CCDS39948.1; -. [P49772-1]
DR PIR; A49265; A49265.
DR PIR; I58343; I58343.
DR RefSeq; NP_038548.3; NM_013520.3. [P49772-1]
DR AlphaFoldDB; P49772; -.
DR SMR; P49772; -.
DR STRING; 10090.ENSMUSP00000123506; -.
DR GlyGen; P49772; 2 sites.
DR PhosphoSitePlus; P49772; -.
DR MaxQB; P49772; -.
DR PaxDb; P49772; -.
DR PRIDE; P49772; -.
DR ABCD; P49772; 7 sequenced antibodies.
DR Antibodypedia; 2271; 422 antibodies from 33 providers.
DR DNASU; 14256; -.
DR Ensembl; ENSMUST00000146760; ENSMUSP00000123506; ENSMUSG00000110206. [P49772-1]
DR Ensembl; ENSMUST00000209238; ENSMUSP00000148156; ENSMUSG00000110206. [P49772-1]
DR Ensembl; ENSMUST00000211246; ENSMUSP00000147278; ENSMUSG00000110206. [P49772-2]
DR GeneID; 14256; -.
DR KEGG; mmu:14256; -.
DR UCSC; uc009gtn.2; mouse. [P49772-1]
DR CTD; 14256; -.
DR MGI; MGI:95560; Flt3l.
DR VEuPathDB; HostDB:ENSMUSG00000110206; -.
DR eggNOG; ENOG502SAIE; Eukaryota.
DR GeneTree; ENSGT00530000064424; -.
DR HOGENOM; CLU_082442_1_0_1; -.
DR InParanoid; P49772; -.
DR OMA; GCLELQC; -.
DR OrthoDB; 1596773at2759; -.
DR PhylomeDB; P49772; -.
DR TreeFam; TF338225; -.
DR Reactome; R-MMU-109704; PI3K Cascade.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-9607240; FLT3 Signaling.
DR Reactome; R-MMU-9706369; Negative regulation of FLT3.
DR Reactome; R-MMU-9706374; FLT3 signaling through SRC family kinases.
DR BioGRID-ORCS; 14256; 3 hits in 38 CRISPR screens.
DR PRO; PR:P49772; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P49772; protein.
DR Bgee; ENSMUSG00000110206; Expressed in bone marrow and 79 other tissues.
DR ExpressionAtlas; P49772; baseline and differential.
DR Genevisible; P49772; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031233; C:intrinsic component of external side of plasma membrane; IDA:MGI.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IDA:MGI.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISO:MGI.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IDA:MGI.
DR GO; GO:0030098; P:lymphocyte differentiation; IMP:MGI.
DR GO; GO:0001779; P:natural killer cell differentiation; IMP:MGI.
DR GO; GO:0071866; P:negative regulation of apoptotic process in bone marrow cell; IGI:MGI.
DR GO; GO:0045787; P:positive regulation of cell cycle; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0071864; P:positive regulation of cell proliferation in bone marrow; IGI:MGI.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; IMP:MGI.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; IMP:MGI.
DR GO; GO:0032825; P:positive regulation of natural killer cell differentiation; IMP:MGI.
DR GO; GO:0090290; P:positive regulation of osteoclast proliferation; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IGI:MGI.
DR GO; GO:0030885; P:regulation of myeloid dendritic cell activation; IMP:MGI.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR004213; Flt3_lig.
DR PANTHER; PTHR11032; PTHR11032; 1.
DR Pfam; PF02947; Flt3_lig; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Cytokine; Disulfide bond;
KW Glycoprotein; Membrane; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..232
FT /note="Fms-related tyrosine kinase 3 ligand"
FT /id="PRO_0000021282"
FT TOPO_DOM 27..189
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 211..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..112
FT /evidence="ECO:0000250"
FT DISULFID 71..156
FT /evidence="ECO:0000250"
FT DISULFID 120..161
FT /evidence="ECO:0000250"
FT VAR_SEQ 159..163
FT /note="VQCQP -> GLIMQARLTLNSKQSSCLSVLSAGIT (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_004256"
FT VAR_SEQ 164..232
FT /note="DSSTLLPPRSPIALEATELPEPRPRQLLLLLLLLLPLTLVLLAAAWGLRWQR
FT ARRRGELHPGVPLPSHP -> GNGGPRAQHHGATRLTATALLTVCPGLLLPLVGTSHMF
FT FLPYFLSFLSSFLKMYLYV (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004253"
FT VAR_SEQ 164..169
FT /note="DSSTLL -> GSHYAG (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004254"
FT VAR_SEQ 170..232
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004255"
FT CONFLICT 141
FT /note="A -> G (in Ref. 1; AAA18000)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="Missing (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 232 AA; 26141 MW; 3A3680D3CB69FBA6 CRC64;
MTVLAPAWSP NSSLLLLLLL LSPCLRGTPD CYFSHSPISS NFKVKFRELT DHLLKDYPVT
VAVNLQDEKH CKALWSLFLA QRWIEQLKTV AGSKMQTLLE DVNTEIHFVT SCTFQPLPEC
LRFVQTNISH LLKDTCTQLL ALKPCIGKAC QNFSRCLEVQ CQPDSSTLLP PRSPIALEAT
ELPEPRPRQL LLLLLLLLPL TLVLLAAAWG LRWQRARRRG ELHPGVPLPS HP
