FLT3L_HUMAN
ID FLT3L_HUMAN Reviewed; 235 AA.
AC P49771; A0AVC2; B9EGH2; Q05C96;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 179.
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;
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] (ISOFORM 1).
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] (ISOFORM 1).
RX PubMed=8180375;
RA Lyman S.D., James L., Johnson L., Brasel K., de Vries P., Escobar S.S.,
RA Downey H., Splett R.R., Beckmann M.P., McKenna H.J.;
RT "Cloning of the human homologue of the murine flt3 ligand: a growth factor
RT for early hematopoietic progenitor cells.";
RL Blood 83:2795-2801(1994).
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 [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain;
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 X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=10881197; DOI=10.1038/75896;
RA Savvides S.N., Boone T., Karplus P.A.;
RT "Flt3 ligand structure and unexpected commonalities of helical bundles and
RT cystine knots.";
RL Nat. Struct. Biol. 7:486-491(2000).
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 (isoform 2).
CC -!- INTERACTION:
CC P49771; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-724977, EBI-3958099;
CC P49771-3; P13473-2: LAMP2; NbExp=3; IntAct=EBI-25872794, EBI-21591415;
CC P49771-3; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-25872794, EBI-2623095;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Membrane-bound;
CC IsoId=P49771-1; Sequence=Displayed;
CC Name=2; Synonyms=Soluble;
CC IsoId=P49771-2; Sequence=VSP_004251, VSP_004252;
CC Name=3;
CC IsoId=P49771-3; Sequence=VSP_054599;
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DR EMBL; U04806; AAA17999.1; -; mRNA.
DR EMBL; U03858; AAA19825.1; -; mRNA.
DR EMBL; U29874; AAA90949.1; -; Genomic_DNA.
DR EMBL; U29874; AAA90950.1; -; Genomic_DNA.
DR EMBL; AK301136; BAG62728.1; -; mRNA.
DR EMBL; AC010619; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028001; AAH28001.1; -; mRNA.
DR EMBL; BC126293; AAI26294.1; -; mRNA.
DR EMBL; BC136464; AAI36465.1; -; mRNA.
DR CCDS; CCDS12767.1; -. [P49771-1]
DR CCDS; CCDS62753.1; -. [P49771-3]
DR PIR; I38440; I38440.
DR PIR; I39076; I39076.
DR RefSeq; NP_001191431.1; NM_001204502.1. [P49771-1]
DR RefSeq; NP_001191432.1; NM_001204503.1. [P49771-1]
DR RefSeq; NP_001265566.1; NM_001278637.1. [P49771-3]
DR RefSeq; NP_001265567.1; NM_001278638.1. [P49771-3]
DR RefSeq; NP_001450.2; NM_001459.3. [P49771-1]
DR RefSeq; XP_011524984.1; XM_011526682.2. [P49771-3]
DR PDB; 1ETE; X-ray; 2.20 A; A/B/C/D=27-160.
DR PDB; 3QS7; X-ray; 4.30 A; A/B/C/D=27-160.
DR PDB; 3QS9; X-ray; 7.80 A; A/B/C/D=27-160.
DR PDB; 7NBI; X-ray; 1.65 A; A/B=27-160.
DR PDBsum; 1ETE; -.
DR PDBsum; 3QS7; -.
DR PDBsum; 3QS9; -.
DR PDBsum; 7NBI; -.
DR AlphaFoldDB; P49771; -.
DR SMR; P49771; -.
DR BioGRID; 108611; 3.
DR DIP; DIP-6220N; -.
DR IntAct; P49771; 5.
DR STRING; 9606.ENSP00000469613; -.
DR GlyGen; P49771; 2 sites.
DR iPTMnet; P49771; -.
DR PhosphoSitePlus; P49771; -.
DR BioMuta; FLT3LG; -.
DR DMDM; 1706818; -.
DR jPOST; P49771; -.
DR PaxDb; P49771; -.
DR PeptideAtlas; P49771; -.
DR PRIDE; P49771; -.
DR ProteomicsDB; 56114; -. [P49771-1]
DR ProteomicsDB; 56115; -. [P49771-2]
DR ABCD; P49771; 7 sequenced antibodies.
DR Antibodypedia; 2271; 422 antibodies from 33 providers.
DR DNASU; 2323; -.
DR Ensembl; ENST00000204637.6; ENSP00000204637.2; ENSG00000090554.13. [P49771-3]
DR Ensembl; ENST00000594009.5; ENSP00000469613.1; ENSG00000090554.13. [P49771-1]
DR Ensembl; ENST00000595510.1; ENSP00000471226.1; ENSG00000090554.13. [P49771-3]
DR Ensembl; ENST00000597551.6; ENSP00000468977.1; ENSG00000090554.13. [P49771-1]
DR Ensembl; ENST00000600429.5; ENSP00000470453.1; ENSG00000090554.13. [P49771-1]
DR GeneID; 2323; -.
DR KEGG; hsa:2323; -.
DR MANE-Select; ENST00000597551.6; ENSP00000468977.1; NM_001459.4; NP_001450.2.
DR UCSC; uc002pnu.4; human. [P49771-1]
DR CTD; 2323; -.
DR DisGeNET; 2323; -.
DR GeneCards; FLT3LG; -.
DR HGNC; HGNC:3766; FLT3LG.
DR HPA; ENSG00000090554; Low tissue specificity.
DR MIM; 600007; gene.
DR neXtProt; NX_P49771; -.
DR OpenTargets; ENSG00000090554; -.
DR PharmGKB; PA28182; -.
DR VEuPathDB; HostDB:ENSG00000090554; -.
DR eggNOG; ENOG502SAIE; Eukaryota.
DR GeneTree; ENSGT00530000064424; -.
DR HOGENOM; CLU_082442_1_0_1; -.
DR InParanoid; P49771; -.
DR OMA; GCLELQC; -.
DR OrthoDB; 1596773at2759; -.
DR PhylomeDB; P49771; -.
DR TreeFam; TF338225; -.
DR PathwayCommons; P49771; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-9607240; FLT3 Signaling.
DR Reactome; R-HSA-9645135; STAT5 Activation.
DR Reactome; R-HSA-9706369; Negative regulation of FLT3.
DR Reactome; R-HSA-9706374; FLT3 signaling through SRC family kinases.
DR Reactome; R-HSA-9706377; FLT3 signaling by CBL mutants.
DR SignaLink; P49771; -.
DR SIGNOR; P49771; -.
DR BioGRID-ORCS; 2323; 27 hits in 1087 CRISPR screens.
DR EvolutionaryTrace; P49771; -.
DR GeneWiki; FLT3LG; -.
DR GenomeRNAi; 2323; -.
DR Pharos; P49771; Tbio.
DR PRO; PR:P49771; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P49771; protein.
DR Bgee; ENSG00000090554; Expressed in granulocyte and 97 other tissues.
DR ExpressionAtlas; P49771; baseline and differential.
DR Genevisible; P49771; HS.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0035162; P:embryonic hemopoiesis; IDA:DFLAT.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cytokine;
KW Disulfide bond; Glycoprotein; Membrane; Reference proteome; Secreted;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..235
FT /note="Fms-related tyrosine kinase 3 ligand"
FT /id="PRO_0000021281"
FT TOPO_DOM 27..184
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 213..235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..111
FT DISULFID 70..153
FT DISULFID 119..158
FT VAR_SEQ 1..82
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_054599"
FT VAR_SEQ 161..178
FT /note="DSSTLPPPWSPRPLEATA -> VETVFHRVSQDGLDLLTS (in isoform
FT 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004251"
FT VAR_SEQ 179..235
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004252"
FT CONFLICT 72
FT /note="G -> A (in Ref. 1; AAA17999)"
FT /evidence="ECO:0000305"
FT HELIX 41..51
FT /evidence="ECO:0007829|PDB:7NBI"
FT STRAND 58..64
FT /evidence="ECO:0007829|PDB:7NBI"
FT HELIX 69..89
FT /evidence="ECO:0007829|PDB:7NBI"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:7NBI"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:7NBI"
FT HELIX 106..110
FT /evidence="ECO:0007829|PDB:7NBI"
FT STRAND 122..125
FT /evidence="ECO:0007829|PDB:7NBI"
FT HELIX 127..141
FT /evidence="ECO:0007829|PDB:7NBI"
FT TURN 142..147
FT /evidence="ECO:0007829|PDB:7NBI"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:7NBI"
SQ SEQUENCE 235 AA; 26416 MW; 73B95BF693B4CECF CRC64;
MTVLAPAWSP TTYLLLLLLL SSGLSGTQDC SFQHSPISSD FAVKIRELSD YLLQDYPVTV
ASNLQDEELC GGLWRLVLAQ RWMERLKTVA GSKMQGLLER VNTEIHFVTK CAFQPPPSCL
RFVQTNISRL LQETSEQLVA LKPWITRQNF SRCLELQCQP DSSTLPPPWS PRPLEATAPT
APQPPLLLLL LLPVGLLLLA AAWCLHWQRT RRRTPRPGEQ VPPVPSPQDL LLVEH
