IL7_HUMAN
ID IL7_HUMAN Reviewed; 177 AA.
AC P13232; A0N0L3; Q5FBY5; Q5FBY9;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Interleukin-7;
DE Short=IL-7;
DE Flags: Precursor;
GN Name=IL7;
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=2643102; DOI=10.1073/pnas.86.1.302;
RA Goodwin R.G., Lupton S., Schmierer A., Hjerrild K.J., Jerzy R.,
RA Clevenger W., Gillis S., Cosman D., Namen A.E.;
RT "Human interleukin 7: molecular cloning and growth factor activity on human
RT and murine B-lineage cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:302-306(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2329282;
RA Lupton S.D., Gimpel S., Jerzy R., Brunton L.L., Hjerrild K.A., Cosman D.,
RA Goodwin R.G.;
RT "Characterization of the human and murine IL-7 genes.";
RL J. Immunol. 144:3592-3601(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RA Sameshima E., Tabata Y., Hayashi A., Iida K., Mitsuyama M., Kanai S.,
RA Furuya T.;
RT "interleukin7 mRNA,nirs splice variant2.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA Nickerson D.A.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [8]
RP FUNCTION.
RX PubMed=7527823;
RA Dittel B.N., LeBien T.W.;
RT "The growth response to IL-7 during normal human B cell ontogeny is
RT restricted to B-lineage cells expressing CD34.";
RL J. Immunol. 154:58-67(1995).
RN [9]
RP DISULFIDE BONDS, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=9407080; DOI=10.1074/jbc.272.52.32995;
RA Cosenza L., Sweeney E., Murphy J.R.;
RT "Disulfide bond assignment in human interleukin-7 by matrix-assisted laser
RT desorption/ionization mass spectroscopy and site-directed cysteine to
RT serine mutational analysis.";
RL J. Biol. Chem. 272:32995-33000(1997).
RN [10]
RP FUNCTION, AND INTERACTION WITH IL7R AND CSF2RG.
RX PubMed=8128231; DOI=10.1126/science.8128231;
RA Kondo M., Takeshita T., Higuchi M., Nakamura M., Sudo T., Nishikawa S.,
RA Sugamura K.;
RT "Functional participation of the IL-2 receptor gamma chain in IL-7 receptor
RT complexes.";
RL Science 263:1453-1454(1994).
RN [11]
RP FUNCTION.
RX PubMed=18523275; DOI=10.4049/jimmunol.180.12.8109;
RA Johnson S.E., Shah N., Bajer A.A., LeBien T.W.;
RT "IL-7 activates the phosphatidylinositol 3-kinase/AKT pathway in normal
RT human thymocytes but not normal human B cell precursors.";
RL J. Immunol. 180:8109-8117(2008).
RN [12]
RP FUNCTION.
RX PubMed=20974963; DOI=10.1073/pnas.1008271107;
RA Rochman Y., Kashyap M., Robinson G.W., Sakamoto K., Gomez-Rodriguez J.,
RA Wagner K.U., Leonard W.J.;
RT "Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases
RT JAK1 and JAK2 reveals a key difference from IL-7-induced signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:19455-19460(2010).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25870237; DOI=10.4049/jimmunol.1400560;
RA Bazdar D.A., Kalinowska M., Panigrahi S., Sieg S.F.;
RT "Recycled IL-7 Can Be Delivered to Neighboring T Cells.";
RL J. Immunol. 194:4698-4704(2015).
RN [14]
RP 3D-STRUCTURE MODELING.
RX PubMed=8862549; DOI=10.1093/protein/9.6.493;
RA Kroemer R.T., Doughty S.W., Robinson A.J., Richards W.G.;
RT "Prediction of the three-dimensional structure of human interleukin-7 by
RT homology modeling.";
RL Protein Eng. 9:493-498(1996).
RN [15]
RP 3D-STRUCTURE MODELING.
RX PubMed=10850801; DOI=10.1110/ps.9.5.916;
RA Cosenza L., Rosenbach A., White J.V., Murphy J.R., Smith T.F.;
RT "Comparative model building of interleukin-7 using interleukin-4 as a
RT template: a structural hypothesis that displays atypical surface chemistry
RT in helix D important for receptor activation.";
RL Protein Sci. 9:916-926(2000).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 26-177 IN COMPLEX WITH IL7R, AND
RP DISULFIDE BONDS.
RX PubMed=19141282; DOI=10.1016/j.str.2008.10.019;
RA McElroy C.A., Dohm J.A., Walsh S.T.;
RT "Structural and biophysical studies of the human IL-7/IL-7Ralpha complex.";
RL Structure 17:54-65(2009).
RN [17]
RP VARIANT EV5 69-ARG--HIS-177 DEL, AND INVOLVEMENT IN EV5.
RX PubMed=25981006; DOI=10.1016/j.jaad.2015.02.1118;
RA Horev L., Unger S., Molho-Pessach V., Meir T., Maly A., Stepensky P.,
RA Zamir M., Keller B., Babay S., Warnatz K., Ramot Y., Zlotogorski A.;
RT "Generalized verrucosis and HPV-3 susceptibility associated with CD4 T-cell
RT lymphopenia caused by inherited human interleukin-7 deficiency.";
RL J. Am. Acad. Dermatol. 72:1082-1084(2015).
CC -!- FUNCTION: Hematopoietic cytokine that plays an essential role in the
CC development, expansion, and survival of naive and memory T-cells and B-
CC cells thereby regulating the number of mature lymphocytes and
CC maintaining lymphoid homeostasis (PubMed:7527823, PubMed:25870237).
CC Mechanistically, exerts its biological effects through a receptor
CC composed of IL7RA subunit and the cytokine receptor common subunit
CC gamma/CSF2RG (PubMed:8128231). Binding to the receptor leads to
CC activation of various kinases including JAK1 or JAK3 depending on the
CC cell type and subsequently propagation of signals through activation of
CC several downstream signaling pathways including the PI3K/Akt/mTOR or
CC the JAK-STAT5 (PubMed:18523275, PubMed:20974963).
CC {ECO:0000269|PubMed:18523275, ECO:0000269|PubMed:20974963,
CC ECO:0000269|PubMed:25870237, ECO:0000269|PubMed:7527823,
CC ECO:0000269|PubMed:8128231}.
CC -!- SUBUNIT: Interacts with IL7R and CSF2RG. {ECO:0000269|PubMed:8128231}.
CC -!- INTERACTION:
CC P13232; P31785: IL2RG; NbExp=2; IntAct=EBI-80516, EBI-80475;
CC P13232; P16871: IL7R; NbExp=10; IntAct=EBI-80516, EBI-80490;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25870237}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P13232-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P13232-2; Sequence=VSP_042926;
CC Name=3;
CC IsoId=P13232-3; Sequence=VSP_047579, VSP_047580;
CC -!- DISEASE: Epidermodysplasia verruciformis 5 (EV5) [MIM:618309]: A form
CC of epidermodysplasia verruciformis, a rare genodermatosis associated
CC with a high risk of skin carcinoma that results from an abnormal
CC susceptibility to infection by specific human papillomaviruses,
CC including the oncogenic HPV5. Infection leads to the early development
CC of disseminated flat wart-like and pityriasis versicolor-like skin
CC lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous
CC cell carcinomas develop in about half of the patients, mainly on sun-
CC exposed skin areas. EV5 patients shows T-cell lymphopenia, particularly
CC affecting CD4+ T cells. EV5 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:25981006}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the IL-7/IL-9 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-7 entry;
CC URL="https://en.wikipedia.org/wiki/Interleukin_7";
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DR EMBL; J04156; AAA59156.1; -; mRNA.
DR EMBL; M29053; AAC63047.1; -; Genomic_DNA.
DR EMBL; M29048; AAC63047.1; JOINED; Genomic_DNA.
DR EMBL; M29049; AAC63047.1; JOINED; Genomic_DNA.
DR EMBL; M29050; AAC63047.1; JOINED; Genomic_DNA.
DR EMBL; M29051; AAC63047.1; JOINED; Genomic_DNA.
DR EMBL; M29052; AAC63047.1; JOINED; Genomic_DNA.
DR EMBL; AB102879; BAD89408.1; -; mRNA.
DR EMBL; AB102883; BAD89412.1; -; mRNA.
DR EMBL; EF064721; ABK41904.1; -; Genomic_DNA.
DR EMBL; AC083837; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC100854; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471068; EAW87060.1; -; Genomic_DNA.
DR EMBL; CH471068; EAW87062.1; -; Genomic_DNA.
DR EMBL; BC047698; AAH47698.1; -; mRNA.
DR CCDS; CCDS56541.1; -. [P13232-2]
DR CCDS; CCDS6224.1; -. [P13232-1]
DR PIR; A43527; A32223.
DR PIR; B32223; B32223.
DR PIR; C32223; C32223.
DR RefSeq; NP_000871.1; NM_000880.3. [P13232-1]
DR RefSeq; NP_001186815.1; NM_001199886.1. [P13232-2]
DR RefSeq; NP_001186816.1; NM_001199887.1.
DR RefSeq; NP_001186817.1; NM_001199888.1.
DR PDB; 3DI2; X-ray; 2.70 A; A/C=26-177.
DR PDB; 3DI3; X-ray; 2.90 A; A=26-177.
DR PDBsum; 3DI2; -.
DR PDBsum; 3DI3; -.
DR AlphaFoldDB; P13232; -.
DR SMR; P13232; -.
DR BioGRID; 109788; 12.
DR DIP; DIP-3044N; -.
DR IntAct; P13232; 2.
DR STRING; 9606.ENSP00000263851; -.
DR GlyGen; P13232; 3 sites.
DR BioMuta; IL7; -.
DR DMDM; 124354; -.
DR MassIVE; P13232; -.
DR PaxDb; P13232; -.
DR PeptideAtlas; P13232; -.
DR PRIDE; P13232; -.
DR ProteomicsDB; 52902; -. [P13232-1]
DR ProteomicsDB; 52903; -. [P13232-2]
DR ProteomicsDB; 62792; -.
DR Antibodypedia; 12401; 780 antibodies from 37 providers.
DR DNASU; 3574; -.
DR Ensembl; ENST00000263851.9; ENSP00000263851.4; ENSG00000104432.14. [P13232-1]
DR Ensembl; ENST00000520269.5; ENSP00000427750.1; ENSG00000104432.14. [P13232-2]
DR GeneID; 3574; -.
DR KEGG; hsa:3574; -.
DR MANE-Select; ENST00000263851.9; ENSP00000263851.4; NM_000880.4; NP_000871.1.
DR UCSC; uc003ybg.3; human. [P13232-1]
DR CTD; 3574; -.
DR DisGeNET; 3574; -.
DR GeneCards; IL7; -.
DR HGNC; HGNC:6023; IL7.
DR HPA; ENSG00000104432; Low tissue specificity.
DR MalaCards; IL7; -.
DR MIM; 146660; gene.
DR MIM; 618309; phenotype.
DR neXtProt; NX_P13232; -.
DR OpenTargets; ENSG00000104432; -.
DR Orphanet; 302; Epidermodysplasia verruciformis.
DR PharmGKB; PA29839; -.
DR VEuPathDB; HostDB:ENSG00000104432; -.
DR eggNOG; ENOG502SW6R; Eukaryota.
DR GeneTree; ENSGT00390000004451; -.
DR InParanoid; P13232; -.
DR OMA; VFFCNDT; -.
DR OrthoDB; 1433958at2759; -.
DR PhylomeDB; P13232; -.
DR TreeFam; TF338065; -.
DR PathwayCommons; P13232; -.
DR Reactome; R-HSA-1266695; Interleukin-7 signaling.
DR SignaLink; P13232; -.
DR SIGNOR; P13232; -.
DR BioGRID-ORCS; 3574; 18 hits in 1059 CRISPR screens.
DR ChiTaRS; IL7; human.
DR EvolutionaryTrace; P13232; -.
DR GeneWiki; Interleukin_7; -.
DR GenomeRNAi; 3574; -.
DR Pharos; P13232; Tbio.
DR PRO; PR:P13232; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P13232; protein.
DR Bgee; ENSG00000104432; Expressed in sperm and 136 other tissues.
DR ExpressionAtlas; P13232; baseline and differential.
DR Genevisible; P13232; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005125; F:cytokine activity; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; ISS:UniProtKB.
DR GO; GO:0005139; F:interleukin-7 receptor binding; TAS:ProtInc.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl.
DR GO; GO:0045453; P:bone resorption; ISS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR GO; GO:0006959; P:humoral immune response; TAS:ProtInc.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IEA:Ensembl.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0035265; P:organ growth; IEA:Ensembl.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0032722; P:positive regulation of chemokine production; IDA:UniProtKB.
DR GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0046622; P:positive regulation of organ growth; IEA:Ensembl.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISS:UniProtKB.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0002360; P:T cell lineage commitment; IEA:Ensembl.
DR Gene3D; 1.20.1250.50; -; 1.
DR InterPro; IPR001181; IL-7.
DR InterPro; IPR018049; IL-7/IL-9_CS.
DR InterPro; IPR038325; IL7_sf.
DR Pfam; PF01415; IL7; 1.
DR PIRSF; PIRSF001942; IL-7; 1.
DR PRINTS; PR00435; INTERLEUKIN7.
DR SMART; SM00127; IL7; 1.
DR PROSITE; PS00255; INTERLEUKIN_7_9; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytokine; Disease variant;
KW Disulfide bond; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..25
FT CHAIN 26..177
FT /note="Interleukin-7"
FT /id="PRO_0000015623"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 27..166
FT /evidence="ECO:0000269|PubMed:19141282,
FT ECO:0000269|PubMed:9407080"
FT DISULFID 59..154
FT /evidence="ECO:0000269|PubMed:19141282,
FT ECO:0000269|PubMed:9407080"
FT DISULFID 72..117
FT /evidence="ECO:0000269|PubMed:19141282,
FT ECO:0000269|PubMed:9407080"
FT VAR_SEQ 1..51
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047579"
FT VAR_SEQ 77..138
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047580"
FT VAR_SEQ 77..120
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_042926"
FT VARIANT 69..177
FT /note="Missing (in EV5)"
FT /evidence="ECO:0000269|PubMed:25981006"
FT /id="VAR_081934"
FT HELIX 34..39
FT /evidence="ECO:0007829|PDB:3DI2"
FT HELIX 41..50
FT /evidence="ECO:0007829|PDB:3DI2"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:3DI2"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:3DI3"
FT HELIX 65..69
FT /evidence="ECO:0007829|PDB:3DI2"
FT HELIX 77..89
FT /evidence="ECO:0007829|PDB:3DI2"
FT HELIX 99..115
FT /evidence="ECO:0007829|PDB:3DI2"
FT HELIX 153..171
FT /evidence="ECO:0007829|PDB:3DI2"
FT TURN 172..176
FT /evidence="ECO:0007829|PDB:3DI2"
SQ SEQUENCE 177 AA; 20187 MW; 8FC5243F9169617F CRC64;
MFHVSFRYIF GLPPLILVLL PVASSDCDIE GKDGKQYESV LMVSIDQLLD SMKEIGSNCL
NNEFNFFKRH ICDANKEGMF LFRAARKLRQ FLKMNSTGDF DLHLLKVSEG TTILLNCTGQ
VKGRKPAALG EAQPTKSLEE NKSLKEQKKL NDLCFLKRLL QEIKTCWNKI LMGTKEH
