IL34_HUMAN
ID IL34_HUMAN Reviewed; 242 AA.
AC Q6ZMJ4; B2RC28; B2Z4A8; B2ZC70; Q8N6L2;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Interleukin-34;
DE Short=IL-34;
DE Flags: Precursor;
GN Name=IL34; Synonyms=C16orf77;
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] (ISOFORMS 1 AND 2), FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT GLN-123.
RX PubMed=18467591; DOI=10.1126/science.1154370;
RA Lin H., Lee E., Hestir K., Leo C., Huang M., Bosch E., Halenbeck R., Wu G.,
RA Zhou A., Behrens D., Hollenbaugh D., Linnemann T., Qin M., Wong J., Chu K.,
RA Doberstein S.K., Williams L.T.;
RT "Discovery of a cytokine and its receptor by functional screening of the
RT extracellular proteome.";
RL Science 320:807-811(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-123.
RC TISSUE=Adipose tissue, and Amygdala;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP FUNCTION, AND INTERACTION WITH CSF1R.
RX PubMed=20489731; DOI=10.1038/cdd.2010.60;
RA Chihara T., Suzu S., Hassan R., Chutiwitoonchai N., Hiyoshi M.,
RA Motoyoshi K., Kimura F., Okada S.;
RT "IL-34 and M-CSF share the receptor Fms but are not identical in biological
RT activity and signal activation.";
RL Cell Death Differ. 17:1917-1927(2010).
RN [7]
RP FUNCTION IN RELEASE OF PRO-INFLAMMATORY CHEMOKINES.
RX PubMed=20829061; DOI=10.1016/j.cyto.2010.08.005;
RA Eda H., Zhang J., Keith R.H., Michener M., Beidler D.R., Monahan J.B.;
RT "Macrophage-colony stimulating factor and interleukin-34 induce chemokines
RT in human whole blood.";
RL Cytokine 52:215-220(2010).
RN [8]
RP FUNCTION, AND INTERACTION WITH CSF1R.
RX PubMed=20504948; DOI=10.1189/jlb.1209822;
RA Wei S., Nandi S., Chitu V., Yeung Y.G., Yu W., Huang M., Williams L.T.,
RA Lin H., Stanley E.R.;
RT "Functional overlap but differential expression of CSF-1 and IL-34 in their
RT CSF-1 receptor-mediated regulation of myeloid cells.";
RL J. Leukoc. Biol. 88:495-505(2010).
CC -!- FUNCTION: Cytokine that promotes the proliferation, survival and
CC differentiation of monocytes and macrophages. Promotes the release of
CC pro-inflammatory chemokines, and thereby plays an important role in
CC innate immunity and in inflammatory processes. Plays an important role
CC in the regulation of osteoclast proliferation and differentiation, and
CC in the regulation of bone resorption. Signaling via CSF1R and its
CC downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND
CC MAPK3/ERK1. {ECO:0000269|PubMed:18467591, ECO:0000269|PubMed:20489731,
CC ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061}.
CC -!- SUBUNIT: Homodimer. Interacts with CSF1R. {ECO:0000269|PubMed:18467591,
CC ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:20504948}.
CC -!- INTERACTION:
CC Q6ZMJ4; Q5T754: LCE1F; NbExp=3; IntAct=EBI-948761, EBI-11958008;
CC Q6ZMJ4-1; P07333: CSF1R; NbExp=9; IntAct=EBI-15978980, EBI-2835440;
CC Q6ZMJ4-1; Q6ZMJ4-1: IL34; NbExp=2; IntAct=EBI-15978980, EBI-15978980;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18467591}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ZMJ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZMJ4-2; Sequence=VSP_035079;
CC -!- TISSUE SPECIFICITY: Detected in the sinusoidal epithelium in the red
CC pulp of spleen (at protein level). Predominantly expressed in spleen.
CC Also detected in a range of other tissues including heart, brain, lung,
CC liver, kidney, thymus, testis, ovary, small intestine, prostate and
CC colon. {ECO:0000269|PubMed:18467591}.
CC -!- SIMILARITY: Belongs to the IL-34 family. {ECO:0000305}.
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DR EMBL; EU599219; ACD13474.1; -; mRNA.
DR EMBL; EU636994; ACD13452.1; -; mRNA.
DR EMBL; AK172744; BAD18731.1; -; mRNA.
DR EMBL; AK314913; BAG37425.1; -; mRNA.
DR EMBL; AC020763; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471241; EAW51801.1; -; Genomic_DNA.
DR EMBL; BC029804; AAH29804.1; -; mRNA.
DR CCDS; CCDS10895.1; -. [Q6ZMJ4-1]
DR RefSeq; NP_001166242.1; NM_001172771.1. [Q6ZMJ4-2]
DR RefSeq; NP_001166243.1; NM_001172772.1. [Q6ZMJ4-1]
DR RefSeq; NP_689669.2; NM_152456.2. [Q6ZMJ4-1]
DR RefSeq; XP_011521204.1; XM_011522902.2.
DR RefSeq; XP_011521205.1; XM_011522903.2.
DR PDB; 4DKC; X-ray; 1.85 A; A/B=21-193.
DR PDB; 4DKD; X-ray; 3.00 A; A/B=21-193.
DR PDB; 4DKE; X-ray; 3.00 A; A/B=21-193.
DR PDB; 4DKF; X-ray; 2.61 A; A/B=21-193.
DR PDBsum; 4DKC; -.
DR PDBsum; 4DKD; -.
DR PDBsum; 4DKE; -.
DR PDBsum; 4DKF; -.
DR AlphaFoldDB; Q6ZMJ4; -.
DR SMR; Q6ZMJ4; -.
DR BioGRID; 126985; 3.
DR DIP; DIP-50037N; -.
DR IntAct; Q6ZMJ4; 3.
DR STRING; 9606.ENSP00000397863; -.
DR GlyGen; Q6ZMJ4; 1 site.
DR BioMuta; IL34; -.
DR DMDM; 74710540; -.
DR MassIVE; Q6ZMJ4; -.
DR PaxDb; Q6ZMJ4; -.
DR PeptideAtlas; Q6ZMJ4; -.
DR PRIDE; Q6ZMJ4; -.
DR ProteomicsDB; 67882; -. [Q6ZMJ4-1]
DR ProteomicsDB; 67883; -. [Q6ZMJ4-2]
DR ABCD; Q6ZMJ4; 2 sequenced antibodies.
DR Antibodypedia; 30010; 392 antibodies from 32 providers.
DR DNASU; 146433; -.
DR Ensembl; ENST00000288098.7; ENSP00000288098.2; ENSG00000157368.12. [Q6ZMJ4-1]
DR Ensembl; ENST00000429149.6; ENSP00000397863.2; ENSG00000157368.12. [Q6ZMJ4-1]
DR GeneID; 146433; -.
DR KEGG; hsa:146433; -.
DR MANE-Select; ENST00000288098.7; ENSP00000288098.2; NM_001393494.1; NP_001380423.1.
DR UCSC; uc002ezh.2; human. [Q6ZMJ4-1]
DR CTD; 146433; -.
DR DisGeNET; 146433; -.
DR GeneCards; IL34; -.
DR HGNC; HGNC:28529; IL34.
DR HPA; ENSG00000157368; Tissue enhanced (lymphoid tissue, skin).
DR MIM; 612081; gene.
DR neXtProt; NX_Q6ZMJ4; -.
DR OpenTargets; ENSG00000157368; -.
DR PharmGKB; PA162392024; -.
DR VEuPathDB; HostDB:ENSG00000157368; -.
DR eggNOG; ENOG502S2ET; Eukaryota.
DR GeneTree; ENSGT00390000000932; -.
DR InParanoid; Q6ZMJ4; -.
DR OMA; CCKQSPI; -.
DR PhylomeDB; Q6ZMJ4; -.
DR TreeFam; TF337386; -.
DR PathwayCommons; Q6ZMJ4; -.
DR Reactome; R-HSA-449836; Other interleukin signaling.
DR SignaLink; Q6ZMJ4; -.
DR SIGNOR; Q6ZMJ4; -.
DR BioGRID-ORCS; 146433; 11 hits in 1067 CRISPR screens.
DR ChiTaRS; IL34; human.
DR GeneWiki; Interleukin_34; -.
DR GenomeRNAi; 146433; -.
DR Pharos; Q6ZMJ4; Tbio.
DR PRO; PR:Q6ZMJ4; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q6ZMJ4; protein.
DR Bgee; ENSG00000157368; Expressed in tibial nerve and 160 other tissues.
DR ExpressionAtlas; Q6ZMJ4; baseline and differential.
DR Genevisible; Q6ZMJ4; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005157; F:macrophage colony-stimulating factor receptor binding; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0061514; P:interleukin-34-mediated signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0061518; P:microglial cell proliferation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IDA:ARUK-UCL.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IDA:CACAO.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; IDA:ARUK-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:ARUK-UCL.
DR GO; GO:0045657; P:positive regulation of monocyte differentiation; IDA:CACAO.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IDA:ARUK-UCL.
DR Gene3D; 1.20.1250.80; -; 1.
DR InterPro; IPR020415; IL-34.
DR InterPro; IPR038328; IL-34_sf.
DR PANTHER; PTHR28606; PTHR28606; 1.
DR Pfam; PF15036; IL34; 1.
DR PRINTS; PR01938; INTRLEUKIN34.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytokine; Glycoprotein; Growth factor;
KW Immunity; Inflammatory response; Innate immunity; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..242
FT /note="Interleukin-34"
FT /id="PRO_0000294348"
FT REGION 210..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 81
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18467591"
FT /id="VSP_035079"
FT VARIANT 123
FT /note="E -> Q (in dbSNP:rs8046424)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:18467591"
FT /id="VAR_033164"
FT VARIANT 195
FT /note="S -> T (in dbSNP:rs7206509)"
FT /id="VAR_056920"
FT HELIX 33..44
FT /evidence="ECO:0007829|PDB:4DKC"
FT HELIX 47..54
FT /evidence="ECO:0007829|PDB:4DKC"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:4DKC"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:4DKC"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:4DKC"
FT HELIX 74..81
FT /evidence="ECO:0007829|PDB:4DKC"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:4DKC"
FT HELIX 87..106
FT /evidence="ECO:0007829|PDB:4DKC"
FT HELIX 116..131
FT /evidence="ECO:0007829|PDB:4DKC"
FT TURN 132..135
FT /evidence="ECO:0007829|PDB:4DKC"
FT HELIX 140..150
FT /evidence="ECO:0007829|PDB:4DKC"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:4DKC"
FT HELIX 161..180
FT /evidence="ECO:0007829|PDB:4DKC"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:4DKF"
FT TURN 186..190
FT /evidence="ECO:0007829|PDB:4DKC"
SQ SEQUENCE 242 AA; 27482 MW; D1D8CC74C77AB23F CRC64;
MPRGFTWLRY LGIFLGVALG NEPLEMWPLT QNEECTVTGF LRDKLQYRSR LQYMKHYFPI
NYKISVPYEG VFRIANVTRL QRAQVSEREL RYLWVLVSLS ATESVQDVLL EGHPSWKYLQ
EVETLLLNVQ QGLTDVEVSP KVESVLSLLN APGPNLKLVR PKALLDNCFR VMELLYCSCC
KQSSVLNWQD CEVPSPQSCS PEPSLQYAAT QLYPPPPWSP SSPPHSTGSV RPVRAQGEGL
LP
