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Protein

Interleukin-34

Gene

IL34

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.4 Publications

GO - Molecular functioni

  • macrophage colony-stimulating factor receptor binding Source: UniProtKB

GO - Biological processi

  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of macrophage differentiation Source: CACAO
  • positive regulation of monocyte differentiation Source: CACAO
  • positive regulation of protein phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-34
Short name:
IL-34
Gene namesi
Name:IL34
Synonyms:C16orf77
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:28529. IL34.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162392024.

Polymorphism and mutation databases

BioMutaiIL34.
DMDMi74710540.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence AnalysisAdd
BLAST
Chaini21 – 242222Interleukin-34PRO_0000294348Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi76 – 761N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ6ZMJ4.
PRIDEiQ6ZMJ4.

Expressioni

Tissue specificityi

Detected in the sinusoidal epithelium in the red pulp of spleen (at protein level). Predominantly expressed in spleen. Also detected in a range of other tissues including heart, brain, lung, liver, kidney, thymus, testis, ovary, small intestine, prostate and colon.1 Publication

Gene expression databases

BgeeiQ6ZMJ4.
CleanExiHS_IL34.
ExpressionAtlasiQ6ZMJ4. baseline.
GenevisibleiQ6ZMJ4. HS.

Organism-specific databases

HPAiHPA055971.

Interactioni

Subunit structurei

Homodimer. Interacts with CSF1R.3 Publications

Protein-protein interaction databases

BioGridi126985. 1 interaction.
DIPiDIP-50037N.
IntActiQ6ZMJ4. 1 interaction.
MINTiMINT-2878814.
STRINGi9606.ENSP00000288098.

Structurei

Secondary structure

1
242
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi33 – 4412Combined sources
Helixi47 – 548Combined sources
Turni55 – 573Combined sources
Beta strandi64 – 663Combined sources
Helixi68 – 703Combined sources
Helixi74 – 818Combined sources
Turni82 – 843Combined sources
Helixi87 – 10620Combined sources
Helixi116 – 13116Combined sources
Turni132 – 1354Combined sources
Helixi140 – 15011Combined sources
Beta strandi157 – 1593Combined sources
Helixi161 – 18020Combined sources
Beta strandi181 – 1844Combined sources
Turni186 – 1905Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4DKCX-ray1.85A/B21-193[»]
4DKDX-ray3.00A/B21-193[»]
4DKEX-ray3.00A/B21-193[»]
4DKFX-ray2.61A/B21-193[»]
ProteinModelPortaliQ6ZMJ4.
SMRiQ6ZMJ4. Positions 32-192.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-34 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG46280.
GeneTreeiENSGT00390000000932.
HOGENOMiHOG000113048.
HOVERGENiHBG108003.
InParanoidiQ6ZMJ4.
OMAiYKISVPY.
PhylomeDBiQ6ZMJ4.
TreeFamiTF337386.

Family and domain databases

InterProiIPR020415. IL-34.
[Graphical view]
PfamiPF15036. IL34. 1 hit.
[Graphical view]
PRINTSiPR01938. INTRLEUKIN34.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6ZMJ4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPRGFTWLRY LGIFLGVALG NEPLEMWPLT QNEECTVTGF LRDKLQYRSR
60 70 80 90 100
LQYMKHYFPI NYKISVPYEG VFRIANVTRL QRAQVSEREL RYLWVLVSLS
110 120 130 140 150
ATESVQDVLL EGHPSWKYLQ EVETLLLNVQ QGLTDVEVSP KVESVLSLLN
160 170 180 190 200
APGPNLKLVR PKALLDNCFR VMELLYCSCC KQSSVLNWQD CEVPSPQSCS
210 220 230 240
PEPSLQYAAT QLYPPPPWSP SSPPHSTGSV RPVRAQGEGL LP
Length:242
Mass (Da):27,482
Last modified:July 5, 2004 - v1
Checksum:iD1D8CC74C77AB23F
GO
Isoform 2 (identifier: Q6ZMJ4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     81-81: Missing.

Show »
Length:241
Mass (Da):27,354
Checksum:iE50A531AF64D0DD2
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti123 – 1231E → Q.2 Publications
Corresponds to variant rs8046424 [ dbSNP | Ensembl ].
VAR_033164
Natural varianti195 – 1951S → T.
Corresponds to variant rs7206509 [ dbSNP | Ensembl ].
VAR_056920

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei81 – 811Missing in isoform 2. 1 PublicationVSP_035079

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU599219 mRNA. Translation: ACD13474.1.
EU636994 mRNA. Translation: ACD13452.1.
AK172744 mRNA. Translation: BAD18731.1.
AK314913 mRNA. Translation: BAG37425.1.
AC020763 Genomic DNA. No translation available.
CH471241 Genomic DNA. Translation: EAW51801.1.
BC029804 mRNA. Translation: AAH29804.1.
CCDSiCCDS10895.1. [Q6ZMJ4-1]
RefSeqiNP_001166242.1. NM_001172771.1. [Q6ZMJ4-2]
NP_001166243.1. NM_001172772.1. [Q6ZMJ4-1]
NP_689669.2. NM_152456.2. [Q6ZMJ4-1]
UniGeneiHs.461214.

Genome annotation databases

EnsembliENST00000288098; ENSP00000288098; ENSG00000157368. [Q6ZMJ4-1]
ENST00000429149; ENSP00000397863; ENSG00000157368. [Q6ZMJ4-1]
GeneIDi146433.
KEGGihsa:146433.
UCSCiuc002ezh.2. human. [Q6ZMJ4-1]
uc002ezi.2. human. [Q6ZMJ4-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU599219 mRNA. Translation: ACD13474.1.
EU636994 mRNA. Translation: ACD13452.1.
AK172744 mRNA. Translation: BAD18731.1.
AK314913 mRNA. Translation: BAG37425.1.
AC020763 Genomic DNA. No translation available.
CH471241 Genomic DNA. Translation: EAW51801.1.
BC029804 mRNA. Translation: AAH29804.1.
CCDSiCCDS10895.1. [Q6ZMJ4-1]
RefSeqiNP_001166242.1. NM_001172771.1. [Q6ZMJ4-2]
NP_001166243.1. NM_001172772.1. [Q6ZMJ4-1]
NP_689669.2. NM_152456.2. [Q6ZMJ4-1]
UniGeneiHs.461214.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4DKCX-ray1.85A/B21-193[»]
4DKDX-ray3.00A/B21-193[»]
4DKEX-ray3.00A/B21-193[»]
4DKFX-ray2.61A/B21-193[»]
ProteinModelPortaliQ6ZMJ4.
SMRiQ6ZMJ4. Positions 32-192.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126985. 1 interaction.
DIPiDIP-50037N.
IntActiQ6ZMJ4. 1 interaction.
MINTiMINT-2878814.
STRINGi9606.ENSP00000288098.

Polymorphism and mutation databases

BioMutaiIL34.
DMDMi74710540.

Proteomic databases

PaxDbiQ6ZMJ4.
PRIDEiQ6ZMJ4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000288098; ENSP00000288098; ENSG00000157368. [Q6ZMJ4-1]
ENST00000429149; ENSP00000397863; ENSG00000157368. [Q6ZMJ4-1]
GeneIDi146433.
KEGGihsa:146433.
UCSCiuc002ezh.2. human. [Q6ZMJ4-1]
uc002ezi.2. human. [Q6ZMJ4-2]

Organism-specific databases

CTDi146433.
GeneCardsiGC16P070613.
H-InvDBHIX0013203.
HGNCiHGNC:28529. IL34.
HPAiHPA055971.
MIMi612081. gene.
neXtProtiNX_Q6ZMJ4.
PharmGKBiPA162392024.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG46280.
GeneTreeiENSGT00390000000932.
HOGENOMiHOG000113048.
HOVERGENiHBG108003.
InParanoidiQ6ZMJ4.
OMAiYKISVPY.
PhylomeDBiQ6ZMJ4.
TreeFamiTF337386.

Miscellaneous databases

GeneWikiiInterleukin_34.
GenomeRNAii146433.
NextBioi85355.
PROiQ6ZMJ4.
SOURCEiSearch...

Gene expression databases

BgeeiQ6ZMJ4.
CleanExiHS_IL34.
ExpressionAtlasiQ6ZMJ4. baseline.
GenevisibleiQ6ZMJ4. HS.

Family and domain databases

InterProiIPR020415. IL-34.
[Graphical view]
PfamiPF15036. IL34. 1 hit.
[Graphical view]
PRINTSiPR01938. INTRLEUKIN34.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Discovery of a cytokine and its receptor by functional screening of the extracellular proteome."
    Lin H., Lee E., Hestir K., Leo C., Huang M., Bosch E., Halenbeck R., Wu G., Zhou A., Behrens D., Hollenbaugh D., Linnemann T., Qin M., Wong J., Chu K., Doberstein S.K., Williams L.T.
    Science 320:807-811(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT GLN-123.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLN-123.
    Tissue: Adipose tissue and Amygdala.
  3. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  6. "IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation."
    Chihara T., Suzu S., Hassan R., Chutiwitoonchai N., Hiyoshi M., Motoyoshi K., Kimura F., Okada S.
    Cell Death Differ. 17:1917-1927(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CSF1R.
  7. "Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood."
    Eda H., Zhang J., Keith R.H., Michener M., Beidler D.R., Monahan J.B.
    Cytokine 52:215-220(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN RELEASE OF PROINFLAMMATORY CHEMOKINES.
  8. "Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells."
    Wei S., Nandi S., Chitu V., Yeung Y.G., Yu W., Huang M., Williams L.T., Lin H., Stanley E.R.
    J. Leukoc. Biol. 88:495-505(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CSF1R.

Entry informationi

Entry nameiIL34_HUMAN
AccessioniPrimary (citable) accession number: Q6ZMJ4
Secondary accession number(s): B2RC28
, B2Z4A8, B2ZC70, Q8N6L2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 10, 2007
Last sequence update: July 5, 2004
Last modified: June 24, 2015
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.