ONCM_HUMAN
ID ONCM_HUMAN Reviewed; 252 AA.
AC P13725; Q6FHP8; Q9UCP6;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Oncostatin-M;
DE Short=OSM;
DE Flags: Precursor;
GN Name=OSM;
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 [GENOMIC DNA].
RX PubMed=2779549; DOI=10.1128/mcb.9.7.2847-2853.1989;
RA Malik N., Kallestad J.C., Gunderson N.L., Austin S.D., Neubauer M.G.,
RA Ochs V., Marquardt H., Zarling J.M., Shoyab M., Wei C.M., Linsley P.S.,
RA Rose T.M.;
RT "Molecular cloning, sequence analysis, and functional expression of a novel
RT growth regulator, oncostatin M.";
RL Mol. Cell. Biol. 9:2847-2853(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 PROTEIN SEQUENCE OF 26-51.
RX PubMed=3540948; DOI=10.1073/pnas.83.24.9739;
RA Zarling J.M., Shoyab M., Marquardt H., Hanson M.B., Lioubin M.N.,
RA Todaro G.J.;
RT "Oncostatin M: a growth regulator produced by differentiated histiocytic
RT lymphoma cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:9739-9743(1986).
RN [8]
RP PROTEIN SEQUENCE OF 26-45, AND FUNCTION.
RC TISSUE=T-cell;
RX PubMed=1542792; DOI=10.1126/science.1542792;
RA Nair B.C., DeVico A.L., Nakamura S., Copeland T.D., Chen Y., Patel A.,
RA O'Neil T., Oroszlan S., Gallo R.C., Sarngadharan M.G.;
RT "Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as
RT oncostatin M.";
RL Science 255:1430-1432(1992).
RN [9]
RP PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF ARG-220 AND ARG-221.
RX PubMed=2325640; DOI=10.1128/mcb.10.5.1882-1890.1990;
RA Linsley P.S., Kallestad J., Ochs V., Neubauer M.;
RT "Cleavage of a hydrophilic C-terminal domain increases growth-inhibitory
RT activity of oncostatin M.";
RL Mol. Cell. Biol. 10:1882-1890(1990).
RN [10]
RP DISULFIDE BONDS.
RX PubMed=2026606; DOI=10.1016/s0021-9258(18)31534-5;
RA Kallestad J.C., Shoyab M., Linsley P.S.;
RT "Disulfide bond assignment and identification of regions required for
RT functional activity of oncostatin M.";
RL J. Biol. Chem. 266:8940-8945(1991).
RN [11]
RP INHIBITION OF M1 MYELOID LEUKEMIC CELLS.
RX PubMed=1717982; DOI=10.1073/pnas.88.19.8641;
RA Rose T.M., Bruce A.G.;
RT "Oncostatin M is a member of a cytokine family that includes leukemia-
RT inhibitory factor, granulocyte colony-stimulating factor, and interleukin
RT 6.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:8641-8645(1991).
RN [12]
RP FUNCTION.
RX PubMed=1542793; DOI=10.1126/science.1542793;
RA Miles S.A., Martinez-Maza O., Rezai A., Magpantay L., Kishimoto T.,
RA Nakamura S., Radka S.F., Linsley P.S.;
RT "Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived
RT cells.";
RL Science 255:1432-1434(1992).
RN [13]
RP INTERACTION WITH OSMR AND IL6ST.
RX PubMed=8999038; DOI=10.1074/jbc.271.51.32635;
RA Mosley B., De Imus C., Friend D., Boiani N., Thoma B., Park L.S.,
RA Cosman D.;
RT "Dual oncostatin M (OSM) receptors. Cloning and characterization of an
RT alternative signaling subunit conferring OSM-specific receptor
RT activation.";
RL J. Biol. Chem. 271:32635-32643(1996).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 26-212.
RX PubMed=10997905; DOI=10.1016/s0969-2126(00)00176-3;
RA Deller M.C., Hudson K.R., Ikemizu S., Bravo J., Jones E.Y., Heath J.K.;
RT "Crystal structure and functional dissection of the cytostatic cytokine
RT oncostatin M.";
RL Structure 8:863-874(2000).
CC -!- FUNCTION: Growth regulator. Inhibits the proliferation of a number of
CC tumor cell lines. Stimulates proliferation of AIDS-KS cells. It
CC regulates cytokine production, including IL-6, G-CSF and GM-CSF from
CC endothelial cells. Uses both type I OSM receptor (heterodimers composed
CC of LIFR and IL6ST) and type II OSM receptor (heterodimers composed of
CC OSMR and IL6ST). Involved in the maturation of fetal hepatocytes,
CC thereby promoting liver development and regeneration (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:1542792, ECO:0000269|PubMed:1542793}.
CC -!- INTERACTION:
CC P13725; P40189: IL6ST; NbExp=2; IntAct=EBI-6595724, EBI-1030834;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: Propeptide processing is not important for receptor binding
CC activity but may be important growth-inhibitory activity.
CC {ECO:0000269|PubMed:2325640}.
CC -!- SIMILARITY: Belongs to the LIF/OSM family. {ECO:0000305}.
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DR EMBL; M27288; AAA36388.1; -; Genomic_DNA.
DR EMBL; M27286; AAA36388.1; JOINED; Genomic_DNA.
DR EMBL; M27287; AAA36388.1; JOINED; Genomic_DNA.
DR EMBL; CR456534; CAG30420.1; -; mRNA.
DR EMBL; CR541703; CAG46504.1; -; mRNA.
DR EMBL; AC004264; AAC05173.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW59864.1; -; Genomic_DNA.
DR EMBL; BC011589; AAH11589.1; -; mRNA.
DR CCDS; CCDS13873.1; -.
DR PIR; A32489; A32489.
DR RefSeq; NP_001306037.1; NM_001319108.1.
DR RefSeq; NP_065391.1; NM_020530.5.
DR PDB; 1EVS; X-ray; 2.20 A; A=26-212.
DR PDBsum; 1EVS; -.
DR AlphaFoldDB; P13725; -.
DR BMRB; P13725; -.
DR SMR; P13725; -.
DR BioGRID; 111049; 13.
DR DIP; DIP-5785N; -.
DR IntAct; P13725; 10.
DR MINT; P13725; -.
DR STRING; 9606.ENSP00000215781; -.
DR GlyGen; P13725; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P13725; -.
DR PhosphoSitePlus; P13725; -.
DR BioMuta; OSM; -.
DR DMDM; 129168; -.
DR MassIVE; P13725; -.
DR PaxDb; P13725; -.
DR PeptideAtlas; P13725; -.
DR PRIDE; P13725; -.
DR ProteomicsDB; 52975; -.
DR Antibodypedia; 10652; 612 antibodies from 35 providers.
DR DNASU; 5008; -.
DR Ensembl; ENST00000215781.3; ENSP00000215781.2; ENSG00000099985.4.
DR GeneID; 5008; -.
DR KEGG; hsa:5008; -.
DR MANE-Select; ENST00000215781.3; ENSP00000215781.2; NM_020530.6; NP_065391.1.
DR UCSC; uc003ahb.4; human.
DR CTD; 5008; -.
DR DisGeNET; 5008; -.
DR GeneCards; OSM; -.
DR HGNC; HGNC:8506; OSM.
DR HPA; ENSG00000099985; Tissue enriched (bone).
DR MIM; 165095; gene.
DR neXtProt; NX_P13725; -.
DR OpenTargets; ENSG00000099985; -.
DR PharmGKB; PA32836; -.
DR VEuPathDB; HostDB:ENSG00000099985; -.
DR eggNOG; ENOG502RVJA; Eukaryota.
DR GeneTree; ENSGT00390000004850; -.
DR HOGENOM; CLU_102028_0_0_1; -.
DR InParanoid; P13725; -.
DR OMA; FMHSVGQ; -.
DR OrthoDB; 1469672at2759; -.
DR PhylomeDB; P13725; -.
DR TreeFam; TF338204; -.
DR PathwayCommons; P13725; -.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-6788467; IL-6-type cytokine receptor ligand interactions.
DR SignaLink; P13725; -.
DR SIGNOR; P13725; -.
DR BioGRID-ORCS; 5008; 9 hits in 1067 CRISPR screens.
DR EvolutionaryTrace; P13725; -.
DR GeneWiki; Oncostatin_M; -.
DR GenomeRNAi; 5008; -.
DR Pharos; P13725; Tbio.
DR PRO; PR:P13725; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P13725; protein.
DR Bgee; ENSG00000099985; Expressed in bone marrow cell and 115 other tissues.
DR ExpressionAtlas; P13725; baseline and differential.
DR Genevisible; P13725; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
DR GO; GO:0008083; F:growth factor activity; IDA:BHF-UCL.
DR GO; GO:0005147; F:oncostatin-M receptor binding; IPI:BHF-UCL.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0046888; P:negative regulation of hormone secretion; IDA:MGI.
DR GO; GO:0038165; P:oncostatin-M-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0002675; P:positive regulation of acute inflammatory response; IC:BHF-UCL.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:BHF-UCL.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:BHF-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IGI:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:CACAO.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; TAS:GO_Central.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR001581; Leukemia_IF/oncostatin.
DR InterPro; IPR019827; Leukemia_IF/oncostatin_CS.
DR InterPro; IPR039578; OSM.
DR PANTHER; PTHR14261; PTHR14261; 1.
DR Pfam; PF01291; LIF_OSM; 1.
DR SMART; SM00080; LIF_OSM; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00590; LIF_OSM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues; Cytokine;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Growth regulation;
KW Mitogen; Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:1542792,
FT ECO:0000269|PubMed:3540948"
FT CHAIN 26..221
FT /note="Oncostatin-M"
FT /evidence="ECO:0000305|PubMed:2325640"
FT /id="PRO_0000017720"
FT PROPEP 222..252
FT /evidence="ECO:0000305|PubMed:2325640"
FT /id="PRO_0000017721"
FT REGION 162..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..246
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..152
FT /evidence="ECO:0000269|PubMed:2026606"
FT DISULFID 74..192
FT /evidence="ECO:0000269|PubMed:2026606"
FT VARIANT 9
FT /note="T -> M (in dbSNP:rs5763919)"
FT /id="VAR_049782"
FT MUTAGEN 74
FT /note="C->S: Inactive."
FT MUTAGEN 192
FT /note="C->S: Inactive."
FT MUTAGEN 201
FT /note="F->G: Inactive."
FT MUTAGEN 209
FT /note="F->G: Inactive."
FT MUTAGEN 220
FT /note="R->G: Inhibits propeptide cleavage."
FT /evidence="ECO:0000269|PubMed:2325640"
FT MUTAGEN 221
FT /note="R->G: Inhibits propeptide cleavage."
FT /evidence="ECO:0000269|PubMed:2325640"
FT HELIX 35..49
FT /evidence="ECO:0007829|PDB:1EVS"
FT HELIX 52..54
FT /evidence="ECO:0007829|PDB:1EVS"
FT HELIX 56..62
FT /evidence="ECO:0007829|PDB:1EVS"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:1EVS"
FT TURN 78..80
FT /evidence="ECO:0007829|PDB:1EVS"
FT HELIX 84..89
FT /evidence="ECO:0007829|PDB:1EVS"
FT HELIX 92..115
FT /evidence="ECO:0007829|PDB:1EVS"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:1EVS"
FT HELIX 123..126
FT /evidence="ECO:0007829|PDB:1EVS"
FT HELIX 130..156
FT /evidence="ECO:0007829|PDB:1EVS"
FT HELIX 184..210
FT /evidence="ECO:0007829|PDB:1EVS"
SQ SEQUENCE 252 AA; 28484 MW; A5BE281175D101B9 CRC64;
MGVLLTQRTL LSLVLALLFP SMASMAAIGS CSKEYRVLLG QLQKQTDLMQ DTSRLLDPYI
RIQGLDVPKL REHCRERPGA FPSEETLRGL GRRGFLQTLN ATLGCVLHRL ADLEQRLPKA
QDLERSGLNI EDLEKLQMAR PNILGLRNNI YCMAQLLDNS DTAEPTKAGR GASQPPTPTP
ASDAFQRKLE GCRFLHGYHR FMHSVGRVFS KWGESPNRSR RHSPHQALRK GVRRTRPSRK
GKRLMTRGQL PR
