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Protein NOV homolog

NameProtein NOV homolog
Synonyms
  • CCN family member 3
  • CCN3
  • IBP-9
  • IGF-binding protein 9
  • IGFBP-9
  • IGFBP9
  • Insulin-like growth factor-binding protein 9
  • Nephroblastoma-overexpressed gene protein homolog
  • NOVH
Gene NameNOV
OrganismHuman
Amino acid sequence
>lcl|BSEQ0019069|Protein NOV homolog
MQSVQSTSFCLRKQCLCLTFLLLHLLGQVAATQRCPPQCPGRCPATPPTCAPGVRAVLDG
CSCCLVCARQRGESCSDLEPCDESSGLYCDRSADPSNQTGICTAVEGDNCVFDGVIYRSG
EKFQPSCKFQCTCRDGQIGCVPRCQLDVLLPEPNCPAPRKVEVPGECCEKWICGPDEEDS
LGGLTLAAYRPEATLGVEVSDSSVNCIEQTTEWTACSKSCGMGFSTRVTNRNRQCEMLKQ
TRLCMVRPCEQEPEQPTDKKGKKCLRTKKSLKAIHLQFKNCTSLHTYKPRFCGVCSDGRC
CTPHNTKTIQAEFQCSPGQIVKKPVMVIGTCTCHTNCPKNNEAFLQELELKTTRGKM
Number of residues357
Molecular Weight39161.82
Theoretical pI7.74
GO Classification
Functions
  • Notch binding
  • heparin binding
  • integrin binding
Processes
  • cell chemotaxis
  • fibroblast migration
  • negative regulation of inflammatory response
  • negative regulation of chondrocyte proliferation
  • angiogenesis
  • cell adhesion mediated by integrin
  • endothelial cell-cell adhesion
  • positive regulation of Notch signaling pathway
  • negative regulation of insulin secretion
  • hematopoietic stem cell homeostasis
  • bone regeneration
  • signal transduction
  • endothelial cell chemotaxis
  • negative regulation of cell growth
  • cell adhesion
  • negative regulation of monocyte chemotaxis
  • negative regulation of cell death
  • negative regulation of sensory perception of pain
  • type B pancreatic cell proliferation
  • cell-cell signaling
  • negative regulation of SMAD protein import into nucleus
  • chondrocyte differentiation
  • smooth muscle cell migration
  • smooth muscle cell proliferation
  • negative regulation of myotube differentiation
  • negative regulation of NF-kappaB import into nucleus
  • regulation of gene expression
Components
  • neuronal cell body
  • proteinaceous extracellular matrix
  • cytoplasm
  • axon
  • extracellular region
  • gap junction
  • intracellular membrane-bounded organelle
  • dendrite
General FunctionNotch binding
Specific FunctionImmediate-early protein playing a role in various cellular processes including proliferation, adhesion, migration, differentiation and survival (PubMed:15181016, PubMed:15611078, PubMed:12695522, PubMed:21344378, PubMed:12050162). Acts by binding to integrins or membrane receptors such as NOTCH1 (PubMed:12695522, PubMed:21344378, PubMed:15611078). Essential regulator of hematopoietic stem and progenitor cell function (PubMed:17463287). Inhibits myogenic differentiation through the activation of Notch-signaling pathway (PubMed:12050162). Inhibits vascular smooth muscle cells proliferation by increasing expression of cell-cycle regulators such as CDKN2B or CDKN1A independently of TGFB1 signaling (PubMed:20139355). Ligand of integrins ITGAV:ITGB3 and ITGA5:ITGB1, acts directly upon endothelial cells to stimulate pro-angiogenic activities and induces angiogenesis. In endothelial cells, supports cell adhesion, induces directed cell migration (chemotaxis) and promotes cell survival (PubMed:12695522). Plays also a role in cutaneous wound healing acting as integrin receptor ligand. Supports skin fibroblast adhesion through ITGA5:ITGB1 and ITGA6:ITGB1 and induces fibroblast chemotaxis through ITGAV:ITGB5. Seems to enhance bFGF-induced DNA synthesis in fibroblasts (PubMed:15611078). Involved in bone regeneration as a negative regulator (By similarity). Enhances the articular chondrocytic phenotype, whereas it repressed the one representing endochondral ossification (PubMed:21871891). Impairs pancreatic beta-cell function, inhibits beta-cell proliferation and insulin secretion (By similarity). Plays a role as negative regulator of endothelial pro-inflammatory activation reducing monocyte adhesion, its anti-inflammatory effects occur secondary to the inhibition of NF-kappaB signaling pathway (PubMed:21063504). Contributes to the control and coordination of inflammatory processes in atherosclerosis (By similarity). Attenuates inflammatory pain through regulation of IL1B- and TNF-induced MMP9, MMP2 and CCL2 expression. Inhibits MMP9 expression through ITGB1 engagement (PubMed:21871891).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID825696
UniProtKB IDP48745
UniProtKB Entry NameNOV_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0019070|Protein NOV homolog (NOV)
ATGCAGAGTGTGCAGAGCACGAGCTTTTGTCTCCGAAAGCAGTGCCTTTGCCTGACCTTC
CTGCTTCTCCATCTCCTGGGACAGGTCGCTGCGACTCAGCGCTGCCCTCCCCAGTGCCCG
GGCCGGTGCCCTGCGACGCCGCCGACCTGCGCCCCCGGGGTGCGCGCGGTGCTGGACGGC
TGCTCATGCTGTCTGGTGTGTGCCCGCCAGCGTGGCGAGAGCTGCTCAGATCTGGAGCCA
TGCGACGAGAGCAGTGGCCTCTACTGTGATCGCAGCGCGGACCCCAGCAACCAGACTGGC
ATCTGCACGGCGGTAGAGGGAGATAACTGTGTGTTCGATGGGGTCATCTACCGCAGTGGA
GAGAAATTTCAGCCAAGCTGCAAATTCCAGTGCACCTGCAGAGATGGGCAGATTGGCTGT
GTGCCCCGCTGTCAGCTGGATGTGCTACTGCCTGAGCCTAACTGCCCAGCTCCAAGAAAA
GTTGAGGTGCCTGGAGAGTGCTGTGAAAAGTGGATCTGTGGCCCAGATGAGGAGGATTCA
CTGGGAGGCCTTACCCTTGCAGCTTACAGGCCAGAAGCCACCCTAGGAGTAGAAGTCTCT
GACTCAAGTGTCAACTGCATTGAACAGACCACAGAGTGGACAGCATGCTCCAAGAGCTGT
GGTATGGGGTTCTCCACCCGGGTCACCAATAGGAACCGTCAATGTGAGATGCTGAAACAG
ACTCGGCTCTGCATGGTGCGGCCCTGTGAACAAGAGCCAGAGCAGCCAACAGATAAGAAA
GGAAAAAAGTGTCTCCGCACCAAGAAGTCACTCAAAGCCATCCACCTGCAGTTCAAGAAC
TGCACCAGCCTGCACACCTACAAGCCCAGGTTCTGTGGGGTCTGCAGTGATGGCCGCTGC
TGCACTCCCCACAATACCAAAACCATCCAGGCAGAGTTTCAGTGCTCCCCAGGGCAAATA
GTCAAGAAGCCAGTGATGGTCATTGGGACCTGCACCTGTCACACCAACTGTCCTAAGAAC
AATGAGGCCTTCCTCCAGGAGCTGGAGCTGAAGACTACCAGAGGGAAAATGTAA
GenBank Gene IDX78351
GeneCard IDNot Available
GenAtlas IDNOV
HGNC IDHGNC:7885
Chromosome Location8
Locus8q24.1
References
  1. Martinerie C, Huff V, Joubert I, Badzioch M, Saunders G, Strong L, Perbal B: Structural analysis of the human nov proto-oncogene and expression in Wilms tumor. Oncogene. 1994 Sep;9(9):2729-32. 7520150
  2. Martinerie C, Chevalier G, Rauscher FJ 3rd, Perbal B: Regulation of nov by WT1: a potential role for nov in nephrogenesis. Oncogene. 1996 Apr 4;12(7):1479-92. 8622864
  3. 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
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  5. Martinerie C, Perbal B: Expression of a gene encoding a novel potential IGF binding protein in human tissues. C R Acad Sci III. 1991;313(8):345-51. 1756408
  6. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. 15340161
  7. Perbal B, Martinerie C, Sainson R, Werner M, He B, Roizman B: The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):869-74. 9927660
  8. Sakamoto K, Yamaguchi S, Ando R, Miyawaki A, Kabasawa Y, Takagi M, Li CL, Perbal B, Katsube K: The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway. J Biol Chem. 2002 Aug 16;277(33):29399-405. Epub 2002 Jun 5. 12050162
  9. Lin CG, Leu SJ, Chen N, Tebeau CM, Lin SX, Yeung CY, Lau LF: CCN3 (NOV) is a novel angiogenic regulator of the CCN protein family. J Biol Chem. 2003 Jun 27;278(26):24200-8. Epub 2003 Apr 13. 12695522
  10. Gellhaus A, Dong X, Propson S, Maass K, Klein-Hitpass L, Kibschull M, Traub O, Willecke K, Perbal B, Lye SJ, Winterhager E: Connexin43 interacts with NOV: a possible mechanism for negative regulation of cell growth in choriocarcinoma cells. J Biol Chem. 2004 Aug 27;279(35):36931-42. Epub 2004 Jun 4. 15181016
  11. Fu CT, Bechberger JF, Ozog MA, Perbal B, Naus CC: CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible mechanism of connexin-mediated growth suppression. J Biol Chem. 2004 Aug 27;279(35):36943-50. Epub 2004 Jun 21. 15213231
  12. Lin CG, Chen CC, Leu SJ, Grzeszkiewicz TM, Lau LF: Integrin-dependent functions of the angiogenic inducer NOV (CCN3): implication in wound healing. J Biol Chem. 2005 Mar 4;280(9):8229-37. Epub 2004 Dec 20. 15611078
  13. Gupta R, Hong D, Iborra F, Sarno S, Enver T: NOV (CCN3) functions as a regulator of human hematopoietic stem or progenitor cells. Science. 2007 Apr 27;316(5824):590-3. 17463287
  14. Shimoyama T, Hiraoka S, Takemoto M, Koshizaka M, Tokuyama H, Tokuyama T, Watanabe A, Fujimoto M, Kawamura H, Sato S, Tsurutani Y, Saito Y, Perbal B, Koseki H, Yokote K: CCN3 inhibits neointimal hyperplasia through modulation of smooth muscle cell growth and migration. Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):675-82. doi: 10.1161/ATVBAHA.110.203356. Epub 2010 Feb 5. 20139355
  15. Lin Z, Natesan V, Shi H, Hamik A, Kawanami D, Hao C, Mahabaleshwar GH, Wang W, Jin ZG, Atkins GB, Firth SM, Rittie L, Perbal B, Jain MK: A novel role of CCN3 in regulating endothelial inflammation. J Cell Commun Signal. 2010 Oct;4(3):141-53. doi: 10.1007/s12079-010-0095-x. Epub 2010 Aug 11. 21063504
  16. Janune D, Kubota S, Nishida T, Kawaki H, Perbal B, Iida S, Takigawa M: Novel effects of CCN3 that may direct the differentiation of chondrocytes. FEBS Lett. 2011 Oct 3;585(19):3033-40. doi: 10.1016/j.febslet.2011.08.024. Epub 2011 Aug 23. 21871891
  17. Tzeng HE, Chen JC, Tsai CH, Kuo CC, Hsu HC, Hwang WL, Fong YC, Tang CH: CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin-dependent pathway. J Cell Physiol. 2011 Dec;226(12):3181-9. doi: 10.1002/jcp.22672. 21344378
  18. Liu J, Ren Y, Kang L, Zhang L: Overexpression of CCN3 inhibits inflammation and progression of atherosclerosis in apolipoprotein E-deficient mice. PLoS One. 2014 Apr 10;9(4):e94912. doi: 10.1371/journal.pone.0094912. eCollection 2014. 24722330