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Protein

Protein NOV homolog

Gene

Nov

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Immediate-early protein playing a role in various cellular processes including proliferation, adhesion, migration, differentiation and survival. Acts by binding to integrins or membrane receptors such as NOTCH1. Essential regulator of hematopoietic stem and progenitor cell function. Inhibits myogenic differentiation through the activation of Notch-signaling pathway. Inhibits vascular smooth muscle cells proliferation by increasing expression of cell-cycle regulators such as CDKN2B or CDKN1A independently of TGFB1 signaling. 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. 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 (By similarity). Involved in bone regeneration as a negative regulator (PubMed:23653360). Enhances the articular chondrocytic phenotype, whereas it repressed the one representing endochondral ossification (By similarity). Impairs pancreatic beta-cell function, inhibits beta-cell proliferation and insulin secretion (PubMed:23705021). 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 (By similarity). Contributes to the control and coordination of inflammatory processes in atherosclerosis (PubMed:24722330). Attenuates inflammatory pain through regulation of IL1B- and TNF-induced MMP9, MMP2 and CCL2 expression. Inhibits MMP9 expression through ITGB1 engagement (By similarity).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Names & Taxonomyi

Protein namesi
Recommended name:
Protein NOV homolog
Short name:
NovH
Alternative name(s):
CCN family member 3
Nephroblastoma-overexpressed gene protein homolog
Gene namesi
Name:Nov
Synonyms:Ccn3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:109185. Nov.

Subcellular locationi

  • Secreted 1 Publication
  • Cytoplasm By similarity
  • Cell junctiongap junction By similarity

  • Note: Localizes at the Gap junction in presence of GJA1/CX43.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Gap junction, Secreted

Pathology & Biotechi

Disruption phenotypei

Mutants develop normally but have enhanced arterial neointimal hyperplasia in response to injury (PubMed:20139355). Animals show an accelerated bone regeneration comparing to in wild-type mice (PubMed:24722330).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 354333Protein NOV homologPRO_0000014416Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi91 – 911N-linked (GlcNAc...)Sequence analysis
Disulfide bondi261 ↔ 298By similarity
Glycosylationi277 – 2771N-linked (GlcNAc...)Sequence analysis
Disulfide bondi278 ↔ 312By similarity
Disulfide bondi289 ↔ 328By similarity
Disulfide bondi292 ↔ 330By similarity
Disulfide bondi297 ↔ 334By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ64299.
PaxDbiQ64299.
PRIDEiQ64299.

Expressioni

Tissue specificityi

Expressed in large vessels including the ascending aorta, carotid arteries, and the thoracic aorta, in medium-sized vessels such as coronary arteries and small pulmonary veins and also in small vessels. In addition, also found to be present in the heart (at protein level) (PubMed:21063504). Expressed in astrocytes (at protein level) (PubMed:15213231). Detected in brain, bone, lung and muscle tissues (PubMed:20139355, PubMed:23653360). Expressed in skin, expression highly increases 5 days post-wounding, peaking on the 7th day to decline after 9 days (PubMed:15611078). Expressed in pancreatic ducts and beta-cell islets (PubMed:23705021).6 Publications

Developmental stagei

Up-regulated in the early phase of bone regeneration.1 Publication

Inductioni

Expression is reduced in atherosclerosis progression.1 Publication

Gene expression databases

BgeeiQ64299.
CleanExiMM_NOV.
GenevisibleiQ64299. MM.

Interactioni

Subunit structurei

Interacts with FBLN1. Interacts (via CTCK domain) with NOTCH1 (via the EGF-like repeat region). Interacts with GJA1/CX43. Interacts with ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB5.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000054389.

Structurei

3D structure databases

ProteinModelPortaliQ64299.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 9975IGFBP N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini102 – 16867VWFCPROSITE-ProRule annotationAdd
BLAST
Domaini202 – 24746TSP type-1PROSITE-ProRule annotationAdd
BLAST
Domaini261 – 33575CTCKPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the CCN family.Curated
Contains 1 CTCK (C-terminal cystine knot-like) domain.PROSITE-ProRule annotation
Contains 1 IGFBP N-terminal domain.PROSITE-ProRule annotation
Contains 1 TSP type-1 domain.PROSITE-ProRule annotation
Contains 1 VWFC domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IH0W. Eukaryota.
ENOG4111F77. LUCA.
GeneTreeiENSGT00760000119225.
HOGENOMiHOG000231462.
HOVERGENiHBG000635.
InParanoidiQ64299.
OMAiQCEMVKQ.
OrthoDBiEOG7N8ZXB.
PhylomeDBiQ64299.
TreeFamiTF326070.

Family and domain databases

InterProiIPR006207. Cys_knot_C.
IPR006208. Glyco_hormone_CN.
IPR009030. Growth_fac_rcpt_.
IPR000867. IGFBP-like.
IPR012395. IGFBP_CNN.
IPR017891. Insulin_GF-bd_Cys-rich_CS.
IPR000884. TSP1_rpt.
IPR001007. VWF_dom.
[Graphical view]
PfamiPF00007. Cys_knot. 1 hit.
PF00219. IGFBP. 1 hit.
PF00093. VWC. 1 hit.
[Graphical view]
PIRSFiPIRSF036495. IGFBP_rP_CNN. 1 hit.
SMARTiSM00041. CT. 1 hit.
SM00121. IB. 1 hit.
SM00209. TSP1. 1 hit.
SM00214. VWC. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS01185. CTCK_1. 1 hit.
PS01225. CTCK_2. 1 hit.
PS00222. IGFBP_N_1. 1 hit.
PS51323. IGFBP_N_2. 1 hit.
PS50092. TSP1. 1 hit.
PS01208. VWFC_1. 1 hit.
PS50184. VWFC_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q64299-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLFLRKRCL CLGFLLFHLL SQVSASLRCP SRCPPKCPSI SPTCAPGVRS
60 70 80 90 100
VLDGCSCCPV CARQRGESCS EMRPCDQSSG LYCDRSADPN NQTGICMVPE
110 120 130 140 150
GDNCVFDGVI YRNGEKFEPN CQYFCTCRDG QIGCLPRCQL DVLLPGPDCP
160 170 180 190 200
APRKVAVPGE CCEKWTCGSD EQGTQGTLGG LALPAYRPEA TVGVEVSDSS
210 220 230 240 250
INCIEQTTEW SACSKSCGMG VSTRVTNRNR QCEMVKQTRL CIVRPCEQEP
260 270 280 290 300
EEVTDKKGKK CLRTKKSLKA IHLQFENCTS LYTYKPRFCG VCSDGRCCTP
310 320 330 340 350
HNTKTIQVEF QCLPGEIIKK PVMVIGTCTC YSNCPQNNEA FLQDLELKTS

RGEI
Length:354
Mass (Da):38,928
Last modified:November 1, 1996 - v1
Checksum:i08ECE8CFC67829DE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61R → G in BAC30363 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X97863 Genomic DNA. Translation: CAA66457.1.
Y09257 mRNA. Translation: CAA70454.1.
X96585 mRNA. Translation: CAA65404.1.
AK039481 mRNA. Translation: BAC30363.1.
AK081944 mRNA. Translation: BAC38378.1.
BC003774 mRNA. Translation: AAH03774.1.
CCDSiCCDS27471.1.
RefSeqiNP_035060.1. NM_010930.4.
UniGeneiMm.5167.

Genome annotation databases

EnsembliENSMUST00000050027; ENSMUSP00000054389; ENSMUSG00000037362.
GeneIDi18133.
KEGGimmu:18133.
UCSCiuc007vrn.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X97863 Genomic DNA. Translation: CAA66457.1.
Y09257 mRNA. Translation: CAA70454.1.
X96585 mRNA. Translation: CAA65404.1.
AK039481 mRNA. Translation: BAC30363.1.
AK081944 mRNA. Translation: BAC38378.1.
BC003774 mRNA. Translation: AAH03774.1.
CCDSiCCDS27471.1.
RefSeqiNP_035060.1. NM_010930.4.
UniGeneiMm.5167.

3D structure databases

ProteinModelPortaliQ64299.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000054389.

Proteomic databases

MaxQBiQ64299.
PaxDbiQ64299.
PRIDEiQ64299.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000050027; ENSMUSP00000054389; ENSMUSG00000037362.
GeneIDi18133.
KEGGimmu:18133.
UCSCiuc007vrn.1. mouse.

Organism-specific databases

CTDi4856.
MGIiMGI:109185. Nov.

Phylogenomic databases

eggNOGiENOG410IH0W. Eukaryota.
ENOG4111F77. LUCA.
GeneTreeiENSGT00760000119225.
HOGENOMiHOG000231462.
HOVERGENiHBG000635.
InParanoidiQ64299.
OMAiQCEMVKQ.
OrthoDBiEOG7N8ZXB.
PhylomeDBiQ64299.
TreeFamiTF326070.

Miscellaneous databases

NextBioi293376.
PROiQ64299.
SOURCEiSearch...

Gene expression databases

BgeeiQ64299.
CleanExiMM_NOV.
GenevisibleiQ64299. MM.

Family and domain databases

InterProiIPR006207. Cys_knot_C.
IPR006208. Glyco_hormone_CN.
IPR009030. Growth_fac_rcpt_.
IPR000867. IGFBP-like.
IPR012395. IGFBP_CNN.
IPR017891. Insulin_GF-bd_Cys-rich_CS.
IPR000884. TSP1_rpt.
IPR001007. VWF_dom.
[Graphical view]
PfamiPF00007. Cys_knot. 1 hit.
PF00219. IGFBP. 1 hit.
PF00093. VWC. 1 hit.
[Graphical view]
PIRSFiPIRSF036495. IGFBP_rP_CNN. 1 hit.
SMARTiSM00041. CT. 1 hit.
SM00121. IB. 1 hit.
SM00209. TSP1. 1 hit.
SM00214. VWC. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS01185. CTCK_1. 1 hit.
PS01225. CTCK_2. 1 hit.
PS00222. IGFBP_N_1. 1 hit.
PS51323. IGFBP_N_2. 1 hit.
PS50092. TSP1. 1 hit.
PS01208. VWFC_1. 1 hit.
PS50184. VWFC_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    Strain: 129/Sv and ICR.
    Tissue: Brain.
  2. "Regulation of nov by WT1: a potential role for nov in nephrogenesis."
    Martinerie C., Chevalier G., Rauscher F.J. III, Perbal B.
    Oncogene 12:1479-1492(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Embryonic head and Spinal cord.
  4. "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].
    Strain: Czech II.
    Tissue: Mammary tumor.
  5. "The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway."
    Sakamoto K., Yamaguchi S., Ando R., Miyawaki A., Kabasawa Y., Takagi M., Li C.L., Perbal B., Katsube K.
    J. Biol. Chem. 277:29399-29405(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NOTCH1.
  6. "CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible mechanism of connexin-mediated growth suppression."
    Fu C.T., Bechberger J.F., Ozog M.A., Perbal B., Naus C.C.
    J. Biol. Chem. 279:36943-36950(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  7. "Integrin-dependent functions of the angiogenic inducer NOV (CCN3): implication in wound healing."
    Lin C.G., Chen C.C., Leu S.J., Grzeszkiewicz T.M., Lau L.F.
    J. Biol. Chem. 280:8229-8237(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
  9. Cited for: TISSUE SPECIFICITY.
  10. Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
  11. "Nov/Ccn3, a novel transcriptional target of FoxO1, impairs pancreatic beta-cell function."
    Paradis R., Lazar N., Antinozzi P., Perbal B., Buteau J.
    PLoS ONE 8:E64957-E64957(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  12. "Overexpression of CCN3 inhibits inflammation and progression of atherosclerosis in apolipoprotein E-deficient mice."
    Liu J., Ren Y., Kang L., Zhang L.
    PLoS ONE 9:E94912-E94912(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY ATHEROSCLEROSIS.

Entry informationi

Entry nameiNOV_MOUSE
AccessioniPrimary (citable) accession number: Q64299
Secondary accession number(s): Q8CA67
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: January 20, 2016
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.