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Protein

Protein NOV homolog

Gene

NOV

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

Functioni

Immediate-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).By similarity9 Publications

GO - Molecular functioni

  • growth factor activity Source: UniProtKB-KW
  • heparin binding Source: GO_Central
  • insulin-like growth factor binding Source: InterPro
  • integrin binding Source: UniProtKB
  • Notch binding Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • bone regeneration Source: UniProtKB
  • cell adhesion mediated by integrin Source: UniProtKB
  • cell-cell signaling Source: GO_Central
  • cell chemotaxis Source: UniProtKB
  • chondrocyte differentiation Source: UniProtKB
  • endothelial cell-cell adhesion Source: UniProtKB
  • endothelial cell chemotaxis Source: UniProtKB
  • fibroblast migration Source: UniProtKB
  • hematopoietic stem cell homeostasis Source: UniProtKB
  • negative regulation of cell death Source: GO_Central
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of chondrocyte proliferation Source: UniProtKB
  • negative regulation of inflammatory response Source: UniProtKB
  • negative regulation of insulin secretion Source: UniProtKB
  • negative regulation of monocyte chemotaxis Source: UniProtKB
  • negative regulation of myotube differentiation Source: UniProtKB
  • negative regulation of NIK/NF-kappaB signaling Source: UniProtKB
  • negative regulation of sensory perception of pain Source: UniProtKB
  • negative regulation of SMAD protein signal transduction Source: UniProtKB
  • positive regulation of Notch signaling pathway Source: UniProtKB
  • regulation of gene expression Source: Ensembl
  • smooth muscle cell migration Source: UniProtKB
  • smooth muscle cell proliferation Source: UniProtKB
  • type B pancreatic cell proliferation Source: UniProtKB

Keywordsi

Molecular functionGrowth factor

Enzyme and pathway databases

SignaLinkiP48745
SIGNORiP48745

Names & Taxonomyi

Protein namesi
Recommended name:
Protein NOV homolog
Short name:
NovH
Alternative name(s):
CCN family member 3
Insulin-like growth factor-binding protein 9
Short name:
IBP-9
Short name:
IGF-binding protein 9
Short name:
IGFBP-9
Nephroblastoma-overexpressed gene protein homolog
Gene namesi
Name:NOV
Synonyms:CCN3, IGFBP9, NOVH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi

Organism-specific databases

EuPathDBiHostDB:ENSG00000136999.4
HGNCiHGNC:7885 NOV
MIMi164958 gene
neXtProtiNX_P48745

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasm, Gap junction, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi4856
OpenTargetsiENSG00000136999
PharmGKBiPA31687

Chemistry databases

DrugBankiDB00030 Insulin Human
DB00071 Insulin Pork

Polymorphism and mutation databases

BioMutaiNOV
DMDMi1352515

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 311 PublicationAdd BLAST31
ChainiPRO_000001441532 – 357Protein NOV homologAdd BLAST326

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi97N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi264 ↔ 301By similarity
Glycosylationi280N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi281 ↔ 315By similarity
Disulfide bondi292 ↔ 331By similarity
Disulfide bondi295 ↔ 333By similarity
Disulfide bondi300 ↔ 337By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP48745
PaxDbiP48745
PeptideAtlasiP48745
PRIDEiP48745

PTM databases

iPTMnetiP48745
PhosphoSitePlusiP48745
SwissPalmiP48745

Expressioni

Tissue specificityi

Expressed in endiothelial cells (at protein level) (PubMed:21063504). Expressed in bone marrow, thymic cells and nephroblastoma. Increased expression in Wilms tumor of the stromal type.2 Publications

Developmental stagei

Expressed in primitive compartments of umbilical vein cord.1 Publication

Inductioni

Expression is down-regulated by WT1. Expression is down-regulated by proinflammatory stimuli such as TNF or IL1B (PubMed:24722330, PubMed:21063504). Expression is induced by laminar shear stress and statins (PubMed:21063504).3 Publications

Gene expression databases

BgeeiENSG00000136999
CleanExiHS_NOV
ExpressionAtlasiP48745 baseline and differential
GenevisibleiP48745 HS

Organism-specific databases

HPAiCAB034423
HPA018449
HPA019684

Interactioni

Subunit structurei

Interacts with FBLN1. Interacts (via CTCK domain) with NOTCH1 (via the EGF-like repeat region) (PubMed:12050162). Interacts with GJA1/CX43 (PubMed:15181016, PubMed:15213231). Interacts with ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB5 (PubMed:12695522, PubMed:15611078).6 Publications

GO - Molecular functioni

  • growth factor activity Source: UniProtKB-KW
  • insulin-like growth factor binding Source: InterPro
  • integrin binding Source: UniProtKB
  • Notch binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110918, 15 interactors
CORUMiP48745
IntActiP48745, 14 interactors
STRINGi9606.ENSP00000259526

Structurei

3D structure databases

ProteinModelPortaliP48745
SMRiP48745
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 105IGFBP N-terminalPROSITE-ProRule annotationAdd BLAST74
Domaini108 – 174VWFCPROSITE-ProRule annotationAdd BLAST67
Domaini205 – 250TSP type-1PROSITE-ProRule annotationAdd BLAST46
Domaini264 – 338CTCKPROSITE-ProRule annotationAdd BLAST75

Sequence similaritiesi

Belongs to the CCN family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IH0W Eukaryota
ENOG4111F77 LUCA
GeneTreeiENSGT00760000119225
HOGENOMiHOG000231462
HOVERGENiHBG000635
InParanoidiP48745
OMAiCEMVKQT
OrthoDBiEOG091G0SQP
PhylomeDBiP48745
TreeFamiTF326070

Family and domain databases

InterProiView protein in InterPro
IPR006207 Cys_knot_C
IPR006208 Glyco_hormone_CN
IPR009030 Growth_fac_rcpt_cys_sf
IPR000867 IGFBP-like
IPR012395 IGFBP_CNN
IPR017891 Insulin_GF-bd_Cys-rich_CS
IPR000884 TSP1_rpt
IPR036383 TSP1_rpt_sf
IPR001007 VWF_dom
PfamiView protein in Pfam
PF00007 Cys_knot, 1 hit
PF00219 IGFBP, 1 hit
PF00093 VWC, 1 hit
PIRSFiPIRSF036495 IGFBP_rP_CNN, 1 hit
SMARTiView protein in SMART
SM00041 CT, 1 hit
SM00121 IB, 1 hit
SM00209 TSP1, 1 hit
SM00214 VWC, 1 hit
SUPFAMiSSF57184 SSF57184, 1 hit
SSF82895 SSF82895, 1 hit
PROSITEiView protein in PROSITE
PS01185 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

Sequencei

Sequence statusi: Complete.

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

P48745-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQSVQSTSFC LRKQCLCLTF LLLHLLGQVA ATQRCPPQCP GRCPATPPTC
60 70 80 90 100
APGVRAVLDG CSCCLVCARQ RGESCSDLEP CDESSGLYCD RSADPSNQTG
110 120 130 140 150
ICTAVEGDNC VFDGVIYRSG EKFQPSCKFQ CTCRDGQIGC VPRCQLDVLL
160 170 180 190 200
PEPNCPAPRK VEVPGECCEK WICGPDEEDS LGGLTLAAYR PEATLGVEVS
210 220 230 240 250
DSSVNCIEQT TEWTACSKSC GMGFSTRVTN RNRQCEMLKQ TRLCMVRPCE
260 270 280 290 300
QEPEQPTDKK GKKCLRTKKS LKAIHLQFKN CTSLHTYKPR FCGVCSDGRC
310 320 330 340 350
CTPHNTKTIQ AEFQCSPGQI VKKPVMVIGT CTCHTNCPKN NEAFLQELEL

KTTRGKM
Length:357
Mass (Da):39,162
Last modified:February 1, 1996 - v1
Checksum:i035D5BF4576BD85B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26 – 27LG → CL (PubMed:1756408).Curated2
Sequence conflicti97N → K in CAG33713 (Ref. 5) Curated1
Sequence conflicti97N → K in AAH15028 (PubMed:15489334).Curated1
Sequence conflicti231R → G in BAG35274 (PubMed:14702039).Curated1
Sequence conflicti357M → I in CAG33713 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04956842R → Q. Corresponds to variant dbSNP:rs2279112Ensembl.1
Natural variantiVAR_049569233R → H. Corresponds to variant dbSNP:rs11538929Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78351
, X78352, X78353, X78354 Genomic DNA Translation: CAA55146.1
X96584 mRNA Translation: CAA65403.1
AY082381 mRNA Translation: AAL92490.1
AK312355 mRNA Translation: BAG35274.1
CR457432 mRNA Translation: CAG33713.1
BC015028 mRNA Translation: AAH15028.1
CCDSiCCDS6328.1
PIRiI38069
RefSeqiNP_002505.1, NM_002514.3
UniGeneiHs.235935

Genome annotation databases

EnsembliENST00000259526; ENSP00000259526; ENSG00000136999
GeneIDi4856
KEGGihsa:4856
UCSCiuc003yoq.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNOV_HUMAN
AccessioniPrimary (citable) accession number: P48745
Secondary accession number(s): B2R5X7
, Q6I9S3, Q96BY5, Q9UDE4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: May 23, 2018
This is version 153 of the entry and version 1 of the sequence. See 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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. SIMILARITY comments
    Index of protein domains and families

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