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Protein

Protein NOV homolog

Gene

NOV

Organism
Homo sapiens (Human)
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 (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

  • heparin binding Source: GO_Central
  • 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 NF-kappaB import into nucleus Source: UniProtKB
  • negative regulation of sensory perception of pain Source: UniProtKB
  • negative regulation of SMAD protein import into nucleus 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
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136999-MONOMER.
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
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:7885. NOV.

Subcellular locationi

GO - Cellular componenti

  • axon Source: Ensembl
  • cytoplasm Source: UniProtKB
  • dendrite Source: Ensembl
  • extracellular region Source: UniProtKB
  • gap junction Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • neuronal cell body Source: Ensembl
  • proteinaceous extracellular matrix Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Gap junction, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi4856.
OpenTargetsiENSG00000136999.
PharmGKBiPA31687.

Chemistry databases

DrugBankiDB00030. Insulin Regular.

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...)Sequence analysis1
Disulfide bondi264 ↔ 301By similarity
Glycosylationi280N-linked (GlcNAc...)Sequence 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.

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

  • integrin binding Source: UniProtKB
  • Notch binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110918. 14 interactors.
IntActiP48745. 1 interactor.
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
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.
InParanoidiP48745.
OMAiQCEMVKQ.
OrthoDBiEOG091G0SQP.
PhylomeDBiP48745.
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.

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 rs2279112dbSNPEnsembl.1
Natural variantiVAR_049569233R → H.Corresponds to variant rs11538929dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP48745.
SMRiP48745.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110918. 14 interactors.
IntActiP48745. 1 interactor.
STRINGi9606.ENSP00000259526.

Chemistry databases

DrugBankiDB00030. Insulin Regular.

PTM databases

iPTMnetiP48745.
PhosphoSitePlusiP48745.

Polymorphism and mutation databases

BioMutaiNOV.
DMDMi1352515.

Proteomic databases

MaxQBiP48745.
PaxDbiP48745.
PeptideAtlasiP48745.
PRIDEiP48745.

Protocols and materials databases

DNASUi4856.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4856.
DisGeNETi4856.
GeneCardsiNOV.
HGNCiHGNC:7885. NOV.
HPAiCAB034423.
HPA018449.
HPA019684.
MIMi164958. gene.
neXtProtiNX_P48745.
OpenTargetsiENSG00000136999.
PharmGKBiPA31687.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IH0W. Eukaryota.
ENOG4111F77. LUCA.
GeneTreeiENSGT00760000119225.
HOGENOMiHOG000231462.
HOVERGENiHBG000635.
InParanoidiP48745.
OMAiQCEMVKQ.
OrthoDBiEOG091G0SQP.
PhylomeDBiP48745.
TreeFamiTF326070.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136999-MONOMER.
SignaLinkiP48745.
SIGNORiP48745.

Miscellaneous databases

ChiTaRSiNOV. human.
GeneWikiiNOV_(gene).
GenomeRNAii4856.
PROiP48745.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136999.
CleanExiHS_NOV.
ExpressionAtlasiP48745. baseline and differential.
GenevisibleiP48745. HS.

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...

Entry informationi

Entry nameiNOV_HUMAN
AccessioniPrimary (citable) accession number: P48745
Secondary accession number(s): B2R5X7
, Q6I9S3, Q96BY5, Q9UDE4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 144 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

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

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.