Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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C345C Netrin C-terminal Domain

SMART accession number:	SM00643
Description:	-
Interpro abstract (IPR018933):	The netrin (NTR) module is an about 130-residue domain found in the C-terminal parts of netrins, complement proteins C3, C4, and C5, secreted frizzled-related proteins, and type I procollagen C-proteinase enhancer proteins (PCOLCEs), as well as in the N-terminal parts of tissue inhibitors of metalloproteinases (TIMPs). The proteins harboring the NTR domain fulfill diverse biological roles ranging from axon guidance, regulation of Wnt signalling, to the control of the activity of metalloproteinases. The NTR domain can be found associated to other domains such as CUB, WAP, Kazal, Kunitz, Ig-like, laminin N-terminal, laminin-type EGF or frizzled. The NTR domain is implicated in inhibition of zinc metalloproteinases of the metzincin family [ (PUBMED:10452607) (PUBMED:11274388) ]. The NTR module is a basic domain containing six conserved cysteines, which are likely to form internal disulphide bonds, and several conserved blocks of hydrophobic residues (including an YLLLG-like motif). The NTR module consists of a beta-barrel with two terminal alpha-helices packed side by side against the face of the beta-barrel (see P16035 ) [ (PUBMED:10452607) ]. This entry includes most netrin modules, but excludes those found in TIMPs.
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 4227 C345C domains in 4219 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing C345C domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with C345C domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing C345C domain in the selected taxonomic class.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 48.21 map04310 Wnt signaling pathway 26.79 map04360 Axon guidance 25.00 map04610 Complement and coagulation cascades This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with C345C domain which could be assigned to a KEGG orthologous group, and not all proteins containing C345C domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of C345C domains in PDB

  PDB code	Main view	Title
  1bqq		CRYSTAL STRUCTURE OF THE MT1-MMP--TIMP-2 COMPLEX
  1br9		HUMAN TISSUE INHIBITOR OF METALLOPROTEINASE-2
  1buv		CRYSTAL STRUCTURE OF THE MT1-MMP-TIMP-2 COMPLEX
  1gxd		proMMP-2/TIMP-2 complex
  1uap		NMR structure of the NTR domain from human PCOLCE1
  1xwe		NMR Structure of C345C (NTR) domain of C5 of complement
  2a73		Human Complement Component C3
  2a74		Human Complement Component C3c
  2b39		Structure of mammalian C3 with an intact thioester at 3A resolution
  2e2d		Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2
  2i07		Human Complement Component C3b
  2ice		CRIg bound to C3c
  2icf		CRIg bound to C3b
  2qki		Human C3c in complex with the inhibitor compstatin
  2tmp		N-TERMINAL DOMAIN OF TISSUE INHIBITOR OF METALLOPROTEINASE-2 (N-TIMP-2), NMR, 49 STRUCTURES
  2wii		Complement C3b in complex with factor H domains 1-4
  2win		C3 convertase (C3bBb) stabilized by SCIN
  2xwb		Crystal Structure of Complement C3b in complex with Factors B and D
  2xwj		Crystal Structure of Complement C3b in Complex with Factor B
  3cu7		Human Complement Component 5
  3frp		Crystal Structure of Cobra Venom Factor, a Co-factor for C3- and C5 convertase CVFBb
  3g6j		C3b in complex with a C3b specific Fab
  3hrz		Cobra Venom Factor (CVF) in complex with human factor B
  3hs0		Cobra Venom Factor (CVF) in complex with human factor B
  3kls		Structure of complement C5 in complex with SSL7
  3km9		Structure of complement C5 in complex with the C-terminal beta-grasp domain of SSL7
  3l3o		Staphylococcal Complement Inhibitor (SCIN) in complex with Human Complement Component C3c
  3l5n		Staphylococcal Complement Inhibitor (SCIN) in complex with Human Complement Component C3b
  3nms		Staphylococcal Complement Inhibitor (SCIN) in complex with Human Complement C3c
  3ohx		Molecular Basis for Complement Recognition and Inhibition Determined by Crystallographic Studies of the Staphylococcal Complement Inhibitor (SCIN) Bound to C3c and C3b
  3prx		Structure of Complement C5 in Complex with CVF and SSL7
  3pvm		Structure of Complement C5 in Complex with CVF
  3t4a		Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution
  4a5w		Crystal structure of C5b6
  4e0s		Crystal Structure of C5b-6
  4fxg		Complement C4 in complex with MASP-2
  4fxk		Human complement C4
  4ilw		Complex of matrix metalloproteinase-10 catalytic domain (MMP-10cd) with tissue inhibitor of metalloproteinases-2 (TIMP-2)
  4xam		4XAM
  5fo7		5FO7
  5fo8		5FO8
  5fo9		5FO9
  5foa		5FOA
  5fob		5FOB
  5hcc		5HCC
  5hcd		5HCD
  5hce		5HCE
  5i5k		5I5K
  5jpm		5JPM
  5jpn		5JPN
  5jtw		5JTW

• Links (links to other resources describing this domain)

• PFAM	NTR/C345C module
  INTERPRO	IPR018933

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