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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HintN Hint (Hedgehog/Intein) domain N-terminal region

SMART accession number:	SM00306
Description:	Hedgehog/Intein domain, N-terminal region. Domain has been split to accommodate large insertions of endonucleases.
Interpro abstract (IPR003587):	Hedgehog proteins are a family of secreted signal molecules required for embryonic cell differentiation. They are synthesised as inactive precursors with an N-terminal signalling domain linked to a C-terminal autoprocessing domain. The three-dimensional structure of the autolytic domain of the hedgehog protein of shows similarity with the beta-strand core of intein splicing domains. It has hence been termed the hint (Hedgehog/Intein) domain [ (PUBMED:9489693) ]. This entry represents the N-terminal region of the hint domain.
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 10871 HintN domains in 9985 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 HintN domain.

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

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

• Disease (disease genes where sequence variants are found in this domain)

• SwissProt sequences and OMIM curated human diseases associated with missense mutations within the HintN domain.

  Protein	Disease
  Sonic hedgehog protein (Q15465) (SMART)	OMIM:600725: Holoprosencephaly-3 OMIM:142945:

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

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 23.24 map00240 Pyrimidine metabolism 23.24 map00230 Purine metabolism 16.20 map03030 DNA replication 16.20 map04340 Hedgehog signaling pathway 5.63 map00190 Oxidative phosphorylation 3.52 map03020 RNA polymerase 2.82 map00500 Starch and sucrose metabolism 1.41 map00520 Nucleotide sugars metabolism 1.41 map00053 Ascorbate and aldarate metabolism 1.41 map00040 Pentose and glucuronate interconversions 1.41 map00790 Folate biosynthesis 0.70 map05120 Epithelial cell signaling in Helicobacter pylori infection 0.70 map00251 Glutamate metabolism 0.70 map03022 Basal transcription factors 0.70 map00530 Aminosugars metabolism 0.70 map04115 p53 signaling pathway 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 HintN domain which could be assigned to a KEGG orthologous group, and not all proteins containing HintN 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 HintN domains in PDB

  PDB code	Main view	Title
  1am2		GYRA INTEIN FROM MYCOBACTERIUM XENOPI
  1at0		17-KDA FRAGMENT OF HEDGEHOG C-TERMINAL AUTOPROCESSING DOMAIN
  1dfa		CRYSTAL STRUCTURE OF PI-SCEI IN C2 SPACE GROUP
  1dq3		CRYSTAL STRUCTURE OF AN ARCHAEAL INTEIN-ENCODED HOMING ENDONUCLEASE PI-PFUI
  1ef0		CRYSTAL STRUCTURE OF PI-SCEI MINIPRECURSOR
  1gpp		Crystal structure of the S.cerevisiae Homing Endonuclease PI-SceI Domain I
  1jva		CRYSTAL STRUCTURE OF THE VMA1-DERIVED ENDONUCLEASE BEARING THE N AND C EXTEIN PROPEPTIDES
  1lws		Crystal structure of the intein homing endonuclease PI-SceI bound to its recognition sequence
  1lwt		Crystal structure of the intein homing endonuclease PI-SceI bound to its substrate DNA (Ca2+ free)
  1mi8		2.0 Angstrom crystal structure of a DnaB intein from Synechocystis sp. PCC 6803
  1um2		Crystal Structure of the Vma1-Derived Endonuclease with the Ligated Extein Segment
  1vde		PI-SCEI, A HOMING ENDONUCLEASE WITH PROTEIN SPLICING ACTIVITY
  1zd7		1.7 Angstrom Crystal Structure Of Post-Splicing Form of a dnaE Intein from Synechocystis Sp. Pcc 6803
  1zde		1.95 Angstrom Crystal Structure of a dnaE Intein Precursor from Synechocystis Sp. Pcc 6803
  2cw7		Crystal structure of intein homing endonuclease II
  2cw8		Crystal structure of intein homing endonuclease II
  2imz		Crystal structure of Mtu recA intein splicing domain
  2in0		crystal structure of Mtu recA intein splicing domain
  2in8		crystal structure of Mtu recA intein, splicing domain
  2in9		crystal structure of Mtu recA intein, splicing domain
  2jmz		Solution structure of a KlbA intein precursor from Methanococcus jannaschii
  2jnq		Solution Structure of a KlbA Intein Precursor from Methanococcus jannaschii
  2keq		Solution structure of DnaE intein from Nostoc punctiforme
  2l8l		Structure of an engineered splicing intein mutant based on Mycobacterium tuberculosis RecA
  2lcj		Solution NMR structure of Pab PolII Intein
  2lqm		Solution Structures of RadA intein from Pyrococcus horikoshii
  2lwy		Solution Structure of Bacterial Intein-Like domain from Clostridium thermocellum
  3ifj		Crystal structure of Mtu recA intein, splicing domain
  3igd		Crystal structure of Mtu recA intein, splicing domain
  3nzm		Crystal structure of DNAE intein with N-extein in redox trap
  4e2t		Crystal Structures of RadA intein from Pyrococcus horikoshii
  4e2u		Crystal Structures of RadAmin intein from Pyrococcus horikoshii
  4gig		crystal structure of T69A mutant of trapped Dnae intein precursor
  4kl5		Crystal structure of NpuDnaE intein
  4kl6		Crystal structure of dimeric form of NpuDnaE intein
  4lx3		4LX3
  4o1r		Crystal structure of NpuDnaB intein
  4o1s		Crystal structure of TvoVMA intein
  4oz6		Structure of the Branched Intermediate in Protein Splicing
  4qfq		4QFQ
  5i0a		5I0A
  5k08		5K08

• Links (links to other resources describing this domain)

• PFAM	Hint
  INTERPRO	IPR003587

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