Annotations: 5FIT

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d5fita_	Alpha and beta proteins (a+b)	HIT-like	HIT-like	HIT (HINT, histidine triad) family of protein kinase-interacting proteins	FHIT (fragile histidine triad protein)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	HIT-like	8034371	3000223	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	HIT	e5fitA1	A: a+b three layers	X: HIT-like	H: HIT-related (From Topology)	T: HIT-related	F: HIT	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.428.10	Alpha Beta	2-Layer Sandwich	HIT family, subunit A	HIT-like	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF01230	HIT domain (HIT)	HIT domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	FRAGILE HISTIDINE TRIAD PROTEIN	pyrophosphatase activity bis(5'-adenosyl)-triphosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity hydrolase activity, acting on acid anhydrides catalytic activity adenylyltransferase activity transferase activity nucleotidyltransferase activity adenylylsulfate-ammonia adenylyltransferase activity transferase activity, transferring phosphorus-containing groups binding nucleoside phosphate binding organic cyclic compound binding pyrophosphatase activity bis(5'-adenosyl)-triphosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity hydrolase activity, acting on acid anhydrides catalytic activity adenylyltransferase activity transferase activity nucleotidyltransferase activity adenylylsulfate-ammonia adenylyltransferase activity transferase activity, transferring phosphorus-containing groups binding nucleoside phosphate binding organic cyclic compound binding nucleotide binding heterocyclic compound binding small molecule binding adenylylsulfatase activity hydrolase activity, acting on acid anhydrides, in sulfonyl-containing anhydrides hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides adenosine 5'-monophosphoramidase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds ubiquitin protein ligase binding protein binding ubiquitin-like protein ligase binding enzyme binding identical protein binding	nucleoside phosphate metabolic process primary metabolic process nucleotide metabolic process purine-containing compound metabolic process nucleobase-containing compound metabolic process purine nucleotide metabolic process organophosphate metabolic process nucleobase-containing small molecule metabolic process phosphate-containing compound metabolic process metabolic process cellular process small molecule metabolic process phosphorus metabolic process catabolic process nucleoside phosphate metabolic process primary metabolic process nucleotide metabolic process purine-containing compound metabolic process nucleobase-containing compound metabolic process purine nucleotide metabolic process organophosphate metabolic process nucleobase-containing small molecule metabolic process phosphate-containing compound metabolic process metabolic process cellular process small molecule metabolic process phosphorus metabolic process catabolic process organophosphate catabolic process diadenosine polyphosphate metabolic process nucleoside phosphate catabolic process nucleobase-containing compound catabolic process diadenosine polyphosphate catabolic process diadenosine triphosphate metabolic process nucleotide catabolic process diadenosine triphosphate catabolic process cellular response to stimulus regulation of biological process regulation of cellular process response to stimulus signaling biological regulation signal transduction by p53 class mediator cell death intracellular signal transduction cell communication apoptotic signaling pathway intrinsic apoptotic signaling pathway by p53 class mediator signal transduction apoptotic process intrinsic apoptotic signaling pathway programmed cell death negative regulation of proteolysis negative regulation of proteolysis involved in protein catabolic process proteolysis involved in protein catabolic process negative regulation of biological process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process regulation of primary metabolic process negative regulation of protein catabolic process regulation of proteolysis involved in protein catabolic process regulation of proteolysis modification-dependent macromolecule catabolic process proteolysis negative regulation of cellular process protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process negative regulation of ubiquitin-dependent protein catabolic process negative regulation of catabolic process negative regulation of proteasomal ubiquitin-dependent protein catabolic process regulation of protein metabolic process negative regulation of metabolic process proteasomal protein catabolic process protein catabolic process regulation of macromolecule metabolic process regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process negative regulation of proteasomal protein catabolic process regulation of proteasomal protein catabolic process ubiquitin-dependent protein catabolic process macromolecule metabolic process regulation of metabolic process regulation of protein catabolic process	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle cytosol cell periphery plasma membrane membrane nucleus membrane-enclosed lumen membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle cytosol cell periphery plasma membrane membrane nucleus membrane-enclosed lumen intracellular membraneless organelle nucleolus intracellular organelle lumen organelle lumen fibrillar center membraneless organelle nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR011146	HIT-like domain	Domain
A	IPR036265	HIT-like superfamily	Homologous Superfamily
A	IPR039383	FHIT family	Family
A	IPR052677	Dinucleoside polyphosphate hydrolase	Family
A	IPR019808	Histidine triad, conserved site	Conserved Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P49789	amphetamine abuse liver cancer prostate cancer non-small cell lung carcinoma sarcomatoid carcinoma carcinoma gastric cancer hereditary diffuse gastric adenocarcinoma lung benign neoplasm Malignant neoplasm of stomach nonpapillary renal cell carcinoma benign urinary system neoplasm renal cell carcinoma cancer schizophrenia amphetamine abuse liver cancer prostate cancer non-small cell lung carcinoma sarcomatoid carcinoma carcinoma gastric cancer hereditary diffuse gastric adenocarcinoma lung benign neoplasm Malignant neoplasm of stomach nonpapillary renal cell carcinoma benign urinary system neoplasm renal cell carcinoma cancer schizophrenia substance dependence gastric neoplasm mesothelioma autism spectrum disorder brain aneurysm sarcoidosis substance abuse clear cell renal carcinoma drug dependence undifferentiated carcinoma endogenous depression hereditary clear cell renal cell carcinoma liver neoplasm osteosarcoma benign mesothelioma breast cancer common variable immunodeficiency substance-related disorder

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	bis(5'-adenosyl)-triphosphatase M-CSA #101	The FHIT protein is a diadenosine P1, P3-triphosphate (ApppA) hydrolase that cleaves diadenosine P1, P3-triphosphate to yield AMP and ADP which is found in animals and fungi. In humans the FHIT gene is found at 3p14.2 and is thought to act as a tumour suppressor gene involved in many human cancers. It belongs to one branch of the Histidine triad (HIT) superfamily of nucleotide-binding proteins which have a conserved His-X-His-X-His-X-X (where X is a hydrophobic amino acid) motif. This was originally thought to be a zinc-ion binding site but is now believed to be the alpha-phosphate binding site [PMID:9323207]. The other branch of this superfamily consists of the HINT (histidine triad nucleotide-binding) proteins, the proposed ancestor of FHIT, galactose-1-phosphate uridylyltransferase, and other nucleotide binding proteins [PMID:9323207]. Dinocleoside polyphoshate hydrolases require millimolar Mn(II) Mg(II) or Ca(II) for optimum activity and are inhibited by Ni(II) Zn(II) and Cd(II).	Defined by 4 residues: GLN:A-83HIS:A-94HIS:A-96HIS:A-98 \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 3.6.1.29 (PDB Primary Data) Search M-CSA Motif + EC 3.6.1.29 EC: 3.6.2.1 (UniProt) Search M-CSA Motif + EC 3.6.2.1 EC: 2.7.7.51 (UniProt) Search M-CSA Motif + EC 2.7.7.51 EC: 3.9.1 (UniProt) Search M-CSA Motif + EC 3.9.1

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.