2I46 | pdb_00002i46

Crystal structure of human TPP1

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	TPP1-like	8044709	4004093	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Nucleic acid-binding proteins	8052151	3000135	SCOP2 (2022-06-29)
B	SCOP2B Superfamily	Nucleic acid-binding proteins	8052151	3000135	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	TPP1	e2i46A1	A: beta barrels	X: OB-fold	H: Nucleic acid-binding proteins (From Topology)	T: Nucleic acid-binding proteins	F: TPP1	ECOD (1.6)
B	TPP1	e2i46B1	A: beta barrels	X: OB-fold	H: Nucleic acid-binding proteins (From Topology)	T: Nucleic acid-binding proteins	F: TPP1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.40.50.960	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)		CATH (4.3.0)
B	2.40.50.960	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF10341	Shelterin complex subunit, TPP1/ACD (TPP1)	Shelterin complex subunit, TPP1/ACD	TPP1 is a component of the telomerase holoenzyme, involved in telomere replication. It has been demonstrated that TPP1 dimerises and binds to DNA and RNA. Furthermore, TPP1 stimulates the dissociation of RNA/DNA hetero-duplexes [1,2]. Yeast telomera ...	TPP1 is a component of the telomerase holoenzyme, involved in telomere replication. It has been demonstrated that TPP1 dimerises and binds to DNA and RNA. Furthermore, TPP1 stimulates the dissociation of RNA/DNA hetero-duplexes [1,2]. Yeast telomerase protein TPP1 (Est3 in yeast) is a novel type of GTPase [3]. The key residues in Swiss:Q03096 are an Asp at residue 86 and the Arg at residue 110. The Asp is totally conserved in the family, whereas the Arg is not so well conserved. The N-terminal of TPP1 is likely to be the binding surface for TINF2, whereas the C-terminus probably binds to POT1, thereby tethering POT1 to the shelterin complex [4]. The complex bound to telomeric DNA increases the activity and processivity of the human telomerase core enzyme, thus helping to maintain the length of the telomeres [5,6]. This domain is conserved from fungi to mammals, hence family Telomere_Pot1 has been merged into the family [7]. The human shelterin complex includes six proteins: telomere repeat binding factor 1 (TRF1), TRF2, repressor/activator protein 1 (RAP1), TRF1-interacting nuclear protein 2 (TIN2), TIN2-interacting protein 1 (TPP1) and protection of telomeres 1 (POT1) [8].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Adrenocortical dysplasia protein homolog	sequence-specific DNA binding DNA binding binding nucleic acid binding telomeric DNA binding protein-containing complex binding enzyme regulator activity RNA-directed DNA polymerase activity catalytic activity, acting on a nucleic acid transferase activity enzyme inhibitor activity nucleotidyltransferase activity telomerase inhibitor activity transferase activity, transferring phosphorus-containing groups sequence-specific DNA binding DNA binding binding nucleic acid binding telomeric DNA binding protein-containing complex binding enzyme regulator activity RNA-directed DNA polymerase activity catalytic activity, acting on a nucleic acid transferase activity enzyme inhibitor activity nucleotidyltransferase activity telomerase inhibitor activity transferase activity, transferring phosphorus-containing groups telomerase activity molecular function inhibitor activity catalytic activity, acting on DNA DNA polymerase activity molecular function regulator activity catalytic activity protein binding DNA polymerase binding enzyme binding	telomere maintenance via telomerase telomere organization chromosome organization primary metabolic process DNA metabolic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process nucleic acid metabolic process RNA-templated DNA biosynthetic process nucleobase-containing compound metabolic process telomere maintenance via telomere lengthening telomere maintenance cellular component organization nucleic acid biosynthetic process organelle organization telomere maintenance via telomerase telomere organization chromosome organization primary metabolic process DNA metabolic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process nucleic acid metabolic process RNA-templated DNA biosynthetic process nucleobase-containing compound metabolic process telomere maintenance via telomere lengthening telomere maintenance cellular component organization nucleic acid biosynthetic process organelle organization biosynthetic process metabolic process cellular process macromolecule metabolic process cellular component organization or biogenesis DNA biosynthetic process developmental process multicellular organism development multicellular organismal process segmentation anatomical structure development pattern specification process regionalization skeletal system development system development urogenital system development cellular component biogenesis cellular component assembly telomere assembly limb development appendage development embryonic limb morphogenesis embryonic morphogenesis embryonic appendage morphogenesis embryo development anatomical structure morphogenesis appendage morphogenesis limb morphogenesis negative regulation of telomere maintenance regulation of cellular process negative regulation of biological process negative regulation of telomere maintenance via telomerase regulation of DNA biosynthetic process regulation of primary metabolic process negative regulation of chromosome organization negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of biological process negative regulation of cellular component organization negative regulation of metabolic process regulation of chromosome organization regulation of telomere maintenance via telomere lengthening regulation of organelle organization negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of metabolic process negative regulation of DNA biosynthetic process regulation of DNA metabolic process regulation of telomere maintenance regulation of cellular component organization negative regulation of telomere maintenance via telomere lengthening negative regulation of cellular process negative regulation of macromolecule metabolic process regulation of biosynthetic process biological regulation regulation of macromolecule metabolic process regulation of telomere maintenance via telomerase negative regulation of organelle organization negative regulation of biosynthetic process negative regulation of DNA metabolic process establishment of protein localization to telomere protein localization regulation of localization establishment of protein localization cellular localization regulation of protein localization localization regulation of protein localization to chromosome, telomeric region cellular macromolecule localization establishment of protein localization to chromosome regulation of establishment of protein localization to chromosome regulation of establishment of protein localization protein localization to chromosome, telomeric region establishment of localization establishment of protein localization to organelle protein localization to chromosome regulation of cellular localization regulation of establishment of protein localization to telomere macromolecule localization protein localization to organelle nitrogen compound transport transport intracellular transport protein transport establishment of localization in cell intracellular protein transport positive regulation of organelle organization positive regulation of cellular component organization positive regulation of biological process positive regulation of metabolic process positive regulation of macromolecule metabolic process positive regulation of cellular process positive regulation of telomere maintenance positive regulation of nucleobase-containing compound metabolic process positive regulation of chromosome organization positive regulation of DNA metabolic process cellular response to stimulus telomere maintenance in response to DNA damage response to stimulus protection from non-homologous end joining at telomere cellular response to stress telomere capping DNA damage response response to stress	membrane-bounded organelle protein-containing complex intracellular anatomical structure catalytic complex nucleus nuclear protein-containing complex intracellular membrane-bounded organelle intracellular organelle telomerase holoenzyme complex cellular anatomical structure organelle ribonucleoprotein complex protein-DNA complex intracellular membraneless organelle membrane-bounded organelle protein-containing complex intracellular anatomical structure catalytic complex nucleus nuclear protein-containing complex intracellular membrane-bounded organelle intracellular organelle telomerase holoenzyme complex cellular anatomical structure organelle ribonucleoprotein complex protein-DNA complex intracellular membraneless organelle chromosome chromosomal region telomere cap complex membraneless organelle chromosome, telomeric repeat region chromosome, telomeric region shelterin complex nuclear telomere cap complex membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen nuclear body

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR028631	Adrenocortical dysplasia protein	Family
A, B	IPR019437	Shelterin complex subunit TPP1/Est3	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q96AP0	dyskeratosis congenita, autosomal dominant 6 dyskeratosis congenita familial melanoma Hoyeraal-Hreidarsson syndrome gastric carcinoma osteosarcoma DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 7 hematopoietic and lymphoid system neoplasm subependymal giant cell astrocytoma

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.