PDBsum entry 2x2u

Transferase

PDB id: 2x2u

Contents

Protein chain

236 a.a. *

Ligands

NAG-NAG

UNX-UNX ×2

UNX ×4

UNX-UNX-UNX

SO4 ×8

BU1 ×2

Waters ×216

* Residue conservation analysis

PDB id:

2x2u

Name:

Transferase

Title:

First two cadherin-like domains from human ret

Structure:

Proto-oncogene tyrosine-protein kinase receptor ret. Chain: a. Fragment: cadherin-like domains 1 and 2, residues 29-270. Synonym: c-ret, ret, cadherin family member 12. Engineered: yes. Mutation: yes. Other_details: asn 151 is glycosylated

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: lec8. Expression_system_organ: ovary.

Resolution:

2.00Å R-factor: 0.184 R-free: 0.228

Authors:

S.Kjaer,S.Hanrahan,A.G.Purkiss-Trew,N.Totty,N.Q.Mcdonald

Key ref:

S.Kjaer et al. (2010). Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations. Nat Struct Biol, 17, 726-731. PubMed id: 20473317

Date:

15-Jan-10 Release date: 19-May-10

Protein chain

P07949  (RET_HUMAN) -  Proto-oncogene tyrosine-protein kinase receptor Ret from Homo sapiens

Seq: 1114 a.a.

Struc: 236 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

L-tyrosyl-[protein] + ATP (Bound ligand (Het Group name = NAG) matches with 47.62% similarity) = O-phospho-L-tyrosyl-[protein] + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Nat Struct Biol 17:726-731 (2010)

PubMed id: 20473317

Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations.

S.Kjaer, S.Hanrahan, N.Totty, N.Q.McDonald.

ABSTRACT

The maturation of human RET is adversely affected by a range of missense mutations found in patients with Hirschsprung's disease (HSCR), a complex multigenic disease. Here we show that two N-terminal cadherin-like domains, CLD1 and CLD2 (CLD(1-2)), from human RET adopt a clam-shell arrangement distinct from that of classical cadherins. CLD1 structural elements and disulfide composition are unique to mammals, indicating an unexpected structural diversity within higher and lower vertebrate RET CLD regions. We identify two unpaired cysteines that predispose human RET to maturation impediments in the endoplasmic reticulum and establish a quantitative cell-based RET maturation assay that offers a biochemical correlate of HSCR disease severity. Our findings provide a key conceptual framework and means of testing and predicting genotype-phenotype correlations in HSCR.