PDBsum entry 6h3c

Signaling protein

PDB id: 6h3c

Contents

Protein chains

255 a.a.

258 a.a.

383 a.a.

237 a.a.

440 a.a.

Metals

_ZN ×2

Waters ×6

PDB id:

6h3c

Name:

Signaling protein

Title:

Cryo-em structure of the brisc complex bound to shmt2

Structure:

Brisc complex subunit abraxas 2. Chain: a, f. Synonym: abraxas brother protein 1,protein fam175b. Engineered: yes. Lys-63-specific deubiquitinase brcc36. Chain: b, g. Synonym: brca1-a complex subunit brcc36,brca1/brca2-containing complex subunit 3,brca1/brca2-containing complex subunit 36,brisc complex subunit brcc36.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: abraxas2, abro1, fam175b, kiaa0157. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five. Gene: brcc3, brcc36, c6.1a, cxorf53. Gene: babam2, brcc45, bre.

Authors:

R.D.Bunker,J.Rabl,N.H.Thoma

Key ref:

J.Rabl et al. (2019). Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation. Mol Cell, 75, 483. PubMed id: 31253574 DOI: 10.1016/j.molcel.2019.06.002

Date:

18-Jul-18 Release date: 10-Jul-19

Protein chains

Q15018  (ABRX2_HUMAN) -  BRISC complex subunit Abraxas 2 from Homo sapiens

Seq: 415 a.a.

Struc: 255 a.a.

Protein chains

P46736  (BRCC3_HUMAN) -  Lys-63-specific deubiquitinase BRCC36 from Homo sapiens

Seq: 316 a.a.

Struc: 258 a.a.

Protein chains

Q9NXR7  (BABA2_HUMAN) -  BRISC and BRCA1-A complex member 2 from Homo sapiens

Seq: 383 a.a.

Struc: 383 a.a.

Protein chains

Q9NWV8  (BABA1_HUMAN) -  BRISC and BRCA1-A complex member 1 from Homo sapiens

Seq: 329 a.a.

Struc: 237 a.a.

Protein chains

P34897  (GLYM_HUMAN) -  Serine hydroxymethyltransferase, mitochondrial from Homo sapiens

Seq: 504 a.a.

Struc: 440 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chains B, G: E.C.3.4.19.- - ?????
• Enzyme class 2: Chains E, J: E.C.2.1.2.1 - glycine hydroxymethyltransferase.

Pathway:

• Reaction: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O = (6S)- 5,6,7,8-tetrahydrofolate + L-serine
• Cofactor: Pyridoxal 5'-phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1016/j.molcel.2019.06.002

Mol Cell 75:483 (2019)

PubMed id: 31253574

Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation.

J.Rabl, R.D.Bunker, A.D.Schenk, S.Cavadini, M.E.Gill, W.Abdulrahman, A.Andrés-Pons, M.S.Luijsterburg, A.F.M.Ibrahim, E.Branigan, J.D.Aguirre, A.H.Marceau, C.Guérillon, T.Bouwmeester, U.Hassiepen, A.H.F.M.Peters, M.Renatus, L.Gelman, S.M.Rubin, N.Mailand, H.van Attikum, R.T.Hay, N.H.Thomä.

ABSTRACT

In mammals, ∼100 deubiquitinases act on ∼20,000 intracellular ubiquitination sites. Deubiquitinases are commonly regarded as constitutively active, with limited regulatory and targeting capacity. The BRCA1-A and BRISC complexes serve in DNA double-strand break repair and immune signaling and contain the lysine-63 linkage-specific BRCC36 subunit that is functionalized by scaffold subunits ABRAXAS and ABRO1, respectively. The molecular basis underlying BRCA1-A and BRISC function is currently unknown. Here we show that in the BRCA1-A complex structure, ABRAXAS integrates the DNA repair protein RAP80 and provides a high-affinity binding site that sequesters the tumor suppressor BRCA1 away from the break site. In the BRISC structure, ABRO1 binds SHMT2α, a metabolic enzyme enabling cancer growth in hypoxic environments, which we find prevents BRCC36 from binding and cleaving ubiquitin chains. Our work explains modularity in the BRCC36 DUB family, with different adaptor subunits conferring diversified targeting and regulatory functions.